TW201919620A - Depot formulations - Google Patents

Depot formulations Download PDF

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TW201919620A
TW201919620A TW107122346A TW107122346A TW201919620A TW 201919620 A TW201919620 A TW 201919620A TW 107122346 A TW107122346 A TW 107122346A TW 107122346 A TW107122346 A TW 107122346A TW 201919620 A TW201919620 A TW 201919620A
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Taiwan
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composition
weight
sirolimus
vitamin
item
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TW107122346A
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Chinese (zh)
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威瑪 坦洛茲
林惠清 蘇
偉琦 林
山田和人
松本直樹
史尼凡蘇 莫杜巴
岡部高明
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美商杜瑞克公司
日商參天製藥股份有限公司
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Priority claimed from US15/637,401 external-priority patent/US10668011B2/en
Application filed by 美商杜瑞克公司, 日商參天製藥股份有限公司 filed Critical 美商杜瑞克公司
Publication of TW201919620A publication Critical patent/TW201919620A/en

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Abstract

Pharmaceutical compositions comprising an active pharmaceutical ingredient, a high viscosity liquid carrier material, a hydrophobic solvent, and a hydrophilic solvent are disclosed. Also disclosed are methods of manufacturing and using the compositions. The compositions are suitable for use, e.g., as depot formulations.

Description

貯庫型調合物Depot blend

本發明關於貯庫型醫藥調合物及其用途，包括眼內貯庫型醫藥調合物。The invention relates to a depot-type pharmaceutical blend and its use, including an intraocular depot-type pharmaceutical blend.

某些眼科症狀，諸如眼色素層炎、濕乾式老年性黃斑部退化(AMD)、糖尿病黃斑部水腫(DME)、糖尿病視網膜病變(DR)及角膜真菌病需要長期治療。雖然藥物治療可經全身性給予(例如經口)，但是此治療使全身暴露於藥物且不能使治療集中於最需要治療的區域。眼內貯庫型調合物應能夠使治療聚集於需要治療的區域，同時減少患者身體全身性暴露於藥劑及降低投予頻率。 　　然而，眼內貯庫型調合物的發展比其他的植入物及貯庫型調合物更具有挑戰性。眼用貯庫物必須最小化或較佳地完全避免影響視力，但是眼睛的空間有限且可能對壓力及/或扭曲敏感。因此，應該限制不論是例如體液內(intra-humorous)或結膜下的眼內貯庫型調合物之物理尺寸，亦即體積。然而，貯庫型調合物同時應含有足夠的活性醫藥成分(API)以避免要常常重複施予(因為施予方法通常為侵入性且不方便，例如藉由在醫院或臨床環境中注射)。 　　關於體液內(例如玻璃體內)貯庫物，因為該等係放入流體環境中，所以使貯庫物保持內聚性亦為重要的。沒有內聚性的貯庫物可能分解成許多獨立的小球體。該等小球體具有比內聚性貯庫物更大的集體表面積，其可影響API釋放速率。大量的小球體亦具有不利地衝擊視力的可能性。 　　經植入或注入之調合物，諸如眼內(例如玻璃體內)貯庫物為高侵入性、不方便且可能需要由醫護專業人員投予。因此，通常認為以醫藥組成物投予患者後展現經控制或延長釋放且較佳地展現經長時期持續的藥效之貯庫型調合物是有利的。 　　對改進之貯庫型調合物(包括眼內貯庫型調合物)及治療眼科症狀之方法仍維持長期的需求。例如，對西羅莫司(sirolimus)貯庫型調合物及其用於治療眼科症狀之方法仍維持長期的需求。對能夠提供持續釋放活性成分之貯庫型調合物(包括眼內貯庫型調合物)仍維持長期的需求。對經由基本上由活性醫藥成分、高黏度液態載體材料(HVLCM)、疏水性溶劑及親水性溶劑所組成之組成物達到持續釋放之貯庫型調合物(較佳為眼內貯庫型調合物)仍維持長期的需求，該組成物較佳地不包含在材質上影響持續釋放速率或程度之其他賦形劑。Certain ophthalmic symptoms, such as uveitis, wet-dry senile macular degeneration (AMD), diabetic macular edema (DME), diabetic retinopathy (DR), and corneal mycosis require long-term treatment. Although drug treatment can be administered systemically (e.g., orally), this treatment exposes the system to the drug and does not focus the treatment in the area where it is most needed. Intraocular depot-type blends should be able to focus treatment on the area in need of treatment, while reducing the systemic exposure of the patient's body to the agent and the frequency of administration. However, the development of intraocular depot blends is more challenging than other implants and depot blends. Ophthalmic depots must be minimized or preferably completely avoided from affecting vision, but the eye has limited space and may be sensitive to stress and / or distortion. Therefore, the physical size, ie, volume, of the intraocular depot type blend, whether for example intra-humorous or subconjunctival, should be limited. However, depot type blends should also contain sufficient active pharmaceutical ingredients (APIs) to avoid frequent repeated administrations (because the methods of administration are often invasive and inconvenient, such as by injection in a hospital or clinical setting). Regarding the storage materials in body fluids (such as the vitreous body), because these systems are placed in a fluid environment, it is also important to keep the storage materials cohesive. Depots without cohesion may break down into many small independent spheres. These small spheres have a larger collective surface area than cohesive depots, which can affect the API release rate. The large number of small spheres also has the potential to adversely impact vision. Implanted or injected formulations, such as intraocular (eg, intravitreal) depots, are highly invasive, inconvenient and may require administration by a healthcare professional. Therefore, it is generally considered advantageous to have a depot type blend that exhibits controlled or prolonged release after administration to a patient as a pharmaceutical composition and preferably exhibits long-lasting medicinal effects.长期 The need for improved depot-type formulations (including intra-ocular depot-type formulations) and methods of treating ophthalmic symptoms remains long-term. For example, there is a continuing need for sirolimus depot type blends and their methods for treating ophthalmic symptoms. There remains a long-term need for depot type formulations (including intraocular depot type formulations) capable of providing sustained release of active ingredients. Depot type blends (preferably intraocular depot type blends) that achieve sustained release via a composition consisting essentially of an active pharmaceutical ingredient, a high viscosity liquid carrier material (HVLCM), a hydrophobic solvent and a hydrophilic solvent ) Still maintaining long-term demand, the composition preferably does not contain other excipients that affect the rate or extent of sustained release on the material.

在下文提供本發明之特定的非限制性態樣： 　　1. 一種組成物，其包含： 　　活性醫藥成分； 　　高黏度液態載體材料(HVLCM)； 　　第一疏水性溶劑；及 　　親水性溶劑； 　　其中組成物在25℃及1大氣壓下為溶液及/或其中組成物在25℃及1大氣壓下具有範圍約1cP至約150cP之黏度。 　　2. 一種組成物，其包含： 　　活性醫藥成分； 　　高黏度液態載體材料(HVLCM)，其中HVLCM係以組成物重量為基準計的範圍約0.5重量%至約15重量%之量存在； 　　第一疏水性溶劑，其中第一疏水性溶劑係以組成物重量為基準計的範圍約30重量%至約50重量%之量存在；及 　　親水性溶劑； 　　其中組成物在25℃及1大氣壓下為溶液及/或其中組成物在25℃及1大氣壓下具有範圍約1cP至約150cP之黏度。 　　3. 一種組成物，其包含： 　　活性醫藥成分； 　　高黏度液態載體材料(HVLCM)，其中HVLCM係以組成物重量為基準計的範圍約0.5重量%至約15重量%之量存在； 　　第一疏水性溶劑，其中第一疏水性溶劑係以組成物重量為基準計的範圍約80重量%至約95重量%之量存在；及 　　親水性溶劑； 　　其中組成物在25℃及1大氣壓下為溶液及/或其中組成物在25℃及1大氣壓下具有範圍約1cP至約150cP之黏度。 　　4. 一種組成物，其包含： 　　活性醫藥成分，其中活性醫藥成分包含西羅莫司； 　　高黏度液態載體材料(HVLCM)； 　　第一疏水性溶劑；及 　　親水性溶劑。 　　5. 一種組成物，其包含： 　　活性醫藥成分，其中活性醫藥成分包含西羅莫司； 　　高黏度液態載體材料(HVLCM)，其中HVLCM係以組成物重量為基準計的範圍約0.5重量%至約15重量%之量存在； 　　第一疏水性溶劑，其中第一疏水性溶劑係以組成物重量為基準計的範圍約30重量%至約50重量%之量存在；及 　　親水性溶劑。 　　6. 一種組成物，其包含： 　　活性醫藥成分，其中活性醫藥成分包含西羅莫司； 　　高黏度液態載體材料(HVLCM)，其中HVLCM係以組成物重量為基準計的範圍約0.5重量%至約15重量%之量存在； 　　第一疏水性溶劑，其中第一疏水性溶劑係以組成物重量為基準計的範圍約80重量%至約95重量%之量存在；及 　　親水性溶劑。 　　7. 一種組成物，其包含： 　　活性醫藥成分； 　　第一疏水性溶劑； 　　不同於第一疏水性溶劑的第二疏水性溶劑，第二疏水性溶劑包含檸檬酸三烷酯及乙醯基檸檬酸三烷酯中至少一者，其中檸檬酸三烷酯及乙醯基檸檬酸三烷酯之各者的烷基相同或不同且具有3至5個碳原子數目；及 　　親水性溶劑。 　　8. 一種組成物，其包含： 　　活性醫藥成分； 　　聚烷二醇； 　　第一疏水性溶劑；及 　　不同於聚烷二醇之親水性溶劑。 　　9. 一種組成物，其包含： 　　活性醫藥成分，其中活性醫藥成分包含西羅莫司； 　　聚烷二醇，其中聚烷二醇係以範圍約40重量%至約55重量%之量存在； 　　第一疏水性溶劑，其中第一疏水性溶劑係以組成物重量為基準計的範圍約30重量%至約50重量%之量存在；及 　　不同於聚烷二醇之親水性溶劑。 　　10. 一種組成物，其包含： 　　活性醫藥成分； 　　泊洛沙姆(poloxamer)； 　　第一疏水性溶劑；及 　　親水性溶劑。 　　11. 一種組成物，其包含： 　　活性醫藥成分； 　　抗氧化劑； 　　第一疏水性溶劑；及 　　親水性溶劑。 　　12. 一種組成物，其包含： 　　活性醫藥成分； 　　抗氧化劑； 　　第一疏水性溶劑，其中第一疏水性溶劑係以組成物重量為基準計的範圍約30重量%至約50重量%之量存在；及 　　親水性溶劑。 　　13. 一種組成物，其包含： 　　活性醫藥成分； 　　抗氧化劑； 　　第一疏水性溶劑，其中第一疏水性溶劑係以組成物重量為基準計的範圍約80重量%至約95重量%之量存在；及 　　親水性溶劑。 　　14. 態樣7至13中任一者之組成物，其中組成物另外包含高黏度液態載體材料(HVLCM)。 　　15. 態樣1、4及14中任一者之組成物，其中HVLCM係以組成物重量為基準計的範圍約0.1重量%至約50重量%之量存在。 　　16. 態樣1、4及14中任一者之組成物，其中HVLCM係以組成物重量為基準計的範圍約0.5重量%至約50重量%之量存在。 　　17. 態樣1、4及14中任一者之組成物，其中HVLCM係以組成物重量為基準計的範圍約30重量%至約60重量%之量存在。 　　18. 態樣15之組成物，其中HVLCM係以組成物重量為基準計的範圍約40重量%至約50重量%之量存在。 　　19. 態樣15之組成物，其中HVLCM係以組成物重量為基準計的範圍約1重量%至約20重量%之量存在。 　　20. 態樣19之組成物，其中HVLCM係以組成物重量為基準計的範圍約5重量%至約15重量%之量存在。 　　21. 態樣15之組成物，其中HVLCM係以組成物重量為基準計的範圍約0.1重量%至約10重量%之量存在。 　　22. 態樣1至6及14中任一者之組成物，其中HVLCM係以組成物重量為基準計的範圍約0.8重量%至約10重量%之量存在。 　　23. 態樣1至6及14中任一者之組成物，其中HVLCM係以組成物重量為基準計的範圍約0.5重量%至約5重量%之量存在。 　　24. 態樣1至6及14至23中任一者之組成物，其中HVLCM包含蔗糖乙酸酯異丁酸酯(SAIB)。 　　25. 態樣1至24中任一者之組成物，其中組成物包含以組成物重量為基準計的約1重量%至約10重量%之活性醫藥成分。 　　26. 態樣25之組成物，其中組成物包含以組成物重量為基準計的約1重量%至約5重量%之活性醫藥成分。 　　27. 態樣1至26中任一者之組成物，其中活性醫藥成分包含抗生素。 　　28. 態樣1至3、7、8及10至27中任一者之組成物，其中活性醫藥成分包含西羅莫司。 　　29. 態樣1至28中任一者之組成物，其中活性醫藥成分包含除了西羅莫司以外的物質。 　　30. 態樣1至28中任一者之組成物，其中活性醫藥成分不包含除了西羅莫司以外的眼藥。 　　31. 態樣1至30中任一者之組成物，其中第一疏水性溶劑係以組成物重量為基準計的範圍約10重量%至約95重量%之量存在。 　　32. 態樣31之組成物，其中第一疏水性溶劑係以組成物重量為基準計的範圍約30重量%至約60重量%之量存在。 　　33. 態樣32之組成物，其中第一疏水性溶劑係以組成物重量為基準計的範圍約40重量%至約50重量%之量存在。 　　34. 態樣1至31中任一者之組成物，其中第一疏水性溶劑係以組成物重量為基準計的範圍約35重量%至約55重量%之量存在。 　　35. 態樣34之組成物，其中第一疏水性溶劑係以組成物重量為基準計的範圍約35重量%至約50重量%之量存在。 　　36. 態樣35之組成物，其中第一疏水性溶劑係以組成物重量為基準計的範圍約35重量%至約45重量%之量存在。 　　37. 態樣31之組成物，其中第一疏水性溶劑係以組成物重量為基準計的範圍約80重量%至約95重量%之量存在。 　　38. 態樣1至37中任一者之組成物，其中第一疏水性溶劑包含苯甲酸甲酯、苯甲酸乙酯、苯甲酸正丙酯、苯甲酸異丙酯、苯甲酸丁酯、苯甲酸異丁酯、苯甲酸二級丁酯、苯甲酸三級丁酯、苯甲酸異戊酯和苯甲酸苯甲酯中至少一者。 　　39. 態樣1至38中任一者之組成物，其中第一疏水性溶劑包含苯甲酸苯甲酯。 　　40. 態樣1至39中任一者之組成物，其中第一疏水性溶劑不包含1,1,1,2四氟乙烷。 　　41. 態樣1至39中任一者之組成物，其中第一疏水性溶劑不包含氟化烴。 　　42. 態樣1至39中任一者之組成物，其中第一疏水性溶劑不包含推進劑。 　　43. 態樣1至42中任一者之組成物，其中親水性溶劑係以組成物重量為基準計的範圍約1重量%至約70重量%之量存在。 　　44. 態樣1至42中任一者之組成物，其中親水性溶劑係以組成物重量為基準計的範圍約2重量%至約60重量%之量存在。 　　45. 態樣43之組成物，其中親水性溶劑係以組成物重量為基準計的範圍約1重量%至約10重量%之量存在。 　　46. 態樣1至45中任一者之組成物，其中親水性溶劑係以組成物重量為基準計少於10重量%之量存在。 　　47. 態樣46之組成物，其中親水性溶劑係以組成物重量為基準計的範圍約1重量%至約7重量%之量存在。 　　48. 態樣1至47中任一者之組成物，其中親水性溶劑係以組成物重量為基準計少於5重量%之量存在。 　　49. 態樣1至48中任一者之組成物，其中親水性溶劑包含乙醇、乙醯基檸檬酸三乙酯(ATEC)、二甲基亞碸(DMSO)、N-甲基吡咯啶酮(NMP)、丙二醇、二甲基乙醯胺(DMA)及聚乙二醇(PEG)中至少一者。 　　50. 態樣1至49中任一者之組成物，其中親水性溶劑包含乙醇。 　　51. 態樣1至49中任一者之組成物，其中親水性溶劑包含ATEC。 　　52. 態樣1至51中任一者之組成物，其中親水性溶劑包含至少乙醇及ATEC。 　　53. 態樣1至52中任一者之組成物，其中親水性溶劑包含PEG。 　　54. 態樣1至7及10至49中任一者之組成物，其中親水性溶劑包含至少乙醇及PEG。 　　55. 態樣1至7及10至54中任一者之組成物，其中親水性溶劑係以組成物重量為基準計的範圍約3重量%至約55重量%之量存在。 　　56. 態樣50、52、54及55中任一者之組成物，其中乙醇係以組成物重量為基準計的範圍約1重量%至約10重量%之量存在。 　　57. 態樣50、52、54及56中任一者之組成物，其中乙醇係以組成物重量為基準計的範圍約3重量%至約10重量%之量存在。 　　58. 態樣53至57中任一者之組成物，其中PEG係以組成物重量為基準計的範圍約30重量%至約60重量%之量存在。 　　59. 態樣58之組成物，其中PEG係以組成物重量為基準計的範圍約35重量%至約50重量%之量存在。 　　60. 態樣58之組成物，其中PEG係以組成物重量為基準計的範圍約40重量%至約55重量%之量存在。 　　61. 態樣59之組成物，其中PEG係以組成物重量為基準計的範圍約40重量%至約50重量%之量存在。 　　62. 態樣1至6及8至61中任一者之組成物，其另外包含檸檬酸三烷酯及/或乙醯基檸檬酸三烷酯，其中檸檬酸三烷酯及乙醯基檸檬酸三烷酯之各者的烷基相同或不同且具有3至5個碳原子數目。 　　63. 態樣7或62之組成物，其中檸檬酸三烷酯及/或乙醯基檸檬酸三烷酯係以組成物重量為基準計的範圍約10重量%至約95重量%之量存在。 　　64. 態樣7或62之組成物，其中檸檬酸三烷酯及/或乙醯基檸檬酸三烷酯係以組成物重量為基準計的範圍約35重量%至約65重量%之量存在。 　　65. 態樣7或62之組成物，其中檸檬酸三烷酯及/或乙醯基檸檬酸三烷酯係以組成物重量為基準計的範圍約30重量%至約60重量%之量存在。 　　66. 態樣65之組成物，其中檸檬酸三烷酯及/或乙醯基檸檬酸三烷酯係以組成物重量為基準計的範圍約40重量%至約50重量%之量存在。 　　67. 態樣7及62至66中任一者之組成物，其中檸檬酸三烷酯及/或乙醯基檸檬酸三烷酯之烷基的碳原子數目為4。 　　68. 態樣7及62至67中任一者之組成物，其中檸檬酸三烷酯為檸檬酸三正丁酯及乙醯基檸檬酸三烷酯為乙醯基檸檬酸三正丁酯。 　　69. 態樣7及62至67中任一者之組成物，其中檸檬酸三烷酯及/或乙醯基檸檬酸三烷酯包含乙醯基檸檬酸三正丁酯。 　　70. 態樣1至69中任一者之組成物，其中組成物包含水。 　　71. 態樣1至70中任一者之組成物，其中組成物包含少於1重量%之水。 　　72. 態樣1至70中任一者之組成物，其中組成物包含少於0.5重量%之水。 　　73. 態樣1至7及11至52、55至57及62至72中任一者之組成物，其中組成物沒有聚合物，除了隨意地包含聚合物之活性醫藥成分以外。 　　74. 態樣1至72中任一者之組成物，其中組成物包括聚烷二醇及泊洛沙姆中至少一者，且其中組成物另外沒有聚合物，除了隨意地包含聚合物之活性醫藥成分以外。 　　75. 態樣1至72中任一者之組成物，其另外包含聚合物。 　　76. 態樣75之組成物，其中聚合物係以組成物重量為基準計的範圍約0.1重量%至約30重量%之量存在。 　　77. 態樣75或76之組成物，其中聚合物包含聚酯。 　　78. 態樣75至77中任一者之組成物，其中聚合物包含聚(乳酸)(乙醇酸)、聚(乳酸)及聚己內酯中至少一者。 　　79. 態樣1至78中任一者之組成物，其另外包含界面活性劑。 　　80. 態樣1至78中任一者之組成物，其另外包含至少一種選自下列之成員：泊洛沙姆、聚乙氧基化蓖麻油、聚氧乙基化羥基硬脂酸、山梨醇酐單油酸酯和山梨醇酐單月桂酸酯。 　　81. 態樣80之組成物，其中至少一種成員係以組成物重量為基準計的範圍約0.1重量%至約10重量%之量存在。 　　82. 態樣1至81中任一者之組成物，其另外包含檸檬酸三乙酯。 　　83. 態樣1至82中任一者之組成物，其另外包含抗壞血酸棕櫚酸酯。 　　84. 態樣1至9、11至72及75至83中任一者之組成物，其另外包含泊洛沙姆。 　　85. 態樣10或84之組成物，其中泊洛沙姆係以範圍約0.5重量%至約10重量%之量存在。 　　86. 態樣10或84之組成物，其中泊洛沙姆係以範圍約0.5重量%至約2重量%之量存在。 　　87. 態樣10或84之組成物，其中泊洛沙姆係以範圍約0.1重量%至約5重量%之量存在。 　　88. 態樣1至87中任一者之組成物，其另外包含酸前驅物。 　　89. 態樣1至88中任一者之組成物，其中在5℃/60% RH下於2毫升波紋密封之玻璃小瓶中儲存18週之後仍剩餘至少98%之活性醫藥成分於組成物中。 　　90. 態樣1至89中任一者之組成物，其中在25℃/60%RH下於2毫升波紋密封之玻璃小瓶中儲存18週之後仍剩餘至少90%之活性醫藥成分於組成物中。 91. 態樣1至10及14至90中任一者之組成物，其中組成物另外包含抗氧化劑。 　　92. 態樣11至13及91中任一者之組成物，其中抗氧化劑係以組成物重量為基準計的範圍約0.5重量%至約5重量%之量存在。 　　93. 態樣11至13、91及92中任一者之組成物，其中抗氧化劑包含維生素E。 　　94. 態樣93之組成物，其中維生素E係以組成物重量為基準計的範圍約1重量%至約50重量%之量存在。 　　95. 態樣93及94中任一者之組成物，其中維生素E係以組成物重量為基準計少於10重量%之量存在。 　　96. 態樣95之組成物，其中維生素E係以組成物重量為基準計的範圍約0.1重量%至約5重量%之量存在。 　　97. 態樣11至13及93至96中任一者之組成物，其中維生素E係以組成物重量為基準計少於5重量%之量存在。 　　98. 態樣97之組成物，其中維生素E係以組成物重量為基準計的範圍約0.5重量%至約2重量%之量存在。 　　99. 態樣93之組成物，其中HVLCM對維生素E之重量比係在約60：1至約1：2之範圍內。 　　100. 態樣93之組成物，其中HVLCM對維生素E之重量比係在約10：1至約1：1.8之範圍內。 　　101. 態樣93之組成物，其中HVLCM對維生素E之重量比係在約5：1至約1：1.5之範圍內。 　　102. 態樣93之組成物，其中HVLCM對維生素E之重量比係在約2：1至約1：1.5之範圍內。 　　103. 態樣99之組成物，其中HVLCM包含SAIB。 　　104. 態樣100之組成物，其中HVLCM包含SAIB。 　　105. 態樣101之組成物，其中HVLCM包含SAIB。 　　106. 態樣102之組成物，其中HVLCM包含SAIB。 　　107. 態樣93之組成物，其中組成物包含SAIB，且組成物具有範圍約0.5至約10的SAIB：維生素E之重量比。 　　108. 態樣93至107中任一者之組成物，其中HVLCM對維生素E之重量比使得由該HVLCM及該維生素E以該重量比所組成之混合物在25℃及1atm下的密度為至少1克/毫升。 　　109. 態樣108之組成物，其中該密度為至少1.05克/毫升。 　　110. 態樣1至109中任一者之組成物，其中組成物另外包含脂質酯。 　　111. 態樣1至110中任一者之組成物，其中組成物另外包含脂肪酯。 　　112. 態樣1至111中任一者之組成物，其中組成物另外包含乳酸月桂酯及月桂基乙二醇中至少一者。 　　113. 態樣1至112中任一者之組成物，其中組成物在25℃及1大氣壓下具有範圍1.02克/毫升至1.15克/毫升之密度。 　　114. 態樣1至113中任一者之組成物，其中組成物在25℃及1大氣壓下具有範圍約1cP至約150cP之黏度。 　　115. 態樣1至113中任一者之組成物，其中組成物在25℃及1大氣壓下具有範圍約5cP至約50cP之黏度。 　　116. 態樣1至113中任一者之組成物，其中組成物在25℃及1大氣壓下具有範圍約10cP至約30cP之黏度。 　　117. 態樣1至116中任一者之組成物，其中組成物不為乳液。 　　118. 態樣1至117中任一者之組成物，其中當藉由將100微升組成物注入由具有0.1重量%之十二烷基硫酸鈉的磷酸鹽緩衝之食鹽水所組成之5毫升釋放介質中以形成樣品及將樣品放在37℃下以30rpm旋轉之迴轉式振盪器上進行檢定時，來自組成物之活性醫藥成分的累積釋放%在T=24小時時少於50%。 　　119. 態樣1至118中任一者之組成物，其中活性醫藥成分包含西羅莫司及其中親水性溶劑包含乙醇。 　　120. 態樣119之組成物，其中HVLCM包含蔗糖乙酸酯異丁酸酯。 　　121. 態樣119或120之組成物，其中第一疏水性溶劑包含苯甲酸苯甲酯。 　　122. 態樣119至121中任一者之組成物，其包含維生素E。 　　123. 態樣119至122中任一者之組成物，其包含乙醯基檸檬酸三正丁酯。 　　124. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的範圍約1重量%至約10重量%之量存在。 　　HVLCM係以組成物重量為基準計的範圍約30重量%至約60重量%之量存在； 　　HVLCM包含SAIB； 　　第一疏水性溶劑係以組成物重量為基準計的範圍約30重量%至約60重量%之量存在； 　　第一疏水性溶劑包含苯甲酸苯甲酯； 　　親水性溶劑係以組成物重量為基準計的範圍約1重量%至約10重量%之量存在； 　　親水性溶劑包含乙醇； 　　組成物另外包含維生素E；及 　　維生素E係以組成物重量為基準計的範圍約0.1重量%至約5重量%之量存在。 　　125. 態樣124之組成物，其中SAIB包含以兩個乙酸及六個異丁酸部分予以酯化之蔗糖。 　　126. 態樣125之組成物，其中以兩個乙酸及六個異丁酸部分予以酯化之蔗糖係以組成物重量為基準計的範圍7重量%至約15重量%之量存在。 　　127. 態樣124至126中任一者之組成物，其另外包含泊洛沙姆，其中泊洛沙姆係以組成物重量為基準計的範圍約0.1重量%至約5重量%之量存在。 　　128. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的範圍約1重量%至約10重量%之量存在； 　　HVLCM係以組成物重量為基準計的範圍約1重量%至約20重量%之量存在； 　　HVLCM包含SAIB； 　　第一疏水性溶劑係以組成物重量為基準計的範圍約30重量%至約60重量%之量存在； 　　第一疏水性溶劑包含苯甲酸苯甲酯； 　　親水性溶劑包含至少乙醇及PEG； 　　乙醇係以組成物重量為基準計的範圍約1重量%至約10重量%之量存在； 　　PEG係以組成物重量為基準計的範圍約30重量%至約60重量%之量存在； 　　組成物另外包含維生素E；及 　　維生素E係以組成物重量為基準計的範圍約0.1重量%至約5重量%之量存在。 　　129. 態樣128之組成物，其中SAIB包含以兩個乙酸及六個異丁酸部分予以酯化之蔗糖。 　　130. 態樣129之組成物，其中以兩個乙酸及六個異丁酸部分予以酯化之蔗糖係以組成物重量為基準計的範圍約0.25重量%至約5重量%之量存在。 　　131. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的範圍約1重量%至約10重量%之量存在； 　　HVLCM係以組成物重量為基準計的範圍約0.1重量%至約10重量%之量存在； 　　HVLCM包含SAIB； 　　第一疏水性溶劑係以組成物重量為基準計的範圍約30重量%至約60重量%之量存在； 　　第一疏水性溶劑包含苯甲酸苯甲酯； 　　親水性溶劑包含至少乙醇及PEG； 　　乙醇係以組成物重量為基準計的範圍約1重量%至約10重量%之量存在； 　　PEG係以組成物重量為基準計的範圍約30重量%至約60重量%之量存在； 　　組成物另外包含維生素E；及 　　維生素E係以組成物重量為基準計的範圍約0.1重量%至約5重量%之量存在。 　　132. 態樣1至131中任一者之組成物，其中： 　　活性醫藥成分包含以組成物重量為基準計的範圍約1重量%至約5重量%之量的西羅莫司； 　　HVLCM包含以組成物重量為基準計的範圍約0.1重量%至約10重量%之量的蔗糖乙酸酯異丁酸酯(SAIB)； 　　第一疏水性溶劑包含以組成物重量為基準計的範圍約30重量%至約45重量%之量的苯甲酸苯甲酯； 　　親水性溶劑包含(i)以組成物重量為基準計的範圍約1重量%至約10重量%之量的乙醇；及(ii)以組成物重量為基準計的範圍約40重量%至約50重量%之量的PEG；及 　　組成物另外包含以組成物重量為基準計的範圍約0.5重量%至約2重量%之量的維生素E。 　　133. 態樣1至132中任一者之組成物，該組成物本質上係由下列所組成： 　　以組成物重量為基準計的範圍約1重量%至約5重量%之量的西羅莫司； 　　以組成物重量為基準計的範圍約0.1重量%至約10重量%之量的SAIB； 　　以組成物重量為基準計的範圍約30重量%至約45重量%之量的苯甲酸苯甲酯； 　　以組成物重量為基準計的範圍約1重量%至約10重量%之量的乙醇； 　　以組成物重量為基準計的範圍約40重量%至約50重量%之量的PEG400；及 　　以組成物重量為基準計的範圍約0.5重量%至約2重量%之量的維生素E。 　　134. 態樣1至133中任一者之組成物，該組成物本質上係由下列所組成： 　　以組成物重量為基準計的範圍約1重量%至約5重量%之量的西羅莫司； 　　以組成物重量為基準計的不超過約10重量%之量的SAIB； 　　苯甲酸苯甲酯； 　　選自由乙醇和PEG400所組成之群組的親水性溶劑；及 　　範圍約0.5重量%至約2重量%之量的維生素E，其中SAIB對維生素E之重量比超過約0.5。 　　135. 態樣131至134中任一者之組成物，其中SAIB包含以兩個乙酸及六個異丁酸部分予以酯化之蔗糖。 　　136. 態樣135之組成物，其中以兩個乙酸及六個異丁酸部分予以酯化之蔗糖係以組成物重量為基準計的範圍約0.025重量%至約2.5重量%之量存在。 　　137. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的範圍約1重量%至約10重量%之量存在； 　　HVLCM係以組成物重量為基準計的範圍約0.1重量%至約10重量%之量存在； 　　HVLCM包含SAIB； 　　第一疏水性溶劑係以組成物重量為基準計的範圍約80重量%至約95重量%之量存在； 　　第一疏水性溶劑包含苯甲酸苯甲酯； 　　親水性溶劑包含至少乙醇； 　　乙醇係以組成物重量為基準計的範圍約1重量%至約10重量%之量存在； 　　組成物另外包含維生素E；及 　　維生素E係以組成物重量為基準計的範圍約0.1重量%至約5重量%之量存在。 　　138. 態樣137之組成物，其中SAIB包含以兩個乙酸及六個異丁酸部分予以酯化之蔗糖。 　　139. 態樣138之組成物，其中以兩個乙酸及六個異丁酸部分予以酯化之蔗糖係以組成物重量為基準計的範圍約0.025重量%至約2.5重量%之量存在。 　　140. 態樣7之組成物，其中活性醫藥成分係以組成物重量為基準計的範圍約1重量%至約10重量%之量存在； 　　活性醫藥成分包含西羅莫司； 　　組成物另外包含以組成物重量為基準計的範圍約0.1重量%至約10重量%之量存在的高黏度液態載體材料(HVLCM)； 　　HVLCM包含SAIB； 　　第一疏水性溶劑係以組成物重量為基準計的範圍約30重量%至約60重量%之量存在； 　　第一疏水性溶劑包含苯甲酸苯甲酯； 　　第二疏水性溶劑係以組成物重量為基準計的範圍約30重量%至約60重量%之量存在； 　　第二疏水性溶劑包含乙醯基檸檬酸三正丁酯(ATBC)； 　　親水性溶劑係以組成物重量為基準計的範圍約1重量%至約10重量%之量存在； 　　親水性溶劑包含乙醇； 　　組成物另外包含維生素E；及 　　維生素E係以組成物重量為基準計的範圍約0.1重量%至約5重量%之量存在。 　　141. 態樣140之組成物，其中SAIB包含以兩個乙酸及六個異丁酸部分予以酯化之蔗糖。 　　142. 態樣141之組成物，其中以兩個乙酸及六個異丁酸部分予以酯化之蔗糖係以組成物重量為基準計的範圍約0.025重量%至約2.5重量%之量存在。 　　143. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的範圍約1重量%至約5重量%之量存在； 　　HVLCM係以組成物重量為基準計的範圍約40重量%至約50重量%之量存在； 　　HVLCM包含SAIB； 　　第一疏水性溶劑係以組成物重量為基準計的範圍約40重量%至約50重量%之量存在； 　　第一疏水性溶劑包含苯甲酸苯甲酯； 　　親水性溶劑係以組成物重量為基準計的範圍約1重量%至約7重量%之量存在； 　　親水性溶劑包含乙醇； 　　組成物另外包含維生素E；及 　　維生素E係以組成物重量為基準計的範圍約0.5重量%至約2重量%之量存在。 　　144. 態樣143之組成物，其中SAIB包含以兩個乙酸及六個異丁酸部分予以酯化之蔗糖。 　　145. 態樣144之組成物，其中以兩個乙酸及六個異丁酸部分予以酯化之蔗糖係以組成物重量為基準計的範圍約10重量%至約13重量%之量存在。 　　146. 態樣143之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM係以組成物重量為基準計的約47.5重量%之量存在於組成物中； 　　第一疏水性溶劑係以組成物重量為基準計的約43.7重量%之量存在於組成物中； 　　乙醇係以組成物重量為基準計的約4.8重量%之量存在於組成物中；及 　　維生素E係以組成物重量為基準計的約1重量%之量存在於組成物中。 　　147. 態樣146之組成物，其中SAIB包含以兩個乙酸及六個異丁酸部分予以酯化之蔗糖。 　　148. 態樣147之組成物，其中以兩個乙酸及六個異丁酸部分予以酯化之蔗糖係以組成物重量為基準計的約12重量%之量存在。 　　149. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的範圍約1重量%至約5重量%之量存在； 　　HVLCM係以組成物重量為基準計的範圍約5重量%至約15重量%之量存在； 　　HVLCM包含SAIB； 　　第一疏水性溶劑係以組成物重量為基準計的範圍約35重量%至約45重量%之量存在； 　　第一疏水性溶劑包含苯甲酸苯甲酯； 　　親水性溶劑包含至少乙醇及PEG； 　　乙醇係以組成物重量為基準計的範圍約1重量%至約10重量%之量存在； 　　PEG係以組成物重量為基準計的範圍約35重量%至約50重量%之量存在； 　　組成物另外包含維生素E；及 　　維生素E係以組成物重量為基準計的範圍約0.5重量%至約2重量%之量存在。 　　150. 態樣149之組成物，其中SAIB包含以兩個乙酸及六個異丁酸部分予以酯化之蔗糖。 　　151. 態樣150之組成物，其中以兩個乙酸及六個異丁酸部分予以酯化之蔗糖係以組成物重量為基準計的範圍約1重量%至約4重量%之量存在。 　　152. 態樣149之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM係以組成物重量為基準計的約9.7重量%之量存在於組成物中； 　　第一疏水性溶劑係以組成物重量為基準計約38.8重量%之量存在於組成物中； 　　乙醇係以組成物重量為基準計的約4.8重量%之量存在於組成物中； 　　PEG係以組成物重量為基準計的約42.7重量%之量存在於組成物中；及 　　維生素E係以組成物重量為基準計的約1重量%之量存在於組成物中。 　　153. 態樣152之組成物，其中SAIB包含以兩個乙酸及六個異丁酸部分予以酯化之蔗糖。 　　154. 態樣153之組成物，其中以兩個乙酸及六個異丁酸部分予以酯化之蔗糖係以組成物重量為基準計的約2.5重量%之量存在。 　　155. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的範圍約1重量%至約5重量%之量存在； 　　HVLCM係以組成物重量為基準計的範圍約0.5重量%至約5重量%之量存在； 　　HVLCM包含SAIB； 　　第一疏水性溶劑係以組成物重量為基準計的範圍約35重量%至約50重量%之量存在； 　　第一疏水性溶劑包含苯甲酸苯甲酯； 　　親水性溶劑包含至少乙醇及PEG； 　　乙醇係以組成物重量為基準計的範圍約1重量%至約10重量%之量存在； 　　PEG係以組成物重量為基準計的範圍約40重量%至約50重量%之量存在； 　　組成物另外包含維生素E；及 　　維生素E係以組成物重量為基準計的範圍約0.5重量%至約2重量%之量存在。 　　156. 態樣155之組成物，其中SAIB包含以兩個乙酸及六個異丁酸部分予以酯化之蔗糖。 　　157. 態樣156之組成物，其中以兩個乙酸及六個異丁酸部分予以酯化之蔗糖係以組成物重量為基準計的範圍約0.1重量%至約1重量%之量存在。 　　158. 態樣155之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM係以組成物重量為基準計的約1重量%之量存在於組成物中； 　　第一疏水性溶劑係以組成物重量為基準計的約43.7重量%之量存在於組成物中； 　　乙醇係以組成物重量為基準計的約4.8重量%之量存在於組成物中； 　　PEG係以組成物重量為基準計的約46.5重量%之量存在於組成物中；及 　　維生素E係以組成物重量為基準計的約1重量%之量存在於組成物中。 　　159. 態樣158之組成物，其中SAIB包含以兩個乙酸及六個異丁酸部分予以酯化之蔗糖。 　　160. 態樣159之組成物，其中以兩個乙酸及六個異丁酸部分予以酯化之蔗糖係以組成物重量為基準計的約0.25重量%之量存在。 　　161. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的範圍約1重量%至約5重量%之量存在； 　　HVLCM係以組成物重量為基準計的範圍約0.5重量%至約5重量%之量存在； 　　HVLCM包含SAIB； 　　第一疏水性溶劑係以組成物重量為基準計的範圍約80重量%至約95重量%之量存在； 　　第一疏水性溶劑包含苯甲酸苯甲酯； 　　親水性溶劑包含至少乙醇； 　　乙醇係以組成物重量為基準計的範圍約1重量%至約10重量%之量存在； 　　組成物另外包含維生素E；及 　　維生素E係以組成物重量為基準計的範圍約0.5重量%至約2重量%之量存在。 　　162. 態樣161之組成物，其中SAIB包含以兩個乙酸及六個異丁酸部分予以酯化之蔗糖。 　　163. 態樣162之組成物，其中以兩個乙酸及六個異丁酸部分予以酯化之蔗糖係以組成物重量為基準計的範圍約0.1重量%至約1重量%之量存在。 　　164. 態樣7之組成物，其中活性醫藥成分係以組成物重量為基準計的範圍約1重量%至約5重量%之量存在； 　　組成物另外包含以組成物重量為基準計的範圍約0.5重量%至約5重量%之量存在的高黏度液態載體材料(HVLCM)； 　　HVLCM包含SAIB； 　　第一疏水性溶劑係以組成物重量為基準計的範圍約35重量%至約50重量%之量存在； 　　第一疏水性溶劑包含苯甲酸苯甲酯； 　　第二疏水性溶劑係以組成物重量為基準計的範圍約40重量%至約50重量%之量存在； 　　第二疏水性溶劑包含乙醯基檸檬酸三正丁酯(ATBC)； 　　親水性溶劑包含乙醇； 　　乙醇係以組成物重量為基準計的範圍約1重量%至約10重量%之量存在； 　　組成物另外包含維生素E；及 　　維生素E係以組成物重量為基準計的範圍約0.5重量%至約2重量%之量存在。 　　165. 態樣164之組成物，其中SAIB包含以兩個乙酸及六個異丁酸部分予以酯化之蔗糖。 　　166. 態樣165之組成物，其中以兩個乙酸及六個異丁酸部分予以酯化之蔗糖係以組成物重量為基準計的範圍約0.1重量%至約1重量%之量存在。 　　167. 態樣164之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM係以組成物重量為基準計的約1重量%之量存在於組成物中； 　　第一疏水性溶劑係以組成物重量為基準計的約43.7重量%之量存在於組成物中； 　　第二親水性溶劑係以組成物重量為基準計的約46.5重量%之量存在於組成物中； 　　乙醇係以組成物重量為基準計的約4.8重量%之量存在於組成物中；及 　　維生素E係以組成物重量為基準計的約1重量%之量存在於組成物中。 　　168. 態樣167之組成物，其中SAIB包含以兩個乙酸及六個異丁酸部分予以酯化之蔗糖。 　　169. 態樣168之組成物，其中以兩個乙酸及六個異丁酸部分予以酯化之蔗糖係以組成物重量為基準計的約0.25重量%之量存在。 　　170. 態樣1至169中任一者之組成物，其中： 　　活性醫藥成分包含以組成物重量為基準計的範圍約1重量%至約5重量%之量的西羅莫司； 　　HVLCM包含以組成物重量為基準計的範圍約0.1重量%至約10重量%之量的蔗糖乙酸酯異丁酸酯(SAIB)； 　　第一疏水性溶劑包含以組成物重量為基準計的範圍約80重量%至約95重量%之量的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的範圍約1重量%至約10重量%之量的乙醇；及 　　組成物另外包含以組成物重量為基準計的範圍約0.5重量%至約2重量%之量的維生素E。 　　171. 態樣1至170中任一者之組成物，組成物本質上係由下列所組成： 　　以組成物重量為基準計的範圍約1重量%至約5重量%之量的西羅莫司； 　　以組成物重量為基準計的範圍約0.1重量%至約10重量%之量的SAIB； 　　以組成物重量為基準計的範圍約80重量%至約95重量%之量的苯甲酸苯甲酯； 　　以組成物重量為基準計的範圍約1重量%至約10重量%之量的乙醇；及 　　以組成物重量為基準計的範圍約0.5重量%至約2重量%之量的維生素E。 　　172. 態樣170或171之組成物，其中SAIB包含以兩個乙酸及六個異丁酸部分予以酯化之蔗糖。 　　173. 態樣172之組成物，其中以兩個乙酸及六個異丁酸部分予以酯化之蔗糖係以組成物重量為基準計的範圍約0.025重量%至約1重量%之量存在。 　　174. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM包含以組成物重量為基準計的約2重量%存在的SAIB； 　　第一疏水性溶劑包含以組成物重量為基準計的約42.7重量%存在的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的約46.5重量%存在的PEG； 　　親水性溶劑另外包含以組成物重量為基準計的約4.8重量%存在的乙醇；及 　　組成物另外包含以組成物重量為基準計的約1重量%存在的維生素E。 　　175. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM包含以組成物重量為基準計的約3重量%存在的SAIB； 　　第一疏水性溶劑包含以組成物重量為基準計的約41.7重量%存在的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的約46.5重量%存在的PEG； 　　親水性溶劑另外包含以組成物重量為基準計的約4.8重量%存在的乙醇；及 　　組成物另外包含以組成物重量為基準計的約1重量%存在的維生素E。 　　176. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM包含以組成物重量為基準計的約4重量%存在的SAIB； 　　第一疏水性溶劑包含以組成物重量為基準計的約40.7重量%存在的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的約46.5重量%存在的PEG； 　　親水性溶劑另外包含以組成物重量為基準計的約4.8重量%存在的乙醇；及 　　組成物另外包含以組成物重量為基準計的約1重量%存在的維生素E。 　　177. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM包含以組成物重量為基準計的約4.9重量%存在的SAIB； 　　第一疏水性溶劑包含以組成物重量為基準計的約39.8重量%存在的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的約46.5重量%存在的PEG； 　　親水性溶劑另外包含以組成物重量為基準計的約4.8重量%存在的乙醇；及 　　組成物另外包含以組成物重量為基準計的約1重量%存在的維生素E。 　　178. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM包含以組成物重量為基準計的約5.9重量%存在的SAIB； 　　第一疏水性溶劑包含以組成物重量為基準計的約38.8重量%存在的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的約46.5重量%存在的PEG； 　　親水性溶劑另外包含以組成物重量為基準計的約4.8重量%存在的乙醇；及 　　組成物另外包含以組成物重量為基準計的約1重量%存在的維生素E。 　　179. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM包含以組成物重量為基準計的約6.8重量%存在的SAIB； 　　第一疏水性溶劑包含以組成物重量為基準計的約37.9重量%存在的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的約46.5重量%存在的PEG； 　　親水性溶劑另外包含以組成物重量為基準計的約4.8重量%存在的乙醇；及 　　組成物另外包含以組成物重量為基準計的約1重量%存在的維生素E。 　　180. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM包含以組成物重量為基準計的約7.8重量%存在的SAIB； 　　第一疏水性溶劑包含以組成物重量為基準計的約36.9重量%存在的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的約46.5重量%存在的PEG； 　　親水性溶劑另外包含以組成物重量為基準計的約4.8重量%存在的乙醇；及 　　組成物另外包含以組成物重量為基準計的約1重量%存在的維生素E。 　　181. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM包含以組成物重量為基準計的約8.8重量%存在的SAIB； 　　第一疏水性溶劑包含以組成物重量為基準計的約35.9重量%存在的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的約46.5重量%存在的PEG； 　　親水性溶劑另外包含以組成物重量為基準計的約4.8重量%存在的乙醇；及 　　組成物另外包含以組成物重量為基準計的約1重量%存在的維生素E。 　　182. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM包含以組成物重量為基準計的約9.7重量%存在的SAIB； 　　第一疏水性溶劑包含以組成物重量為基準計的約35重量%存在的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的約46.5重量%存在的PEG； 　　親水性溶劑另外包含以組成物重量為基準計的約4.8重量%存在的乙醇；及 　　組成物另外包含以組成物重量為基準計的約1重量%存在的維生素E。 　　183. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM包含以組成物重量為基準計的約1重量%存在的SAIB； 　　第一疏水性溶劑包含以組成物重量為基準計的約90.2重量%存在的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的約4.8重量%存在的乙醇；及 　　組成物另外包含以組成物重量為基準計的約1重量%存在的維生素E。 　　184. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM包含以組成物重量為基準計的約2重量%存在的SAIB； 　　第一疏水性溶劑包含以組成物重量為基準計的約89.2重量%存在的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的約4.8重量%存在的乙醇；及 　　組成物另外包含以組成物重量為基準計的約1重量%存在的維生素E。 　　185. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM包含以組成物重量為基準計的約2.9重量%存在的SAIB； 　　第一疏水性溶劑包含以組成物重量為基準計的約88.3重量%存在的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的約4.8重量%存在的乙醇；及 　　組成物另外包含以組成物重量為基準計的約1重量%存在的維生素E。 　　186. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM包含以組成物重量為基準計的約3.9重量%存在的SAIB； 　　第一疏水性溶劑包含以組成物重量為基準計的約87.3重量%存在的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的約4.8重量%存在的乙醇；及 　　組成物另外包含以組成物重量為基準計的約1重量%存在的維生素E。 　　187. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM包含以組成物重量為基準計的約4.9重量%存在的SAIB； 　　第一疏水性溶劑包含以組成物重量為基準計的約86.3重量%存在的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的約4.8重量%存在的乙醇；及 　　組成物另外包含以組成物重量為基準計的約1重量%存在的維生素E。 　　188. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM包含以組成物重量為基準計的約5.8重量%存在的SAIB； 　　第一疏水性溶劑包含以組成物重量為基準計的約85.4重量%存在的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的約4.8重量%存在的乙醇；及 　　組成物另外包含以組成物重量為基準計的約1重量%存在的維生素E。 　　189. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM包含以組成物重量為基準計的約6.8重量%存在的SAIB； 　　第一疏水性溶劑包含以組成物重量為基準計的約84.4重量%存在的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的約4.8重量%存在的乙醇；及 　　組成物另外包含以組成物重量為基準計的約1重量%存在的維生素E。 　　190. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM包含以組成物重量為基準計的約7.8重量%存在的SAIB； 　　第一疏水性溶劑包含以組成物重量為基準計的約83.4重量%存在的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的約4.8重量%存在的乙醇；及 　　組成物另外包含以組成物重量為基準計的約1重量%存在的維生素E。 　　191. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM包含以組成物重量為基準計的約8.7重量%存在的SAIB； 　　第一疏水性溶劑包含以組成物重量為基準計的約82.5重量%存在的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的約4.8重量%存在的乙醇；及 　　組成物另外包含以組成物重量為基準計的約1重量%存在的維生素E。 　　192. 態樣4之組成物，其中活性醫藥成分係以組成物重量為基準計的約3重量%之量存在於組成物中； 　　HVLCM包含以組成物重量為基準計的約9.7重量%存在的SAIB； 　　第一疏水性溶劑包含以組成物重量為基準計的約81.5重量%存在的苯甲酸苯甲酯； 　　親水性溶劑包含以組成物重量為基準計的約4.8重量%存在的乙醇；及 　　組成物另外包含以組成物重量為基準計的約1重量%存在的維生素E。 　　193. 一種組成物，其包含： 　　活性醫藥成分，其中活性醫藥成分包含西羅莫司； 　　當組成物投予需要其之患者時用於延長醫藥活性成分之釋放輪廓的設備。 　　194. 態樣1至193中任一者之組成物，其中當組成物以單劑經眼內投予兔子時，組成物提供在圖13的C908之釋放輪廓的± 20%之內的醫藥活性成分之中位釋放輪廓。 　　195. 態樣194之組成物，其中該單劑包含30微升。 　　196. 態樣194或195中任一者之組成物，其中活性醫藥成分包含0.9毫克西羅莫司。 　　197. 態樣1至196中任一者之組成物，其中當組成物以單劑經眼內投予兔子時，在投予後1個月自組成物釋放之醫藥活性成分的中位量係在投予時組成物中的醫藥活性成分總量的1%至20%或2%至15%之範圍內。 　　198. 態樣1至197中任一者之組成物，其中當組成物以單劑經眼內投予兔子時，在投予後3個月自組成物釋放之醫藥活性成分的中位量係在投予時組成物中的醫藥活性成分總量的10%至60%或20%至50%之範圍內。 　　199. 態樣1至198中任一者之組成物，其中當組成物以單劑經眼內投予兔子時，在投予後6個月自組成物釋放之醫藥活性成分的中位量係在投予時組成物中的醫藥活性成分總量的30%至100%或40%至90%之範圍內。 　　200. 態樣1至199中任一者之組成物，其中當組成物在37℃下放入具有0.1%(w/v)十二烷基硫酸鈉的磷酸鹽緩衝之食鹽水中時，在放入磷酸鹽緩衝之食鹽水中1天時自組成物釋放之醫藥活性成分的量係在組成物中的醫藥活性成分總量的5%至50%或10%至40%之範圍內。 　　201. 態樣200之組成物，其中被放入之組成物包含75微升。 　　202. 態樣200或201中任一者之組成物，其中活性醫藥成分構成以組成物重量為基準計的3重量%。 　　203. 態樣1至202中任一者之組成物，其中當組成物在37℃下放入具有0.1%(w/v)SDS的磷酸鹽緩衝之食鹽水中時，在放入磷酸鹽緩衝之食鹽水中5天時自組成物釋放之醫藥活性成分的量係在組成物中的醫藥活性成分總量的5%至75%或10%至50%之範圍內。 　　204. 態樣1至203中任一者之組成物，其中當組成物在37℃下放入具有0.1%(w/v)SDS的磷酸鹽緩衝之食鹽水中時，在放入磷酸鹽緩衝之食鹽水中10天時自組成物釋放之醫藥活性成分的量係在組成物中的醫藥活性成分總量的5%至85%或15%至60%之範圍內。 　　205. 態樣1至204中任一者之組成物，當組成物以單劑經眼內投予人類患者時，組成物含有足以維持活性醫藥成分之治療有效濃度至少3個月時期之比的組份。 　　206. 態樣1至205中任一者之組成物，當組成物以單劑經眼內投予人類患者時，組成物含有足以維持活性醫藥成分之治療有效的視網膜-脈絡膜濃度至少3個月時期之比的組份。 　　207. 態樣1至206中任一者之組成物，組成物包含SAIB及維生素E，組成物具有範圍約0.5至約20的SAIB：維生素E之重量比。 　　208. 態樣1至207中任一者之組成物，其中組成物為醫藥上可接受的。 　　209. 態樣1至208中任一者之組成物，其中組成物經調配用於注射。 　　210. 態樣1至209中任一者之組成物，其包含 　　以組成物重量為基準計的約3重量%之量的西羅莫司； 　　以組成物重量為基準計的約1重量%之量的SAIB； 　　以組成物重量為基準計的約43.7重量%之量的苯甲酸苯甲酯； 　　以組成物重量為基準計的約4.8重量%之量的乙醇； 　　以組成物重量為基準計的約46.5重量%之量存在的PEG400；及 　　以組成物重量為基準計的約1重量%之量的維生素E。 　　211. 一種治療受眼疾所苦的個體之方法，該方法包含： 　　對其有需要之個體的眼睛投予組成物，其中組成物包含能夠治療眼疾之有效量的活性醫藥成分，組成物包含： 　　活性醫藥成分； 　　高黏度液態載體材料(HVLCM)； 　　第一疏水性溶劑；及 　　親水性溶劑。 　　212. 一種治療受眼疾所苦的個體之方法，該方法包含： 　　對其有需要之個體的眼睛投予組成物，其中組成物包含能夠治療眼疾之有效量的活性醫藥成分，組成物包含： 　　活性醫藥成分； 　　高黏度液態載體材料(HVLCM)，其中HVLCM係以組成物重量為基準計的範圍約0.5重量%至約15重量%之量存在； 　　第一疏水性溶劑，其中第一疏水性溶劑係以組成物重量為基準計的範圍約30重量%至約50重量%之量存在；及 　　親水性溶劑。 　　213. 一種治療受眼疾所苦的個體之方法，該方法包含： 　　對其有需要之個體的眼睛投予組成物，其中組成物包含能夠治療眼疾之有效量的活性醫藥成分，組成物包含： 　　活性醫藥成分； 　　高黏度液態載體材料(HVLCM)，其中HVLCM係以組成物重量為基準計的範圍約0.5重量%至約15重量%之量存在； 　　第一疏水性溶劑，其中第一疏水性溶劑係以組成物重量為基準計的範圍約80重量%至約95重量%之量存在；及 　　親水性溶劑。 　　214. 一種治療受眼疾所苦的個體之方法，該方法包含： 　　對其有需要之個體的眼睛投予態樣1至210中任一者之組成物，其中組成物包含能夠治療眼疾之有效量的活性醫藥成分。 　　215. 態樣211至214中任一者之方法，其中眼疾包含眼色素層炎、糖尿病黃斑部水腫或濕式老年性黃斑部退化。 　　216. 態樣211至214中任一者之方法，其中眼疾包含眼色素層炎或濕式老年性黃斑部退化。 　　217. 態樣211至216中任一者之方法，其中投予包含注射。 　　218. 態樣217之方法，其中注射至多50微升組成物。 　　219. 態樣217之方法，其中注射約20微升至約30微升組成物。 　　220. 態樣211至219中任一者之方法，其中組成物係以具有範圍27G至30G之尺寸的針注射。 　　221. 態樣211至220中任一者之方法，其中組成物係以具有範圍1公分至3公分之長度的針注射。 　　222. 態樣211至221中任一者之方法，其中所投予之活性醫藥成分總量的至少20%係在組成物注入患者的玻璃體後三個月剩餘在患者的玻璃體中。 　　223. 一種治療受眼疾所苦的個體之方法，該方法包含： 　　對其有需要之個體的玻璃體投予態樣1至210中任一者之組成物，其中組成物包含能夠治療眼疾之有效量的活性醫藥成分。 　　224. 一種方法，其包含： 　　對患者投予如態樣1至210中任一者所定義之組成物， 　　其中組成物提供在圖13的C908之釋放輪廓的±20%之內的醫藥活性成分之中位釋放輪廓。 　　225. 態樣224之方法，其為如態樣211至223中任一者所定義之方法。 　　226. 態樣211至225中任一者之方法，其中組成物係以單劑經眼內投予人類患者，且在投予後1個月自組成物釋放之醫藥活性成分的中位量係在投予時組成物中的醫藥活性成分總量的1%至20%或2%至15%之範圍內。 　　227. 態樣211至226中任一者之方法，其中組成物係以單劑經眼內投予人類患者，且在投予後3個月自組成物釋放之醫藥活性成分的中位量係在投予時組成物中的醫藥活性成分總量的10%至60%或20%至50%之範圍內。 　　228. 態樣211至227中任一者之方法，其中組成物係以單劑經眼內投予人類患者，且在投予後6個月自組成物釋放之醫藥活性成分的中位量係在投予時組成物中的醫藥活性成分總量的30%至100%或40%至90%之範圍內。 　　229. 態樣211至228中任一者之方法，其中組成物包含0.1毫克至500毫克醫藥活性成分。 　　230. 態樣211至229中任一者之方法，其中醫藥活性成分之血漿Cmax係在1毫微克/毫升至10毫微克/毫升之範圍內。 　　231. 態樣211至230中任一者之方法，其中醫藥活性成分之血漿Cmax少於10毫微克/毫升。 　　232. 如態樣1至210中任一者所定義之組成物，其係用作為藥劑。 　　233. 如態樣1至210中任一者所定義之組成物，其係用治療眼疾，其中活性醫藥成分包含眼藥。 　　234. 態樣233之組成物，其中眼疾包含眼色素層炎、糖尿病黃斑部水腫或濕式老年性黃斑部退化。 　　235. 態樣233之組成物，其中眼疾包含眼色素層炎或濕式老年性黃斑部退化。 　　236. 態樣232至235中任一者之組成物，其中活性醫藥成分包含西羅莫司。 　　237. 態樣232至236中任一者之組成物，其中組成物之使用包含以單劑之組成物經眼內投予人類患者，且在投予後1個月自組成物釋放之醫藥活性成分的中位量係在投予時組成物中的醫藥活性成分總量的1%至20%或2%至15%之範圍內。 　　238. 態樣232至237中任一者之組成物，其中組成物之使用包含以單劑的組成物經眼內投予人類患者，且在投予後3個月自組成物釋放之醫藥活性成分的中位量係在投予時組成物中的醫藥活性成分總量的10%至60%或20%至50%之範圍內。 　　239. 態樣232至238中任一者之組成物，其中組成物之使用包含以單劑的組成物經眼內投予人類患者，且在投予後6個月自組成物釋放之醫藥活性成分的中位量係在投予時組成物中的醫藥活性成分總量的30%至100%或40%至90%之範圍內。 　　240. 態樣232至239中任一者之組成物，其中組成物包含0.1毫克至500毫克醫藥活性成分。 　　241. 態樣232至240中任一者之組成物，其中醫藥活性成分之血漿Cmax係在1毫微克/毫升至10毫微克/毫升之範圍內。 　　242. 態樣232至241中任一者之組成物，其中醫藥活性成分之血漿Cmax少於10毫微克/毫升。 　　243. 如態樣1至210中任一者所定義之組成物中的組份之組合於製造用於治療眼疾之藥劑的用途或組成物於製造用於治療眼疾之藥劑的用途，其中活性醫藥成分包含眼藥。 　　244. 態樣243之用途，其中眼疾包含眼色素層炎、糖尿病黃斑部水腫或濕式老年性黃斑部退化。 　　245. 態樣243之用途，其中眼疾包含眼色素層炎或濕式老年性黃斑部退化。 　　246. 態樣243至245中任一者之用途，其中活性醫藥成分包含西羅莫司。 　　247. 態樣243至246中任一者之用途，其中組成物係以單劑經眼內投予人類患者，且在投予後1個月自組成物釋放之醫藥活性成分的中位量係在投予時組成物中的醫藥活性成分總量的1%至20%或2%至15%之範圍內。 　　248. 態樣243至247中任一者之用途，其中組成物係以單劑經眼內投予人類患者，且在投予後3個月自組成物釋放之醫藥活性成分的中位量係在投予時組成物中的醫藥活性成分總量的10%至60%或20%至50%之範圍內。 　　249. 態樣243至248中任一者之用途，其中組成物係以單劑經眼內投予人類患者，且在投予後6個月自組成物釋放之醫藥活性成分的中位量係在投予時組成物中的醫藥活性成分總量的30%至100%或40%至90%之範圍內。 　　250. 態樣243至249中任一者之用途，其中組成物包含0.1毫克至500毫克醫藥活性成分。 　　251. 態樣243至250中任一者之用途，其中醫藥活性成分之血漿Cmax係在1毫微克/毫升至10毫微克/毫升之範圍內。 　　252. 態樣243至251中任一者之用途，其中醫藥活性成分之血漿Cmax少於10毫微克/毫升。 　　253. 一種形成貯庫物之方法，其包含使態樣1至210中任一者之組成物與水、磷酸鹽緩衝溶液、體液或模擬之體液接觸。 　　254. 一種形成貯庫物之方法，其包含使態樣1至210中任一者之組成物與患者的玻璃體液接觸。 　　255. 一種包含態樣1至210中任一者之組成物的單位劑型(unit dosage form)，其中單位劑型包含0.4毫克至1毫克醫藥活性成分。 　　256. 態樣255之單位劑型，其中組成物係容納在小瓶內。 　　257. 態樣255之單位劑型，其中組成物係容納在注射器(syringe)內。 　　258. 態樣255之單位劑型，其中組成物容納在無針式注射器(needle-free injector)內。 　　259. 一種容納態樣1至210中任一者之組成物的容器。 　　260. 一種包含態樣1至210中任一者之組成物的無針式注射器，其中組成物包含醫藥活性成分。 　　261. 一種用於治療人類個體之眼疾的方法中之組成物，其中： 　　- 組成物包含0.2至3.1重量%之西羅莫司、0.9至1.1重量%之蔗糖乙酸酯異丁酸酯(SAIB)、43.4至45.0重量%之苯甲酸苯甲酯、4.7至5.1重量%之乙醇、46.2至48.0重量%之聚乙二醇及0.01至1.5重量%之維生素E；且 　　- 方法包含將5至100微升體積的該組成物注射至個體的玻璃體中，隨後經至少1個月不投予另外的西羅莫司至該個體的該玻璃體中。 　　262. 態樣261之組成物，其中組成物包含2.9至3.1重量%之西羅莫司。 　　263. 態樣261或262之組成物，其中組成物包含43.4至44.2重量%之苯甲酸苯甲酯、4.7至4.9重量%之乙醇及46.2至47.0重量%之聚乙二醇。 　　264. 態樣261至263中任一者之組成物，其中組成物包含0.02至1重量%之維生素E。 　　265. 態樣261至264中任一者之組成物，其中組成物包含少於1重量%之維生素E。 　　266. 態樣261至265中任一者之組成物，其中組成物包含0.5重量%或更少的維生素E。 　　267. 態樣261至266中任一者之組成物，其中組成物包含少於0.1重量%之維生素E。 　　268. 態樣261至267中任一者之組成物，其中組成物包含0.02至0.09重量%之維生素E。 　　269. 態樣261至264中任一者之組成物，其中組成物包含約3重量%之西羅莫司、約1重量%之SAIB、約43.7重量%之苯甲酸苯甲酯、約4.8重量%之乙醇、約46.5重量%之聚乙二醇及約1重量%之維生素E。 　　270. 態樣261至269中任一者之組成物，其中聚乙二醇為PEG400。 　　271. 態樣261至270中任一者之組成物，其中組成物基本上由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇、聚乙二醇及維生素E所組成。 　　272. 態樣261至271中任一者之組成物，其中組成物係由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇、聚乙二醇及維生素E所組成。 　　273. 態樣261至272中任一者之組成物，其中方法包含將10微升至30微升體積的該組成物注射至個體的玻璃體中，隨後經至少1個月不投予另外的西羅莫司至該個體的該玻璃體中。 　　274. 態樣261至273中任一者之組成物，其中方法包含將19微升或更少體積的該組成物注射至個體的玻璃體中，隨後經至少1個月不投予另外的西羅莫司至該個體的該玻璃體中。 　　275. 態樣261至272中任一者之組成物，其中方法包含將51微升或更多體積的該組成物注射至個體的玻璃體中，隨後經至少1個月不投予另外的西羅莫司至該個體的該玻璃體中。 　　276. 態樣261至275中任一者之組成物，其中眼疾為眼色素層炎、糖尿病黃斑部水腫或濕式老年性黃斑部退化。 　　277. 態樣276之組成物，其中眼疾為眼色素層炎。 　　278. 態樣276之組成物，其中眼疾為糖尿病黃斑部水腫。 　　279. 態樣276之組成物，其中眼疾為濕式老年性黃斑部退化。 　　280. 態樣261至279中任一者之組成物，其中方法包含將該體積的該組成物注射至個體的玻璃體中，隨後經至少2個月不投予另外的西羅莫司至該個體的該玻璃體中。 　　281. 態樣261至280中任一者之組成物，其中方法包含將該體積的該組成物注射至個體的玻璃體中，隨後經至少3個月不投予另外的西羅莫司至該個體的該玻璃體中。 　　282. 態樣261至281中任一者之組成物，其中所述將該體積的該組成物注射至個體的玻璃體中係在任何先前投予西羅莫司至該個體的該玻璃體中之後至少一個月發生。 　　283. 態樣261至282中任一者之組成物，其中所述將該體積的該組成物注射至個體的玻璃體中係在任何先前投予西羅莫司至該個體的該玻璃體中之後至少兩個月發生。 　　284. 態樣261至283中任一者之組成物，其中所述將該體積的該組成物注射至個體的玻璃體中係在任何先前投予西羅莫司至該個體的該玻璃體中之後至少三個月發生。 　　285. 態樣261至284中任一者之組成物，其中方法包含注射呈一劑之該體積的該組成物。 　　286. 態樣261至285中任一者之組成物，其中該組成物係呈單位劑量型式(unit dose form)，該單位劑量型式含有單位劑量的該組成物，該單位劑量等於該方法中注射之該組成物的體積。 　　287. 態樣286之組成物，其中該單位劑量係容納在預填充之注射器內或適合於將該單位劑量轉移至注射器之容器中。 　　288. 態樣261至287中任一者之組成物，其中方法包含自注射器注射該體積的該組成物，該注射器包含玻璃。 　　289. 態樣261至287中任一者之組成物，其中方法包含自注射器注射該體積的該組成物，該注射器包含聚合物。 　　290. 態樣289之組成物，其中該注射器包含聚合物，其包含至少一種選自環狀烯烴聚合物、環狀烯烴共聚物和聚丙烯之成員。 　　291. 態樣261至290中任一者之組成物，其中方法包含自注射器注射該體積的該組成物，該注射器包含金屬柱塞。 　　292. 態樣291之組成物，其中金屬柱塞為不銹鋼柱塞。 　　293. 態樣261至292中任一者之組成物，其中方法包含自魯爾鎖(leur-lock)注射器注射該體積的該組成物。 　　294. 一種組成物，其： 　　(i) 包含以A至I中任一者所示以重量計之量的西羅莫司、蔗糖乙酸酯異丁酸酯、苯甲酸苯甲酯、聚乙二醇、乙醇及維生素E：；或 　　(ii) 包含以J至T中任一者所示以重量計之量的西羅莫司、蔗糖乙酸酯異丁酸酯、苯甲酸苯甲酯、乙醇及維生素E：295. 態樣294之組成物，其中組成物包含2.9至3.1重量%之西羅莫司。 　　296. 態樣286之組成物，其中組成物包含0.02至1重量%之維生素E。 　　297. 態樣294或295之組成物，其： 　　(i) 包含以A′至I′中任一者所示以重量計之大約量的西羅莫司、蔗糖乙酸酯異丁酸酯、苯甲酸苯甲酯、聚乙二醇、乙醇及維生素E：；或 　　(ii) 包含以J′至T′中任一者所示以重量計之大約量的西羅莫司、蔗糖乙酸酯異丁酸酯、苯甲酸苯甲酯、乙醇及維生素E：298. 態樣294至297中任一者之組成物，其中聚乙二醇為PEG400。 　　299. 態樣294至298中任一者之組成物，其中組成物(i)基本上由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇、聚乙二醇及維生素E所組成；而組成物(ii)基本上由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇及維生素E所組成。 　　300. 態樣294至290中任一者之組成物，其中組成物(i)係由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇、聚乙二醇及維生素E所組成；而組成物(ii)係由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇及維生素E所組成。 　　301. 一種單位劑量型式，其含有5至100微升體積之如態樣294至300中任一者所定義之組成物的單位劑量。 　　302. 態樣301之單位劑量型式，其中組成物的體積為10至30微升。 　　303. 一種如態樣294至300中任一者所定義之組成物或如態樣301或302所定義之單位劑量型式，其係用於一種治療人類個體眼疾之方法。 　　304. 態樣303之組成物或單位劑量型式，其中方法包含將該組成物或單位劑量型式至注射個體的玻璃體中，隨後經至少1個月不投予另外的西羅莫司至該個體的該玻璃體中。 　　305. 態樣303或304之組成物或單位劑量型式，其中眼疾為眼色素層炎、糖尿病黃斑部水腫或濕式老年性黃斑部退化。 　　306. 一種組成物，其包含0.2至3.1重量%之西羅莫司、0.9至1.1重量%之蔗糖乙酸酯異丁酸酯(SAIB)、43.4至45.0重量%之苯甲酸苯甲酯、4.7至5.1重量%之乙醇、46.2至48.0重量%之聚乙二醇及至少0.01重量%但少於1重量%之維生素E。 　　307. 態樣306之組成物，其中組成物包含2.9至3.1重量%之西羅莫司。 　　308. 態樣306或307之組成物，其包含0.02至0.9重量%之維生素E。 　　309. 態樣306至308中任一者之組成物，其包含0.5重量%或更少的維生素E。 　　310. 態樣306至309中任一者之組成物，其包含少於0.1重量%之維生素E。 　　311. 態樣306至310中任一者之組成物，其包含0.02至0.09重量%之維生素E。 　　312. 態樣306至311中任一者之組成物，其中聚乙二醇為PEG400。 　　313. 態樣306至312中任一者之組成物，其中組成物基本上由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇、聚乙二醇及維生素E所組成。 　　314. 態樣306至313中任一者之組成物，其中組成物係由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇、聚乙二醇及維生素E所組成。 　　315. 一種單位劑量型式，其含有5至100微升體積之如態樣306至314中任一者所定義之組成物的單位劑量。 　　316. 態樣315之單位劑量型式，其中組成物的體積為10至30微升。 　　317. 一種如態樣306至314中任一者所定義之組成物或如態樣315或316所定義之單位劑量型式，其係用於一種治療人類個體眼疾之方法。 　　318. 態樣317之組成物或單位劑量型式，其中方法包含將該組成物或單位劑量型式注射至個體的玻璃體中，隨後經至少1個月不投予另外的西羅莫司至該個體的該玻璃體中。 　　319. 態樣317或318之組成物或單位劑量型式，其中眼疾為眼色素層炎、糖尿病黃斑部水腫或濕式老年性黃斑部退化。 　　320. 一種劑型，其包含容納組成物之小瓶，其中： 　　組成物包含活性醫藥成分、高黏度液態載體材料(HVLCM)、第一疏水性溶劑及親水性溶劑；及 　　組成物具有範圍約35微升至約1900微升之體積。 　　321. 態樣320之劑型，其中組成物具有範圍約50微升至約1000微升之體積。 　　322. 態樣320至321中任一者之劑型，其中組成物在25℃及1大氣壓下為溶液及/或其中組成物在25℃及1大氣壓下具有範圍約1cP至約150cP之黏度。 　　323. 態樣320至322中任一者之劑型，其中： 　　HVLCM係以組成物重量為基準計的範圍約0.5重量%至約15重量%之量存在，及 　　第一疏水性溶劑係以組成物重量為基準計的範圍約30重量%至約50重量%之量存在。 　　324. 態樣320至323中任一者之劑型，其中： 　　HVLCM係以組成物重量為基準計的範圍約0.5重量%至約15重量%之量存在，及 　　第一疏水性溶劑係以組成物重量為基準計的範圍約80重量%至約95重量%之量存在。 　　325. 態樣320至324中任一者之劑型，其中組成物另外包含抗氧化劑。 　　326. 態樣320至325中任一者之劑型，其中組成物另外包含聚烷二醇。 　　327. 態樣326之劑型，其中聚烷二醇係以範圍約40重量%至約55重量%之量存在。 　　328. 態樣320至326中任一者之劑型，其中活性醫藥成分包含西羅莫司。 　　329. 態樣320之劑型，其中組成物包含0.2至3.1重量%之西羅莫司、0.9至1.1重量%之蔗糖乙酸酯異丁酸酯(SAIB)、43.4至45.0重量%之苯甲酸苯甲酯、4.7至5.1重量%之乙醇、46.2至48.0重量%之聚乙二醇及0.01至1.5重量%之維生素E。 　　330. 態樣320至329中任一者之劑型，其中組成物包含0.02至1重量%之維生素E。 　　331. 態樣320至330中任一者之劑型，其中組成物包含少於1重量%之維生素E。 　　332. 態樣320至331中任一者之劑型，其中組成物包含0.5重量%更少的維生素E。 　　333. 態樣320至332中任一者之劑型，其中組成物包含少於0.1重量%之維生素E。 　　334. 態樣320至333中任一者之劑型，其中組成物包含0.02至0.09重量%之維生素E。 　　335. 態樣320至329中任一者之劑型，其中組成物包含約3重量%之西羅莫司、約1重量%之SAIB、約43.7重量%之苯甲酸苯甲酯、約4.8重量%之乙醇、約46.5重量%之聚乙二醇及約1重量%之維生素E。 　　336. 態樣326至335中任一者之劑型，其中聚烷二醇為PEG400。 　　337. 態樣320至336中任一者之劑型，其中組成物基本上由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇、聚乙二醇及維生素E所組成。 　　338. 態樣320至336中任一者之劑型，其中組成物係由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇、聚乙二醇及維生素E所組成。 　　339. 態樣320至228中任一者之劑型，其中組成物係如態樣261至319中任一者所定義。 　　340. 一種劑型，其包含容納組成物之注射器，其中： 　　組成物包含活性醫藥成分、高黏度液態載體材料(HVLCM)、第一疏水性溶劑及親水性溶劑；及 　　組成物具有範圍約5微升至約100微升之體積。 　　341. 態樣340之劑型，其中組成物在25℃及1大氣壓下為溶液及/或其中組成物在25℃及1大氣壓下具有範圍約1cP至約150cP之黏度。 　　342. 態樣340及341中任一者之劑型，其中： 　　HVLCM係以組成物重量為基準計的範圍約0.5重量%至約15重量%之量存在，及 　　第一疏水性溶劑係以組成物重量為基準計的範圍約30重量%至約50重量%之量存在。 　　343. 態樣340至341中任一者之劑型，其中： 　　HVLCM係以組成物重量為基準計的範圍約0.5重量%至約15重量%之量存在，及 　　第一疏水性溶劑係以組成物重量為基準計的範圍約80重量%至約95重量%之量存在。 　　344. 態樣340至343中任一者之劑型，其中組成物另外包含抗氧化劑。 　　345. 態樣340至344中任一者之劑型，其中組成物另外包含聚烷二醇。 　　346. 態樣345之劑型，其中聚烷二醇係以範圍約40重量%至約55重量%之量存在。 　　347. 態樣340至346中任一者之劑型，其中活性醫藥成分包含西羅莫司。 　　348. 態樣340之劑型，其中組成物包含0.2至3.1重量%之西羅莫司、0.9至1.1重量%之蔗糖乙酸酯異丁酸酯(SAIB)、43.4至45.0重量%之苯甲酸苯甲酯、4.7至5.1重量%之乙醇、46.2至48.0重量%之聚乙二醇及0.01至1.5重量%之維生素E。 　　349. 態樣340至348中任一者之劑型，其中組成物包含0.02至1重量%之維生素E。 　　350. 態樣340至348中任一者之劑型，其中組成物包含少於1重量%之維生素E。 　　351. 態樣340至348中任一者之劑型，其中組成物包含0.5重量%或更少的維生素E。 　　352. 態樣329至337中任一者之劑型，其中組成物包含少於0.1重量%之維生素E。 　　353. 態樣340至348中任一者之劑型，其中組成物包含0.02至0.09重量%之維生素E。 　　354. 態樣340至348中任一者之劑型，其中組成物包含約3重量%之西羅莫司、約1重量%之SAIB、約43.7重量%之苯甲酸苯甲酯、約4.8重量%之乙醇、約46.5重量%之聚乙二醇及約1重量%之維生素E。 　　355. 態樣345至354中任一者之劑型，其中聚烷二醇為PEG400。 　　356. 態樣340至355中任一者之劑型，其中組成物基本上由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇、聚乙二醇及維生素E所組成。 　　357. 態樣340至355中任一者之劑型，其中組成物係由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇、聚乙二醇及維生素E所組成。 　　358. 態樣340至357中任一者之劑型，其中注射器包含玻璃。 　　359. 態樣340至357中任一者之劑型，其中注射器包含聚合物。 　　360. 態樣359之劑型，其中聚合物包含至少一種選自環狀烯烴聚合物、環狀烯烴共聚物及聚丙烯之成員。 　　316. 態樣340至360中任一者之劑型，其中注射器包含金屬柱塞。 　　362. 態樣361之劑型，其中金屬柱塞包含不銹鋼柱塞。 　　363. 態樣340至262中任一者之劑型，其中注射器包含魯爾鎖注射器。 　　364. 態樣340至363中任一者之劑型，其中注射器係容納在容器內。 　　365. 態樣364之劑型，其中容器包含盒子。 　　366. 態樣340至365中任一者之劑型，其中組成物係如態樣261至319中任一者所定義。 　　367. 一種組成物，其包含： 　　活性醫藥成分； 　　高黏度液態載體材料(HVLCM)； 　　第一疏水性溶劑； 　　親水性溶劑；及 　　維生素E，其中維生素係以少於0.1重量%之量存在。 　　368. 態樣367之組成物，其中維生素係以範圍0.02重量%至0.09重量%之量存在。 　　369. 態樣367至368中任一者之組成物，其中組成物在25℃及1大氣壓下為溶液及/或其中組成物在25℃及1大氣壓下具有範圍約1cP至約150cP之黏度。 　　370. 態樣367至369中任一者之組成物，其中： 　　HVLCM係以組成物重量為基準計的範圍約0.5重量%至約15重量%之量存在，及 　　第一疏水性溶劑係以組成物重量為基準計的範圍約30重量%至約50重量%之量存在。 　　371. 態樣367至369中任一者之組成物，其中： 　　HVLCM係以組成物重量為基準計的範圍約0.5重量%至約15重量%之量存在，及 　　第一疏水性溶劑係以組成物重量為基準計的範圍約80重量%至約95重量%之量存在。 　　372. 態樣367至371中任一者之組成物，其中組成物另外包含聚烷二醇。 　　373. 態樣372之組成物，其中聚烷二醇係以範圍約40重量%至約55重量%之量存在。 　　374. 態樣367至373中任一者之組成物，其中活性醫藥成分包含西羅莫司。 　　375. 態樣367之組成物，其中組成物包含0.2至3.1重量%之西羅莫司、0.9至1.1重量%之蔗糖乙酸酯異丁酸酯(SAIB)、43.4至45.0重量%之苯甲酸苯甲酯、4.7至5.1重量%之乙醇、46.2至48.0重量%之聚乙二醇及0.02至0.09重量%之維生素E。 　　376. 態樣371至375中任一者之組成物，其中聚烷二醇為PEG400。 　　377. 態樣367至376中任一者之組成物，其中組成物基本上由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇、聚乙二醇及維生素E所組成。 　　378. 態樣367至376中任一者之組成物，其中組成物係由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇、聚乙二醇及維生素E所組成。 　　379. 態樣367至378中任一者之劑量，其中組成物係由態樣261至319中任一者所定義。 　　380. 一種組成物，其包含0.2至3.1重量%之西羅莫司、0.9至1.1重量%之蔗糖乙酸酯異丁酸酯(SAIB)、89.6至93重量%之苯甲酸苯甲酯、4.9至5.1重量%之乙醇及至少0.01重量%但少於1重量%之維生素E。 　　381. 態樣380之組成物，其中組成物包含2.9至3.1重量%之西羅莫司。 　　382. 態樣380或381之組成物，其包含0.02至0.9重量%之維生素E。 　　383. 態樣380至382中任一者之組成物，其包含0.5重量%或更少的維生素E。 　　384. 態樣380至383中任一者之組成物，其包含少於0.1重量%之維生素E。 　　385. 態樣380至384中任一者之組成物，其包含0.02至0.09重量%之維生素E。 　　386. 態樣380至385中任一者之組成物，其中組成物基本上由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇及維生素E所組成。 　　387. 態樣380至386中任一者之組成物，其中組成物係由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇及維生素E所組成。 　　388. 一種單位劑量型式，其含有5至100微升體積之如態樣380至387中任一者所定義之組成物的單位劑量。 　　389. 態樣388之單位劑量型式，其中組成物的體積為10至30微升。 　　390. 一種如態樣380至387中任一者所定義之組成物或如態樣388或389所定義之單位劑量型式，其係用於一種治療人類個體眼疾之方法。 　　391. 態樣390之組成物或單位劑量型式，其中方法包含將該組成物或單位劑量型式注射至個體的玻璃體中，隨後經至少1個月不投予另外的西羅莫司至該個體的該玻璃體中。 　　392. 態樣390或391之組成物或單位劑量型式，其中眼疾為眼色素層炎、糖尿病黃斑部水腫或濕式老年性黃斑部退化。Specific non-limiting aspects of the invention are provided below: 1. A composition comprising: an active pharmaceutical ingredient; a high-viscosity liquid carrier material (HVLCM); a first hydrophobic solvent; and a hydrophilic solvent; wherein the composition is a solution at 25 ° C and 1 atmosphere and / or the composition is It has a viscosity ranging from about 1 cP to about 150 cP at 25 ° C and 1 atmosphere. 2. A composition comprising: an active pharmaceutical ingredient; a high-viscosity liquid carrier material (HVLCM), wherein the range of HVLCM based on the weight of the composition is about 0. 5% to about 15% by weight; a first hydrophobic solvent, wherein the first hydrophobic solvent is present in an amount ranging from about 30% to about 50% by weight based on the weight of the composition; and hydrophilic Solvent; where the composition is a solution at 25 ° C and 1 atmosphere and / or where the composition has a viscosity ranging from about 1 cP to about 150 cP at 25 ° C and 1 atmosphere. 3. A composition comprising: an active pharmaceutical ingredient; a high-viscosity liquid carrier material (HVLCM), wherein the range of HVLCM based on the weight of the composition is about 0. 5% to about 15% by weight; a first hydrophobic solvent, wherein the first hydrophobic solvent is present in an amount ranging from about 80% to about 95% by weight based on the weight of the composition; and hydrophilic Solvent; where the composition is a solution at 25 ° C and 1 atmosphere and / or where the composition has a viscosity ranging from about 1 cP to about 150 cP at 25 ° C and 1 atmosphere. 4. A composition comprising: an active pharmaceutical ingredient, wherein the active pharmaceutical ingredient comprises sirolimus; a high-viscosity liquid carrier material (HVLCM); a first hydrophobic solvent; and a hydrophilic solvent. 5. A composition comprising: an active pharmaceutical ingredient, wherein the active pharmaceutical ingredient comprises sirolimus; a high-viscosity liquid carrier material (HVLCM), wherein the range of HVLCM based on the weight of the composition is about 0. 5% to about 15% by weight; a first hydrophobic solvent, wherein the first hydrophobic solvent is present in an amount ranging from about 30% to about 50% by weight based on the weight of the composition; and hydrophilic Solvent. 6. A composition comprising: an active pharmaceutical ingredient, wherein the active pharmaceutical ingredient comprises sirolimus; a high-viscosity liquid carrier material (HVLCM), wherein the range of HVLCM based on the weight of the composition is about 0. 5% to about 15% by weight; a first hydrophobic solvent, wherein the first hydrophobic solvent is present in an amount ranging from about 80% to about 95% by weight based on the weight of the composition; and hydrophilic Solvent. 7. A composition comprising: an active pharmaceutical ingredient; a first hydrophobic solvent; a second hydrophobic solvent different from the first hydrophobic solvent, and the second hydrophobic solvent comprises trialkyl citrate and triethyl citrate At least one of the esters, wherein the alkyl groups of each of the trialkyl citrate and the triethyl ethanoate are the same or different and have a number of 3 to 5 carbon atoms; and a hydrophilic solvent. 8. A composition comprising: an active pharmaceutical ingredient; a polyalkylene glycol; a first hydrophobic solvent; and a hydrophilic solvent different from the polyalkylene glycol. 9. A composition comprising: an active pharmaceutical ingredient, wherein the active pharmaceutical ingredient comprises sirolimus; a polyalkylene glycol, wherein the polyalkylene glycol is present in an amount ranging from about 40% by weight to about 55% by weight; a first hydrophobic The first hydrophobic solvent is present in an amount ranging from about 30% by weight to about 50% by weight based on the weight of the composition; and a hydrophilic solvent different from the polyalkylene glycol. 10. A composition comprising: an active pharmaceutical ingredient; poloxamer; a first hydrophobic solvent; and a hydrophilic solvent. 11. A composition comprising: an active pharmaceutical ingredient; an antioxidant; a first hydrophobic solvent; and a hydrophilic solvent. 12. A composition comprising: an active pharmaceutical ingredient; an antioxidant; a first hydrophobic solvent, wherein the first hydrophobic solvent is present in an amount ranging from about 30% by weight to about 50% by weight based on the weight of the composition; and Hydrophilic solvents. 13. A composition comprising: an active pharmaceutical ingredient; an antioxidant; a first hydrophobic solvent, wherein the first hydrophobic solvent is present in an amount ranging from about 80% by weight to about 95% by weight based on the weight of the composition; and Hydrophilic solvents. 14. The composition of any one of aspects 7 to 13, wherein the composition further comprises a high-viscosity liquid carrier material (HVLCM). 15. The composition of any one of aspects 1, 4, and 14, wherein the range of HVLCM based on the weight of the composition is about 0. It is present in an amount of 1% to about 50% by weight. 16. The composition of any one of aspects 1, 4, and 14, wherein the range of HVLCM based on the weight of the composition is about 0. It is present in an amount of 5% to about 50% by weight. 17. The composition of any one of aspects 1, 4, and 14, wherein HVLCM is present in an amount ranging from about 30% by weight to about 60% by weight based on the weight of the composition. 18. The composition of aspect 15, wherein HVLCM is present in an amount ranging from about 40% by weight to about 50% by weight based on the weight of the composition. 19. The composition of aspect 15, wherein HVLCM is present in an amount ranging from about 1% by weight to about 20% by weight based on the weight of the composition. 20. The composition of aspect 19, wherein HVLCM is present in an amount ranging from about 5% to about 15% by weight based on the weight of the composition. twenty one. Composition of aspect 15, wherein the range of HVLCM based on the weight of the composition is about 0. It is present in an amount of 1% to about 10% by weight. twenty two. The composition of any one of aspects 1 to 6, and 14, wherein the range of HVLCM based on the weight of the composition is about 0. It is present in an amount of 8% to about 10% by weight. twenty three. The composition of any one of aspects 1 to 6, and 14, wherein the range of HVLCM based on the weight of the composition is about 0. It is present in an amount of 5% to about 5% by weight. twenty four. The composition of any one of aspects 1 to 6 and 14 to 23, wherein HVLCM comprises sucrose acetate isobutyrate (SAIB). 25. The composition according to any one of aspects 1 to 24, wherein the composition includes about 1% to about 10% by weight of the active pharmaceutical ingredient based on the weight of the composition. 26. The composition of aspect 25, wherein the composition comprises about 1% to about 5% by weight of the active pharmaceutical ingredient based on the weight of the composition. 27. The composition according to any one of aspects 1 to 26, wherein the active pharmaceutical ingredient comprises an antibiotic. 28. The composition of any one of aspects 1 to 3, 7, 8, and 10 to 27, wherein the active pharmaceutical ingredient comprises sirolimus. 29. The composition according to any one of aspects 1 to 28, wherein the active pharmaceutical ingredient contains a substance other than sirolimus. 30. The composition according to any one of aspects 1 to 28, wherein the active pharmaceutical ingredient does not include ophthalmic drugs other than sirolimus. 31. The composition of any one of aspects 1 to 30, wherein the first hydrophobic solvent is present in an amount ranging from about 10% by weight to about 95% by weight based on the weight of the composition. 32. The composition of aspect 31, wherein the first hydrophobic solvent is present in an amount ranging from about 30% by weight to about 60% by weight based on the weight of the composition. 33. The composition of aspect 32, wherein the first hydrophobic solvent is present in an amount ranging from about 40% by weight to about 50% by weight based on the weight of the composition. 34. The composition of any one of aspects 1 to 31, wherein the first hydrophobic solvent is present in an amount ranging from about 35% by weight to about 55% by weight based on the weight of the composition. 35. The composition of aspect 34, wherein the first hydrophobic solvent is present in an amount ranging from about 35% by weight to about 50% by weight based on the weight of the composition. 36. The composition of aspect 35, wherein the first hydrophobic solvent is present in an amount ranging from about 35% by weight to about 45% by weight based on the weight of the composition. 37. The composition of aspect 31, wherein the first hydrophobic solvent is present in an amount ranging from about 80% by weight to about 95% by weight based on the weight of the composition. 38. The composition of any one of aspects 1 to 37, wherein the first hydrophobic solvent includes methyl benzoate, ethyl benzoate, n-propyl benzoate, isopropyl benzoate, butyl benzoate, isopropyl benzoate At least one of butyl ester, secondary butyl benzoate, tertiary butyl benzoate, isoamyl benzoate, and benzoyl benzoate. 39. The composition of any one of aspects 1 to 38, wherein the first hydrophobic solvent comprises benzyl benzoate. 40. The composition of any one of aspects 1 to 39, wherein the first hydrophobic solvent does not include 1,1,1,2 tetrafluoroethane. 41. The composition of any one of aspects 1 to 39, wherein the first hydrophobic solvent does not include a fluorinated hydrocarbon. 42. The composition of any one of aspects 1 to 39, wherein the first hydrophobic solvent does not include a propellant. 43. The composition according to any one of aspects 1 to 42, wherein the hydrophilic solvent is present in an amount ranging from about 1% by weight to about 70% by weight based on the weight of the composition. 44. The composition according to any one of aspects 1 to 42, wherein the hydrophilic solvent is present in an amount ranging from about 2% by weight to about 60% by weight based on the weight of the composition. 45. The composition of aspect 43, wherein the hydrophilic solvent is present in an amount ranging from about 1% by weight to about 10% by weight based on the weight of the composition. 46. The composition according to any one of aspects 1 to 45, wherein the hydrophilic solvent is present in an amount of less than 10% by weight based on the weight of the composition. 47. The composition of aspect 46, wherein the hydrophilic solvent is present in an amount ranging from about 1% by weight to about 7% by weight based on the weight of the composition. 48. The composition according to any one of aspects 1 to 47, wherein the hydrophilic solvent is present in an amount of less than 5% by weight based on the weight of the composition. 49. The composition of any one of aspects 1 to 48, wherein the hydrophilic solvent includes ethanol, triethyl citrate (ATEC), dimethylsulfinium (DMSO), N-methylpyrrolidone (NMP ), Propylene glycol, dimethylacetamide (DMA), and polyethylene glycol (PEG). 50. The composition according to any one of aspects 1 to 49, wherein the hydrophilic solvent includes ethanol. 51. The composition according to any one of aspects 1 to 49, wherein the hydrophilic solvent contains ATEC. 52. The composition of any one of aspects 1 to 51, wherein the hydrophilic solvent includes at least ethanol and ATEC. 53. The composition of any one of aspects 1 to 52, wherein the hydrophilic solvent includes PEG. 54. The composition of any one of aspects 1 to 7 and 10 to 49, wherein the hydrophilic solvent includes at least ethanol and PEG. 55. The composition of any one of aspects 1 to 7 and 10 to 54, wherein the hydrophilic solvent is present in an amount ranging from about 3% by weight to about 55% by weight based on the weight of the composition. 56. The composition of any one of aspects 50, 52, 54, and 55, wherein the ethanol is present in an amount ranging from about 1% by weight to about 10% by weight based on the weight of the composition. 57. The composition of any one of aspects 50, 52, 54, and 56, wherein the ethanol is present in an amount ranging from about 3% by weight to about 10% by weight based on the weight of the composition. 58. The composition of any one of aspects 53 to 57, wherein the PEG is present in an amount ranging from about 30% by weight to about 60% by weight based on the weight of the composition. 59. The composition of Aspect 58, wherein PEG is present in an amount ranging from about 35% by weight to about 50% by weight based on the weight of the composition. 60. The composition of Aspect 58, wherein the PEG is present in an amount ranging from about 40% by weight to about 55% by weight based on the weight of the composition. 61. The composition of aspect 59, wherein the PEG is present in an amount ranging from about 40% by weight to about 50% by weight based on the weight of the composition. 62. The composition of any one of aspects 1 to 6 and 8 to 61, further comprising a trialkyl citrate and / or an ethyl trialkyl citrate, wherein the tri alkyl citrate and the triethyl citrate The alkyl groups of each of the alkyl esters are the same or different and have a number of 3 to 5 carbon atoms. 63. The composition of aspect 7 or 62, wherein the trialkyl citrate and / or triethyl citrate are present in an amount ranging from about 10% by weight to about 95% by weight based on the weight of the composition. 64. The composition of aspect 7 or 62, wherein trialkyl citrate and / or triethyl citrate are present in an amount ranging from about 35% by weight to about 65% by weight based on the weight of the composition. 65. The composition of aspect 7 or 62, wherein the trialkyl citrate and / or triethyl citrate is present in an amount ranging from about 30% by weight to about 60% by weight based on the weight of the composition. 66. The composition of aspect 65, wherein trialkyl citrate and / or triethyl citrate are present in an amount ranging from about 40% by weight to about 50% by weight based on the weight of the composition. 67. The composition according to any one of aspects 7 and 62 to 66, wherein the number of carbon atoms in the alkyl group of the trialkyl citrate and / or the trialkyl ethoxylate is 4. 68. The composition of any one of aspects 7 and 62 to 67, wherein the trialkyl citrate is tri-n-butyl citrate and the triethyl citrate is tri-n-butyl ethoxylate. 69. The composition according to any one of aspects 7 and 62 to 67, wherein the trialkyl citrate and / or the triethyl citrate contains tri-n-butyl acetyl citrate. 70. The composition of any one of aspects 1 to 69, wherein the composition includes water. 71. The composition of any of aspects 1 to 70, wherein the composition contains less than 1% by weight of water. 72. The composition of any one of aspects 1 to 70, wherein the composition contains less than 0. 5 wt% water. 73. The composition of any one of aspects 1 to 7 and 11 to 52, 55 to 57 and 62 to 72, wherein the composition does not have a polymer, except that it optionally contains an active pharmaceutical ingredient of the polymer. 74. The composition of any one of aspects 1 to 72, wherein the composition includes at least one of a polyalkylene glycol and poloxamer, and wherein the composition is also free of a polymer, except for an active pharmaceutical ingredient which optionally contains a polymer other than. 75. The composition of any one of aspects 1 to 72, further comprising a polymer. 76. Aspect 75 of the composition, wherein the polymer is based on the weight of the composition in the range of about 0. It is present in an amount of 1% to about 30% by weight. 77. The composition of aspect 75 or 76, wherein the polymer comprises a polyester. 78. The composition according to any one of aspects 75 to 77, wherein the polymer includes at least one of poly (lactic acid) (glycolic acid), poly (lactic acid), and polycaprolactone. 79. The composition of any one of aspects 1 to 78, further comprising a surfactant. 80. The composition of any one of aspects 1 to 78, further comprising at least one member selected from the group consisting of poloxamer, polyethoxylated castor oil, polyoxyethylated hydroxystearic acid, sorbitan Monooleate and sorbitan monolaurate. 81. Composition of aspect 80, wherein at least one member is based on the weight of the composition as a range of about 0. It is present in an amount of 1% to about 10% by weight. 82. The composition of any one of aspects 1 to 81, further comprising triethyl citrate. 83. The composition of any one of aspects 1 to 82, which further comprises ascorbyl palmitate. 84. The composition of any one of aspects 1 to 9, 11 to 72, and 75 to 83, further comprising poloxamer. 85. Composition of aspect 10 or 84, wherein the poloxamer is in a range of about 0. It is present in an amount of 5% to about 10% by weight. 86. Composition of aspect 10 or 84, wherein the poloxamer is in a range of about 0. An amount of 5% to about 2% by weight is present. 87. Composition of aspect 10 or 84, wherein the poloxamer is in a range of about 0. It is present in an amount of 1% to about 5% by weight. 88. The composition of any one of aspects 1 to 87, further comprising an acid precursor. 89. The composition of any one of aspects 1 to 88, wherein at least 98% of the active pharmaceutical ingredient remains in the composition after being stored in a 2 ml corrugated glass vial at 5 ° C / 60% RH for 18 weeks. 90. The composition of any one of aspects 1 to 89, wherein at least 90% of the active pharmaceutical ingredient remains in the composition after being stored in a 2 ml corrugated glass vial at 25 ° C / 60% RH for 18 weeks. 91. The composition of any one of aspects 1 to 10 and 14 to 90, wherein the composition further comprises an antioxidant. 92. The composition of any one of aspects 11 to 13 and 91, wherein the antioxidant is in the range of about 0 based on the weight of the composition. It is present in an amount of 5% to about 5% by weight. 93. The composition of any one of aspects 11 to 13, 91, and 92, wherein the antioxidant includes vitamin E. 94. The composition of aspect 93, wherein vitamin E is present in an amount ranging from about 1% by weight to about 50% by weight based on the weight of the composition. 95. The composition of any one of aspects 93 and 94, wherein vitamin E is present in an amount of less than 10% by weight based on the weight of the composition. 96. Composition of aspect 95, wherein the range of vitamin E based on the weight of the composition is about 0. It is present in an amount of 1% to about 5% by weight. 97. The composition of any one of aspects 11 to 13 and 93 to 96, wherein vitamin E is present in an amount of less than 5% by weight based on the weight of the composition. 98. Composition of aspect 97, wherein the range of vitamin E based on the weight of the composition is about 0. An amount of 5% to about 2% by weight is present. 99. The composition of aspect 93, wherein the weight ratio of HVLCM to vitamin E is in the range of about 60: 1 to about 1: 2. 100. Composition of aspect 93, wherein the weight ratio of HVLCM to vitamin E is from about 10: 1 to about 1: 1. Within the range of 8. 101. Composition of aspect 93, wherein the weight ratio of HVLCM to vitamin E is from about 5: 1 to about 1: 1. Within the range of 5. 102. The composition of aspect 93, wherein the weight ratio of HVLCM to vitamin E is from about 2: 1 to about 1: 1. Within the range of 5. 103. The composition of aspect 99, wherein HVLCM comprises SAIB. 104. The composition of aspect 100, wherein HVLCM comprises SAIB. 105. The composition of aspect 101, wherein HVLCM comprises SAIB. 106. The composition of aspect 102, wherein HVLCM comprises SAIB. 107. Aspect 93 of the composition, wherein the composition comprises SAIB, and the composition has a range of about 0. SAIB: Vitamin E weight ratio of 5 to about 10. 108. The composition of any one of aspects 93 to 107, wherein the weight ratio of HVLCM to vitamin E is such that the density of the mixture composed of the HVLCM and the vitamin E in the weight ratio is at least 1 g / 25 at 25 ° C. Ml. 109. Composition of aspect 108, wherein the density is at least 1. 05 g / ml. 110. The composition of any one of aspects 1 to 109, wherein the composition further comprises a lipid ester. 111. The composition of any one of aspects 1 to 110, wherein the composition further comprises a fatty ester. 112. The composition of any one of aspects 1 to 111, wherein the composition further comprises at least one of lauryl lactate and lauryl glycol. 113. The composition of any one of aspects 1 to 112, wherein the composition has a range of 1 at 25 ° C and 1 atmosphere. 02 g / ml to 1. 15 g / ml density. 114. The composition of any one of aspects 1 to 113, wherein the composition has a viscosity ranging from about 1 cP to about 150 cP at 25 ° C and 1 atmosphere. 115. The composition of any one of aspects 1 to 113, wherein the composition has a viscosity ranging from about 5 cP to about 50 cP at 25 ° C and 1 atmosphere. 116. The composition of any one of aspects 1 to 113, wherein the composition has a viscosity ranging from about 10 cP to about 30 cP at 25 ° C and 1 atmosphere. 117. The composition of any one of aspects 1 to 116, wherein the composition is not an emulsion. 118. The composition of any one of aspects 1 to 117, wherein when 100 microliters of composition is injected by having 0. 1 wt% sodium lauryl sulfate phosphate buffered saline in 5 ml of release medium to form a sample and place the sample on a rotary shaker rotating at 30 rpm at 37 ° C for testing. The cumulative release% of the active pharmaceutical ingredient of the composition is less than 50% at T = 24 hours. 119. The composition according to any one of aspects 1 to 118, wherein the active pharmaceutical ingredient comprises sirolimus and the hydrophilic solvent thereof comprises ethanol. 120. The composition of aspect 119, wherein HVLCM comprises sucrose acetate isobutyrate. 121. The composition of aspect 119 or 120, wherein the first hydrophobic solvent comprises benzyl benzoate. 122. The composition of any one of aspects 119 to 121, which contains vitamin E. 123. The composition of any one of aspects 119 to 122, which comprises tri-n-butyl acetamyl citrate. 124. The composition of aspect 4, wherein the active pharmaceutical ingredient is present in an amount ranging from about 1% by weight to about 10% by weight based on the weight of the composition. HVLCM is present in an amount ranging from about 30% by weight to about 60% by weight based on the weight of the composition; HVLCM includes SAIB; the first hydrophobic solvent is in a range of about 30% by weight to about 60 based on the weight of the composition The first hydrophobic solvent includes benzyl benzoate; the hydrophilic solvent is present in an amount ranging from about 1% to about 10% by weight based on the weight of the composition; the hydrophilic solvent includes ethanol; The composition additionally contains vitamin E; and the range of vitamin E based on the weight of the composition is about 0. It is present in an amount of 1% to about 5% by weight. 125. The composition of aspect 124, wherein SAIB comprises sucrose esterified with two acetic acid and six isobutyric acid moieties. 126. The composition of aspect 125, wherein the sucrose esterified with two acetic acid and six isobutyric acid moieties is present in an amount ranging from 7% to about 15% by weight based on the weight of the composition. 127. The composition of any one of aspects 124 to 126, further comprising poloxamer, wherein the range of poloxamer is about 0 based on the weight of the composition. It is present in an amount of 1% to about 5% by weight. 128. The composition of aspect 4, wherein the active pharmaceutical ingredient is present in an amount ranging from about 1% by weight to about 10% by weight based on the weight of the composition; HVLCM is about 1% by weight to about 1% by weight based on the weight of the composition Present in an amount of about 20% by weight; HVLCM comprises SAIB; the first hydrophobic solvent is present in an amount ranging from about 30% to about 60% by weight based on the weight of the composition; the first hydrophobic solvent comprises benzoic acid benzoic acid Ester; hydrophilic solvent contains at least ethanol and PEG; ethanol is present in an amount ranging from about 1% to about 10% by weight based on the weight of the composition; PEG is about 30% by weight based on the weight of the composition Present in an amount of up to about 60% by weight; the composition further comprises vitamin E; and vitamin E is based on the weight of the composition as a range of about 0. It is present in an amount of 1% to about 5% by weight. 129. The composition of aspect 128, wherein SAIB comprises sucrose esterified with two acetic acid and six isobutyric acid moieties. 130. Composition of aspect 129, wherein two acetic acid and six isobutyric acid portions are esterified sucrose based on the weight of the composition in the range of about 0. It is present in an amount of 25% to about 5% by weight. 131. Composition of aspect 4, wherein the active pharmaceutical ingredient is present in an amount ranging from about 1% by weight to about 10% by weight based on the weight of the composition; HVLCM is in the range of about 0 based on the weight of the composition. 1 to 10% by weight; HVLCM contains SAIB; the first hydrophobic solvent is present in an amount ranging from about 30% to about 60% by weight based on the weight of the composition; the first hydrophobic solvent comprises Benzyl benzoate; The hydrophilic solvent contains at least ethanol and PEG; Ethanol is present in an amount ranging from about 1% to about 10% by weight based on the weight of the composition; PEG is a range based on the weight of the composition About 30% by weight to about 60% by weight is present; the composition further comprises vitamin E; and vitamin E is based on the weight of the composition in the range of about 0. It is present in an amount of 1% to about 5% by weight. 132. The composition of any one of aspects 1 to 131, wherein: the active pharmaceutical ingredient comprises sirolimus in an amount ranging from about 1% to about 5% by weight based on the weight of the composition; HVLCM includes the composition The weight is based on a range of about 0. Sucrose acetate isobutyrate (SAIB) in an amount of 1% to about 10% by weight; the first hydrophobic solvent comprises an amount ranging from about 30% to about 45% by weight based on the weight of the composition Benzyl benzoate; a hydrophilic solvent comprising (i) ethanol in an amount ranging from about 1% to about 10% by weight based on the weight of the composition; and (ii) in a range of about 40% by weight to about 50% by weight of PEG; and the composition further comprises a range of about 0 based on the weight of the composition. Vitamin E in an amount of 5% to about 2% by weight. 133. The composition of any one of aspects 1 to 132, which is essentially composed of the following: sirolimus in an amount ranging from about 1% by weight to about 5% by weight based on the weight of the composition; The range based on the weight of the composition is about 0. SAIB in an amount of 1% to about 10% by weight; benzyl benzoate in an amount ranging from about 30% to about 45% by weight based on the weight of the composition; range of about 1% by weight to about 10% by weight of ethanol; PEG400 in an amount ranging from about 40% to about 50% by weight based on the weight of the composition; and a range of about 0 based on the weight of the composition Vitamin E in an amount of 5% to about 2% by weight. 134. The composition of any one of aspects 1 to 133, which is essentially composed of the following: sirolimus in an amount ranging from about 1% by weight to about 5% by weight based on the weight of the composition; Based on the weight of the composition of not more than about 10% by weight of SAIB; benzyl benzoate; a hydrophilic solvent selected from the group consisting of ethanol and PEG400; and a range of about 0. 5% to about 2% by weight of vitamin E, wherein the weight ratio of SAIB to vitamin E exceeds about 0. 5. 135. The composition of any one of aspects 131 to 134, wherein the SAIB comprises sucrose esterified with two acetic acid and six isobutyric acid moieties. 136. Composition of aspect 135, wherein two acetic acid and six isobutyric acid portions are esterified sucrose based on the weight of the composition in the range of about 0. 025% by weight to about 2. An amount of 5% by weight is present. 137. Composition of aspect 4, wherein the active pharmaceutical ingredient is present in an amount ranging from about 1% by weight to about 10% by weight based on the weight of the composition; HVLCM is in the range of about 0 based on the weight of the composition. 1 to about 10% by weight; HVLCM contains SAIB; first hydrophobic solvent is present in an amount ranging from about 80% to about 95% by weight based on the weight of the composition; the first hydrophobic solvent contains Benzyl benzoate; a hydrophilic solvent containing at least ethanol; ethanol is present in an amount ranging from about 1% to about 10% by weight based on the weight of the composition; the composition additionally contains vitamin E; and vitamin E is based on the composition The weight is about 0 on the basis of the gauge. It is present in an amount of 1% to about 5% by weight. 138. The composition of aspect 137, wherein SAIB comprises sucrose esterified with two acetic acid and six isobutyric acid moieties. 139. Aspect 138 of the composition, wherein two acetic acid and six isobutyric acid portions are esterified sucrose based on the weight of the composition in the range of about 0. 025% by weight to about 2. An amount of 5% by weight is present. 140. The composition of aspect 7, wherein the active pharmaceutical ingredient is present in an amount ranging from about 1% to about 10% by weight based on the weight of the composition; the active pharmaceutical ingredient comprises sirolimus; the composition further comprises the composition The weight is based on a range of about 0. High viscosity liquid carrier material (HVLCM) present in an amount of 1% to about 10% by weight; HVLCM includes SAIB; the first hydrophobic solvent is in a range of about 30% to about 60% by weight based on the weight of the composition The first hydrophobic solvent contains benzyl benzoate; the second hydrophobic solvent is present in an amount ranging from about 30% to about 60% by weight based on the weight of the composition; the second hydrophobic solvent contains ethyl Tris-n-butyl citrate (ATBC); hydrophilic solvent is present in an amount ranging from about 1% to about 10% by weight based on the weight of the composition; the hydrophilic solvent contains ethanol; the composition additionally contains vitamin E ; And vitamin E based on the weight of the composition as a range of about 0. It is present in an amount of 1% to about 5% by weight. 141. The composition of aspect 140, wherein SAIB comprises sucrose esterified with two acetic acid and six isobutyric acid moieties. 142. Aspect 141 of the composition, wherein two acetic acid and six isobutyric acid portions are esterified sucrose based on the weight of the composition in the range of about 0. 025% by weight to about 2. An amount of 5% by weight is present. 143. The composition of aspect 4, wherein the active pharmaceutical ingredient is present in an amount ranging from about 1% by weight to about 5% by weight based on the weight of the composition; HVLCM is in a range of about 40% by weight to based on the weight of the composition Present in an amount of about 50% by weight; HVLCM comprises SAIB; the first hydrophobic solvent is present in an amount ranging from about 40% to about 50% by weight based on the weight of the composition; the first hydrophobic solvent comprises benzoic acid benzoate Ester; a hydrophilic solvent is present in an amount ranging from about 1% to about 7% by weight based on the weight of the composition; the hydrophilic solvent includes ethanol; the composition further includes vitamin E; and the vitamin E is based on the weight of the composition as The range of the reference gauge is about 0. An amount of 5% to about 2% by weight is present. 144. The composition of aspect 143, wherein SAIB comprises sucrose esterified with two acetic acid and six isobutyric acid moieties. 145. The composition of aspect 144, wherein the sucrose esterified with two acetic acid and six isobutyric acid moieties is present in an amount ranging from about 10% by weight to about 13% by weight based on the weight of the composition. 146. Composition of aspect 143, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM is about 47 based on the weight of the composition. An amount of 5 wt% is present in the composition; the first hydrophobic solvent is about 43 based on the weight of the composition. 7wt% amount is present in the composition; ethanol is about 4. based on the weight of the composition. An amount of 8% by weight is present in the composition; and vitamin E is present in the composition in an amount of about 1% by weight based on the weight of the composition. 147. The composition of aspect 146, wherein SAIB comprises sucrose esterified with two acetic acid and six isobutyric acid moieties. 148. The composition of aspect 147, wherein the sucrose esterified with two acetic acid and six isobutyric acid portions is present in an amount of about 12% by weight based on the weight of the composition. 149. The composition of aspect 4, wherein the active pharmaceutical ingredient is present in an amount ranging from about 1% to about 5% by weight based on the weight of the composition; HVLCM is in a range of about 5% to about 5% by weight based on the weight of the composition Present in an amount of about 15% by weight; HVLCM comprises SAIB; the first hydrophobic solvent is present in an amount ranging from about 35% to about 45% by weight based on the weight of the composition; the first hydrophobic solvent comprises benzoic acid benzoic acid Ester; hydrophilic solvent contains at least ethanol and PEG; ethanol is present in an amount ranging from about 1% to about 10% by weight based on the weight of the composition; PEG is about 35% by weight based on the weight of the composition Present in an amount of up to about 50% by weight; the composition further comprises vitamin E; and vitamin E based on the weight of the composition as a range of about 0. An amount of 5% to about 2% by weight is present. 150. The composition of aspect 149, wherein SAIB comprises sucrose esterified with two acetic acid and six isobutyric acid moieties. 151. The composition of aspect 150, wherein the sucrose esterified with two acetic acid and six isobutyric acid parts is present in an amount ranging from about 1% by weight to about 4% by weight based on the weight of the composition. 152. Composition of aspect 149, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM is about 9. based on the weight of the composition. An amount of 7% by weight is present in the composition; the first hydrophobic solvent is about 38 based on the weight of the composition. An amount of 8% by weight is present in the composition; ethanol is about 4. based on the weight of the composition. An amount of 8% by weight is present in the composition; PEG is about 42 based on the weight of the composition. 7% by weight is present in the composition; and vitamin E is present in the composition in an amount of about 1% by weight based on the weight of the composition. 153. The composition of aspect 152, wherein SAIB comprises sucrose esterified with two acetic acid and six isobutyric acid moieties. 154. The composition of aspect 153, wherein the sucrose which is esterified with two acetic acid and six isobutyric acid parts is about 2. based on the weight of the composition. An amount of 5% by weight is present. 155. Composition of aspect 4, wherein the active pharmaceutical ingredient is present in an amount ranging from about 1% by weight to about 5% by weight based on the weight of the composition; HVLCM is in the range of about 0 based on the weight of the composition. HVLCM contains SAIB; the first hydrophobic solvent is present in an amount ranging from about 35 wt% to about 50 wt% based on the weight of the composition; the first hydrophobic solvent comprises Benzyl benzoate; The hydrophilic solvent contains at least ethanol and PEG; Ethanol is present in an amount ranging from about 1% to about 10% by weight based on the weight of the composition; PEG is a range based on the weight of the composition An amount of about 40% by weight to about 50% by weight is present; the composition further comprises vitamin E; and vitamin E is based on the weight of the composition as a range of about 0. An amount of 5% to about 2% by weight is present. 156. The composition of aspect 155, wherein SAIB comprises sucrose esterified with two acetic acid and six isobutyric acid moieties. 157. Composition of aspect 156, wherein two acetic acid and six isobutyric acid portions are esterified sucrose based on the weight of the composition in the range of about 0. It is present in an amount of 1% to about 1% by weight. 158. The composition of aspect 155, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM is present in an amount of about 1% by weight based on the weight of the composition In the composition; the first hydrophobic solvent is about 43 based on the weight of the composition. 7wt% amount is present in the composition; ethanol is about 4. based on the weight of the composition. An amount of 8% by weight is present in the composition; PEG is about 46 based on the weight of the composition. An amount of 5% by weight is present in the composition; and vitamin E is present in the composition in an amount of about 1% by weight based on the weight of the composition. 159. The composition of aspect 158, wherein SAIB comprises sucrose esterified with two acetic acid and six isobutyric acid moieties. 160. Aspect 159 of the composition, wherein two acetic acid and six isobutyric acid portions are esterified sucrose based on the weight of the composition of about 0. An amount of 25% by weight is present. 161. Composition of aspect 4, wherein the active pharmaceutical ingredient is present in an amount ranging from about 1% by weight to about 5% by weight based on the weight of the composition; HVLCM is in the range of about 0 based on the weight of the composition. HVLCM contains SAIB; the first hydrophobic solvent is present in an amount ranging from about 80% to about 95% by weight based on the weight of the composition; the first hydrophobic solvent comprises Benzyl benzoate; a hydrophilic solvent containing at least ethanol; ethanol is present in an amount ranging from about 1% to about 10% by weight based on the weight of the composition; the composition additionally contains vitamin E; and vitamin E is based on the composition The weight is about 0 on the basis of the gauge. An amount of 5% to about 2% by weight is present. 162. The composition of aspect 161, wherein SAIB comprises sucrose esterified with two acetic acid and six isobutyric acid moieties. 163. Composition of aspect 162, in which two acetic acid and six isobutyric acid portions are esterified sucrose based on the weight of the composition in the range of about 0. It is present in an amount of 1% to about 1% by weight. 164. Composition of aspect 7, wherein the active pharmaceutical ingredient is present in an amount ranging from about 1% by weight to about 5% by weight based on the weight of the composition; the composition further comprises a range of about 0 based on the weight of the composition. High viscosity liquid carrier material (HVLCM) present in an amount of 5% to about 5% by weight; HVLCM contains SAIB; the first hydrophobic solvent is in a range of about 35% to about 50% by weight based on the weight of the composition The first hydrophobic solvent contains benzyl benzoate; the second hydrophobic solvent is present in an amount ranging from about 40% to about 50% by weight based on the weight of the composition; the second hydrophobic solvent contains ethyl Tri-n-butyl citrate (ATBC); the hydrophilic solvent contains ethanol; ethanol is present in an amount ranging from about 1% to about 10% by weight based on the weight of the composition; the composition additionally contains vitamin E; and Vitamin E is in the range of about 0 based on the weight of the composition. An amount of 5% to about 2% by weight is present. 165. The composition of aspect 164, wherein SAIB comprises sucrose esterified with two acetic acid and six isobutyric acid moieties. 166. Aspect 165 of the composition, wherein two acetic acid and six isobutyric acid parts to be esterified sucrose based on the weight of the composition range of about 0. It is present in an amount of 1% to about 1% by weight. 167. The composition of aspect 164, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM is present in an amount of about 1% by weight based on the weight of the composition In the composition; the first hydrophobic solvent is about 43 based on the weight of the composition. 7 wt% amount is present in the composition; the second hydrophilic solvent is about 46 based on the weight of the composition. An amount of 5 wt% is present in the composition; ethanol is about 4. based on the weight of the composition. An amount of 8% by weight is present in the composition; and vitamin E is present in the composition in an amount of about 1% by weight based on the weight of the composition. 168. The composition of aspect 167, wherein SAIB comprises sucrose esterified with two acetic acid and six isobutyric acid moieties. 169. Composition of aspect 168, in which two acetic acid and six isobutyric acid portions are esterified sucrose based on the weight of the composition of about 0. An amount of 25% by weight is present. 170. The composition of any one of aspects 1 to 169, wherein: the active pharmaceutical ingredient comprises sirolimus in an amount ranging from about 1% by weight to about 5% by weight based on the weight of the composition; HVLCM includes the composition The weight is based on a range of about 0. Sucrose acetate isobutyrate (SAIB) in an amount of 1% to about 10% by weight; the first hydrophobic solvent comprises an amount ranging from about 80% to about 95% by weight based on the weight of the composition Benzyl benzoate; a hydrophilic solvent comprising ethanol in an amount ranging from about 1% by weight to about 10% by weight based on the weight of the composition; and the composition further comprises a range of about 0 based on the weight of the composition. Vitamin E in an amount of 5% to about 2% by weight. 171. The composition of any one of aspects 1 to 170, which is essentially composed of the following: sirolimus in an amount ranging from about 1% by weight to about 5% by weight based on the weight of the composition; The weight of the composition is in the range of about 0 on the basis of a gauge. SAIB in an amount of 1% to about 10% by weight; benzyl benzoate in an amount ranging from about 80% to 95% by weight based on the weight of the composition; 1% to about 10% by weight of ethanol; and a range of about 0 based on the weight of the composition. Vitamin E in an amount of 5% to about 2% by weight. 172. The composition of aspect 170 or 171, wherein SAIB comprises sucrose esterified with two acetic acid and six isobutyric acid moieties. 173. Composition of aspect 172, in which two acetic acid and six isobutyric acid portions are esterified sucrose based on the weight of the composition in the range of about 0. It is present in an amount of 025% to about 1% by weight. 174. The composition of aspect 4, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM contains about 2% by weight of SAIB based on the weight of the composition; The first hydrophobic solvent contains about 42 based on the weight of the composition. 7% by weight of benzyl benzoate; a hydrophilic solvent containing about 46 based on the weight of the composition. 5 wt% of PEG is present; the hydrophilic solvent further comprises about 4. based on the weight of the composition. 8% by weight of ethanol present; and the composition additionally contains about 1% by weight of vitamin E present based on the weight of the composition. 175. The composition of aspect 4, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM comprises about 3% by weight of SAIB based on the weight of the composition; The first hydrophobic solvent contains about 41.based on the weight of the composition. 7% by weight of benzyl benzoate; a hydrophilic solvent containing about 46 based on the weight of the composition. 5 wt% of PEG is present; the hydrophilic solvent further comprises about 4. based on the weight of the composition. 8% by weight of ethanol present; and the composition additionally contains about 1% by weight of vitamin E present based on the weight of the composition. 176. The composition of aspect 4, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM comprises about 4% by weight of SAIB based on the weight of the composition; The first hydrophobic solvent contains about 40 based on the weight of the composition. 7% by weight of benzyl benzoate; a hydrophilic solvent containing about 46 based on the weight of the composition. 5 wt% of PEG is present; the hydrophilic solvent further comprises about 4. based on the weight of the composition. 8% by weight of ethanol present; and the composition additionally contains about 1% by weight of vitamin E present based on the weight of the composition. 177. Composition of aspect 4, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM contains about 4. based on the weight of the composition. 9% by weight of SAIB; the first hydrophobic solvent contains about 39. based on the weight of the composition 8% by weight of benzyl benzoate; a hydrophilic solvent containing about 46 based on the weight of the composition. 5 wt% of PEG is present; the hydrophilic solvent further comprises about 4. based on the weight of the composition. 8% by weight of ethanol present; and the composition additionally contains about 1% by weight of vitamin E present based on the weight of the composition. 178. Composition of aspect 4, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM contains about 5. based on the weight of the composition. 9% by weight of SAIB; the first hydrophobic solvent contains about 38 based on the weight of the composition. 8% by weight of benzyl benzoate; a hydrophilic solvent containing about 46 based on the weight of the composition. 5 wt% of PEG is present; the hydrophilic solvent further comprises about 4. based on the weight of the composition. 8% by weight of ethanol present; and the composition additionally contains about 1% by weight of vitamin E present based on the weight of the composition. 179. Composition of aspect 4, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM contains about 6. based on the weight of the composition. 8% by weight of SAIB; the first hydrophobic solvent contains about 37 based on the weight of the composition. 9% by weight of benzyl benzoate; a hydrophilic solvent containing about 46 based on the weight of the composition. 5 wt% of PEG is present; the hydrophilic solvent further comprises about 4. based on the weight of the composition. 8% by weight of ethanol present; and the composition additionally contains about 1% by weight of vitamin E present based on the weight of the composition. 180. Composition of aspect 4, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM contains about 7. based on the weight of the composition. 8% by weight of SAIB; the first hydrophobic solvent contains about 36. based on the weight of the composition. 9% by weight of benzyl benzoate; a hydrophilic solvent containing about 46 based on the weight of the composition. 5 wt% of PEG is present; the hydrophilic solvent further comprises about 4. based on the weight of the composition. 8% by weight of ethanol present; and the composition additionally contains about 1% by weight of vitamin E present based on the weight of the composition. 181. Composition of aspect 4, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM contains about 8. based on the weight of the composition. 8% by weight of SAIB; the first hydrophobic solvent contains about 35 based on the weight of the composition. 9% by weight of benzyl benzoate; a hydrophilic solvent containing about 46 based on the weight of the composition. 5 wt% of PEG is present; the hydrophilic solvent further comprises about 4. based on the weight of the composition. 8% by weight of ethanol present; and the composition additionally contains about 1% by weight of vitamin E present based on the weight of the composition. 182. Composition of aspect 4, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM contains about 9. based on the weight of the composition. 7% by weight of SAIB; the first hydrophobic solvent contains about 35% by weight of benzyl benzoate based on the weight of the composition; the hydrophilic solvent contains about 46 based on the weight of the composition. 5 wt% of PEG is present; the hydrophilic solvent further comprises about 4. based on the weight of the composition. 8% by weight of ethanol present; and the composition additionally contains about 1% by weight of vitamin E present based on the weight of the composition. 183. The composition of aspect 4, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM contains about 1% by weight of SAIB based on the weight of the composition; The first hydrophobic solvent contains about 90. based on the weight of the composition. 2% by weight of benzyl benzoate; a hydrophilic solvent containing about 4. based on the weight of the composition. 8% by weight of ethanol present; and the composition additionally contains about 1% by weight of vitamin E present based on the weight of the composition. 184. The composition of aspect 4, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM contains about 2% by weight of SAIB based on the weight of the composition; The first hydrophobic solvent contains about 89.based on the weight of the composition. 2% by weight of benzyl benzoate; a hydrophilic solvent containing about 4. based on the weight of the composition. 8% by weight of ethanol present; and the composition additionally contains about 1% by weight of vitamin E present based on the weight of the composition. 185. Composition of aspect 4, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM contains about 2. based on the weight of the composition. 9% by weight of SAIB; the first hydrophobic solvent contains about 88 based on the weight of the composition. 3% by weight of benzyl benzoate; a hydrophilic solvent containing about 4. based on the weight of the composition. 8% by weight of ethanol present; and the composition additionally contains about 1% by weight of vitamin E present based on the weight of the composition. 186. Composition of aspect 4, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM contains about 3. based on the weight of the composition. 9% by weight of SAIB; the first hydrophobic solvent contains about 87 based on the weight of the composition. 3% by weight of benzyl benzoate; a hydrophilic solvent containing about 4. based on the weight of the composition. 8% by weight of ethanol present; and the composition additionally contains about 1% by weight of vitamin E present based on the weight of the composition. 187. Composition of aspect 4, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM contains about 4. based on the weight of the composition. 9% by weight of SAIB; the first hydrophobic solvent contains about 86. based on the weight of the composition. 3% by weight of benzyl benzoate; a hydrophilic solvent containing about 4. based on the weight of the composition. 8% by weight of ethanol present; and the composition additionally contains about 1% by weight of vitamin E present based on the weight of the composition. 188. Composition of aspect 4, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM contains about 5. based on the weight of the composition. 8% by weight of SAIB; the first hydrophobic solvent contains about 85 based on the weight of the composition. 4% by weight of benzyl benzoate; a hydrophilic solvent containing about 4. based on the weight of the composition. 8% by weight of ethanol present; and the composition additionally contains about 1% by weight of vitamin E present based on the weight of the composition. 189. Composition of aspect 4, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM contains about 6. based on the weight of the composition. 8% by weight of SAIB; the first hydrophobic solvent contains about 84. based on the weight of the composition. 4% by weight of benzyl benzoate; a hydrophilic solvent containing about 4. based on the weight of the composition. 8% by weight of ethanol present; and the composition additionally contains about 1% by weight of vitamin E present based on the weight of the composition. 190. Composition of aspect 4, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM contains about 7. based on the weight of the composition. 8% by weight of SAIB; the first hydrophobic solvent contains about 83 based on the weight of the composition. 4% by weight of benzyl benzoate; a hydrophilic solvent containing about 4. based on the weight of the composition. 8% by weight of ethanol present; and the composition additionally contains about 1% by weight of vitamin E present based on the weight of the composition. 191. Composition of aspect 4, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM contains about 8. based on the weight of the composition. 7% by weight of SAIB; the first hydrophobic solvent contains about 82 based on the weight of the composition. 5% by weight of benzyl benzoate; a hydrophilic solvent containing about 4. based on the weight of the composition. 8% by weight of ethanol present; and the composition additionally contains about 1% by weight of vitamin E present based on the weight of the composition. 192. Composition of aspect 4, wherein the active pharmaceutical ingredient is present in the composition in an amount of about 3% by weight based on the weight of the composition; HVLCM contains about 9. based on the weight of the composition. 7% by weight of SAIB; the first hydrophobic solvent contains about 81. based on the weight of the composition. 5% by weight of benzyl benzoate; a hydrophilic solvent containing about 4. based on the weight of the composition. 8% by weight of ethanol present; and the composition additionally contains about 1% by weight of vitamin E present based on the weight of the composition. 193. A composition comprising: an active pharmaceutical ingredient, wherein the active pharmaceutical ingredient comprises sirolimus; and a device for extending the release profile of a medicinal active ingredient when the composition is administered to a patient in need thereof. 194. The composition according to any one of aspects 1 to 193, wherein when the composition is administered intraocularly to the rabbit in a single dose, the composition provides the pharmaceutical active ingredient within ± 20% of the release profile of C908 in FIG. 13 Neutral release contour. 195. The composition of aspect 194, wherein the single agent contains 30 microliters. 196. Composition of any one of aspects 194 or 195, wherein the active pharmaceutical ingredient comprises 0. 9 mg of sirolimus. 197. The composition according to any one of aspects 1 to 196, wherein when the composition is administered intraocularly to a rabbit in a single dose, the median amount of the pharmaceutically active ingredient released from the composition 1 month after administration is administered The composition has a range of 1% to 20% or 2% to 15% of the total pharmaceutically active ingredients in the composition. 198. The composition of any one of aspects 1 to 197, wherein when the composition is administered intraocularly to the rabbit in a single dose, the median amount of the pharmaceutically active ingredient released from the composition 3 months after administration is administered The total amount of pharmaceutically active ingredients in the composition is in the range of 10% to 60% or 20% to 50%. 199. The composition of any one of aspects 1 to 198, wherein when the composition is administered intraocularly to the rabbit in a single dose, the median amount of the pharmaceutically active ingredient released from the composition 6 months after administration is administered The composition has a range of 30% to 100% or 40% to 90% of the total pharmaceutically active ingredients in the composition. 200. The composition of any one of aspects 1 to 199, wherein when the composition is put at 37 ° C. with 0. When 1% (w / v) sodium lauryl sulfate in phosphate-buffered saline, the amount of the pharmaceutically active ingredient released from the composition when placed in phosphate-buffered saline for 1 day is based on the composition Within the range of 5% to 50% or 10% to 40% of the total active pharmaceutical ingredients. 201. The composition of aspect 200, wherein the composition put therein contains 75 microliters. 202. The composition of any one of aspects 200 or 201, wherein the active pharmaceutical ingredient constitutes 3% by weight based on the weight of the composition. 203. The composition of any one of aspects 1 to 202, wherein when the composition is placed at 37 ° C and has a 0. When 1% (w / v) SDS is in phosphate-buffered saline, the amount of pharmaceutically active ingredient released from the composition when placed in phosphate-buffered saline for 5 days is the total amount of pharmaceutically active ingredient in the composition 5% to 75% or 10% to 50%. 204. The composition of any one of aspects 1 to 203, wherein when the composition is placed at 37 ° C and has 0. When 1% (w / v) SDS is in phosphate-buffered saline, the amount of pharmaceutically active ingredient released from the composition when put in phosphate-buffered saline for 10 days is the total amount of pharmaceutically active ingredient in the composition 5% to 85% or 15% to 60%. 205. When the composition of any one of aspects 1 to 204 is administered to a human patient intraocularly in a single dose, the composition contains a component sufficient to maintain a therapeutically effective concentration of the active pharmaceutical ingredient at a ratio of at least 3 months . 206. When the composition of any one of aspects 1 to 205 is administered to a human patient intraocularly in a single dose, the composition contains a sufficient retinal-choroid concentration to maintain a therapeutically effective concentration of the active pharmaceutical ingredient for at least 3 months Than the components. 207. The composition of any one of aspects 1 to 206, the composition includes SAIB and vitamin E, and the composition has a range of about 0. SAIB: Vitamin E weight ratio of 5 to about 20. 208. The composition of any one of aspects 1 to 207, wherein the composition is pharmaceutically acceptable. 209. The composition of any of aspects 1 to 208, wherein the composition is formulated for injection. 210. The composition of any one of aspects 1 to 209, comprising sirolimus in an amount of about 3% by weight based on the weight of the composition; SAIB; about 43 based on the weight of the composition Benzyl benzoate in an amount of 7% by weight; based on the weight of the composition of about 4. 8% by weight of ethanol; based on the weight of the composition of about 46. PEG400 present in an amount of 5% by weight; and vitamin E in an amount of about 1% by weight based on the weight of the composition. 211. A method for treating an individual suffering from an eye disease, the method comprising: administering a composition to an eye of an individual in need thereof, wherein the composition comprises an effective amount of an active pharmaceutical ingredient capable of treating an eye disorder, and the composition comprises: an active pharmaceutical ingredient High-viscosity liquid carrier material (HVLCM); first hydrophobic solvent; and hydrophilic solvent. 212. A method for treating an individual suffering from an eye disease, the method comprising: administering a composition to an eye of an individual in need thereof, wherein the composition comprises an effective amount of an active pharmaceutical ingredient capable of treating an eye disorder, and the composition comprises: an active pharmaceutical ingredient ; High viscosity liquid carrier material (HVLCM), wherein the range of HVLCM based on the weight of the composition is about 0. 5% to about 15% by weight; a first hydrophobic solvent, wherein the first hydrophobic solvent is present in an amount ranging from about 30% to about 50% by weight based on the weight of the composition; and hydrophilic Solvent. 213. A method for treating an individual suffering from an eye disease, the method comprising: administering a composition to an eye of an individual in need thereof, wherein the composition comprises an effective amount of an active pharmaceutical ingredient capable of treating an eye disorder, and the composition comprises: an active pharmaceutical ingredient ; High viscosity liquid carrier material (HVLCM), wherein the range of HVLCM based on the weight of the composition is about 0. 5% to about 15% by weight; a first hydrophobic solvent, wherein the first hydrophobic solvent is present in an amount ranging from about 80% to about 95% by weight based on the weight of the composition; and hydrophilic Solvent. 214. A method for treating an individual suffering from eye disease, the method comprising: administering to the eye of an individual in need thereof a composition according to any one of aspects 1 to 210, wherein the composition comprises an effective amount of an activity capable of treating eye disease Pharmaceutical ingredients. 215. The method of any one of aspects 211 to 214, wherein the eye disease comprises uveitis, diabetic macular edema, or wet senile macular degeneration. 216. The method of any one of aspects 211 to 214, wherein the eye disease comprises uveitis or wet age-related macular degeneration. 217. The method of any one of aspects 211 to 216, wherein administering comprises injection. 218. Aspect 217, wherein up to 50 microliters of the composition is injected. 219. Aspect 217, wherein about 20 microliters to about 30 microliters of the composition is injected. 220. The method of any one of aspects 211 to 219, wherein the composition is injected with a needle having a size ranging from 27G to 30G. 221. The method of any one of aspects 211 to 220, wherein the composition is injected with a needle having a length ranging from 1 cm to 3 cm. 222. The method of any one of aspects 211 to 221, wherein at least 20% of the total amount of the active pharmaceutical ingredient administered is in the vitreous of the patient three months after the composition is injected into the vitreous of the patient. 223. A method for treating an individual suffering from an eye disorder, the method comprising: administering to a subject in need thereof a composition of any one of aspects 1 to 210, wherein the composition comprises an effective amount of an activity capable of treating an eye disorder Pharmaceutical ingredients. 224. A method comprising: administering to a patient a composition as defined in any one of aspects 1 to 210, wherein the composition is provided among the medicinal active ingredients within ± 20% of the release profile of C908 in FIG. 13 Bit release contour. 225. The method of aspect 224 is a method as defined in any one of aspects 211 to 223. 226. The method of any one of aspects 211 to 225, wherein the composition is administered intraocularly to a human patient in a single dose, and the median amount of the pharmaceutically active ingredient released from the composition 1 month after administration is administered The composition has a range of 1% to 20% or 2% to 15% of the total pharmaceutically active ingredients in the composition. 227. The method of any one of aspects 211 to 226, wherein the composition is administered intraocularly to a human patient in a single dose, and the median amount of the pharmaceutically active ingredient released from the composition 3 months after administration is administered The total amount of pharmaceutically active ingredients in the composition is in the range of 10% to 60% or 20% to 50%. 228. The method of any one of aspects 211 to 227, wherein the composition is administered intraocularly to a human patient in a single dose, and the median amount of the pharmaceutically active ingredient released from the composition 6 months after administration is administered The composition has a range of 30% to 100% or 40% to 90% of the total pharmaceutically active ingredients in the composition. 229. The method of any one of aspects 211 to 228, wherein the composition comprises 0. 1 mg to 500 mg of medicinal active ingredient. 230. The method of any one of aspects 211 to 229, wherein the plasma Cmax of the pharmaceutically active ingredient is in a range of 1 nanogram / ml to 10 nanograms / ml. 231. The method of any one of aspects 211 to 230, wherein the plasma Cmax of the pharmaceutically active ingredient is less than 10 nanograms / ml. 232. The composition as defined in any one of aspects 1 to 210, which is used as a medicament. 233. The composition as defined in any one of aspects 1 to 210, which is used for treating eye diseases, wherein the active pharmaceutical ingredient comprises an ophthalmic medicine. 234. The composition of aspect 233, wherein the eye disease includes uveitis, diabetic macular edema, or wet age-related macular degeneration. 235. The composition of aspect 233, wherein the eye disease includes uveitis or wet age-related macular degeneration. 236. The composition of any one of aspects 232 to 235, wherein the active pharmaceutical ingredient comprises sirolimus. 237. The composition of any one of aspects 232 to 236, wherein the use of the composition includes a single dose of the composition which is administered intraocularly to a human patient, and among the pharmaceutically active ingredients released from the composition 1 month after the administration The amount is within the range of 1% to 20% or 2% to 15% of the total amount of the pharmaceutically active ingredient in the composition at the time of administration. 238. The composition according to any one of aspects 232 to 237, wherein the use of the composition includes a single dose of the composition which is administered intraocularly to a human patient, and among the pharmaceutically active ingredients released from the composition 3 months after the administration The amount is within the range of 10% to 60% or 20% to 50% of the total amount of the pharmaceutically active ingredient in the composition at the time of administration. 239. The composition of any one of aspects 232 to 238, wherein the use of the composition comprises a single dose of the composition which is administered intraocularly to a human patient, and among the pharmaceutically active ingredients released from the composition 6 months after the administration The bit amount is within a range of 30% to 100% or 40% to 90% of the total amount of the pharmaceutically active ingredient in the composition at the time of administration. 240. The composition of any one of aspects 232 to 239, wherein the composition contains 0. 1 mg to 500 mg of medicinal active ingredient. 241. The composition of any one of aspects 232 to 240, wherein the plasma Cmax of the pharmaceutically active ingredient is in the range of 1 nanogram / ml to 10 nanograms / ml. 242. The composition of any one of aspects 232 to 241, wherein the plasma Cmax of the pharmaceutically active ingredient is less than 10 nanograms / ml. 243. Use of a combination of components in a composition as defined in any one of aspects 1 to 210 for the manufacture of a medicament for the treatment of eye diseases or use of the composition for the manufacture of a medicament for the treatment of eye diseases, wherein the active pharmaceutical ingredient comprises eyedrops. 244. Use of aspect 243, wherein the eye diseases include uveitis, diabetic macular edema, or wet age-related macular degeneration. 245. Use of aspect 243, wherein the eye disease includes uveitis or wet age-related macular degeneration. 246. Use of any one of aspects 243 to 245, wherein the active pharmaceutical ingredient comprises sirolimus. 247. The use of any one of aspects 243 to 246, wherein the composition is administered intraocularly to a human patient as a single dose, and the median amount of the pharmaceutically active ingredient released from the composition 1 month after administration is administered The composition has a range of 1% to 20% or 2% to 15% of the total pharmaceutically active ingredients in the composition. 248. The use of any one of aspects 243 to 247, wherein the composition is administered intraocularly to a human patient in a single dose, and the median amount of the pharmaceutically active ingredient released from the composition 3 months after administration is administered The total amount of pharmaceutically active ingredients in the composition is in the range of 10% to 60% or 20% to 50%. 249. The use of any one of aspects 243 to 248, wherein the composition is administered intraocularly to a human patient in a single dose, and the median amount of the pharmaceutically active ingredient released from the composition 6 months after administration is administered The composition has a range of 30% to 100% or 40% to 90% of the total pharmaceutically active ingredients in the composition. 250. Aspect 243 to 249, wherein the composition comprises 0. 1 mg to 500 mg of medicinal active ingredient. 251. The use of any one of aspects 243 to 250, wherein the plasma Cmax of the medicinal active ingredient is in the range of 1 ng / ml to 10 ng / ml. 252. The use of any one of aspects 243 to 251, wherein the plasma Cmax of the pharmaceutically active ingredient is less than 10 nanograms / ml. 253. A method of forming a depot comprising contacting the composition of any one of aspects 1 to 210 with water, a phosphate buffer solution, a body fluid, or a simulated body fluid. 254. A method of forming a depot comprising contacting the composition of any one of aspects 1 to 210 with a vitreous fluid of a patient. 255. A unit dosage form comprising the composition of any one of aspects 1 to 210, wherein the unit dosage form contains 0. 4 mg to 1 mg of medicinal active ingredient. 256. The unit dosage form of aspect 255, wherein the composition is contained in a vial. 257. The unit dosage form of aspect 255, wherein the composition is contained in a syringe. 258. The unit dosage form of aspect 255, wherein the composition is contained in a needle-free injector. 259. A container containing the composition of any one of aspects 1 to 210. 260. A needleless syringe comprising the composition of any one of aspects 1 to 210, wherein the composition contains a pharmaceutically active ingredient. 261. A composition for use in a method for treating eye diseases in a human individual, wherein:-the composition contains 0. 2 to 3. 1% by weight of sirolimus, 0. 9 to 1. 1% by weight of sucrose acetate isobutyrate (SAIB), 43. 4 to 45. 0% by weight of benzyl benzoate, 4. 7 to 5. 1% by weight of ethanol, 46. 2 to 48. 0% by weight of polyethylene glycol and 0. 01 to 1. 5% by weight of vitamin E; and-the method comprises injecting a volume of 5 to 100 microliters of the composition into the vitreous of the subject and subsequently not administering additional sirolimus to the vitreous of the subject for at least 1 month in. 262. Composition of aspect 261, wherein the composition comprises 2. 9 to 3. 1% by weight of sirolimus. 263. Composition of aspect 261 or 262, wherein the composition comprises 43. 4 to 44. 2% by weight of benzyl benzoate, 4. 7 to 4. 9% by weight of ethanol and 46. 2 to 47. 0% by weight of polyethylene glycol. 264. The composition of any one of aspects 261 to 263, wherein the composition contains 0. 02 to 1% by weight of vitamin E. 265. The composition of any one of aspects 261 to 264, wherein the composition contains less than 1% by weight of vitamin E. 266. The composition of any one of aspects 261 to 265, wherein the composition contains 0. 5% by weight or less of Vitamin E. 267. The composition of any one of aspects 261 to 266, wherein the composition contains less than 0. 1% by weight of Vitamin E. 268. The composition of any one of aspects 261 to 267, wherein the composition contains 0. 02 to 0. 09% by weight of Vitamin E. 269. Aspect 261 to 264 of the composition, wherein the composition comprises about 3% by weight of sirolimus, about 1% by weight of SAIB, about 43. 7% by weight of benzyl benzoate, about 4. 8% by weight of ethanol, about 46. 5% by weight of polyethylene glycol and about 1% by weight of vitamin E. 270. The composition of any one of aspects 261 to 269, wherein the polyethylene glycol is PEG400. 271. The composition of any one of aspects 261 to 270, wherein the composition is basically composed of sirolimus, SAIB, benzyl benzoate, ethanol, polyethylene glycol, and vitamin E. 272. The composition of any one of aspects 261 to 271, wherein the composition is composed of sirolimus, SAIB, benzyl benzoate, ethanol, polyethylene glycol, and vitamin E. 273. The composition of any one of aspects 261 to 272, wherein the method comprises injecting a volume of 10 to 30 microliters of the composition into the vitreous of the subject, and then not administering another sirolimus for at least 1 month Into the vitreous body of the individual. 274. The composition of any one of aspects 261 to 273, wherein the method comprises injecting a volume of 19 microliters or less of the composition into the vitreous of the subject, followed by not administering additional sirolimus for at least 1 month Into the vitreous of the individual. 275. The composition of any one of aspects 261 to 272, wherein the method comprises injecting 51 microliters or more of the composition into the vitreous of the subject, and then not administering additional sirolimus for at least 1 month Into the vitreous of the individual. 276. The composition of any one of aspects 261 to 275, wherein the eye disease is uveitis, diabetic macular edema, or wet age-related macular degeneration. 277. The composition of aspect 276, wherein the eye disease is uveitis. 278. The composition of aspect 276, wherein the eye disease is diabetic macular edema. 279. The composition of aspect 276, wherein the eye disease is wet age-related macular degeneration. 280. The composition of any of aspects 261 to 279, wherein the method comprises injecting the volume of the composition into the vitreous body of the subject, and then not administering additional sirolimus to the subject's In the vitreous. 281. The composition of any one of aspects 261 to 280, wherein the method comprises injecting the volume of the composition into the vitreous body of the subject, and then not administering additional sirolimus to the subject's In the vitreous. 282. The composition of any of aspects 261 to 281, wherein said injecting the volume of the composition into the vitreous body of the subject is at least one month after any previously administered sirolimus into the vitreous body of the subject occur. 283. The composition of any one of aspects 261 to 282, wherein said injecting the volume of the composition into the vitreous body of the subject is at least two after any previously administered sirolimus into the vitreous body of the subject Happened. 284. The composition of any of aspects 261 to 283, wherein said injecting the volume of the composition into the vitreous body of the subject is at least three after any previous administration of sirolimus to the vitreous body of the subject Happened. 285. The composition of any of aspects 261 to 284, wherein the method comprises injecting the composition in a volume of the dose. 286. The composition of any one of aspects 261 to 285, wherein the composition is in a unit dose form containing a unit dose of the composition, and the unit dose is equal to the amount injected in the method. The volume of the composition. 287. Composition of aspect 286, wherein the unit dose is contained in a pre-filled syringe or a container suitable for transferring the unit dose to the syringe. 288. The composition of any of aspects 261 to 287, wherein the method comprises injecting the volume of the composition from a syringe, the syringe comprising glass. 289. The composition of any of aspects 261 to 287, wherein the method comprises injecting the volume of the composition from a syringe, the syringe comprising a polymer. 290. The composition of aspect 289, wherein the syringe comprises a polymer including at least one member selected from a cyclic olefin polymer, a cyclic olefin copolymer, and polypropylene. 291. The composition of any of aspects 261 to 290, wherein the method comprises injecting the volume of the composition from a syringe, the syringe comprising a metal plunger. 292. The composition of aspect 291, wherein the metal plunger is a stainless steel plunger. 293. The composition of any of aspects 261 to 292, wherein the method comprises injecting the volume of the composition from a leur-lock syringe. 294. A composition comprising: (i) sirolimus, sucrose acetate isobutyrate, benzyl benzoate, polyethylene glycol in an amount by weight as shown in any of A to I , Ethanol and vitamin E: ; Or (ii) contains sirolimus, sucrose acetate isobutyrate, benzyl benzoate, ethanol, and vitamin E in an amount by weight as shown in any of J to T: 295. The composition of aspect 294, wherein the composition comprises 2.9 to 3.1% by weight of sirolimus. 296. The composition of aspect 286, wherein the composition comprises 0.02 to 1% by weight of vitamin E. 297. The composition of aspect 294 or 295, which: (i) comprises an approximate amount by weight of sirolimus, sucrose acetate isobutyrate, Benzoyl benzoate, polyethylene glycol, ethanol and vitamin E: ; Or (ii) contains an approximate amount of sirolimus, sucrose acetate isobutyrate, benzyl benzoate, ethanol, and vitamin E by weight, shown in any of J 'to T': 298. The composition of any one of aspects 294 to 297, wherein the polyethylene glycol is PEG400. 299. The composition of any of aspects 294 to 298, wherein composition (i) consists essentially of sirolimus, SAIB, benzyl benzoate, ethanol, polyethylene glycol, and vitamin E; and Composition (ii) is basically composed of sirolimus, SAIB, benzyl benzoate, ethanol, and vitamin E. 300. The composition of any one of aspects 294 to 290, wherein composition (i) is composed of sirolimus, SAIB, benzyl benzoate, ethanol, polyethylene glycol, and vitamin E; and Compound (ii) is composed of sirolimus, SAIB, benzyl benzoate, ethanol and vitamin E. 301. A unit dosage form comprising a unit dose of a composition as defined in any one of aspects 294 to 300 in a volume of 5 to 100 microliters. 302. The unit dosage form of aspect 301, wherein the volume of the composition is 10 to 30 microliters. 303. A composition as defined in any one of aspects 294 to 300 or a unit dosage form as defined in aspects 301 or 302, which is a method for treating an eye disease in a human individual. 304. The composition or unit-dose form of aspect 303, wherein the method comprises administering the composition or unit-dose form to the vitreous of an injected individual, and subsequently not administering additional sirolimus to the individual's The glass body. 305. The composition or unit dosage form of Aspect 303 or 304, wherein the eye disease is uveitis, diabetic macular edema, or wet senile macular degeneration. 306. A composition comprising 0.2 to 3.1% by weight of sirolimus, 0.9 to 1.1% by weight of sucrose acetate isobutyrate (SAIB), 43.4 to 45.0% by weight of benzyl benzoate, 4.7 To 5.1% by weight of ethanol, 46.2 to 48.0% by weight of polyethylene glycol and at least 0.01% by weight but less than 1% by weight of vitamin E. 307. The composition of aspect 306, wherein the composition comprises 2.9 to 3.1% by weight of sirolimus. 308. The composition of aspect 306 or 307, which comprises 0.02 to 0.9% by weight of vitamin E. 309. The composition of any one of aspects 306 to 308, comprising 0.5% by weight or less of vitamin E. 310. The composition of any one of aspects 306 to 309, which contains less than 0.1% by weight of vitamin E. 311. The composition of any one of aspects 306 to 310, which comprises 0.02 to 0.09% by weight of vitamin E. 312. The composition of any one of aspects 306 to 311, wherein the polyethylene glycol is PEG400. 313. The composition of any one of aspects 306 to 312, wherein the composition is basically composed of sirolimus, SAIB, benzyl benzoate, ethanol, polyethylene glycol, and vitamin E. 314. The composition of any one of aspects 306 to 313, wherein the composition is composed of sirolimus, SAIB, benzyl benzoate, ethanol, polyethylene glycol, and vitamin E. 315. A unit dosage form comprising a unit dose of a composition as defined in any of aspects 306 to 314 in a volume of 5 to 100 microliters. 316. The unit dosage form of aspect 315, wherein the volume of the composition is 10 to 30 microliters. 317. A composition as defined in any one of aspects 306 to 314 or a unit dosage form as defined in aspects 315 or 316 for use in a method for treating an eye disease in a human individual. 318. The composition or unit dosage form of Aspect 317, wherein the method comprises injecting the composition or unit dosage form into the vitreous body of an individual, and subsequently not administering additional sirolimus to the individual for at least one month The glass body. 319. The composition or unit dosage form of Aspect 317 or 318, wherein the eye disease is uveitis, diabetic macular edema, or wet senile macular degeneration. 320. A dosage form comprising a vial containing a composition, wherein: the composition comprises an active pharmaceutical ingredient, a high viscosity liquid carrier material (HVLCM), a first hydrophobic solvent and a hydrophilic solvent; and the composition has a range of about 35 microliters To a volume of about 1900 microliters. 321. The dosage form of aspect 320, wherein the composition has a volume ranging from about 50 microliters to about 1000 microliters. 322. The dosage form of any one of aspects 320 to 321, wherein the composition is a solution at 25 ° C and 1 atmosphere and / or wherein the composition has a viscosity ranging from about 1 cP to about 150 cP at 25 ° C and 1 atmosphere. 323. The dosage form of any one of aspects 320 to 322, wherein: HVLCM is present in an amount ranging from about 0.5% by weight to about 15% by weight based on the weight of the composition, and the first hydrophobic solvent is in the composition The weight is present in an amount ranging from about 30% by weight to about 50% by weight. 324. The dosage form of any of aspects 320 to 323, wherein: HVLCM is present in an amount ranging from about 0.5% by weight to about 15% by weight based on the weight of the composition, and the first hydrophobic solvent is in the composition The weight is present in an amount ranging from about 80% by weight to about 95% by weight. 325. The dosage form of any one of aspects 320 to 324, wherein the composition further comprises an antioxidant. 326. The dosage form of any of aspects 320 to 325, wherein the composition further comprises a polyalkylene glycol. 327. The dosage form of aspect 326, wherein the polyalkylene glycol is present in an amount ranging from about 40% by weight to about 55% by weight. 328. The dosage form of any of aspects 320 to 326, wherein the active pharmaceutical ingredient comprises sirolimus. 329. The dosage form of aspect 320, wherein the composition comprises 0.2 to 3.1% by weight of sirolimus, 0.9 to 1.1% by weight of sucrose acetate isobutyrate (SAIB), and 43.4 to 45.0% by weight of benzoic acid benzene Methyl ester, 4.7 to 5.1% by weight of ethanol, 46.2 to 48.0% by weight of polyethylene glycol, and 0.01 to 1.5% by weight of vitamin E. 330. The dosage form of any one of aspects 320 to 329, wherein the composition comprises 0.02 to 1% by weight of vitamin E. 331. The dosage form of any of aspects 320 to 330, wherein the composition comprises less than 1% by weight of vitamin E. 332. The dosage form of any of aspects 320 to 331, wherein the composition comprises 0.5% by weight or less of vitamin E. 333. The dosage form of any one of aspects 320 to 332, wherein the composition comprises less than 0.1% by weight of vitamin E. 334. The dosage form of any one of aspects 320 to 333, wherein the composition comprises 0.02 to 0.09% by weight of vitamin E. 335. The dosage form of any one of aspects 320 to 329, wherein the composition comprises about 3% by weight of sirolimus, about 1% by weight of SAIB, about 43.7% by weight of benzyl benzoate, and about 4.8% by weight Ethanol, about 46.5% by weight of polyethylene glycol and about 1% by weight of vitamin E. 336. The dosage form of any one of aspects 326 to 335, wherein the polyalkylene glycol is PEG400. 337. The dosage form of any one of aspects 320 to 336, wherein the composition consists essentially of sirolimus, SAIB, benzyl benzoate, ethanol, polyethylene glycol, and vitamin E. 338. The dosage form of any one of aspects 320 to 336, wherein the composition is composed of sirolimus, SAIB, benzyl benzoate, ethanol, polyethylene glycol, and vitamin E. 339. The dosage form of any one of aspects 320 to 228, wherein the composition is as defined in any one of aspects 261 to 319. 340. A dosage form comprising a syringe containing the composition, wherein: the composition comprises an active pharmaceutical ingredient, a high viscosity liquid carrier material (HVLCM), a first hydrophobic solvent and a hydrophilic solvent; and the composition has a range of about 5 microliters To a volume of about 100 microliters. 341. The dosage form of aspect 340, wherein the composition is a solution at 25 ° C and 1 atmosphere and / or wherein the composition has a viscosity ranging from about 1 cP to about 150 cP at 25 ° C and 1 atmosphere. 342. The dosage form of any one of aspects 340 and 341, wherein: HVLCM is present in an amount ranging from about 0.5% by weight to about 15% by weight based on the weight of the composition, and the first hydrophobic solvent is in the composition The weight is present in an amount ranging from about 30% by weight to about 50% by weight. 343. The dosage form of any one of aspects 340 to 341, wherein: HVLCM is present in an amount ranging from about 0.5% by weight to about 15% by weight based on the weight of the composition, and the first hydrophobic solvent is in the composition The weight is present in an amount ranging from about 80% by weight to about 95% by weight. 344. The dosage form of any one of aspects 340 to 343, wherein the composition further comprises an antioxidant. 345. The dosage form of any one of aspects 340 to 344, wherein the composition further comprises a polyalkylene glycol. 346. The dosage form of aspect 345, wherein the polyalkylene glycol is present in an amount ranging from about 40% by weight to about 55% by weight. 347. The dosage form of any one of aspects 340 to 346, wherein the active pharmaceutical ingredient comprises sirolimus. 348. The dosage form of aspect 340, wherein the composition comprises 0.2 to 3.1% by weight of sirolimus, 0.9 to 1.1% by weight of sucrose acetate isobutyrate (SAIB), and 43.4 to 45.0% by weight of benzoic acid benzene Methyl ester, 4.7 to 5.1% by weight of ethanol, 46.2 to 48.0% by weight of polyethylene glycol, and 0.01 to 1.5% by weight of vitamin E. 349. The dosage form of any one of aspects 340 to 348, wherein the composition comprises 0.02 to 1% by weight of vitamin E. 350. The dosage form of any one of aspects 340 to 348, wherein the composition comprises less than 1% by weight of vitamin E. 351. The dosage form of any one of aspects 340 to 348, wherein the composition comprises 0.5% by weight or less of vitamin E. 352. The dosage form of any one of aspects 329 to 337, wherein the composition comprises less than 0.1% by weight of vitamin E. 353. The dosage form of any one of aspects 340 to 348, wherein the composition comprises 0.02 to 0.09% by weight of vitamin E. 354. The dosage form of any one of aspects 340 to 348, wherein the composition comprises about 3% by weight of sirolimus, about 1% by weight of SAIB, about 43.7% by weight of benzyl benzoate, and about 4.8% by weight Ethanol, about 46.5% by weight of polyethylene glycol and about 1% by weight of vitamin E. 355. The dosage form of any one of aspects 345 to 354, wherein the polyalkylene glycol is PEG400. 356. The dosage form of any one of aspects 340 to 355, wherein the composition consists essentially of sirolimus, SAIB, benzyl benzoate, ethanol, polyethylene glycol, and vitamin E. 357. The dosage form of any one of aspects 340 to 355, wherein the composition is composed of sirolimus, SAIB, benzyl benzoate, ethanol, polyethylene glycol, and vitamin E. 358. The dosage form of any of aspects 340 to 357, wherein the syringe comprises glass. 359. The dosage form of any of aspects 340 to 357, wherein the syringe comprises a polymer. 360. The dosage form of aspect 359, wherein the polymer comprises at least one member selected from the group consisting of a cyclic olefin polymer, a cyclic olefin copolymer, and polypropylene. 316. The dosage form of any of aspects 340 to 360, wherein the syringe comprises a metal plunger. 362. The dosage form of aspect 361, wherein the metal plunger comprises a stainless steel plunger. 363. The dosage form of any of aspects 340 to 262, wherein the syringe comprises a Luer lock syringe. 364. The dosage form of any of aspects 340 to 363, wherein the syringe is contained in a container. 365. The dosage form of aspect 364, wherein the container contains a box. 366. The dosage form of any one of aspects 340 to 365, wherein the composition is as defined in any of aspects 261 to 319. 367. A composition comprising: an active pharmaceutical ingredient; a high viscosity liquid carrier material (HVLCM); a first hydrophobic solvent; a hydrophilic solvent; and vitamin E, wherein the vitamin is present in an amount of less than 0.1% by weight. 368. The composition of aspect 367, wherein the vitamin is present in an amount ranging from 0.02% by weight to 0.09% by weight. 369. The composition of any of aspects 367 to 368, wherein the composition is a solution at 25 ° C and 1 atmosphere and / or wherein the composition has a viscosity in the range of about 1 cP to about 150 cP at 25 ° C and 1 atmosphere. 370. The composition of any one of aspects 367 to 369, wherein: HVLCM is present in an amount ranging from about 0.5% to about 15% by weight based on the weight of the composition, and the first hydrophobic solvent is composed of The weight of the substance is present in an amount ranging from about 30% by weight to about 50% by weight. 371. The composition of any one of aspects 367 to 369, wherein: HVLCM is present in an amount ranging from about 0.5% to about 15% by weight based on the weight of the composition, and the first hydrophobic solvent is composed of The weight of the substance is present in an amount ranging from about 80% by weight to about 95% by weight. 372. The composition of any one of aspects 367 to 371, wherein the composition further comprises a polyalkylene glycol. 373. The composition of aspect 372, wherein the polyalkylene glycol is present in an amount ranging from about 40% by weight to about 55% by weight. 374. The composition of any one of aspects 367 to 373, wherein the active pharmaceutical ingredient comprises sirolimus. 375. The composition of aspect 367, wherein the composition comprises 0.2 to 3.1% by weight of sirolimus, 0.9 to 1.1% by weight of sucrose acetate isobutyrate (SAIB), and 43.4 to 45.0% by weight of benzoic acid Phenyl methyl ester, 4.7 to 5.1% by weight of ethanol, 46.2 to 48.0% by weight of polyethylene glycol, and 0.02 to 0.09% by weight of vitamin E. 376. The composition of any one of aspects 371 to 375, wherein the polyalkylene glycol is PEG400. 377. The composition according to any one of aspects 367 to 376, wherein the composition consists essentially of sirolimus, SAIB, benzyl benzoate, ethanol, polyethylene glycol, and vitamin E. 378. The composition of any one of aspects 367 to 376, wherein the composition is composed of sirolimus, SAIB, benzyl benzoate, ethanol, polyethylene glycol, and vitamin E. 379. The dose of any of aspects 367 to 378, wherein the composition is defined by any of aspects 261 to 319. 380. A composition comprising 0.2 to 3.1% by weight of sirolimus, 0.9 to 1.1% by weight of sucrose acetate isobutyrate (SAIB), 89.6 to 93% by weight of benzyl benzoate, 4.9 To 5.1% by weight of ethanol and at least 0.01% by weight but less than 1% by weight of vitamin E. 381. The composition of aspect 380, wherein the composition comprises 2.9 to 3.1% by weight of sirolimus. 382. The composition of aspect 380 or 381, which comprises 0.02 to 0.9% by weight of vitamin E. 383. The composition of any one of aspects 380 to 382, which contains 0.5% by weight or less of vitamin E. 384. The composition of any one of aspects 380 to 383, which contains less than 0.1% by weight of vitamin E. 385. The composition of any one of aspects 380 to 384, which comprises 0.02 to 0.09% by weight of vitamin E. 386. The composition according to any one of aspects 380 to 385, wherein the composition consists essentially of sirolimus, SAIB, benzyl benzoate, ethanol, and vitamin E. 387. The composition of any of aspects 380 to 386, wherein the composition is composed of sirolimus, SAIB, benzyl benzoate, ethanol, and vitamin E. 388. A unit dosage form comprising a unit dose of the composition as defined in any of aspects 380 to 387 in a volume of 5 to 100 microliters. 389. The unit dosage form of aspect 388, wherein the volume of the composition is 10 to 30 microliters. 390. A composition as defined in any one of aspects 380 to 387 or a unit dosage form as defined in aspects 388 or 389 for use in a method for treating an eye disease in a human individual. 391. The composition or unit dosage form of Aspect 390, wherein the method comprises injecting the composition or unit dosage form into the vitreous body of an individual and subsequently not administering additional sirolimus to the individual for at least 1 month The glass body. 392. The composition or unit dosage form of Aspect 390 or 391, wherein the eye disease is uveitis, diabetic macular edema, or wet senile macular degeneration.

量在本文可說明為一組上限較佳值及一組下限較佳值。較佳的範圍包括由上限較佳值及下限較佳值，以及由兩個下限較佳值及兩個上限較佳值所構成的任何範圍。實例亦揭示量(例如重量百分比、比率等)。較佳的範圍亦包括由實例中所揭示之兩個值所構成的範圍，及由實例中所揭示之一個值及在一組上限或下限值中所揭示之另一值所構成的範圍。在本文明確地揭示所有的此等範圍。 　　除非另有其他指示，本文述及之組成物、單位劑量型式及類似者的特定體積指示在20℃之溫度及1大氣壓之壓力下所測量之體積。 　　根據本發明之調合物通常包含在載體組成物中的活性醫藥成分(API)。在一些例子中，載體組成物包含高黏度液態載體材料(HVLCM)、疏水性溶劑、親水性溶劑及抗氧化劑中之一或多者。在一些例子中，載體組成物包含高黏度液態載體材料(HVLCM)、疏水性溶劑、親水性溶劑、聚合物、抗氧化劑及其他賦形劑中之一或多者。 　　適合於貯庫型調合物之任何生物活性物質(BAS)或活性醫藥成分(API)或活性化合物可用於本發明組成物中。此外，意欲使如本文所使用關於本文列舉與BAS、API或活性化合物中任一者有關的本發明之投予、劑量、重量百分比及類似的態樣之說明亦適用於其他物質、成分或化合物，除非另有其他註記。API的一些例示性類別包括免疫抑制劑、抗發炎藥及抗生素。本文所述之生物活性物質、API及活性化合物亦包括其醫藥上可接受的前藥、衍生物、類似物、鹽、衍生物及酯。 　　如本文所使用的術語〝生物活性物質〞係指當於活體內投予動物(包括但不限於鳥和哺乳動物，包括人類)時引起生物效應之無機或有機分子，包括藥物、胜肽、蛋白質、碳水化合物(包括單醣、寡醣和多醣)、核蛋白、黏蛋白、脂蛋白、合成性多胜肽或蛋白質或連結至蛋白質之小分子、糖蛋白、類固醇、核酸(任何形式的DNA(包括cDNA或RNA)或其片段)、核苷酸、核苷、寡核苷酸(包括反義寡核苷酸)、基因、脂質、激素或其組合。 　　適合的蛋白質包括但不限於人類生長激素、纖維母細胞生長因子(FGF)、紅血球生成素(EPO)、血小板衍生性生長因子(PDGF)、粒細胞集落刺激因子(g-CSF)、牛生長激素(BST)、腫瘤壞死因子(TNF)、轉化生長因子-β(TGF-Beta)、介白素、胰島素和干擾素(諸如α-干擾素、β-干擾素)及類似者。 　　如本文所使用的術語藥物(或活性醫藥成分，API)係指在內部或外部用作為治療、治癒或預防疾病或病症之藥的任何物質，且包括但不限於免疫抑制劑、麻醉劑、止痛劑、化療劑、類固醇(包括類視色素)、激素、抗生素、抗病毒劑、抗真菌劑、抗增生劑、抗組織胺、抗凝血劑、抗光老化劑、促黑素胜肽、非類固醇和類固醇抗發炎化合物、抗精神病藥及輻射吸收劑(包括UV-吸收劑)。 　　術語生物活性物質亦包括諸如殺昆蟲劑、殺蟲劑、殺真菌劑、殺鼠劑及植物營養素和生長促進劑之劑。 　　術語醫藥上可接受的意指安全且有效的醫藥使用，其可包括人類或獸醫使用，較佳為人類使用。醫藥上可接受的組成物較佳地適合用於治療動物或人類的醫學症狀。醫藥上可接受的組成物較佳地包含一或多種活性醫藥成分與一或多種醫藥上可接受的賦形劑之組合，基本上由一或多種活性醫藥成分與一或多種醫藥上可接受的賦形劑之組合所組成，或由一或多種活性醫藥成分與一或多種醫藥上可接受的賦形劑之組合所組成。 　　免疫抑制劑包括任何有用於貯庫型調合物之免疫抑制劑，包括巨環內酯、環孢素及其他等。免疫抑制劑包括具有免疫抑制活性之API，即使API主要不用作為任何特別的調合物或其用途中的免疫抑制劑。 　　可使用之治療劑包括但不限於藉由結合細胞蛋白質的免疫親和素家族成員而起作用之化合物。已知此等化合物為〝免疫親和素結合化合物〞。免疫親和素結合化合物包括但不限於巨環內酯化合物的〝莫司(limus)〞家族。可使用之莫司化合物的實例包括但不限於西羅莫司(雷帕黴素(rapamycin))及其水溶性類似物SDZ-RAD(Novartis)、TAFA-93(Isotechnika)、他克莫司(tacrolimus)、依維莫司(everolimus)、RAD-001(Novartis)、吡美莫司(pimecrolimus)、坦羅莫司(temsirolimus)、CCI-779(Wyeth)、AP23841(Ariad)、AP23573 (Ariad)和ABT-578(Abbott Laboratories)。可使用之莫司化合物類似物及衍生物包括但不限於美國專利案號5,527,907、6,376,517、6,329,386及6,890,546中所述之化合物，將各者以其全文併入本文以供參考。治療劑亦包括莫司化合物之類似物、前藥、鹽、衍生物及酯。 　　在本發明之一些組成物中，治療劑包含莫司化合物，基本上由莫司化合物所組成，或由莫司化合物所組成。在本發明之一些組成物中，治療劑包含免疫親和素結合化合物，基本上由免疫親和素結合化合物所組成，或由免疫親和素結合化合物所組成。在本發明之一些組成物中，治療劑包含mTOR抑制劑或其類似物、衍生物、鹽、酯或前藥(例如TAFA93)，基本上由mTOR抑制劑或其類似物、衍生物、鹽、酯或前藥(例如TAFA93)所組成，或由mTOR抑制劑或其類似物、衍生物、鹽、酯或前藥(例如TAFA93)所組成。在本發明之一些組成物中，治療劑包含親環素或FK-506結合蛋白質(FKBP)，基本上由親環素或FK-506結合蛋白質(FKBP)所組成，或由親環素或FK-506結合蛋白質(FKBP)所組成。 　　可使用之其他西羅莫司衍生物包括而不限於7-表-雷帕黴素、7-硫甲基-雷帕黴素、7-表-三甲氧基苯基-雷帕黴素、7-表-硫甲基-雷帕黴素、7-去甲氧基-雷帕黴素、32-去甲氧基-雷帕黴素、2-去甲基-雷帕黴素、雷帕黴素之單酯和二酯衍生物、雷帕黴素之27-肟、雷帕黴素之42-側氧基類似物、雙環雷帕黴素、雷帕黴素二聚物、雷帕黴素之矽醚、雷帕黴素芳基磺酸酯和胺磺酸酯、30-去甲氧基雷帕黴素之位置31和42上的單酯和二酯及在下列中所述之其他衍生物：Vezina等人之"Rapamycin(AY-22,989), A New Antifungal Antibiotic. I. Taxonomy Of The Producing Streptomycete And Isolation Of The Active Principle" J. Antibiot.(Tokyo) 28：721-726(1975)；Sehgal等人之"Rapamycin(AY-22,989), A New Antifungal Antibiotic. II. Fermentation, Isolation And Characterization" J. Antibiot.(Tokyo) 28：727-732(1975)；Sehgal等人之"Demethoxyrapamycin(AY-24,668), A New Antifungal Antibiotic" J. Antibiot.(Tokyo) 36：351-354(1983)；及Paiva等人之"Incorporation Of Acetate, Propionate, And Methionine Into Rapamycin By Streptomycetes hygroscopicus" J Nat Prod 54：167-177(1991)、WO 92/05179、EP 467606；Caufield等人之"Hydrogenated Rapamycin Derivatives"美國專利案號5,023,262；Kao等人之"Bicyclic Rapamycins"美國專利案號5,120,725；Kao等人之"Rapamycin Dimers"美國專利案號5,120,727；Failli等人之"Silyl Ethers Of Rapamycin"美國專利案號5,120,842；Failli等人之"Rapamycin 42-Sulfonates And 42-(N-carboalkoxy) Sulfamates Useful As Immunosuppressive Agents"美國專利案號5,177,203；Nicolaou等人之"Total Synthesis Of Rapamycin" J. Am. Chem. Soc. 115： 4419-4420(1993)；Romo等人之"Total Synthesis Of (-) Rapamycin Using An Evans-Tishchenko Fragment Coupling" J. Am. Chem. Soc. 115：7906-7907(1993)；及Hayward等人之"Total Synthesis Of Rapamycin Via A Novel Titanium-Mediated Aldol Macrocyclization Reaction" J. Am. Chem. Soc., 115：9345-9346(1993)，將各者以其全文併入本文以供參考。 　　莫司家族之化合物可用於治療、預防、抑制、延遲本文所述之疾病及症狀開始或引起本文所述之疾病及症狀退化之調合物及方法中。 　　醫藥材料的額外非限制性實例包括抗感染藥類，諸如硝糠(nitrofurazone)、丙酸鈉、抗生素類(包括青黴素(penicillin)、四環素(tetracycline)、土黴素(oxytetracycline)、氯四環素(chlorotetracycline)、枯草菌素(bacitracin)、耐絲菌素(nystatin)、鏈黴素、新黴素(neomycin)、多黏菌素(polymyxin)、短桿菌素(gramicidin)、氯黴素(chloramphenicol)、紅黴素(erythromycin)和阿奇毒素(azithromycin)；磺醯胺類，包括磺胺乙醯胺(sulfacetamide)、磺胺甲噻二唑(sulfamethizole)、磺胺二甲嘧啶(sulfamethazine)、磺胺嘧啶(sulfadiazine)、磺胺甲嘧啶(sulfamerazine)和磺胺異噁唑(sulfisoxazole)；及抗病毒劑類，包括碘苷(idoxuridine)、更昔洛韋(ganciclovir)、曲氟尿苷(trifluridine)和阿糖腺苷(vidarabine)；抗發炎藥類，諸如NSAID(包括乙醯基水楊酸、布洛芬、酮洛芬(ketoprofen)、萘普生(naproxen)、希樂可舒葆(celecoxib)、雙氯芬酸(diclofenac)、二氟尼柳(diflunisal)、愛特多雷克(etodolac)、吲哚美辛(indomethacin)、酮洛酸(ketorolac)、萘丁美酮(nabumetone)、奧沙普秦(oxiprozin)、吡羅昔康(piroxicam)、雙水楊酯(salsalate)和托美丁(tolmetin))；類固醇類或糖皮質類固醇類(glucocorticosteroid)(包括強的松龍(prednisolone)、強的松(prednisone)、甲基強的松龍(medrol)、倍氯米松(beclomethasone)、布***(budesonide)、氟尼縮松(flunisolide)、氟替卡松(fluticasone)和曲安西龍)；止痛劑類，諸如NSAID、類鴉片(包括嗎啡、芬太尼(fentanyl)、曲馬多(tramadol)、羥考酮(oxycodone)、***(methadone)、氫可酮(hydrocodone)、氫嗎啡酮(hydromorphone)、洛哌丁胺(loperamide)、配西汀(meperidine)、塔噴他多(tapentadol)、氧嗎啡酮(oxymorphone)、丙氧芬(propoxyphene)、瑞芬太尼(remifentanil)、舒芬太尼(sufentanil)、阿芬太尼(alfentanil)、左嗎汎(levorphanol)、可待因(codeine)和二氫可待因(dihydrocodeine))及撲熱息痛(paracetamol)(乙醯胺基酚(acetaminophen))；抗過敏藥類，諸如安他唑啉(antazoline)、美舍吡倫(methapyritene)、氯苯那敏(chlorpheniramine)、美吡拉敏(pyrilamine)、非尼拉敏(prophenpyridamine)、氫化可的松(hydrocortisone)、可的松(cortisone)、氫化可的松乙酸鹽、***(dexamethasone)、***21-磷酸鹽、氟辛龍、曲安西龍、甲羥松(medrysone)、強的松龍、強的松龍21-琥珀酸鈉和強的松龍乙酸鹽；去過敏劑類，諸如豚草花粉(ragweed pollen)抗原、花粉熱(hay fever pollen)抗原、塵抗原和奶抗原；疫苗類，諸如天花、黃熱病、瘟熱(distemper)、豬瘟、水痘、抗毒液素(antivenom)、猩紅熱、白喉類毒素、破傷風類毒素、鴿痘、百日咳、流行性感冒、狂犬病、流行性腮腺炎、麻疹、小兒痲痺症和新城雞瘟(Newcastle disease)；去充血劑類，諸如苯腎上腺素(phenylephrine)、萘甲唑林(naphazoline)和四氫唑啉(tetrahydrazoline)；縮瞳藥類和抗膽鹼酯酶類，諸如毛果芸香鹼(pilocarpine)、埃斯波素(esperine)水楊酸鹽、卡巴膽鹼(carbachol)、氟磷酸二異丙酯、碘依可酯(phospholine iodide)和地美溴銨(demecarium bromide)；副交感神經阻滯藥類，諸如硫酸阿托品(atropine sulfate)、環噴托酯(cyclopentolate)、厚馬托品(homatropine)、莨菪鹼、托吡卡胺(tropicamide)、優卡托品(eucatropine)和(羥基安非他明(hydroxyamphetamine)；擬交感神經藥類，諸如腎上腺素；抗精神病藥類，諸如奧氮平(olanzapine)、利培酮(risperidone)；麻醉拮抗劑類，諸如納曲酮(naltrexone)、納洛酮(naloxone)、納諾芬(nalnothene)；鎮靜劑類和***類，諸如戊巴比托鈉(pentobarbital sodium)、戊巴比托(phenobarbital)、巴可巴比特魯鈉(secobarbital sodium)、可待因、(a-溴異戊醯基)脲、卡溴脲(carbromal)；精神強奮劑類(psychic energizer)，諸如3-(2-胺基丙基)吲哚乙酸鹽和3-(2-胺基丁基)吲哚乙酸鹽；寧神劑類，諸如利舍平(reserpine)、氯丙秦(chlorpromayline)和硫普哌秦(thiopropazate)；麻醉劑類，諸如苯佐卡因(benzocaine)、布比卡因(bupivacaine)、依替卡因(etidocaine)、利多卡因(lidocaine)、甲派卡因(mepivacaine)、普莫卡因(pramoxine)、丙胺卡因(prilocaine)、普魯卡因(procaine)、普洛拍拉卡因(proparacaine)、羅派卡因(ropivacaine)、丁卡因(tetracaine)、左布比卡因(levobupivacaine)、氯普魯卡因(chloroprocaine)、布塔卡因(butacaine)、丙氧卡因(propoxycaine)、芬那卡因(phenacaine)、海克卡因(hexylcaine)、異布卡因(isobucaine)、環甲卡因(cyclomethycaine)、倍能視耐(benoxinate)、地哌冬(diperodon)、待布卡因(dibucaine)、美普卡因(meprylcaine)、二甲異喹(dimethisoquin)、普莫卡因(pramoxine)、胺苯丁酯(butamben)、達克羅寧(dyclonine)(具有和不具有擴充(augmenting)劑類，諸如***或腎上腺素)；三環抗抑鬱劑類，諸如阿米替林(amitriptyline)或去甲替林(nortriptyline)；雄激素類固醇類，諸如***(methyl-testosterone)和氟羥甲睪酮(fluorymesterone)；***類，諸如雌酮、17-fl-***、乙烯***和己烯雌酚(diethyl stilbestrol)；助孕劑類，諸如助孕酮、甲地孕酮(megestrol)、美侖孕酮(melengestrol)、氯地孕酮(chlormadinone)、羥脫水孕酮(ethisterone)、羥炔諾酮(norethynodrel)、19-去甲孕酮(norprogesterone)、炔諾酮(norethindrone)、甲羥孕酮(medroxyprogesterone)和17-0-羥助孕酮(hydroxy-progesterone)；體液劑類，諸如***素，例如PGEI、PGE2和PGF2；退熱劑類，諸如阿司匹靈、水楊酸鈉和水楊醯胺(salicylamide)；鎮痙劑類，諸如阿托品(atropine)、甲胺太林(methantheline)、罌粟鹼(papaverin)和溴化甲基莨菪鹼(methscopolamine bromide)；抗瘧劑類，諸如4-胺基喹啉、8-胺基喹啉、氯喹(chloroquine)和乙胺嘧啶(pyrimethamine)；抗組織胺類，諸如苯海拉明(diphenhydramine)、茶苯海明(dimenhydrinate)、曲吡那明(tripelennamine)、奮乃靜(perphenazine)和氯苯那明(chlorphenazine)；強心劑類(cardioactive agent)，諸如二苯並氫氟甲噻秦(dibenzhydroflume thiazide)、氟甲噻秦(flumethiazide)、氯噻秦(chlorothiazide)和胺曲特(aminotrate)；他汀(statin)類，諸如阿托伐他汀(atorvastatin)、西立伐他汀(cerivastatin)、氟伐他汀(fluvastatin)、洛伐他汀(lovastatin)、普伐他汀(pravastatin)、辛伐他汀(simvastatin)和相關的化合物；止喘藥類，諸如色甘酸(cromolyn)；骨吸收預防劑類，諸如雙膦酸鹽類，包括作為非限制實例的阿侖膦酸(alendronate)、利塞膦酸(risendronate)、唑來膦酸(zolendronate)、帕米膦酸(pamidronate)和伊班膦酸(ibandronate)；鈣調節激素類，諸如降鈣素；營養劑類，諸如天然及合成生物活性胜肽；及蛋白質類，包括生長因子、細胞黏附因子、細胞介素和生物反應調節劑。 　　在本發明之一些組成物中，活性醫藥成分能夠治療眼疾，例如該組成物包含能夠治療眼疾的物質。此物質亦已知為眼藥。在本發明之一些組成物中，活性醫藥成分不包含除了西羅莫司以外的眼藥，且在一些態樣中，活性醫藥成分不包含眼藥。 　　活性化合物係以足以使有效量遞輸至宿主人類或動物的量包括在組成物中，以達成所欲效應。併入組成物中的藥物或生物活性成分的量係取決於所欲釋放輪廓、生物效應所需之藥物濃度及藥物的所欲釋放時期而定。 　　在組成物中的活性化合物濃度亦取決於藥物的吸收、失活及***率以及那些熟習此項技術者已知的其他因素而定。應注意劑量值亦隨著欲減緩之症狀的嚴重性而改變。應進一步瞭解用於任何特別個體之特定的劑量方案應根據個體需求及管理或監督組成物投予之人的專業判斷而隨時調整，且本文所列舉之濃度範圍為範例而已，並不意欲限制所主張之組成物的範圍或實施。組成物可以一個劑量投予或可分成數個較小的劑量以不同的時間間隔投予。 　　生物活性物質通常係以能夠對需要生物活性物質之患者投予有效量的量及/或濃度存在。量及/或濃度係取決於所使用之生物活性物質且亦可取決於投予位置而定。生物活性物質的量及/或濃度可由一般熟習此項技術者使用本說明書的指導決定。一般而言，以較高的濃度較佳，因為這可容許投予具有較小體積的貯庫物。濃度通常不應該太高而使得BAS或其他組份具有高沈澱概率，因為這可能影響性能(例如生物利用率)及/或具有其他不利的效應。在一些眼內貯庫物的例子中，以高濃度/低體積較佳，但是應避免沈澱，因為這可影響視力及/或衝擊BAS(例如西羅莫司)之生物利用率。不限制本發明，生物活性物質通常係以組成物重量為基準計的至少0.05重量%、0.1重量%、0.5重量%、1重量%或2重量%之量存在於本發明組成物中。生物活性物質通常係以組成物重量為基準計的至多20重量%、10重量%、7重量%、5重量%、4重量%或3重量%之量存在於組成物中。在一些例子中，生物活性物質係以組成物重量為基準計的範圍約0.2重量%至10重量%之量存在，諸如約0.2重量%至約3.1重量%或約0.3重量%至約1重量%。在一些例子中，生物活性物質包含以組成物重量為基準計的範圍1重量%至10重量%之量存在的西羅莫司。 　　本發明組成物可包括一或多種生物活性物質(BAS)、API或活性化合物。當使用二或多種BAS時，則彼等可來自相同的治療類別或不同的治療類別。例如，活性醫藥成分可包含西羅莫司及至少一種另外的治療劑，例如至少一種另外的眼藥。一些可能的BAS組合包括西羅莫司與他克莫司；西羅莫司與環孢素；及西羅莫司與強的松龍。 　　本發明組成物較佳地包含醫藥上可接受的高黏度液態載體材料(HVLCM)，較佳為醫藥上可接受用於眼內貯庫物。HVLCM為非聚合物、非水溶性且在37℃下具有至少5,000cP(且隨意為至少10,000；15,000；20,000；25,000；或甚至50,000cP)之黏度。HVLCM較佳地在周圍條件或個體的生理條件下不勻稱地結晶。術語非水溶性係指在周圍條件下(例如室溫或23℃)以少於1重量%之程度溶於水的材料。在本上下文中的術語〝非聚合物〞係指基本上於酯之酸部分中沒有重複單元的酯或混合酯，以及具有其中在酸部分中的官能單元重複次數很少的酸部分之酯或混合酯(亦即寡聚物)。通常如本文所使用的術語〝非聚合物〞排除在酯的酸部分中具有超過五個相同及相鄰的重複單元或聚合物之材料，但是含有二聚物、三聚物、四聚物或五聚物之材料包括在此術語的範圍內。 　　HVLCM可包含蔗糖乙酸酯異丁酸酯(〝SAIB〞)，基本上由蔗糖乙酸酯異丁酸酯(〝SAIB〞)所組成，或由蔗糖乙酸酯異丁酸酯(〝SAIB〞)所組成。SAIB為HVLCM的範例。 　　術語〝SAIB〞係指蔗糖分子，其8個天然羥基分別經–COCH3 (乙醯基)或–COCH(CH3 )2 (異丁醯基)部分予以酯化。SAIB為市場上可取得的產品，例如以具有不同的乙醯基及異丁醯基取代圖樣(例如不同比率的乙醯基對異丁醯基部分及/或不同的環位置之乙醯基及異丁醯基部分)的天然蔗糖羥基之化合物的混合物形式銷售。熟習此項技術者將瞭解SAIB通常包含經不同取代之〝同功型(isoform)〞的混合物，其包括名義上較佳地經兩個乙酸及六個異丁酸部分予以酯化之蔗糖分子。因此，HVLCM可包含SAIB、基本上由SAIB所組成或由SAIB所組成，其中天然蔗糖分子經兩個乙酸及六個異丁酸部分予以酯化–其結構列舉於美國專利5,747,058中，將其全文併入本文以供參考。 　　SAIB為經口無毒的且於食品工中用以穩定乳液。其為非常黏的液體且具有以少量加熱或添加溶劑而有顯著的黏度變化之不尋常特性。其可溶於很多生物相容性溶劑中。當呈溶液或乳液時，SAIB可經由注射或烟霧劑噴霧施予。SAIB與可影響物質的遞輸速率之纖維素酯及其他聚合物相容。 　　HVLCM可包含非聚合性聚烷二醇，基本上由非聚合性聚烷二醇所組成，或由非聚合性聚烷二醇所組成。非聚合性聚乙二醇(PEG)為較佳的聚烷二醇。當HVLCM包含PEG時，PEG較佳地具有少於約220或200道耳頓之分子量。亦即較佳地n ≤5，其中n 為PEG中的乙二醇單元之平均數目。對包含PEG之HVLCM而言，較佳的n 值包括n =5、4、3或2。 　　在其他的實施態樣中，HVLCM可為硬脂酸酯(諸如那些丙二醇、甘油基、二乙基胺基乙基和乙二醇之硬脂酸酯)、硬脂酸醯胺及其他的長鏈脂肪酸醯胺(諸如N,N'-二硬脂醯乙二胺(ethylene distearamide)、硬脂醯胺MEA和DEA、雙硬脂醯乙二胺(ethylene bistearamide)、椰油氧化胺(cocoamine oxide))、長鏈脂肪醇(諸如鯨蠟醇和硬脂醇)、長鏈酯(諸如肉豆蔻酸肉豆蔻酯、芥酸山萮酯(beheny erucate)和磷酸甘油酯)。HVLCM可包含乙醯化蔗糖二硬脂酸酯(Crodesta A-10)。 　　HVLCM係以達成所欲特性(例如黏度及/或內聚性)之任何量存在於組成物中。HVLCM較佳地以醫藥組成物重量為基準計的等於或少於99.5重量%，95重量%，85重量%，60重量%或50重量%之量存在。HVLCM較佳地以醫藥組成物重量為基準計的等於或大於0.1重量%，0.5重量%，1重量%，10重量%，25重量%或40重量%之量存在於本發明之醫藥組成物中。由該等量或實施例中所揭示之該等量的組合所構成之所有範圍亦較佳，例如0.5重量%至50重量%，25重量%至85重量%，及10重量%至40重量%。在一些例子中，HVLCM包含以組成物重量為基準計的範圍約0.1重量%至60重量%之量存在的SAIB，諸如約0.5重量%至約50重量%，約30重量%至約60重量%，及約0.1重量%至約10重量%(例如約0.5重量%至約5重量%)。 　　本發明組成物較佳地包含醫藥上可接受的疏水性溶劑，包括那些用於眼內貯庫物的醫藥上可接受的溶劑。有用的疏水性溶劑在水中展現少於1重量%，較佳為少於0.5重量%，更佳為少於0.1重量%之溶解度。尤其佳的是在水中具有少於0.05重量%之溶解度的疏水性溶劑。溶解度係在25℃下測量。疏水性溶劑的一些實例包括苯甲酸苯甲酯(BB)、肉豆蔻酸異丙酯(IPM)、棕櫚酸異丙酯、乙醯基檸檬酸三烷酯(例如乙醯基檸檬酸三丁酯(ATBC))和檸檬酸三烷酯(例如檸檬酸三丁酯(TBC))。BB及IPM為市場上可取得的產品。苯甲酸苯甲酯為較佳的疏水性溶劑。 　　其他適合的疏水性溶劑包括三酸甘油酯(例如辛酸/癸酸三酸甘油酯(Miglyol 810))和棕櫚酸二甲酯，以及脂肪酯和醚，諸如油酸乙酯和癸酸乙酯。 　　當使用時，檸檬酸三烷酯(TAC)可包含由下式(A)代表的化合物或基本上由下式(A)代表的化合物所組成。在式(A)中，Ra 、Rb 和Rc 代表相同或不同的烷基，各者具有3至5個碳原子。烷基較佳為直鏈或支鏈烷基，且更佳為具有4個碳數目的直鏈或支鏈烷基。一些較佳的檸檬酸三烷酯包括那些具有正丙基、正丁基、正戊基、異丙基、異丁基、二級丁基、三級丁基、異戊基等的檸檬酸三烷酯。以具有三個正丁基之檸檬酸三烷酯(在本文稱為檸檬酸三丁酯或TBC)更佳。在式(A)中，Ra 、Rb 和Rc 各自可相同，或可不同。Ra 、Rb 和Rc 較佳為相同。 　　當使用時，乙醯基檸檬酸三烷酯(ATAC)可包含由下式(B)代表的化合物或基本上由下式(B)代表的化合物所組成，其亦稱為乙醯基檸檬酸三烷酯及2-乙醯氧基丙烷-1,2,3-三烷基三羧酸。在式(B)中，Ra 、Rb 和Rc 各自代表具有3至5個碳數目的烷基。烷基較佳為直鏈或支鏈烷基，較佳地具有4個碳數目。一些較佳的乙醯基檸檬酸三烷酯包括那些具有正丙基、正丁基、正戊基、異丙基、異丁基、二級丁基、三級丁基、異戊基等的乙醯基檸檬酸三烷酯。以具有三個正丁基之乙醯基檸檬酸三烷酯(在本文稱為乙醯基檸檬酸三烷酯或ATBC)更佳。在式(B)中，Ra 、Rb 和Rc 各自可相同，或可不同。Ra 、Rb 和Rc 較佳為相同。 　　TAC或ATAC可個別或彼此組合用作為疏水性溶劑。TAC及/或ATAC亦可與一或多種其他的疏水性溶劑組合使用。當組合使用時，可使用任何比率的TAC：ATAC。TAC：ATAC的一些比率(體積：體積)包括0：100、0.1：99.9、5：95、10：90、15：85、30：70、50：50、70：30、85：15、90：10、95：5、99.9：0.1及100：0。以該等比率中任二者所構成之範圍亦較佳。 　　本發明組成物可包含任何量的疏水性溶劑以賦予組成物適合的特性。當本發明組成物包含疏水性溶劑時，其較佳地包含至少0.1重量%、1重量%、2重量%、10重量%、20重量%、30重量%及40重量%。當本發明組成物包含疏水性溶劑時，其較佳地包含至多99重量%、95重量%、90重量%、80重量%、70重量%、60重量%和50重量%。在一些例子中，本發明組成物含有以組成物重量為基準計的約80重量%至約95重量%之疏水性溶劑。在一些例子中，疏水性溶劑包含以組成物重量為基準計的範圍約30重量%至約60重量%，或約35重量%至約45重量%之量的苯甲酸苯甲酯。在其他的例子中，疏水性溶劑包含以組成物重量為基準計的範圍約30重量%至約60重量%，或約35重量%至約50重量%之量的ATBC。 　　本發明組成物較佳地包含醫藥上可接受的親水性溶劑，包括用於眼內貯庫物的那些醫藥上可接受的溶劑。當使用親水性溶劑時，其較佳為非聚合物，例如除了聚烷二醇或聚乙二醇以外。當在25℃下測量時，親水性溶劑較佳地在水中具有至少1重量%、2重量%、10重量%、25重量%、50重量%，至多且包括與水的互混性之溶解度。當使用疏水性溶劑時，親水性溶劑在水中展現大於疏水性溶劑之溶解度。一些較佳的親水性溶劑包括乙醇、乳酸乙酯(EL)、二甲基亞碸(DMSO)、N-甲基-2-吡咯啶酮(NMP)、聚烷二醇、乙酸乙酯、丙二醇、碳酸丙烯酯、甘油和三乙酸甘油酯(TA)。 　　市場上可取得的親水性溶劑可包括少量的水。當希望減少或消除在本發明之醫藥組成物中的水時，最好可使用無水(或乾燥)親水性溶劑。親水性溶劑可於市場上以無水(或低含水)形式獲得，及/或可使含有水的親水性溶劑乾燥。該等相同的考量適用於本發明組成物的其他組份，以及本發明之醫藥組成物。與水形成共沸物的組份(例如乙醇)較佳地以無水形式使用。無水乙醇包括例如表明為99.5%EtOH、純乙醇(200proof)及/或包含少於0.005%水之產品。 　　乙醇、乳酸乙酯、二甲基亞碸、N-甲基-2-吡咯啶酮、聚烷二醇和三乙酸甘油酯全部為廣泛於市場上可取得的商業產品。當使用乙醇時，其較佳為不變性乙醇。在一些例子中，乙醇係以組成物重量為基準計的範圍約1重量%至約10重量%之量存在(例如約1重量%至約7重量%，諸如約1重量%至約5重量%)。 　　當親水性溶劑包括聚烷二醇時，可使用任何分子量(或聚合度)，但是需預警的是為了充當為親水性溶劑，聚烷二醇在周圍溫度(例如23℃)下應為液體。較佳的聚烷二醇為聚乙二醇(PEG)。PEG 300(n 為約7)、PEG 400(n 為約9)及PEG 600(n 為約13)在23℃下為液體，而PEG 800(n 為約18)在23℃下為糊狀物。作為親水性溶劑之較佳的PEG包括PEG 600、PEG 400及PEG 300，例如PEG 400。 　　當使用親水性溶劑時，其通常係以組成物重量的至多70重量%，至多60重量%，至多50重量%，至多40重量%，至多30重量%，至多20重量%，至多15重量%，或至多10重量%之量存在。雖然通常沒有下限，但是當使用親水性溶劑時，其通常係以至少0.1重量%，至少1重量%，至少2重量%，至少3重量%，至少4重量%，或至少5重量%之量存在。在一些例子中，親水性溶劑包含以組成物重量為基準計的範圍約1重量%至約20重量%，或約2重量%至約10重量%之量的乙醇。在一些例子中，親水性溶劑包含以組成物重量為基準計的範圍約30重量%至約60重量%，或約40重量%至約50重量%之量的PEG。在一些例子中，本發明組成物可含有乙醇及PEG二者，例如其中乙醇及PEG之量分別各自落在本文概述之例證量範圍內。 　　有可能以足夠低分子量(例如n ≤5)之PEG充當為HVLCM及親水性溶劑二者，在該例子中，總量可於兩個組份之間分配，或可單獨地歸屬於兩種組份中之一者。 　　在一些例子中，媒液調合物包含SAIB、BB及乙醇。在一些其他的例子中，媒液調合物包含SAIB、BB及乙醇與額外的組份以提供具有更合意的釋放輪廓之調合物。在一些例子中，調合物提供自以單劑經眼內投予哺乳動物個體(例如人類個體)(或患者)的組成物可重複釋放之西羅莫司。 　　本發明組成物隨意地包括一或多種聚合物。包括聚合物可賦予組成物有益的特性。例如，聚合物的使用可助於減緩API釋放，有助於得到更持續的釋放率。這可助於延長貯庫物的壽命。降低釋放率亦可助於控制藥物暴露，及/或可助於控制暴露至安全且有效的水平，及/或消除或降低過度暴露。 　　一些較佳的聚合物包括泊洛沙姆、聚烷二醇、聚(乳酸)(乙醇酸)、聚(乳酸)(或聚***酯)、聚己內酯、聚乙交酯、聚己內酯、聚酐、聚胺、聚胺甲酸酯、聚酯醯胺、聚原酸酯、聚二氧環己酮(polydioxanone)、聚縮醛、聚縮酮、聚碳酸酯、聚磷酸酯、聚氧酯(polyoxyester)、聚原碳酸酯(polyorthocarbonate)、聚磷腈(polyphosphazene)、琥珀酸酯、聚(蘋果酸)、聚(胺基酸)、聚乙烯基吡咯啶酮、聚乙二醇、聚羥基纖維素、甲殼素、聚葡萄胺糖、玻尿酸及其共聚物、三聚物和混合物。以在室溫下為液體或在室溫下可溶於所揭示之組成物中的聚合物較佳。 　　泊洛沙姆為非離子性三嵌段共聚物，其包含聚氧丙烯(聚(環氧丙烷))的中間疏水鏈與聚氧乙烯(聚(環氧乙烷))的兩個親水鏈。泊洛沙姆係於市場上取得且以各種商業名稱銷售，諸如SYNPERONICS、PLURONICS和KOLLIPHOR 。可使用任何適合的等級，以泊洛沙姆P188較佳。 　　當聚合物包括聚烷二醇時，可使用任何分子量(或聚合度)，但是需預警的是為了充當為本發明中除了HVLCM以外的聚合物，聚烷二醇應具有大於5(亦即n ＞5)之聚合度。較佳的聚烷二醇為聚乙二醇(PEG)。以PEG 300(n 為約7)、PEG 400(n 為約9)及PEG 800(n 為約18)作為此等聚合物較佳。 　　有可能以適合的分子量之PEG充當為聚合物(例如n ＞5)及親水性溶劑(例如n ＜18)二者，在該例子中，總量可在於兩個組份之間分配，或可單獨地歸屬於兩種組份中之一者。 　　聚***酯為基於乳酸之聚合物，其可單獨地基於乳酸或可為共聚物，例如基於乳酸、乙醇酸及/或己內酯，其可包括不實質地影響依照本發明可達成的有利結果之少量的其他共單體。如本文所使用之術語〝乳酸〞包括異構物L-乳酸、D-乳酸、DL-乳酸和***酯，而術語〝乙醇酸〞包括乙交酯。最佳的是下列聚合物中之一或多者：聚***酯聚合物，常稱為PLA；聚(***酯-共-乙交酯)共聚物，常稱為PLGA；及聚(己內酯-共-乳酸)(PCL-co-LA)。聚合物可具有約100：0至約10：90之乳酸/乙醇酸的單體比，諸如100：0至15：85，較佳為約75：25至約30：70，更佳為約60：40至約40：60，且尤其有用的共聚物具有約50：50之乳酸/乙醇酸的單體比。 　　聚(己內酯-共-乳酸)(PCL-co-LA)聚合物較佳地具有約10：90至約90：10，約50：50；較佳為約35：65至約65：35；且更佳為約25：75至約75：25之己內酯/乳酸的共單體比。在特定的實施態樣中，基於乳酸之聚合物可包含約0%至約90%之己內酯、約0%至約100%之乳酸與約0%至約60%之乙醇酸的摻合物。 　　其他適合的聚合物包括PEG-PLGA、聚(乙烯醇)及聚(原酸酯)。 　　聚合物可具有約1,000至約120,000之平均分子量，諸如約5,000至約50,000或約8,000至約30,000，如以凝膠滲透層析術(GPC)所測定。例如，基於乳酸之聚合物較佳地具有約1,000至約120,000，較佳為約5,000至約50,000，更佳為約8,000至約30,000之平均分子量，如以凝膠滲透層析術(GPC)所測定。如美國專利案號5,242,910所指示，聚合物可依照美國專利案號4,443,340之指導製備。另一選擇地，基於乳酸之聚合物可依照美國專利案號5,310,865所列舉之技術直接自乳酸或乳酸與乙醇酸(具有或不具有另外的共單體)之混合物製備。併入所有該等專利的內容以供參考。適合的基於乳酸之聚合物係於市場上取得。例如，具有8,000、10,000、30,000及100,000之分子量的50：50之乳酸：乙醇酸共聚物係取自Boehringer Ingelheim Chemicals, Inc.(Petersburg, Va.)、Medisorb Technologies International L.P.(Cincinnati, Ohio)及Lactel Absorbable Polymers(以前的Birmingham Polymers, Inc.)，如下文所述。 　　適合的***酯聚合物之實例包括但不限於聚(D,L-***酯) RESOMER L104、PLA-L104、聚(D,L-***酯-共-乙交酯) 50：50 RESOMER RG502、聚(D,L-***酯-共-乙交酯) 50：50 RESOMER RG502H、聚(D,L-***酯-共-乙交酯) 50：50 RESOMER RG503、聚(D,L-***酯-共-乙交酯) 50：50 RESOMER RG506、聚L-***酯 MW 2,000(RESOMER L 206、RESOMER L 207、RESOMER L 209、RESOMER L 214)、聚D,L-***酯(RESOMER R 104、RESOMER R 202、RESOMER R 203、RESOMER R 206、RESOMER R 207、RESOMER R 208)、聚L-***酯-共-D,L-***酯 90：10(RESOMER LR 209)、聚乙交酯(RESOMER G 205)、聚D,L-***酯-共-乙交酯50：50(RESOMER RG 504H、RESOMER RG 504、RESOMER RG 505)、聚D-L-***酯-共-乙交酯75：25(RESOMER RG 752、RESOMER RG755、RESOMER RG 756)、聚D,L-***酯-共-乙交酯 85：15(RESOMER RG 858)、及聚L-***酯-共-碳酸三亞甲酯70：30(RESOMER LT 706)(Boehringer Ingelheim Chemicals, Inc., Petersburg, Va.)。 　　額外的實例包括但不限於DL-***酯/乙交酯100：0(MEDISORB Polymer 100 DL High、MEDISORB Polymer 100 DL Low)；DL-***酯/乙交酯85/15(MEDISORB Polymer 8515 DL High、MEDISORB Polymer 8515 DL Low)；DL-***酯/乙交酯75/25(MEDISORB Polymer 7525 DL High、MEDISORB Polymer 7525 DL Low)；DL-***酯/乙交酯65/35(MEDISORB Polymer 6535 DL High、MEDISORB Polymer 6535 DL Low)；DL-***酯/乙交酯54/46(MEDISORB Polymer 5050 DL High、MEDISORB Polymer 5050 DL Low)；及DL-***酯/乙交酯54/46(MEDISORB Polymer 5050 DL 2A(3)、MEDISORB Polymer 5050 DL 3A(3)、MEDISORB Polymer 5050 DL 4A(3))(Medisorb Technologies International L.P., Cincinnati, Ohio)；及聚D,L-***酯-共-乙交酯50：50；聚D,L-***酯-共-乙交酯65：35；聚D,L-***酯-共-乙交酯75：25；聚D,L-***酯-共-乙交酯85：15；聚DL-***酯；聚L-***酯；聚乙交酯；聚ε-己內酯；聚DL-***酯-共-己內酯25：75；及聚DL-***酯-共-己內酯75：25(Birmingham Polymers, Inc., Birmingham, Ala.)。 　　聚合物可以醫藥組成物的至多40重量%、30重量%、20重量%或10重量%之量存在。當使用聚合物時，其可以醫藥組成物的至少0.1重量%、1重量%、2重量%、3重量%、4重量%或5重量%之量存在。 　　泊洛沙姆(諸如上文所揭示者)具有界面活性劑特性。本發明組成物可隨意地包含一或多種界面活性劑。界面活性劑在具有親水性及疏水性組份二者(例如乙醇及SAIB或疏水性溶劑)的組成物中特別有用。可使用適合用於貯庫型調合物(例如眼內貯庫型調合物)的任何界面活性劑。以非離子性界面活性劑用於眼內組成物較佳。一些適合的界面活性劑包括例如泊洛沙姆、聚乙氧基化蓖麻油、聚氧乙基化羥基硬脂酸、丙二醇脂肪酯和山梨醇酐脂肪酯。以泊洛沙姆較佳。在一些例子中，泊洛沙姆係以組成物重量為基準計的範圍0.1重量%至約5重量%之量存在。 　　一些聚乙氧基化蓖麻油包括聚氧乙烯5蓖麻油、聚氧乙烯9蓖麻油、聚氧乙烯15蓖麻油、聚氧乙烯35蓖麻油、聚氧乙烯40蓖麻油、聚氧乙烯40氫化蓖麻油和聚氧乙烯60氫化蓖麻油。一些較佳的聚乙氧基化蓖麻油包括聚氧乙烯35蓖麻油(例如KOLLIPHOR EL)、聚氧乙烯40氫化蓖麻油(例如CREMOPHOR RH40)和聚氧乙烯60氫化蓖麻油(例如CREMOPHOR RH60)，該等係取自BASF Corporation of Midland, Mich。 　　聚氧乙基化硬脂酸包括聚氧乙烯硬脂酸酯，亦稱為聚乙二醇(macrogol)硬脂酸酯，包含一系列的硬脂酸之聚乙氧基化衍生物。該等通常包括聚乙二醇硬脂酸酯和聚乙二醇二硬脂酸酯。適合用於本發明的一些聚乙氧基化硬脂酸包括聚氧乙烯2硬脂酸酯、聚氧乙烯4硬脂酸酯、聚氧乙烯6硬脂酸酯、聚氧乙烯8硬脂酸酯、聚氧乙烯12硬脂酸酯、聚氧乙烯20硬脂酸酯、聚氧乙烯2硬脂酸酯、聚氧乙烯30硬脂酸酯、聚氧乙烯40硬脂酸酯、聚氧乙烯50硬脂酸酯、聚氧乙烯100硬脂酸酯、聚氧乙烯2硬脂酸酯、聚氧乙烯150硬脂酸酯、聚氧乙烯4二硬脂酸酯、聚氧乙烯8二硬脂酸酯、聚氧乙烯12二硬脂酸酯、聚氧乙烯32二硬脂酸酯和聚氧乙烯150二硬脂酸酯。聚乙二醇硬脂酸酯係於市場上自許多供應商以包括MYRJ(Croda)、HODAG(Calgene)、KESSCO(Stepan Co.)和PROTAMATE(Protameen Chemicals )之商品名稱取得。 　　其他適合的界面活性劑包括聚山梨酸酯80(Tween 80)、Solutol HS-15、d-生育酚聚乙二醇1000琥珀酸酯(TPGS)、聚氧乙烯8硬脂酸酯(PEG 400單硬脂酸酯)和聚氧乙烯40硬脂酸酯(PEG 1750單硬脂酸酯)。 　　脂肪酸酯為適合的界面活性劑。在該等之中，丙二醇脂肪酸酯及山梨醇酐脂肪酸酯為適合的非離子性界面活性劑，且包括單酯、倍半酯和二酯。山梨醇酐脂肪酸酯可另外包括三酯。該等酯的脂肪酸部分通常為C12 -C18 。較佳的脂肪酸部分包括硬脂酸酯、異硬脂酸酯、月桂酸酯、棕櫚酸酯和油酸酯。一些較佳的酯包括山梨醇酐單油酸酯、丙二醇單月桂酸酯和山梨醇酐單月桂酸酯。 　　羧酸之脂肪酸酯(較佳為C12 -C18 )亦較佳。該等包括乳酸、蘋果酸、己二酸及棕櫚酸之酯。一些適合的界面活性劑包括Ceraphyl 31(乳酸月桂酯，Ashland Inc.)、Labrafac PG(丙二醇二辛酸酯/二癸酸酯NF，Gattefosse)及Lauroglycol 90(丙二醇單月桂酸酯(II型)EP/NF；Gattefosse)。 　　其他適合的界面活性劑包括PEG 300辛酸/癸酸甘油酯(Softigen 767)、PEG 300亞麻油酸甘油酯(Labrafil M-2125CS)、單油酸甘油酯(PECEOL)、丙二醇單月桂酸酯(Lauroglycol FCC)。 　　當使用界面活性劑時，可使用任何適合的量。本發明之醫藥組成物可包含以組成物重量為基準計的至多50重量%之界面活性劑，至多40重量%之界面活性劑，至多30重量%之界面活性劑，至多20重量%之界面活性劑，至多10重量%之界面活性劑，至多5重量%之界面活性劑，至多4重量%之界面活性劑，至多3重量%之界面活性劑，至多2重量%之界面活性劑，至多1.5重量%之界面活性劑或至多1重量%之界面活性劑。包含界面活性劑的本發明之醫藥組成物通常包含以組成物重量為基準計的至少0.01重量%之界面活性劑，至少0.1重量%之界面活性劑，至少0.2重量%之界面活性劑，至少0.4重量%之界面活性劑，至少0.6重量%之界面活性劑或至少0.8重量%之界面活性劑。例如，界面活性劑之量可為0.01重量%至5重量%，0.2重量%之3重量%，或0.6重量%至2重量%。 　　一些該等賦形劑具有多重功能，例如作為疏水性溶劑及/或界面活性劑。當組份具有多重功能時，例如具有界面活性劑特性的巨分子(例如泊洛沙姆、聚乙氧基化蓖麻油等)，該等功能可在組份之間分配，例如界面活性劑及聚合物組份，或可單獨地歸屬於組份中之一者。 　　本發明組成物隨意地包含至少一種抗氧化劑，較佳為適合用於眼內貯庫物之抗氧化劑。當貯庫物在投予位置可能易受到氧化時，則抗氧化劑特別佳。例如，玻璃體貯庫物可能暴露於光及因此可能易受到光引發之自由基形成作用，所以可能較佳的是包括能夠中和自由基的抗氧化劑。在此等實施態樣中，至少一種抗氧化劑較佳地包含生育酚、生育三烯酚或其組合。抗氧化劑較佳地可溶於本發明組成物中。其他適合的抗氧化劑可包括下列中之一或多者：麩胱甘肽、類脂酸、尿酸、胡蘿蔔素(例如維生素A和其衍生物及類似物)、褪黑激素、泛醇(ubiquinol)(輔酶Q)、抗壞血酸、硫代硫酸鈉、半胱胺酸、依地酸鈉(sodium edetate)、抗壞血酸棕櫚酸酯、丁基化羥基苯甲醚(BHA)、丁基化羥基甲苯(BHT)、五倍子酸丙酯、單硫代甘油、三級丁基氫醌(TBHQ)和偏二亞硫酸鉀。以生育酚和其衍生物及類似物較佳，其中以維生素E較佳。維生素E包括具有抗氧化劑特性的所有形式之生育酚，且包括維生素E乙酸酯、α-生育酚和γ-生育酚；且包括D-、L-和DL-形式，諸如DL-α-生育酚。 　　當使用抗氧化劑時，例如生育酚，其可以賦予組成物在適合的時期內有用的抗氧化劑特性之任何量存在。較佳的時期為產品的儲存壽命，例如至多其失效日期。較佳的時期包括3個月、6個月、12個月或1年、18個月或1.5年、24個月或2年、30個月或2.5年、3年和4年。 　　當使用抗氧化劑時，其較佳地以組成物重量為基準計的至多50重量%、10重量%、5重量%、1重量%、0.1重量%,或0.01重量%之量存在。較佳的範圍包括該等值及/或在實施例中的值所構成的那些範圍。在一些例子中，維生素E係以組成物重量為基準計的範圍0.1重量%至5重量%之量存在。驚訝地發現維生素E在甚至更低的濃度仍有效。減少維生素E之量常常是益的，因為維生素E在玻璃體液中相對緩慢地降解。驚訝地發現降低維生素E之量在一些例子中亦增加維生素E之相對降解量。因此，在一些例子中，維生素E係以組成物重量為基準計的範圍約0.01重量%至約5重量%之量存在，諸如約0.01重量%至約1.5重量%，約0.02重量%至約1重量%，及約0.02重量%至約0.09重量%。在一些例子中，組成物包含以組成物重量為基準計的少於1重量%之維生素E，諸如0.5重量%或更少的維生素E，或少於0.1重量%之維生素E。 　　當HVLCM(較佳為SAIB)用於眼內貯庫型調合物時，其似乎具有許多未預期的有益特性。雖然HVLCM(例如SAIB)調節貯庫物的黏度及/或內聚性，但是其存在亦促成延長之玻璃體內釋放輪廓，在此時可維持貯庫物密度而使其不漂浮。以包括至少約0.5重量%之HVLCM可特別有利。 　　在較佳的實施態樣中，當HVLCM與溶劑混合以形成可與API組合以形成醫藥組成物的低黏度液態載體時，HVLCM可顯著地降低黏度。低黏度醫藥組成物通常比高黏度組成物更容易放入體內，因為例如其更容易流進及流出注射器或其他的植入裝置。醫藥組成物可具有任何所欲黏度。已發現在25℃及1大氣壓下以少於約400cP，且更特別為少於200cP，少於100cP，少於50cP或少於25cP之黏度範圍的醫藥組成物通常有用於活體內應用。雖然沒有更低的目標黏度，但是在25℃及1大氣壓下的黏度通常為至少1cP，至少2cP，至少4cP，至少6cP，至少8cP，至少10cP，或至少15cP。 　　在包含SAIB及維生素E(VE)之組成物中，可使用提供安全且有效的組成物之任何重量比的SAIB：VE。在本發明的一些態樣中，可選擇SAIB：VE之重量比以控制組成物密度(在使用前、注射時及長期(例如在1、2、4、6或12個月)的密度)。例如，在包含SAIB及VE之眼內貯庫物組成物中，SAIB：VE之重量比可為10、7.5、5、3、2、1、0.8、0.6、0.5、0.4、0.3或0.2。該等值之各者可為SAIB：VE之比(例如〝至少1〞或〝少於1〞)的開放式或封閉式上限或下限。SAIB：VE之重量比的適合範圍(具有開放式或封閉式端值)包括自等值的任何配對所構成的範圍。例如，SAIB：VE之重量比可為0.5至10，0.5至5，0.5至2或1至3。一種選擇SAIB/VE之比的方式為假設組成物不含有任何其他可剩餘在玻璃體中的賦形劑(例如使得組成物不漂浮在玻璃體中)。在一些例子中，HVLCM(例如SAIB)對維生素E之重量比使得由該HVLCM與該維生素E以該重量比所組成之混合物在25℃及1大氣壓下的密度為至少1克/毫升，諸如至少1.05克/毫升。在一些例子中，組成物在25℃及1大氣壓下具有範圍為1.02克/毫升至1.15克/毫升之密度。 　　在一些例子中，最好可使醫藥組成物具有低的過氧化物含量，因為過氧化物為已知可能的氧化劑且可造成化學不穩定性。在此等情況中最好可自具有低的過氧化物含量之組份製備醫藥組成物。已知SAIB製造方法可造成過氧化物產生。當需要或希望包含SAIB的低過氧化物之醫藥組成物時，最好可使用低過氧化物之SAIB。低過氧化物之SAIB揭示於美國專利發表案2012/0330005，將其揭示內容以其全文併入本文以供參考。 　　當材料遇到光時，該等可以許多不同的方式彼此經物理交互作用。該等交互作用係取決於光本性(其波長、頻率、能量等)及材料本性而定。光波通常係藉由例如吸收、反射及透射/折射的一些組合而與物體交互作用。透明性為容許光不漫射地通過材料之物理特性。半透明性係指容許光漫射地通過材料之特性。不透明性係指不容許光通過材料之特性。光學透明材料容許大部分落在其上的光透射、少量光漫射、反射或吸收。不容許光透射之材料被稱為不透明的。 　　在本發明之特定態樣中，諸如玻璃體內貯庫物，醫藥組成物之光學透明性為有益且較佳的特性。在其他的態樣中，醫藥組成物較佳為半透明的或不透明的。當希望光學透明性時，本發明組成物可不漫射地透射至少約75%之光，約80%之光，約85%之光，約90%之光，約95%之光。本發明組成物可不漫射地透射至多100%之光，99%之光，98%之光，97%之光，或96%之光。不漫射地透射之光的百分比可在特定的頻率下(例如420至440奈米、535至555奈米及/或565至580奈米)測量或在可見光譜上求平均。 　　本發明組成物可經滅菌過濾。 　　本發明組成物可儲存在各種條件下。例如，本發明組成物可儲存在範圍約0℃至約30℃之溫度下，諸如約2℃至約25℃，約4℃至約20℃，約5℃至約15℃，或約7℃至約10℃。驚訝地發現本發明組成物通常相對穩定且可在2℃至約30℃下(諸如在約5℃或約25℃下)儲存兩年或更久。本發明組成物可儲存在各種容器中，例如玻璃容器。 　　本發明組成物可用於治療以局部用組成物或液態貯庫物可治療的任何症狀。可以西羅莫司治療之眼科症狀包括在美國專利8,367,097中所揭示之症狀，將其全文併入本文以供參考。本發明之貯庫型調合物可用作為例如眼疾之藥，例如用於老年性黃斑部退化、糖尿病視網膜病變、早產兒視網膜病變、視網膜靜脈閉塞、視網膜動脈閉塞、多足型脈絡膜血管病變、視網膜血管瘤狀增生、近視性脈絡膜新生血管病變、糖尿病黃斑部水腫、眼腫瘤、放射線視網膜病變、虹膜血管增生、新生血管性青光眼、增生性玻璃體視網膜病變(PVR)、原發性開角型青光眼、繼發性開角型青光眼、正常眼壓性青光眼、分泌過多性青光眼、原發性閉角型青光眼、繼發性閉角型青光眼、高褶虹膜型青光眼、組合機制型青光眼(combined mechanism glaucoma )、發育性青光眼、類固醇誘發性青光眼、剝脫性青光眼、澱粉樣蛋白青光眼、新生血管性青光眼、惡性青光眼、晶狀體之囊膜性青光眼、高褶虹膜症候群、眼內壓過高、眼色素層炎、眼內感染等。本發明之貯庫型調合物更佳地可用作為下列疾病之預防劑或治療劑：老年性黃斑部退化、糖尿病視網膜病變、原發性開角型青光眼、正常眼壓性青光眼、原發性閉角型青光眼、高眼壓、眼色素層炎、眼內感染等。較佳的症狀包括眼色素層炎、濕乾式老年性黃斑部退化(AMD)、糖尿病黃斑部水腫(DME)、糖尿病視網膜病變(DR)和角膜真菌病。 　　在組成物據稱為一種〝基本上由〞經給出所示之特定組份〝所組成之〞組成物時，這可表明組成物係由特定組份所組成或包含特定組份及一或多種非特定組份二者，先決條件為一或多種非特定組份不使組成物不適合於其意欲用途。例如，關於包含適合於治療給出之症狀的經給出之活性醫藥成分的此等組成物，可有一或多種非特定組份的存在，先決條件為該非特定組份不使組成物不適合於治療該症狀。通常在〝基本上由〞經給出所示之特定組份〝所組成之〞組成物中，除了特定組份以外的任何組份以組成物重量為基準計的總量不超過20重量%，較佳為不超過10重量%，更佳為不超過5重量%，且最佳為不超過2重量%。 　　在本發明組成物放入液態介質中(例如試管內或活體內)之後，本發明組成物的體積隨著時間減少尺寸。 　　在本發明組成物放入液態介質中之後，在本發明組成物中的活性醫藥成分(例如西羅莫司)常常不沈澱。若組成物係用於眼睛中，則不沈澱可能是有益的，因為沈澱可能干擾視力。在一些例子中，不沈澱可能是有益的，因為使刺激減至最低。隨著時間不沈澱是令人驚訝的。 　　本發明組成物可容納於小瓶內。容納在小瓶內的組成物體積可在例如約35微升至約1000微升之範圍內，諸如約40微升至約900微升，約45微升至約800微升，約50微升至約700微升，約55微升至約600微升，約60微升至約500微升，約65微升至約400微升，約70微升至約300微升，約75微升至約200微升，約80微升至約100微升，及約300微升至約500微升。 　　當於眼內使用時，本發明組成物可作為玻璃體及/或結膜下貯庫物施予。 　　組成物通常係自已預填充醫藥組成物之標準的皮下注射器、導管或套針注射。常常較佳的是使用最小尺寸的針(亦即最小的直徑)或導管進行注射，以降低在人類或動物的眼內、皮下、肌肉內、血管內(高/低流動)、心肌內、外膜、腫瘤內或腦內部位、創傷位置、緊密的關節空間或體腔注射時對個體的不舒服感。在一些例子中，投予包含玻璃體內注射及/或結膜下注射。可使用適合於注射位置的任何針或導管尺寸。通常以較高的量規尺寸較佳(例如為了降低疼痛或受傷)。然而，過高的量規可導致複雜化，諸如由於毛細管作用及/或黏度而延長注射時間或增加注射施力。希望能夠通過範圍為16號量規及更高，20號量規及更高，22號量規及更高，24號量規及更高，25號量規及更高，26號量規及更高，27號量規及更高，28號量規及更高，或29號量規及更高之針或導管注射醫藥組成物。針或導管通常為34號量規及更小，33號量規及更小，32號量規及更小，31號量規及更小，或30號量規及更小。例如，量規可在23至32之範圍內，諸如27至30。 　　當使用注射器時，可使用適合於注射位置的任何針長度。針較佳地足夠長而允許頂端有效到達目標貯庫物位置。針較佳地足夠短而使操作者(例如醫師或護士)維持對注射器及/或注射程序的控制。用於眼內貯庫物之針可為至少0.5公分，1公分，1.5公分或2公分長度。用於眼內貯庫物之針可為至多4公分，3公分或2.5公分長度。 　　一般熟習此項技術者可使用本說明書作為指南以決定適當的針尺寸(例如量規及/或長度)。 　　注射器應由與其容納之組成物可相容的材料製成。例如，注射器可包含玻璃或聚合物(例如環狀烯烴聚合物、環狀烯烴共聚物和聚丙烯)。注射器可包含金屬柱塞，諸如不銹鋼柱塞。在一些例子中，注射器為魯爾鎖注射器。在一些例子中，注射器係容納在容器內，諸如盒子。 　　容納在注射器內的組成物體積可在例如約5微升至約100微升之範圍內，諸如約5微升至約75微升，約10微升至約50微升，約15微升至約40微升，及約20微升至約30微升。據此，注射器體積常常在約5微升至約100微升，約10微升至約75微升，約15微升至約50微升，及約20微升至約40微升之範圍內，且可能少於約50微升。驚訝的是此等小的體積可提供有效的劑量。 　　本發明組成物之釋放輪廓及效應持續期間令人驚訝。在一些例子中，在給藥後3個月內釋放之活性醫藥成分的量為最初給藥之組成物中的活性醫藥成分總量的約30%至約70%，諸如約40%至約60%或約50%。在一些例子中，當組成物作為單劑經眼內投予人類患者時，則自組成物釋放之醫藥活性成分的中位量係：(1)在投予後1個月在投予時組成物中的醫藥活性成分總量的1%至20%或2%至15%之範圍內；(2)在投予後3個月在投予時組成物中的醫藥活性成分總量的10%至60%或20%至50%之範圍內；及(3)在投予後6個月在投予時組成物中的醫藥活性成分總量的30%至100%或40%至90%之範圍內。在一些例子中，來自組成物之活性醫藥成分的釋放率係在約1微克/天至約30微克/天之範圍內，諸如約2微克/天至約20微克/天或約5微克/天至約15微克/天。 　　在連續投予本發明之貯庫型調合物的例子中，沒有特別的劑量間隔限制，只要間隔足以致力於所欲藥效；然而，以3天一次至5年一次的間隔投予可能較佳，諸如1個月一次至每9個月一次，或每6個月一次至每8個月一次。例如，組成物可以3天一次，5天一次，1週一次，2週一次，1個月一次，2個月一次，3個月一次，4個月一次，5個月一次，6個月一次，7個月一次，8個月一次，9個月一次，1年一次，2年一次，3年一次，4年一次或5年一次之間隔投予，以該間隔可能較佳，且常以2個月一次，3個月一次，4個月一次，5個月一次，6個月一次或1年一次之間隔投予較佳。另外，可在適當時改變劑量間隔。 　　 實施例 　　在下文實施例中所列舉之材料係於市場上自許多來源取得。在本文揭示一些市場供應商。可自其他的市場供應商取得產品。提及之產品可能的市場供應商並不是以任何方式限制本發明。 　　聚合物(PLGA：經十二烷醇引發，L/G 85/15，MW 13.9KDa)、(PLA：經十二烷醇引發，MW 13.9KDa)及(聚己內酯PCL：經十二烷醇引發，MW 95.3KDa)係於市場上自Durect Corporation以LACTEL品牌取得。SAIB係自Durect Corporation獲得。 　　溶劑包括苯甲醇(BA)、苯甲酸苯甲酯、丙二醇及脫水且不變性純乙醇(200 proof ethanol)，USP級，諸如市場上取自Spectrum Chemicals。N-甲基-2-吡咯啶酮(NMP)係於市場上取自ISP。超級精製PEG 400-LQ-(MH)係於市場上取自CRODA，及二甲基亞碸(DMSO)係於市場上取自Gaylord。蓖麻油係於市場上取自Spectrum Chemicals。KolliSolve®GTA(三乙酸甘油酯)係於市場上取自BASF，及檸檬酸三乙酯(TEC)99%係於市場上取自Sigma Aldrich。高純度乙醯基檸檬酸三丁酯(ATBC)NF，USP級係於市場上取自Mutchler Inc.。 　　Synperonic PE/F68-FL-CQ(泊洛沙姆188)係於市場上取自CRODA。在市場上取自Sigma-Aldrich的杜貝可(Dulbecco)氏磷酸鹽緩衝之食鹽水(PBS)、玻尿酸(HA)及十二烷基硫酸鈉(SDS)係用於釋放介質製備中。 　　維生素E(DL-α-生育酚)係於市場上取自BASF。 　　西羅莫司係於市場上取自Althea through Santen Pharmaceutical Company。 實施例1 　　參考下文表1和2，西羅莫司的溶解度係在室溫下於溶劑中及苯甲酸苯甲酯與乙醇之混合物中測試。 參考以下表4，將西羅莫司(SRL)溶解在各種溶劑中且在室溫下8天後測試濃度。使樣品避光，但是暴露於周圍濕度。 　　化學穩定性測試： 　　將約2毫升西羅莫司調合物放入在周圍濕度下每個2毫升波紋密封之玻璃小瓶中且儲存在5℃及25℃下，避免暴露於光。以HPLC分析樣品以測定西羅莫司濃度。HPLC儀器及參數係如下： 移動相： A：20 mM甲酸銨，在pH 4.0下 B：乙腈檢測：λ=276奈米 管柱溫度：50℃ 　　西羅莫司溶液調合物之製備： 　　將聚合物以表5中所示之重量比溶解在溶劑/溶劑混合物中且混合，直到均勻為止。將SAIB以表5中所示之重量比添加至聚合物/溶劑溶液中且在50℃下混合，直到形成均勻的溶液為止。將西羅莫司以3重量%至5重量%濃度溶解在各媒液中。 　　試管內藥物釋放測試： 　　將西羅莫司調合物以介於50至100微升注入在37℃下平衡的5毫升釋放介質(包括0.1%SDS或0.05%HA之PBS)中。將樣品放在37℃下以30rpm或50rpm旋轉之迴轉式振盪器上。在不同的時間點(例如對一些調合物以1、4、8、24小時及至多50天)以抽取整個釋放介質進行取樣且以37℃下平衡的新鮮製備之釋放介質更換。注意在取樣期間不要碰到貯庫藥物。以HPLC分析樣品以測定西羅莫司濃度。 　　實施例1的結果： 　　西羅莫司在水性介質及溶劑中的溶解度： 　　添加0.1%SDS增強西羅莫司在PBS中的水性溶解度(表1)。西羅莫司在苯甲酸苯甲酯/乙醇中的溶解度比在苯甲酸苯甲酯或乙醇中的溶解度增加。如表2中所見，在苯甲酸苯甲酯/乙醇之比為7時觀察到最高的溶解度。 　　西羅莫司在釋放測試介質中的化學穩定性及與溶劑的相容性： 　　表3顯示在用作為藥物釋放測試之釋放介質的含有0.1%SDS之PBS中的穩定性。測試溶劑與西羅莫司之相容性。表4顯示西羅莫司在室溫下儲存於溶劑中後的回收率。 原型調合物的評估： 　　西羅莫司溶液調合物具有低黏度(可通過27G及30G針注射)。在PBS中的試管內藥物釋放測試中，0.1%SDS顯示藥物釋放在37℃下≥50天(圖1a、1b和1c)及在HA中≥18天，圖2(僅測試組成物C115)。在圖1中，組成物C105b使用媒液V105，但是具有4.5重量%之西羅莫司濃度。 　　表6的數據指出西羅莫司在25℃及5℃下暴露於周圍濕度最少2個月之調合物中的穩定性，除了含有NMP之調合物(C107、C108和C110)以外。在25℃及5℃下儲存對市場上的產品為較佳的條件。關於本發明較佳的組成物，沒必要將西羅莫司調合物儲存在惰性條件下及/或零度以下的溫度下。 　　製造在以下表5和6中所示之媒液及醫藥組成物。 實施例2 　　西羅莫司溶液調合物之製備： 　　將泊洛沙姆188溶解在苯甲酸苯甲酯與乙醇之混合物中(重量比顯示於表8中)且混合，直到均勻為止。添加SAIB(重量比顯示於表8中)且在50℃下混合，直到形成均勻的溶液為止。在溶液冷卻之後，添加三乙酸甘油酯或乙醯基檸檬酸三乙酯(重量比顯示於表8中)且徹底混合。將西羅莫司以3重量%至4.5重量%之重量溶解在各媒液中。 　　化學穩定性測試： 　　將約2毫升西羅莫司調合物放入在周圍濕度下每個2毫升波紋密封之玻璃小瓶中且儲存在5℃及40℃下，避免暴露於光。 　　實施例2的結果： 　　試管內測試： 　　將測試之調合物組成物列示於表9中。 表8 含有泊洛沙姆188的媒液組成物 表9 含有泊洛沙姆188之調合物組成物 表10顯示具有及不具有泊洛沙姆之調合物的化學穩定性數據之比較。 表10 在2週之後，西羅莫司在溶液調合物中的化學穩定性 實施例3 　　黏度測試： 　　媒液之黏度係使用布氏(Brookfield)DVIII+可程式流變儀測量。測量係使用具有CPE-52主軸的錐板進行。黏度係以布氏TC-602D冷卻浴/可程式控制器維持在25±0.5℃下測量。 　　化學穩定性測試： 　　將約2毫升西羅莫司調合物放入在周圍濕度下每個2毫升波紋密封之玻璃小瓶中且儲存在5℃、25℃及40℃下，避免暴露於光。 　　調合物之製備 　　將1%泊洛沙姆188溶解在苯甲酸苯甲酯與乙醇之混合物中(顯示於表13中)且混合，直到均勻為止。添加SAIB(以表13顯示之比)且在50℃下混合，直到形成均勻的溶液為止。在溶液冷卻至室溫之後，添加PEG 400或乙醯基檸檬酸三丁酯(以表13顯示之比)且徹底混合。添加維生素E且徹底混合。添加3%濃度之西羅莫司且攪拌，直到全部溶解為止。 　　在表11中所示之組成物係以黏度、化學穩定性及在水性釋放介質中的西羅莫司釋放(至多24小時)進行評估。該等組成物具有如表12中所示之低黏度。 將西羅莫司調合物在5℃、25℃及40℃下儲存1和2週後的化學穩定性列示於表13中。將西羅莫司調合物在40℃下儲存2週後的化學穩定性，以及在37℃下在含有0.1%SDS之PBS中24小時之後累積釋放之西羅莫司%的總結列示於表14及圖3中。 當HVLCM的量增加時，通常使組成物的黏度增加。例如，當SAIB的量自1%增加至49%時，則組成物的黏度自11增加至46cP。HVLCM(例如SAIB)的量對西羅莫司的化學穩定性似乎沒有影響。HVLCM(例如SAIB)的量對藥物(例如西羅莫司)釋放的最初速率似乎僅有些微影響。在ATBC的存在下，SAIB(1至10重量%)對化學穩定性似乎具有很小至沒有影響。 　　聚合物(例如泊洛沙姆)似乎降低了藥物(例如西羅莫司)的試管內最初釋放。以1重量%之聚合物(例如泊洛沙姆)似乎不影響組成物的黏度。在含有ATBC之調合物中，在1%泊洛沙姆存在下的1%維生素E對增強化學穩定性似乎具有很小或沒有影響。 　　在所評估的化學穩定性增強劑之中，生育酚(例如維生素E)似乎是對西羅莫司最有效的化學穩定性增強劑。生育酚在ATBC的存在下(有或沒有泊洛沙姆)似乎增強了西羅莫司的穩定性。維生素E自1重量%增加至10重量%似乎不顯著地進一步增強化學穩定性。 實施例4：活體內PK研究 　　製備具有表15中所示之組份及量的醫藥組成物。 　　將雄性日本白兔全身麻醉且隨後將兩隻眼睛以投予奧布卡因鹽酸鹽(oxybuprocaine hydrochloride)(0.5%)眼滴劑而於表面上麻醉。兔子接受20或30微升調合物的單一雙眼玻璃體內注射。將兔子在投予後1個月、2個月、3個月和6個月安樂死。將摘除之眼睛解剖同時冷凍，且分離玻璃體液及視網膜-脈絡膜。西羅莫司的量係使用液相層析術與串聯式質譜法之組合測定。在玻璃體液中的西羅莫司之剩餘率顯示於表16中(以4至6隻眼睛為基礎)。在視網膜-脈絡膜中的西羅莫司濃度顯示於表17中(以3至6隻眼睛為基礎)。剩餘量係以平均±SD提供。 圖4和5顯示經6個月時期剩餘在貯庫物中的西羅莫司量及在玻璃體液中的西羅莫司濃度之數據。 　　稱為C401和C407之調合物係在不同的場合以相同的組份及其比率製得。如表16和17及圖4和5所示，在具有由SAIB、BB及EtOH所組成之媒液的調合物C401和C407之西羅莫司釋放輪廓有變異性。 實施例5：活體內PK研究 　　製備具有表18中所示之組份及量的醫藥組成物。 　　將雄性日本白兔全身麻醉且隨後將兩隻眼睛以投予奧布卡因鹽酸鹽(0.5%)眼滴劑而於表面上麻醉。兔子接受20或30微升調合物的單一雙眼玻璃體內注射。將兔子在投予後1個月、2個月、3個月和6個月安樂死。將摘除之眼睛解剖同時冷凍，且分離玻璃體液及視網膜-脈絡膜。西羅莫司的量係使用液相層析術與串聯式質譜法之組合測定。表19顯示在玻璃體內貯庫物中的西羅莫司之剩餘率。表20顯示在視網膜/脈絡膜中的西羅莫司濃度。量係以平均±SD表示(以2至4隻眼睛為基礎)。 圖6和7顯示經6個月時期剩餘在貯庫物中的西羅莫司量及在玻璃體液中的西羅莫司濃度之數據。 　　西羅莫司之血液濃度係以30天間隔測量。將結果顯示於圖8中。 實施例6：活體內PK研究 　　所使用的溶劑如下：SAIB和乙醯基檸檬酸三丁酯(諸如在市場上取自Sigma-Aldrich)、苯甲酸苯甲酯和乙醇(99.5)(諸如在市場上取自Nacalai Tesque, Inc.)、維生素E(諸如在市場上取自Riken Vitamin)。 　　西羅莫司係於市場上自許多來源取得，包括Santen Pharmaceutical Company。 　　西羅莫司溶液調合物之製備： 　　將240毫克西羅莫司量測至標準瓶中，且藉由添加4.4毫升預混合之SD/BB/EtOH(10/40/5，v/v/v)、3.6毫升預混合之BB/EtOH(40/5，v/v)或3.68毫升預混合之VitE/BB/EtOH(1/40/5，v/v/v)而溶解。接著分別添加3.6毫升、4.4毫升或4.32毫升乙醯基檸檬酸三丁酯且混合，藉此製備SD/BB/EtOH/ATBC(10/40/5/45，v/v/v/v)、BB/EtOH/ATBC(40/5/55，v/v/v)或VitE/BB/EtOH/ATBC(1/40/5/54，v/v/v/v)之調合物。亦製備包含EtOH/PEG400/SRL(4/92/4，w/w/w)之對照組成物。組成物及劑量顯示於表21中。在玻璃體內注射西羅莫司溶液調合物後進行兔子PK研究： 　　將雄性日本白兔全身麻醉且隨後將兩隻眼睛以投予奧布卡因鹽酸鹽(0.5%)眼滴劑而於表面上麻醉。兔子接受30微升試驗調合物或20微升在PEG400/EtOH(94/2)中的4%西羅莫司的單一雙眼玻璃體內注射。將兔子在投予後4週和12週安樂死。將摘除之眼睛解剖同時冷凍，且分離玻璃體液。在玻璃體中的西羅莫司量係使用液相層析術與串聯式質譜法之組合測定。 　　表22顯示在玻璃體內貯庫物中的剩餘劑量。圖9顯示經12週時期剩餘在貯庫物中的西羅莫司量之數據。因為貯庫物不可以單獨地自玻璃體液移出，所以在本發明中假設剩餘在貯庫物中的西羅莫司量等於組合之玻璃體液與貯庫物中的西羅莫司量。 實施例7：醫藥組成物 　　組成物係依照表23a和23b製備。賦形劑的量係以重量份表示。醫藥組成物含有3毫克/毫升濃度之西羅莫司。 實施例8 　　持續釋放性評估試驗： 　　評估本發明之貯庫型調合物在動物中的藥物持續釋放性。 　　試驗物品之製備： 　　將240毫克西羅莫司秤重至標準瓶中，隨後藉由添加0.8毫升二甲基亞碸、7.2毫升乙醯基檸檬酸三乙酯而溶解且混合，接著以0.20微米孔徑之過濾器進行滅菌過濾，藉此製備比較用組成物調合物C801。 　　將240毫克西羅莫司秤重至標準瓶中，隨後藉由添加事先混合之3.6毫升苯甲酸苯甲酯/乙醇(40：5之體積比)或3.68毫升維生素E/苯甲酸苯甲酯/乙醇(1：40：5之體積比)而溶解，添加4.4毫升或4.32毫升乙醯基檸檬酸三正丁酯酯且混合，接著以0.20微米孔徑之過濾器進行滅菌過濾，藉此製備調合物C802和C803。 　　兔子藥物動力學評估： 　　使用配備有30G針的Hamilton注射器經玻璃體內投予每隻白兔(albino rabbit)眼睛0.03毫升貯庫型調合物C801(比較用)、C802和C803。在投予後4週後和12週後，以靜脈內投予之戊巴比托鈉麻醉劑進行安樂死且摘除眼球。將摘除之眼球立即冷凍且將玻璃體收集在含有貯庫型調合物的狀態中。在每一收集時間點的玻璃體中之西羅莫司濃度係使用LC-MS/MS測量，且評估在投予後的藥物殘留量。 　　試驗結果及考量： 　　試驗結果顯示於表24中。 表24 如表24中所示，在投予比較用調合物C801後4週僅剩餘10.0%之所投予的西羅莫司量；反之，剩餘71.1%之所投予的調合物C802量及83.7%之所投予的調合物C803量。 　　根據上述結果，確認以本發明之貯庫型調合物改進持續釋放性。 實施例9：醫藥組成物及活體內PK研究 　　組成物係依照表25製備。賦形劑的量係以重量份表示。醫藥組成物含有30毫克/克之西羅莫司濃度。在玻璃體內注射西羅莫司溶液調合物後進行兔子PK研究： 　　將雄性日本白兔全身麻醉且隨後將兩隻眼睛以投予奧布卡因鹽酸鹽(0.5%)眼滴劑而於表面上麻醉。兔子接受30微升試驗調合物的單一雙眼玻璃體內注射。將兔子在投予後4週和12週安樂死。將摘除之眼睛解剖同時冷凍，且分離玻璃體液。在玻璃體中的西羅莫司量係使用液相層析術與串聯式質譜法之組合測定。 　　表26顯示在玻璃體內貯庫物中的剩餘劑量。圖10顯示經6個月時期涉及調合物C901至C905剩餘在貯庫物中的西羅莫司量之數據。如上文註記，在本發明中假設剩餘在貯庫物中的西羅莫司量等於在組合之玻璃體液與貯庫物中的西羅莫司量。表27和圖11顯示經6個月時期涉及調合物C901至C905之視網膜-脈絡膜中的西羅莫司濃度之數據。調合物C901至C905之西羅莫司的血液濃度係以30天間隔測量。將結果顯示於圖12中。 實施例10：醫藥組成物及活體內PK研究 　　組成物係依照表28製備。賦形劑的量係以重量份表示。醫藥組成物含有30毫克/克之西羅莫司濃度。在玻璃體內注射西羅莫司溶液調合物後進行兔子PK研究： 　　將雄性日本白兔全身麻醉且隨後將兩隻眼睛以投予奧布卡因鹽酸鹽(0.5%)眼滴劑而於表面上麻醉。兔子接受30微升試驗調合物的單一雙眼玻璃體內注射。將兔子在投予後4週和12週安樂死。將摘除之眼睛解剖同時冷凍，且分離玻璃體液。在玻璃體中的西羅莫司量係使用液相層析術與串聯式質譜法之組合測定。 　　表29顯示在玻璃體內貯庫物中的剩餘劑量。圖13顯示經6個月時期涉及調合物C906至C909剩餘在貯庫物中的西羅莫司量之數據。如上文註記，在本發明中假設剩餘在貯庫物中的西羅莫司量等於在組合之玻璃體液與貯庫物中的西羅莫司量。表30和圖14顯示經6個月時期涉及調合物C906至C909之視網膜-脈絡膜中的西羅莫司濃度之數據。調合物C906至C909之西羅莫司的血液濃度係以30天間隔測量。將結果顯示於圖15中。 實施例11：醫藥組成物及活體內PK研究 　　組成物係依照表31製備。賦形劑的量係以重量份表示。醫藥組成物含有30毫克/克之西羅莫司濃度。在玻璃體內注射西羅莫司溶液調合物後進行兔子PK研究： 　　將雄性日本白兔全身麻醉且隨後將兩隻眼睛以投予奧布卡因鹽酸鹽(0.5%)眼滴劑而於表面上麻醉。兔子接受30微升試驗調合物的單一雙眼玻璃體內注射。將兔子在投予後4週和12週安樂死。將摘除之眼睛解剖同時冷凍，且分離玻璃體液。在玻璃體中的西羅莫司量係使用液相層析術與串聯式質譜法之組合測定。 　　表32及圖16顯示經6個月時期涉及調合物C907至C909、C914和C915剩餘在玻璃體液中的西羅莫司量之數據。表33和圖17顯示經6個月時期涉及調合物C907至C909、C914和C915之視網膜-脈絡膜中的西羅莫司濃度之數據。調合物C907至C909、C914和C915之西羅莫司的血液濃度係以30天間隔測量。將結果顯示於圖18中。 實施例12：醫藥組成物及活體內PK研究 　　組成物係依照表34製備。賦形劑的量係以重量份表示。醫藥組成物含有30毫克/克之西羅莫司濃度。在玻璃體內注射西羅莫司溶液調合物後進行兔子PK研究： 　　將雄性日本白兔全身麻醉且隨後將兩隻眼睛以投予奧布卡因鹽酸鹽(0.5%)眼滴劑而於表面上麻醉。兔子接受30微升試驗調合物的單一雙眼玻璃體內注射。將兔子在投予後4週和12週安樂死。將摘除之眼睛解剖同時冷凍，且分離玻璃體液。在玻璃體中的西羅莫司量係使用液相層析術與串聯式質譜法之組合測定。 　　表35及圖19顯示經6個月時期涉及調合物C914剩餘在玻璃體液中的西羅莫司量之數據。表36和圖20顯示經6個月時期涉及調合物C914之視網膜-脈絡膜中的西羅莫司濃度之數據。調合物C914之西羅莫司的血液濃度係以30天間隔測量。將結果顯示於圖21中。 實施例13 　　將組成物列示於表37中。賦形劑的量係以重量份表示。醫藥組成物含有介於10至35毫克/克之間的西羅莫司濃度。 　　試驗物品之製備： 　　將苯甲酸苯甲酯、乙醇及乙醯基檸檬酸三正丁酯秤重至瓶中且徹底混合。添加維生素E且混合。添加表37中所示之濃度的西羅莫司，攪拌溶液，直到全部溶解為止。將所得溶液使用0.2微米孔徑之滅菌過濾器進行滅菌過濾。在玻璃體內注射西羅莫司溶液調合物後進行兔子PK研究： 　　將雄性日本白兔全身麻醉且隨後將兩隻眼睛以投予奧布卡因鹽酸鹽(0.4%)眼滴劑而於表面上麻醉。兔子接受30微升或50微升試驗調合物的單一雙眼玻璃體內注射。經由耳動脈收集血液。將兔子在投予後4週安樂死。將摘除之眼睛解剖同時冷凍，且分離玻璃體液及視網膜-脈絡膜。在玻璃體液、視網膜-脈絡膜及全血中的西羅莫司量係使用液相層析術與串聯式質譜法之組合測定。 　　表38顯示經6個月時期涉及調合物C1001至C1006剩餘在玻璃體液中的西羅莫司量之數據。表39顯示經6個月時期涉及調合物C1001至C1006之視網膜-脈絡膜中的西羅莫司濃度之數據。測量調合物C1001至C1006之西羅莫司的血液濃度。結果顯示於表40中。實施例14：醫藥組成物 　　組成物係依照表41製備。賦形劑的量係以重量份表示。醫藥組成物含有30毫克/克之西羅莫司濃度。實施例15：SAIB/維生素E混合物 　　SAIB/維生素E混合物之製備： 　　將SAIB溶解在維生素E(以表42顯示之重量比)中且將混合物混合，直到均勻為止。 　　密度測試： 　　將約2毫升混合物注入密度計中於25℃下測量混合物的密度。 　　如表42中所示，密度係取決於SAIB：維生素E之重量比而增加。另外，SAIB：維生素E之重量比及在25℃下的密度係呈線性相關，如圖22中所示。根據線性近似公式 　　密度(在25℃下)=0.0016×(SAIB：維生素E之重量比)+0.9445， 　　當密度為1時，則SAIB：維生素E之重量比為約34.7%。因此，當SAIB：維生素E之重量比低於約34.7%時，則混合物可漂浮在水中。 　　玻璃體液具有比水略高的密度(約1.0053克/毫升)且通常在體溫(37℃)下而不是25℃。將包括SAIB及維生素E的本發明之貯庫型調合物注入玻璃體液中且釋放API及其他賦形劑。在釋放時間結束時，貯庫物主要由SAIB、維生素E及API所組成，因為已釋放幾乎所有的其他賦形劑。若在貯庫型調合物中的SAIB：維生素E之重量比低於約38%時，則貯庫物可漂浮在玻璃體液中，引起患者的不舒服感。實施例16：丙酮氟辛龍(Fluocinolone Acetonide)調合物 　　在表43中所示之組成物係藉由添加3%w/w氟辛龍至媒液中而製備。所得調合物為具有一些過量固體的溶液。在表43中的賦形劑量係以重量份表示。氟辛龍調合物的試管內釋放測試： 　　將50微升調合物使用具有23G針的1毫升EXEL注射器注入5毫升釋放介質(在37℃下平衡的含有0.2%SDS之PBS)中。將樣品放在37℃下以50rpm旋轉之迴轉式振盪器上。在各時間點汲取4.5毫升介質且以新鮮的4.5毫升介質更換。注意在取樣期間不要碰到貯庫型藥物。以HPLC分析樣品以測定氟辛龍濃度。製備一式三份的樣品。氟辛龍調合物之釋放輪廓展示於圖23中。 實施例17：曲安西龍調合物 　　在表44中所示之組成物係藉由添加3%w/w曲安西龍至媒液中而製備。所得調合物為具有一些過量固體的溶液。在表44中的賦形劑量係以重量份表示。曲安西龍調合物的試管內釋放測試： 　　將50微升調合物使用具有23G針的1毫升EXEL注射器注入5毫升釋放介質(在37℃下平衡的含有0.2%SDS之PBS)中。將樣品放在37℃下以50rpm旋轉之迴轉式振盪器上。在各時間點汲取4.5毫升介質且以新鮮的4.5毫升介質更換。注意在取樣期間不要碰到貯庫型藥物。以HPLC分析樣品以測定曲安西龍濃度。製備一式三份的樣品。曲安西龍調合物之釋放輪廓展示於圖24中。 實施例18：布洛芬調合物 　　在表45中所示之組成物係藉由添加3%w/w布洛芬至媒液中而製備。所得調合物為澄清溶液。在表45中的賦形劑量係以重量份表示。布洛芬調合物的試管內釋放測試： 　　將50微升調合物使用具有23G針的1毫升EXEL注射器注入5毫升釋放介質(在37℃下平衡的含有0.2%SDS之PBS)中。將樣品放在37℃下以50rpm旋轉之迴轉式振盪器上。在各時間點汲取4.5毫升介質且以新鮮的4.5毫升介質更換。注意在取樣期間不要碰到貯庫型藥物。以HPLC分析樣品以測定布洛芬濃度。製備一式三份的樣品。布洛芬調合物之釋放輪廓展示於圖25中。 實施例19：醫藥組成物 　　組成物係依照表46和47製備。媒液之組份量係以每100份組成物計的重量份表示。在表46和47中的所有組成物具有30毫克/克之西羅莫司濃度。 實施例20：醫藥組成物及活體內PK研究 　　組成物係依照表48製備。媒液之組份量係以每100份組成物計的重量份表示。在表48中的所有組成物具有30毫克/克之西羅莫司濃度。將雄性日本白兔以靜脈內注射戊巴比托鈉而全身麻醉且隨後將奧布卡因鹽酸鹽(0.4%)眼滴劑經局部投予兩隻眼睛而於表面麻醉。兔子接受10或30微升試驗調合物的單一雙眼玻璃體內注射。經由耳動脈收集血液。將兔子在投予後1個月安樂死。將摘除之眼睛解剖同時冷凍，且分離玻璃體液及視網膜-脈絡膜。在玻璃體液、視網膜-脈絡膜及全血中的西羅莫司係使用液相層析術與串聯式質譜法之組合定量。 　　表49和圖26顯示經1個月時期涉及調合物C1701和C1711剩餘在玻璃體液中的西羅莫司量之數據。表50顯示經1個月時期涉及調合物C1701和C1711在視網膜-脈絡膜中的西羅莫司濃度之數據。調合物C1701和C1702之西羅莫司的血液濃度係經30天測量。結果顯示於圖27中。 實施例21：醫藥組成物及活體內PK研究 　　組成物係依照表51製備。媒液之組份量係以每100份組成物計的重量份表示。將雄性日本白兔以靜脈內注射戊巴比托鈉而全身麻醉且隨後將奧布卡因鹽酸鹽(0.4%)眼滴劑經局部投予兩隻眼睛而於表面麻醉。兔子接受10或30微升調合物C2101至2108或20微升調合物C2109和C2110的單一雙眼玻璃體內注射。經由耳動脈收集血液。將兔子在投予後1個月安樂死。將摘除之眼睛解剖同時冷凍，且分離玻璃體液及視網膜-脈絡膜。在玻璃體液、視網膜-脈絡膜及全血中的西羅莫司係使用液相層析術與串聯式質譜法之組合定量。 　　表52和圖28顯示經1個月時期涉及表51所示之調合物剩餘在玻璃體液中的西羅莫司量之數據。ND：低於檢測限度 　　表53顯示經1個月時期涉及表51所示之調合物在視網膜-脈絡膜中的西羅莫司濃度之數據。ND：低於檢測限度 　　表51所示之調合物之西羅莫司的血液濃度係以30天間隔測量。將結果顯示於圖29中。 實施例22：西羅莫司在水中的穩定性 　　組成物係依照表54製備。賦形劑的量係以重量份表示。醫藥組成物含有30毫克/克之西羅莫司濃度。將30微升該等組成物注入填充在玻璃小瓶中的4毫升水中。將樣品儲存在37℃和60℃下且隨著時間取出。特別地在儲存後自樣品取出1毫升水作為水樣品。另外，將7毫升乙腈添加至剩餘的3毫升水及貯庫物中以溶解樣品中的貯庫物及調整體積至10毫升。取出約1毫升溶解貯庫物的樣品作為混合物樣品。在該等樣品中的西羅莫司量係使用液相層析術測定，且在貯庫物中的西羅莫司量係以水樣品及混合物樣品中的量為基礎測定。 　　表55和圖30顯示在60℃下儲存後剩餘的西羅莫司量。表56和圖31顯示在37℃下儲存後剩餘的西羅莫司量。在前述實施例中所揭示及在本發明整篇中所指導之所有組成物(藥物及媒液)可於臨床前及/或臨床研究中使用，包括試管內研究、動物研究及/或臨床研究，該等研究中任一者可針對例如特性(例如藥物釋放速率)、藥物動力學、藥物藥效學、毒物學、安全性及/或功效。組成物可在治療上於人類(臨床用途)或動物(獸醫用途)、需要此等治療法的人類或動物中使用。Amounts can be described herein as a set of upper and lower preferred values. The preferred range includes any range consisting of upper and lower preferred values, and two lower and upper preferred values. Examples also disclose amounts (e.g., weight percentages, ratios, etc.). A preferred range also includes a range composed of two values disclosed in the examples, and a range composed of one value disclosed in the examples and another value disclosed in a set of upper or lower limits. All such ranges are explicitly disclosed herein. Unless otherwise indicated, the specific volume of the composition, unit dosage form, and the like referred to herein indicates the volume measured at a temperature of 20 ° C and a pressure of 1 atmosphere. The blends according to the invention usually comprise an active pharmaceutical ingredient (API) in a carrier composition. In some examples, the carrier composition includes one or more of a high viscosity liquid carrier material (HVLCM), a hydrophobic solvent, a hydrophilic solvent, and an antioxidant. In some examples, the carrier composition comprises one or more of a high viscosity liquid carrier material (HVLCM), a hydrophobic solvent, a hydrophilic solvent, a polymer, an antioxidant, and other excipients. Any biologically active substance (BAS) or active pharmaceutical ingredient (API) or active compound suitable for a depot type blend can be used in the composition of the present invention. In addition, the descriptions of the administration, dosage, weight percentage, and similar aspects of the present invention related to any of the BAS, API, or active compounds listed herein are intended to apply to other substances, ingredients, or compounds as used herein Unless otherwise noted. Some exemplary categories of API include immunosuppressants, anti-inflammatory drugs, and antibiotics. The biologically active substances, APIs and active compounds described herein also include their pharmaceutically acceptable prodrugs, derivatives, analogs, salts, derivatives and esters. The term "bioactive substance" as used herein refers to inorganic or organic molecules, including drugs, peptides, proteins, that cause biological effects when administered to animals (including but not limited to birds and mammals, including humans) in vivo. , Carbohydrates (including monosaccharides, oligosaccharides and polysaccharides), nucleoproteins, mucins, lipoproteins, synthetic peptides or proteins or small molecules linked to proteins, glycoproteins, steroids, nucleic acids (any form of DNA ( Including cDNA or RNA) or fragments thereof), nucleotides, nucleosides, oligonucleotides (including antisense oligonucleotides), genes, lipids, hormones, or combinations thereof. Suitable proteins include, but are not limited to, human growth hormone, fibroblast growth factor (FGF), erythropoietin (EPO), platelet-derived growth factor (PDGF), granulocyte colony-stimulating factor (g-CSF), bovine growth hormone (BST), tumor necrosis factor (TNF), transforming growth factor-beta (TGF-Beta), interleukins, insulin and interferons (such as alpha-interferon, beta-interferon), and the like. The term drug (or active pharmaceutical ingredient, API) as used herein refers to any substance used internally or externally as a medicine to treat, cure, or prevent a disease or disorder, and includes, but is not limited to, immunosuppressive agents, anesthetics, analgesics , Chemotherapeutics, steroids (including retinoids), hormones, antibiotics, antiviral agents, antifungals, antiproliferative agents, antihistamines, anticoagulants, anti-light aging agents, melanin peptides, non-steroids And steroids anti-inflammatory compounds, antipsychotics and radiation absorbers (including UV-absorbers). The term bioactive substance also includes agents such as insecticides, insecticides, fungicides, rodenticides, and phytonutrients and growth promoters. The term pharmaceutically acceptable means safe and effective medical use, which may include human or veterinary use, preferably human use. Pharmaceutically acceptable compositions are preferably suitable for use in treating medical conditions in animals or humans. The pharmaceutically acceptable composition preferably comprises a combination of one or more active pharmaceutical ingredients and one or more pharmaceutically acceptable excipients, basically consisting of one or more active pharmaceutical ingredients and one or more pharmaceutically acceptable A combination of excipients, or a combination of one or more active pharmaceutical ingredients and one or more pharmaceutically acceptable excipients. Immunosuppressive agents include any immunosuppressant that is useful in depot type blends, including macrolides, cyclosporine, and others. Immunosuppressants include APIs with immunosuppressive activity, even though APIs are not primarily used as immunosuppressants in any particular blend or use thereof. Therapeutic agents that can be used include, but are not limited to, compounds that act by binding to members of the immunophilin family of cellular proteins. These compounds are known as "immunavidin-binding compounds". Immunavidin-binding compounds include, but are not limited to, the "limus" family of macrolide compounds. Examples of moss compounds that can be used include, but are not limited to, sirolimus (rapamycin) and its water-soluble analogs SDZ-RAD (Novartis), TAFA-93 (Isotechnika), tacrolimus ( tacrolimus), everolimus, RAD-001 (Novartis), pimecrolimus, temsirolimus, CCI-779 (Wyeth), AP23841 (Ariad), AP23573 (Ariad) And ABT-578 (Abbott Laboratories). Moss compound analogs and derivatives that can be used include, but are not limited to, the compounds described in US Patent Nos. 5,527,907, 6,376,517, 6,329,386, and 6,890,546, each of which is incorporated herein by reference in its entirety. Therapeutic agents also include analogs, prodrugs, salts, derivatives and esters of the moss compound. In some compositions of the invention, the therapeutic agent comprises a moss compound, consisting essentially of a moss compound, or a moss compound. In some compositions of the present invention, the therapeutic agent comprises an immunophilin-binding compound, consisting essentially of an immunophilin-binding compound, or an immunophilin-binding compound. In some compositions of the invention, the therapeutic agent comprises an mTOR inhibitor or an analog, derivative, salt, ester, or prodrug thereof (e.g., TAFA93), and consists essentially of an mTOR inhibitor or an analog, derivative, salt, An ester or prodrug (e.g. TAFA93) or an mTOR inhibitor or its analog, derivative, salt, ester or prodrug (e.g. TAFA93). In some compositions of the invention, the therapeutic agent comprises a cyclophilin or FK-506 binding protein (FKBP), consists essentially of a cyclophilin or FK-506 binding protein (FKBP), or consists of a cyclophilin or FK -506 Binding Protein (FKBP). Other sirolimus derivatives that can be used include, but are not limited to, 7-epi-rapamycin, 7-thiomethyl-rapamycin, 7-epi-trimethoxyphenyl-rapamycin, 7 -Table-thiomethyl-rapamycin, 7-desmethoxy-rapamycin, 32-desmethoxy-rapamycin, 2-desmethyl-rapamycin, rapamycin Monoester and Diester Derivatives of Glucotin, 27-oxime of Rapamycin, 42-Pendoxy Analogue of Rapamycin, Bicyclic Rapamycin, Rapamycin Dimer, Rapamycin Silyl ethers, rapamycin aryl sulfonates and sulfamates, mono- and diesters at positions 31 and 42 of 30-demethoxyrapamycin and other derivatives described below Property: "Rapamycin (AY-22,989), A New Antifungal Antibiotic. I. Taxonomy Of The Producing Streptomycete And Isolation Of The Active Principle" by Vezina et al. J. Antibiot. (Tokyo) 28: 721-2726 (1975); Sehgal "Rapamycin (AY-22,989), A New Antifungal Antibiotic. II. Fermentation, Isolation And Characterization" J. Antibiot. (Tokyo) 28: 727-732 (1975); Sehgal et al. "Demethoxyrapamycin (AY-24,668) ), A New Antifungal Antibiotic "J. Antibiot. (Tokyo) 36: 351-354 (1983); and" Incorporation Of Acetate, Propionate, And Methionine Into Rapamycin By Streptomycetes hygroscopicus "J Nat Prod 54: 167-177 (1991), Paiva et al. WO 92/05179, EP 467606; "Hydrogenated Rapamycin Derivatives" by Caufield et al. US Patent No. 5,023,262; "Bicyclic Rapamycins" by Kao et al. US Patent No. 5,120,725; "Rapamycin Dimers" by Kao et al. US Patent No. 5,120,727 "Silyl Ethers Of Rapamycin" US Patent No. 5,120,842; "Rapamycin 42-Sulfonates And 42- (N-carboalkoxy) Sulfamates Useful As Immunosuppressive Agents" US Patent No. 5,177,203; Nicolaou et al. "Total Synthesis Of Rapamycin" J. Am. Chem. Soc. 115: 4419-4420 (1993); "Total Synthesis Of (-) Rapamycin Using An Evans-Tishchenko Fragment Coupling" J. Am. Chem. Soc 115: 7906-7907 (1993); and "Total Synthesis Of Rapamycin Via A Novel Titanium-Mediated Aldol Macrocyclization Reaction" by Hayward et al. J. Am. Chem. So c., 115: 9345-9346 (1993), each of which is incorporated herein by reference in its entirety. Compounds of the mousse family are useful in the formulations and methods of treating, preventing, inhibiting, delaying the onset or causing the deterioration of the diseases and symptoms described herein. Additional non-limiting examples of pharmaceutical materials include anti-infectives such as nitrofurazone, sodium propionate, antibiotics (including penicillin, tetracycline, oxytetracycline, chlorotetracycline ), Bacitracin, nystatin, streptomycin, neomycin, polymyxin, gramicidin, chloramphenicol, Erythromycin and azithromycin; Sulfonamides, including sulfacetamide, sulfamethizole, sulfamethazine, sulfadiazine , Sulfamerazine, and sulfisoxazole; and antivirals, including iodoxuridine, ganciclovir, trifluridine, and arabinoside (trifluridine) vidarabine); anti-inflammatory drugs, such as NSAID (including ethoxysalicylic acid, ibuprofen, ketoprofen, naproxen, celecoxib, diclofenac Diflunisal (diflunisal), etodolac, indomethacin, ketorolac, nabumetone, oxiprozin, piroxicam ), Salsalate and tolmetin); steroids or glucocorticosteroids (including prednisolone, prednisone, methylprednisolone Medrol, beclomethasone, budesonide, flunisolide, fluticasone, and triamcinolone; analgesics, such as NSAID, opioids (including morphine, Fentanyl, tramadol, oxycodone, methadone, hydrocodone, hydromorphone, loperamide, poxitin (meperidine), tapentadol, oxymorphone, propoxyphene, remifentanil, sufentanil, alfentanil, Levorphanol, codeine and dihydrocodeine) and paracetamol Paracetamol (acetaminophen); antiallergic drugs such as antazoline, methapyritene, chlorpheniramine, mepyramine (pyrilamine), prophenpyridamine, hydrocortisone, cortisone, hydrocortisone acetate, dexamethasone, dexamethasone 21-phosphate, fluorine Xinlong, triamcinolone, medrysone, prednisolone, prednisolone sodium 21-succinate, and prednisolone acetate; allergic agents, such as ragweed pollen antigen , Hay fever pollen antigen, dust antigen and milk antigen; vaccines such as smallpox, yellow fever, distemper, swine fever, chicken pox, antivenom, scarlet fever, diphtheria toxoid, tetanus Toxoids, pigeon pox, whooping cough, influenza, rabies, mumps, measles, polio and Newcastle disease; decongestants such as phenylephrine, naprozole ( naphazoline) and tetrahydrozoline (tetra hydrazoline); miotics and anticholinesterases, such as pilocarpine, esperine salicylate, carbachol, diisopropyl fluorophosphate, ecoate (phospholine iodide) and demecarium bromide; parasympathetic blockers such as atropine sulfate, cyclopentolate, homatropine, scopolamine, topiramate Tropicamide, eucatropine, and (hydroxyamphetamine); sympathomimetics, such as epinephrine; antipsychotics, such as olanzapine, risperidone (risperidone); narcotic antagonists, such as naltrexone, naloxone, nalnothene; sedatives and sleeping pills, such as pentobarbital sodium, pentobarb Phenobarbital, secobarbital sodium, codeine, (a-bromoisopentyl) urea, carcarbal; psychic energizers, such as 3- (2-aminopropyl) indole acetate and 3- ( 2-Aminobutyl) indole acetate; Nings such as reserpine, chlorpromayline and thiopropazate; Anesthetics such as benzocaine ), Bupivacaine, etidocaine, lidocaine, mepivacaine, pramoxine, prilocaine, prolucaine Procaine, proparacaine, ropivacaine, tetracaine, levobupivacaine, chloroprocaine, cloth Butacaine, propoxycaine, phenacaine, hexylcaine, isobucaine, cyclomethycaine, pirene Benoxinate, diperodon, dibucaine, meprylcaine, dimethisoquin, pramoxine, butamben ), Dyclonine (with and without augmenting agents, such as dexamethasone or epinephrine); tricyclic antisuppression Agents such as amitriptyline or nortriptyline; androgenic steroids such as methyl-testosterone and fluorymesterone; estrogen such as estrone, 17-fl-estradiol, estradiol, and diethyl stilbestrol; fertility aids such as progesterone, megestrol, melengestrol, chlormadinone ), Ethisterone, norethynodrel, 19-norprogesterone, norethindrone, medroxyprogesterone, and 17-0-hydroxyprogesterone Hydroxy-progesterone; body fluids such as prostaglandins such as PGEI, PGE2 and PGF2; antipyretics such as aspirin, sodium salicylate and salicylamide; antispasmodics, Such as atropine, methantheline, papaverin, and methscopolamine bromide; antimalarials, such as 4-aminoquinoline, 8-aminoquinoline , Chloroquine, and pyrimethamine; anti-tissue Classes such as diphenhydramine, dimenhydrinate, tripelennamine, perphenazine and chlorphenazine; cardioactive agents such as Dibenzhydroflume thiazide, flumethiazide, chlorothiazide, and aminotrate; statins, such as atorvastatin, atorvastatin, Cerivastatin, fluvastatin, lovastatin, pravastatin, simvastatin, and related compounds; anti-asthma drugs, such as cromolyn ); Bone resorption preventives, such as bisphosphonates, including, as non-limiting examples, alendronate, risendronate, zolendronate, pamidronate ( pamidronate) and ibandronate; calcium-regulating hormones, such as calcitonin; nutritional agents, such as natural and synthetic biologically active peptides; and proteins, including growth factors, cell adhesion factors, cytokines, and The reaction was modifiers. In some compositions of the present invention, the active pharmaceutical ingredient is capable of treating eye diseases, for example, the composition contains a substance capable of treating eye diseases. This substance is also known as eye drops. In some compositions of the present invention, the active pharmaceutical ingredient does not include ophthalmic drugs other than sirolimus, and in some aspects, the active pharmaceutical ingredient does not include ophthalmic drugs. The active compound is included in the composition in an amount sufficient to deliver an effective amount to the host human or animal to achieve the desired effect. The amount of the drug or biologically active ingredient incorporated into the composition depends on the desired release profile, the concentration of the drug required for the biological effect, and the desired release period of the drug. The active compound concentration in the composition also depends on the absorption, inactivation, and excretion rates of the drug and other factors known to those skilled in the art. It should be noted that the dose value also varies with the severity of the symptoms to be alleviated. It should be further understood that the specific dosage regimen used for any particular individual should be adjusted at any time according to individual needs and the professional judgment of the person who manages or supervises the administration of the composition, and the concentration ranges listed herein are only examples and are not intended to limit all The scope or implementation of the claimed composition. The composition may be administered in one dose or may be divided into several smaller doses to be administered at different time intervals. The bioactive substance is usually present in an amount and / or concentration that is capable of being administered to a patient in need of the bioactive substance in an effective amount. The amount and / or concentration depends on the bioactive substance used and can also depend on the location of administration. The amount and / or concentration of the biologically active substance can be determined by those skilled in the art using the instructions of this specification. In general, higher concentrations are better, as this allows the administration of depots with smaller volumes. Concentrations should generally not be so high that BAS or other components have a high probability of precipitation, as this may affect performance (eg, bioavailability) and / or have other adverse effects. In some examples of intraocular depots, high concentrations / low volumes are preferred, but precipitation should be avoided as this can affect vision and / or impact the bioavailability of BAS (such as sirolimus). Without limiting the present invention, the bioactive substance is generally present in the composition of the present invention in an amount of at least 0.05% by weight, 0.1% by weight, 0.5% by weight, 1% by weight, or 2% by weight based on the weight of the composition. The bioactive substance is generally present in the composition in an amount of up to 20% by weight, 10% by weight, 7% by weight, 5% by weight, 4% by weight, or 3% by weight based on the weight of the composition. In some examples, the bioactive substance is present in an amount ranging from about 0.2% to 10% by weight based on the weight of the composition, such as about 0.2% to about 3.1% or about 0.3% to about 1% by weight . In some examples, the bioactive substance comprises sirolimus in an amount ranging from 1% to 10% by weight based on the weight of the composition. Compositions of the invention may include one or more biologically active substances (BAS), APIs or active compounds. When two or more BAS are used, they may be from the same treatment category or different treatment categories. For example, the active pharmaceutical ingredient may include sirolimus and at least one additional therapeutic agent, such as at least one additional eye drop. Some possible BAS combinations include sirolimus and tacrolimus; sirolimus and cyclosporine; and sirolimus and prednisolone. The composition of the present invention preferably contains a pharmaceutically acceptable high-viscosity liquid carrier material (HVLCM), and is preferably pharmaceutically acceptable for an intraocular reservoir. HVLCM is non-polymeric, water-insoluble and has a viscosity of at least 5,000 cP (and optionally at least 10,000; 15,000; 20,000; 25,000; or even 50,000 cP) at 37 ° C. HVLCM preferably crystallizes unevenly under ambient conditions or the physiological conditions of the individual. The term water-insoluble refers to a material that is soluble in water to the extent of less than 1% by weight under ambient conditions (such as room temperature or 23 ° C). The term "non-polymer" in this context refers to an ester or mixed ester having essentially no repeating units in the acid portion of the ester, and an ester or acid portion having an acid portion in which the functional units in the acid portion are repeated a few times. Mixed esters (ie oligomers). The term "non-polymer" as generally used herein excludes materials having more than five identical and adjacent repeating units or polymers in the acid portion of the ester, but containing dimers, trimers, tetramers or Pentamer materials are included within the scope of this term. HVLCM may contain sucrose acetate isobutyrate ("SAIB"), which basically consists of sucrose acetate isobutyrate ("SAIB"), or consists of sucrose acetate isobutyrate ("SAIB") ). SAIB is an example of HVLCM. The term "SAIB" refers to the sucrose molecule, whose eight natural hydroxyl groups are respectively -COCH 3 (Ethenyl) or --COCH (CH 3 ) 2 The (isobutylfluorenyl) moiety is esterified. SAIB is a product available on the market, for example, with different ethyl and isobutyl fluorenyl substitution patterns (such as different ratios of ethyl and ethyl isobutyl fluorenyl moieties and / or different cyclic positions of ethyl and isobutyl fluorenyl moieties) Is sold as a mixture of natural sucrose hydroxyl compounds. Those skilled in the art will understand that SAIB typically comprises a mixture of differently substituted "isoforms", including sucrose molecules that are nominally preferably esterified with two acetic acid and six isobutyric acid moieties. Therefore, HVLCM may comprise, consist essentially of, or consist of SAIB, in which natural sucrose molecules are esterified with two acetic acid and six isobutyric acid moieties-the structure of which is listed in US Patent 5,747,058, which is incorporated in its entirety Incorporated herein by reference. SAIB is orally non-toxic and is used in food industry to stabilize emulsions. It is a very viscous liquid and has the unusual characteristics of significant viscosity changes with little heating or addition of solvents. It is soluble in many biocompatible solvents. When in solution or emulsion, SAIB can be administered via injection or aerosol spray. SAIB is compatible with cellulose esters and other polymers that can affect the delivery rate of a substance. The HVLCM may comprise a non-polymerizable polyalkanediol, consisting essentially of a non-polymerizable polyalkanediol, or a non-polymerizable polyalkanediol. Non-polymerizable polyethylene glycol (PEG) is a preferred polyalkylene glycol. When the HVLCM comprises PEG, the PEG preferably has a molecular weight of less than about 220 or 200 channels. That is preferably n ≤5, of which n Is the average number of ethylene glycol units in PEG. For HVLCM containing PEG, it is preferred n Values include n = 5, 4, 3, or 2. In other embodiments, the HVLCM may be stearates (such as those of propylene glycol, glyceryl, diethylaminoethyl, and ethylene glycol stearate), ammonium stearate, and others. Chain fatty acid amides (such as N, N'-distearamide ethylene distearamide, stearylamine MEA and DEA, ethylene stearylamine, ethylene bistearamide, cocoamine oxide )), Long-chain fatty alcohols (such as cetyl alcohol and stearyl alcohol), long-chain esters (such as myristyl myristate, beheny erucate, and glyceryl phosphate). HVLCM may include ethylated sucrose distearate (Crodesta A-10). HVLCM is present in the composition in any amount that achieves the desired characteristics, such as viscosity and / or cohesion. The HVLCM is preferably present in an amount equal to or less than 99.5%, 95% by weight, 85% by weight, 60% by weight, or 50% by weight based on the weight of the pharmaceutical composition. The HVLCM is preferably present in the pharmaceutical composition of the present invention in an amount equal to or greater than 0.1% by weight, 0.5% by weight, 1% by weight, 10% by weight, 25% by weight or 40% by weight based on the weight of the pharmaceutical composition. . All ranges constituted by these amounts or combinations of these amounts disclosed in the examples are also preferred, such as 0.5% to 50% by weight, 25% to 85% by weight, and 10% to 40% by weight . In some examples, HVLCM comprises SAIB present in an amount ranging from about 0.1% to 60% by weight based on the weight of the composition, such as about 0.5% to about 50% by weight, and about 30% to about 60% by weight And about 0.1% to about 10% by weight (for example, about 0.5% to about 5% by weight). The compositions of the present invention preferably include pharmaceutically acceptable hydrophobic solvents, including those used in intraocular depots. Useful hydrophobic solvents exhibit a solubility in water of less than 1% by weight, preferably less than 0.5% by weight, and more preferably less than 0.1% by weight. Particularly preferred are hydrophobic solvents having a solubility in water of less than 0.05% by weight. Solubility is measured at 25 ° C. Some examples of hydrophobic solvents include benzyl benzoate (BB), isopropyl myristate (IPM), isopropyl palmitate, trialkyl ethionate citrate (e.g. tributyl ethylate citrate) (ATBC)) and trialkyl citrates (such as tributyl citrate (TBC)). BB and IPM are products available on the market. Benzoyl benzoate is a preferred hydrophobic solvent. Other suitable hydrophobic solvents include triglycerides (such as caprylic / capric triglyceride (Miglyol 810)) and dimethyl palmitate, as well as fatty esters and ethers such as ethyl oleate and ethyl caprate. When used, the trialkyl citrate (TAC) may include a compound represented by the following formula (A) or consist essentially of a compound represented by the following formula (A). In formula (A), R a , R b And R c Represents the same or different alkyl groups, each having 3 to 5 carbon atoms. The alkyl group is preferably a linear or branched alkyl group, and more preferably a linear or branched alkyl group having 4 carbon numbers. Some of the preferred trialkyl citrates include those having n-propyl, n-butyl, n-pentyl, isopropyl, isobutyl, secondary butyl, tertiary butyl, isopentyl, etc. Alkyl esters. It is more preferred to use tri-n-butyl citrate (referred to herein as tributyl citrate or TBC). In formula (A), R a , R b And R c Each may be the same or may be different. R a , R b And R c Preferably, they are the same. When used, acetamyl citrate (ATAC) may include or consist essentially of a compound represented by the following formula (B), which is also referred to as acetamyl citrate Trialkyl esters and 2-ethoxypropane-1,2,3-trialkyltricarboxylic acids. In formula (B), R a , R b And R c Each represents an alkyl group having a number of 3 to 5 carbons. The alkyl group is preferably a linear or branched alkyl group, and preferably has a number of 4 carbons. Some of the preferred ethanoyl tricitrates include those having n-propyl, n-butyl, n-pentyl, isopropyl, isobutyl, secondary butyl, tertiary butyl, isopentyl, etc Acetyl tricitrate. Ethyl triethyl citrate with three n-butyl groups (referred to herein as trialkyl ethoxy citrate or ATBC) is more preferred. In formula (B), R a , R b And R c Each may be the same or may be different. R a , R b And R c Preferably, they are the same. TAC or ATAC can be used individually or in combination with each other as a hydrophobic solvent. TAC and / or ATAC can also be used in combination with one or more other hydrophobic solvents. When used in combination, any ratio of TAC: ATAC can be used. Some ratios (volume: volume) of TAC: ATAC include 0: 100, 0.1: 99.9, 5:95, 10:90, 15:85, 30:70, 50:50, 70:30, 85:15, 90: 10, 95: 5, 99.9: 0.1 and 100: 0. The range constituted by any of these ratios is also preferable. The composition of the present invention may include any amount of a hydrophobic solvent to impart suitable properties to the composition. When the composition of the present invention includes a hydrophobic solvent, it preferably contains at least 0.1% by weight, 1% by weight, 2% by weight, 10% by weight, 20% by weight, 30% by weight, and 40% by weight. When the composition of the present invention contains a hydrophobic solvent, it preferably contains at most 99% by weight, 95% by weight, 90% by weight, 80% by weight, 70% by weight, 60% by weight, and 50% by weight. In some examples, the composition of the present invention contains from about 80% to about 95% by weight of a hydrophobic solvent based on the weight of the composition. In some examples, the hydrophobic solvent comprises benzyl benzoate in an amount ranging from about 30% to about 60% by weight, or from about 35% to about 45% by weight, based on the weight of the composition. In other examples, the hydrophobic solvent includes ATBC in an amount ranging from about 30% to about 60% by weight, or from about 35% to about 50% by weight based on the weight of the composition. The composition of the present invention preferably comprises pharmaceutically acceptable hydrophilic solvents, including those used in intraocular depots. When a hydrophilic solvent is used, it is preferably non-polymeric, such as other than polyalkylene glycols or polyethylene glycols. When measured at 25 ° C, the hydrophilic solvent preferably has a solubility in water of at least 1%, 2%, 10%, 25%, 50% by weight, up to and including miscibility with water. When a hydrophobic solvent is used, the hydrophilic solvent exhibits greater solubility in water than the hydrophobic solvent. Some preferred hydrophilic solvents include ethanol, ethyl lactate (EL), dimethylsulfinium (DMSO), N-methyl-2-pyrrolidone (NMP), polyalkylene glycol, ethyl acetate, propylene glycol , Propylene carbonate, glycerol and glycerol triacetate (TA). Commercially available hydrophilic solvents may include small amounts of water. When it is desired to reduce or eliminate water in the pharmaceutical composition of the present invention, it is preferable to use an anhydrous (or dry) hydrophilic solvent. Hydrophilic solvents are commercially available in anhydrous (or low water) form and / or hydrophilic solvents containing water can be dried. These same considerations apply to other components of the composition of the present invention, as well as to the pharmaceutical composition of the present invention. Components that form an azeotrope with water, such as ethanol, are preferably used in anhydrous form. Anhydrous ethanol includes, for example, products that are indicated as 99.5% EtOH, pure ethanol (200proof), and / or contain less than 0.005% water. Ethanol, ethyl lactate, dimethylsulfinium, N-methyl-2-pyrrolidone, polyalkanediol, and glyceryl triacetate are all commercially available products that are widely available on the market. When ethanol is used, it is preferably invariant ethanol. In some examples, ethanol is present in an amount ranging from about 1% to about 10% by weight based on the weight of the composition (e.g., about 1% to about 7%, such as about 1% to about 5% by weight) ). When the hydrophilic solvent includes a polyalkanediol, any molecular weight (or degree of polymerization) can be used, but it is necessary to warn that in order to act as a hydrophilic solvent, the polyalkanediol should be liquid at ambient temperature (eg, 23 ° C). The preferred polyalkanediol is polyethylene glycol (PEG). PEG 300 ( n About 7), PEG 400 ( n About 9) and PEG 600 ( n About 13) is liquid at 23 ° C, while PEG 800 ( n About 18) is a paste at 23 ° C. Preferred PEGs as hydrophilic solvents include PEG 600, PEG 400, and PEG 300, such as PEG 400. When a hydrophilic solvent is used, it is usually at most 70% by weight, at most 60% by weight, at most 50% by weight, at most 40% by weight, at most 30% by weight, at most 15% by weight, Or present in an amount of up to 10% by weight. Although there is generally no lower limit, when a hydrophilic solvent is used, it is usually present in an amount of at least 0.1% by weight, at least 1% by weight, at least 2% by weight, at least 3% by weight, at least 4% by weight, or at least 5% by weight. . In some examples, the hydrophilic solvent comprises ethanol in an amount ranging from about 1% to about 20% by weight, or from about 2% to about 10% by weight, based on the weight of the composition. In some examples, the hydrophilic solvent comprises PEG in an amount ranging from about 30% to about 60% by weight, or from about 40% to about 50% by weight, based on the weight of the composition. In some examples, the composition of the present invention may contain both ethanol and PEG, for example, where the amounts of ethanol and PEG each fall within the exemplified amount ranges outlined herein, respectively. It is possible to have a sufficiently low molecular weight (e.g. n ≤5) PEG acts as both HVLCM and hydrophilic solvent. In this example, the total amount can be divided between the two components, or can be separately attributed to one of the two components. In some examples, the vehicle blend includes SAIB, BB, and ethanol. In some other examples, the vehicle blend contains SAIB, BB, and ethanol with additional components to provide a blend with a more desirable release profile. In some examples, the blend provides sirolimus that is a composition that can be re-released in a single dose for intraocular administration to a mammalian subject (e.g., a human subject) (or a patient). The composition of the invention optionally includes one or more polymers. Including polymers can impart beneficial properties to the composition. For example, the use of polymers can help slow API release and help achieve more sustained release rates. This can help extend the life of the depot. Reducing the release rate can also help control drug exposure, and / or can help control exposure to safe and effective levels, and / or eliminate or reduce overexposure. Some preferred polymers include poloxamer, polyalkanediol, poly (lactic acid) (glycolic acid), poly (lactic acid) (or polylactide), polycaprolactone, polyglycolide, polycaprolactone Esters, polyanhydrides, polyamines, polyurethanes, polyesteramines, polyorthoesters, polydioxanone, polyacetals, polyketals, polycarbonates, polyphosphates, Polyoxyester, polyorthocarbonate, polyphosphazene, succinate, poly (malic acid), poly (amino acid), polyvinylpyrrolidone, polyethylene glycol , Polyhydroxycellulose, chitin, polyglucosamine, hyaluronic acid and its copolymers, trimers and mixtures. Polymers that are liquid at room temperature or soluble in the disclosed composition are preferred. Poloxamer is a non-ionic triblock copolymer, which includes two hydrophilic chains of a polyoxypropylene (poly (propylene oxide)) intermediate hydrophobic chain and polyoxyethylene (poly (ethylene oxide)). Poloxamer is available on the market and is sold under various commercial names such as SYNPERONICS, PLURONICS and KOLLIPHOR. Any suitable grade can be used, preferably poloxamer P188. When the polymer includes polyalkylene glycol, any molecular weight (or degree of polymerization) can be used, but it is necessary to warn that in order to serve as a polymer other than HVLCM in the present invention, the polyalkylene glycol should have a greater than 5 (ie n > 5) degree of polymerization. The preferred polyalkanediol is polyethylene glycol (PEG). With PEG 300 ( n About 7), PEG 400 ( n About 9) and PEG 800 ( n About 18) is preferred as these polymers. It is possible to use PEGs of suitable molecular weight as polymers (e.g. n > 5) and hydrophilic solvents (e.g. n <18) Both, in this example, the total amount may be distributed between the two components, or may be separately attributed to one of the two components. Polylactide is a lactic acid-based polymer, which can be based on lactic acid alone or can be a copolymer, such as based on lactic acid, glycolic acid, and / or caprolactone, which can include non-substantial effects on the advantageous results achieved in accordance with the present invention A small amount of other comonomers. The term "lactic acid" as used herein includes the isomers L-lactic acid, D-lactic acid, DL-lactic acid, and lactide, and the term "glycolic acid" includes glycolide. Most preferred are one or more of the following polymers: polylactide polymers, often referred to as PLA; poly (lactide-co-glycolide) copolymers, often referred to as PLGA; and poly (caprolactone) -Co-lactic acid) (PCL-co-LA). The polymer may have a lactic acid / glycolic acid monomer ratio of about 100: 0 to about 10:90, such as 100: 0 to 15:85, preferably about 75:25 to about 30:70, and more preferably about 60 : 40 to about 40:60, and particularly useful copolymers have a lactic acid / glycolic acid monomer ratio of about 50:50. The poly (caprolactone-co-lactic acid) (PCL-co-LA) polymer preferably has about 10:90 to about 90:10, about 50:50; preferably about 35:65 to about 65:35 And more preferably a co-monomer ratio of caprolactone / lactic acid of about 25:75 to about 75:25. In a particular embodiment, the lactic acid-based polymer may include a blend of about 0% to about 90% caprolactone, about 0% to about 100% lactic acid, and about 0% to about 60% glycolic acid. Thing. Other suitable polymers include PEG-PLGA, poly (vinyl alcohol) and poly (orthoester). The polymer may have an average molecular weight of about 1,000 to about 120,000, such as about 5,000 to about 50,000 or about 8,000 to about 30,000, as determined by gel permeation chromatography (GPC). For example, the lactic acid-based polymer preferably has an average molecular weight of about 1,000 to about 120,000, preferably about 5,000 to about 50,000, and more preferably about 8,000 to about 30,000, as measured by gel permeation chromatography (GPC). Determination. As indicated in U.S. Patent No. 5,242,910, polymers can be prepared according to the guidelines of U.S. Patent No. 4,443,340. Alternatively, lactic acid-based polymers can be prepared directly from lactic acid or a mixture of lactic acid and glycolic acid (with or without additional comonomers) according to the techniques listed in US Patent No. 5,310,865. The contents of all such patents are incorporated by reference. Suitable lactic acid-based polymers are commercially available. For example, 50:50 lactic acid: glycolic acid copolymers with molecular weights of 8,000, 10,000, 30,000, and 100,000 are taken from Boehringer Ingelheim Chemicals, Inc. (Petersburg, Va.), Medisorb Technologies International LP (Cincinnati, Ohio), and Lactel Absorbable Polymers (formerly Birmingham Polymers, Inc.), as described below. Examples of suitable lactide polymers include, but are not limited to, poly (D, L-lactide) RESOMER L104, PLA-L104, poly (D, L-lactide-co-glycolide) 50:50 RESOMER RG502, poly (D, L-lactide-co-glycolide) 50:50 RESOMER RG502H, poly (D, L-lactide-co-glycolide) 50:50 RESOMER RG503, poly (D, L-lactide- Co-glycolide) 50:50 RESOMER RG506, Poly L-lactide MW 2,000 (RESOMER L 206, RESOMER L 207, RESOMER L 209, RESOMER L 214), Poly D, L-lactide (RESOMER R 104, RESOMER R 202, RESOMER R 203, RESOMER R 206, RESOMER R 207, RESOMER R 208), poly-L-lactide-co-D, L-lactide 90:10 (RESOMER LR 209), polyglycolide (RESOMER G 205), poly D, L-lactide-co-glycolide 50:50 (RESOMER RG 504H, RESOMER RG 504, RESOMER RG 505), poly DL-lactide-co-glycolide 75:25 (RESOMER RG 752, RESOMER RG755, RESOMER RG 756), poly D, L-lactide-co-glycolide 85:15 (RESOMER RG 858), and poly L-lactide-co-trimethylene carbonate 70:30 (RESOMER LT 706) (Boehringer Ingelheim Chemicals, Inc., Petersburg, Va.). Additional examples include, but are not limited to, DL-lactide / glycolide 100: 0 (MEDISORB Polymer 100 DL High, MEDISORB Polymer 100 DL Low); DL-lactide / glycolide 85/15 (MEDISORB Polymer 8515 DL High, MEDISORB Polymer 8515 DL Low); DL-lactide / glycolide 75/25 (MEDISORB Polymer 7525 DL High, MEDISORB Polymer 7525 DL Low); DL-lactide / glycolide 65/35 (MEDISORB Polymer 6535 DL High, MEDISORB Polymer 6535 DL Low); DL-lactide / glycolide 54/46 (MEDISORB Polymer 5050 DL High, MEDISORB Polymer 5050 DL Low); and DL-lactide / glycolide 54/46 (MEDISORB Polymer 5050 DL 2A) (3), MEDISORB Polymer 5050 DL 3A (3), MEDISORB Polymer 5050 DL 4A (3)) (Medisorb Technologies International LP, Cincinnati, Ohio); and Poly D, L-lactide-co-glycolide 50:50 ; Poly D, L-lactide-co-glycolide 65:35; Poly D, L-lactide-co-glycolide 75:25; Poly D, L-lactide-co-glycolide 85: 15; Poly DL-lactide; Poly L-lactide; Polyglycolide; Poly epsilon-caprolactone; Poly DL-lactide-co-caprolactone 25:75; and Poly DL-lactide-co- Caprolactone 75:25 (Birmingh am Polymers, Inc., Birmingham, Ala.). The polymer may be present in an amount of up to 40%, 30%, 20% or 10% by weight of the pharmaceutical composition. When a polymer is used, it may be present in an amount of at least 0.1% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, or 5% by weight of the pharmaceutical composition. Poloxamers, such as those disclosed above, have surfactant properties. The composition of the invention may optionally contain one or more surfactants. Surfactants are particularly useful in compositions having both hydrophilic and hydrophobic components, such as ethanol and SAIB or a hydrophobic solvent. Any surfactant suitable for use in a depot type blend (e.g., an intraocular depot type blend) can be used. A nonionic surfactant is preferably used for the intraocular composition. Some suitable surfactants include, for example, poloxamer, polyethoxylated castor oil, polyoxyethylated hydroxystearic acid, propylene glycol fatty esters, and sorbitan fatty esters. Poloxamer is preferred. In some examples, poloxamer is present in an amount ranging from 0.1% to about 5% by weight based on the weight of the composition. Some polyethoxylated castor oils include polyoxyethylene 5 castor oil, polyoxyethylene 9 castor oil, polyoxyethylene 15 castor oil, polyoxyethylene 35 castor oil, polyoxyethylene 40 castor oil, polyoxyethylene 40 hydrogenated castor oil. Sesame oil and polyoxyethylene 60 hydrogenated castor oil. Some preferred polyethoxylated castor oils include polyoxyethylene 35 castor oil (such as KOLLIPHOR EL), polyoxyethylene 40 hydrogenated castor oil (such as CREMOPHOR RH40), and polyoxyethylene 60 hydrogenated castor oil (such as CREMOPHOR RH60), These are taken from BASF Corporation of Midland, Mich. Polyoxyethylated stearic acid includes polyoxyethylene stearate, also known as macrogol stearate, which contains a series of polyethoxylated derivatives of stearic acid. These typically include polyethylene glycol stearate and polyethylene glycol distearate. Some polyethoxylated stearic acids suitable for use in the present invention include polyoxyethylene 2 stearate, polyoxyethylene 4 stearate, polyoxyethylene 6 stearate, polyoxyethylene 8 stearic acid Ester, polyoxyethylene 12 stearate, polyoxyethylene 20 stearate, polyoxyethylene 2 stearate, polyoxyethylene 30 stearate, polyoxyethylene 40 stearate, polyoxyethylene 50 stearate, polyoxyethylene 100 stearate, polyoxyethylene 2 stearate, polyoxyethylene 150 stearate, polyoxyethylene 4 distearate, polyoxyethylene 8 distearate Acid esters, polyoxyethylene 12 distearate, polyoxyethylene 32 distearate, and polyoxyethylene 150 distearate. Polyethylene glycol stearate is commercially available from many suppliers under the trade names of MYRJ (Croda), HODAG (Calgene), KESSCO (Stepan Co.), and PROTAMATE (Protameen Chemicals). Other suitable surfactants include polysorbate 80 (Tween 80), Solutol HS-15, d-tocopherol polyethylene glycol 1000 succinate (TPGS), polyoxyethylene 8 stearate (PEG 400 mono Stearate) and polyoxyethylene 40 stearate (PEG 1750 monostearate). Fatty acid esters are suitable surfactants. Among these, propylene glycol fatty acid esters and sorbitan fatty acid esters are suitable nonionic surfactants, and include monoesters, sesquiesters, and diesters. The sorbitan fatty acid ester may additionally include a triester. The fatty acid portion of these esters is usually C 12 -C 18 . Preferred fatty acid moieties include stearates, isostearates, laurates, palmitates, and oleates. Some preferred esters include sorbitan monooleate, propylene glycol monolaurate, and sorbitan monolaurate. Fatty acid esters of carboxylic acids (preferably C 12 -C 18 ) Is also better. These include esters of lactic acid, malic acid, adipic acid, and palmitic acid. Some suitable surfactants include Ceraphyl 31 (lauryl lactate, Ashland Inc.), Labrafac PG (propylene glycol dicaprylate / didecanoate NF, Gattefosse), and Lauroglycol 90 (propylene glycol monolaurate (type II) EP / NF; Gattefosse). Other suitable surfactants include PEG 300 caprylic / capric glyceride (Softigen 767), PEG 300 glyceryl linoleate (Labrafil M-2125CS), glyceryl monooleate (PECEOL), propylene glycol monolaurate (Lauroglycol) FCC). When a surfactant is used, any suitable amount can be used. The pharmaceutical composition of the present invention may include up to 50% by weight of a surfactant, up to 40% by weight of a surfactant, up to 30% by weight of a surfactant, and up to 20% by weight of a surfactant based on the weight of the composition. Agent, up to 10% by weight of surfactant, up to 5% by weight of surfactant, up to 4% by weight of surfactant, up to 3% by weight of surfactant, up to 2% by weight of surfactant, up to 1.5% by weight % Of surfactant or up to 1% by weight of surfactant. The pharmaceutical composition of the present invention containing a surfactant usually contains at least 0.01% by weight of a surfactant, at least 0.1% by weight of a surfactant, at least 0.2% by weight of a surfactant, and at least 0.4 based on the weight of the composition. % By weight of surfactant, at least 0.6% by weight of surfactant or at least 0.8% by weight of surfactant. For example, the amount of the surfactant may be 0.01 to 5% by weight, 3 to 0.2% by weight, or 0.6 to 2% by weight. Some of these excipients have multiple functions, such as acting as a hydrophobic solvent and / or a surfactant. When components have multiple functions, such as macromolecules with surfactant properties (such as poloxamer, polyethoxylated castor oil, etc.), these functions can be distributed among components, such as surfactants and The polymer component, or may be individually attributed to one of the components. The composition of the present invention optionally contains at least one antioxidant, preferably an antioxidant suitable for use in an intraocular reservoir. Antioxidants are particularly preferred when the depot may be susceptible to oxidation at the site of administration. For example, the vitreous reservoir may be exposed to light and therefore may be susceptible to light-induced free radical formation, so it may be preferable to include an antioxidant capable of neutralizing free radicals. In these embodiments, at least one antioxidant preferably comprises tocopherol, tocotrienol, or a combination thereof. The antioxidant is preferably soluble in the composition of the present invention. Other suitable antioxidants may include one or more of the following: glutathione, fatty acid, uric acid, carotene (such as vitamin A and its derivatives and analogs), melatonin, ubiquinol (Coenzyme Q), ascorbic acid, sodium thiosulfate, cysteine, sodium edetate, ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) , Propyl gallic acid, monothioglycerol, tertiary butyl hydroquinone (TBHQ) and potassium metabisulphite. Tocopherol and its derivatives and the like are preferred, and vitamin E is preferred. Vitamin E includes all forms of tocopherols with antioxidant properties, and includes vitamin E acetate, α-tocopherol, and γ-tocopherol; and includes D-, L-, and DL-forms such as DL-α-tocopherol phenol. When antioxidants are used, such as tocopherols, they can be present in any amount that imparts useful antioxidant properties to the composition over a suitable period of time. The preferred period is the shelf life of the product, such as at most its expiration date. Preferred periods include 3 months, 6 months, 12 months or 1 year, 18 months or 1.5 years, 24 months or 2 years, 30 months or 2.5 years, 3 years and 4 years. When an antioxidant is used, it is preferably present in an amount of up to 50% by weight, 10% by weight, 5% by weight, 1% by weight, 0.1% by weight, or 0.01% by weight based on the weight of the composition. Preferred ranges include those values and / or ranges in the examples. In some examples, vitamin E is present in an amount ranging from 0.1% to 5% by weight based on the weight of the composition. It was surprisingly found that vitamin E was still effective at even lower concentrations. It is often beneficial to reduce the amount of vitamin E because vitamin E is relatively slowly degraded in the vitreous fluid. It was surprisingly found that reducing the amount of vitamin E also increased the relative amount of degradation of vitamin E in some examples. Therefore, in some examples, vitamin E is present in an amount ranging from about 0.01% to about 5% by weight based on the weight of the composition, such as about 0.01% to about 1.5% by weight, and about 0.02% to about 1%. % By weight, and from about 0.02% by weight to about 0.09% by weight. In some examples, the composition includes less than 1% by weight of vitamin E based on the weight of the composition, such as 0.5% by weight or less of vitamin E, or less than 0.1% by weight of vitamin E. When HVLCM (preferably SAIB) is used in an intraocular depot type blend, it appears to have many unexpected beneficial properties. Although HVLCM (such as SAIB) regulates the viscosity and / or cohesion of the reservoir, its presence also contributes to a prolonged intravitreal release profile, at which time the density of the reservoir can be maintained without floating. It may be particularly advantageous to include at least about 0.5% by weight of HVLCM. In a preferred embodiment, when HVLCM is mixed with a solvent to form a low-viscosity liquid carrier that can be combined with API to form a pharmaceutical composition, HVLCM can significantly reduce viscosity. Low-viscosity pharmaceutical compositions are generally easier to put into the body than high-viscosity compositions because, for example, they flow more easily into and out of syringes or other implanted devices. The pharmaceutical composition may have any desired viscosity. It has been found that pharmaceutical compositions having a viscosity range of less than about 400 cP, and more specifically less than 200 cP, less than 100 cP, less than 50 cP, or less than 25 cP at 25 ° C and 1 atmosphere are generally useful for in vivo applications. Although there is no lower target viscosity, the viscosity at 25 ° C and 1 atmosphere is usually at least 1 cP, at least 2 cP, at least 4 cP, at least 6 cP, at least 8 cP, at least 10 cP, or at least 15 cP. In compositions containing SAIB and Vitamin E (VE), SAIB: VE can be used in any weight ratio that provides a safe and effective composition. In some aspects of the invention, the weight ratio of SAIB: VE can be selected to control the density of the composition (density before use, at the time of injection, and for a long period of time (eg, at 1, 2, 4, 6 or 12 months)). For example, in an intraocular depot composition comprising SAIB and VE, the weight ratio of SAIB: VE may be 10, 7.5, 5, 3, 2, 1, 0.8, 0.6, 0.5, 0.4, 0.3, or 0.2. Each of these values can be an open or closed upper or lower limit of the SAIB: VE ratio (for example, "at least 1" or "less than 1"). The suitable range of the SAIB: VE weight ratio (with open or closed end values) includes the range formed by any pair of self-equivalents. For example, the weight ratio of SAIB: VE may be 0.5 to 10, 0.5 to 5, 0.5 to 2, or 1 to 3. One way to select the SAIB / VE ratio is to assume that the composition does not contain any other excipients that may remain in the vitreous body (eg, so that the composition does not float in the vitreous body). In some examples, the weight ratio of HVLCM (e.g., SAIB) to vitamin E is such that the density of a mixture consisting of the HVLCM and the vitamin E at the weight ratio is at least 1 g / ml at 25 ° C and 1 atmosphere, such as at least 1.05 g / ml. In some examples, the composition has a density in the range of 1.02 g / ml to 1.15 g / ml at 25 ° C and 1 atmosphere. In some cases, it may be desirable to have a pharmaceutical composition with a low peroxide content because peroxides are known as possible oxidants and can cause chemical instability. In these cases, it is preferable to prepare a pharmaceutical composition from a component having a low peroxide content. It is known that SAIB manufacturing methods can cause peroxide generation. When a low-peroxide pharmaceutical composition containing SAIB is needed or desired, a low-peroxide SAIB is preferably used. The SAIB of low peroxide is disclosed in U.S. Patent Publication 2012/0330005, the disclosure of which is incorporated herein by reference in its entirety. When materials encounter light, these can physically interact with each other in many different ways. These interactions depend on the nature of the light (its wavelength, frequency, energy, etc.) and the nature of the material. Light waves usually interact with objects through some combination, such as absorption, reflection, and transmission / refraction. Transparency is a physical property that allows light to pass through the material without diffusion. Translucency refers to the property of allowing light to diffuse through a material. Opaque refers to a property that does not allow light to pass through the material. Optically transparent materials allow most of the light falling on them to transmit, a small amount of light to diffuse, reflect, or absorb. Materials that do not allow light to be transmitted are called opaque. In certain aspects of the invention, such as intravitreal reservoirs, the optical transparency of pharmaceutical compositions is a beneficial and preferred characteristic. In other aspects, the pharmaceutical composition is preferably translucent or opaque. When optical transparency is desired, the composition of the present invention can transmit at least about 75% of light, about 80% of light, about 85% of light, about 90% of light, and about 95% of light without diffusing. The composition of the present invention can transmit up to 100% of light, 99% of light, 98% of light, 97% of light, or 96% of light without diffusing. The percentage of light that is transmitted non-diffusively can be measured at specific frequencies (eg, 420 to 440 nm, 535 to 555 nm, and / or 565 to 580 nm) or averaged over the visible spectrum. The composition of the present invention can be sterilized and filtered. The composition of the present invention can be stored under various conditions. For example, the composition of the invention can be stored at a temperature ranging from about 0 ° C to about 30 ° C, such as about 2 ° C to about 25 ° C, about 4 ° C to about 20 ° C, about 5 ° C to about 15 ° C, or about 7 ° C. To about 10 ° C. It was surprisingly found that the composition of the invention is generally relatively stable and can be stored at 2 ° C to about 30 ° C, such as at about 5 ° C or about 25 ° C, for two years or more. The composition of the present invention can be stored in various containers, such as glass containers. The composition of the present invention can be used to treat any symptoms treatable with a topical composition or a liquid depot. Ophthalmic symptoms that can be treated with sirolimus include those disclosed in US Patent No. 8,367,097, which is incorporated herein by reference in its entirety. The depot-type blend of the present invention can be used as, for example, a medicine for eye diseases, for example, in senile macular degeneration, diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, retinal artery occlusion, multifoot choroidal vascular disease, retinal blood vessels Neoplastic hyperplasia, myopic choroidal neovascularization, diabetic macular edema, eye tumors, radiation retinopathy, iris angiogenesis, neovascular glaucoma, proliferative vitreoretinopathy (PVR), primary open-angle glaucoma, Open-angle glaucoma, normal pressure glaucoma, hypersecretory glaucoma, primary angle-closure glaucoma, secondary angle-closure glaucoma, high-pleat iris glaucoma, combined mechanism glaucoma, Developmental glaucoma, steroid-induced glaucoma, exfoliative glaucoma, amyloid glaucoma, neovascular glaucoma, malignant glaucoma, capsular glaucoma of the lens, high pleated iris syndrome, intraocular pressure, hyperophthalmitis, Intraocular infections. The depot-type blend of the present invention can be more preferably used as a preventive or therapeutic agent for the following diseases: senile macular degeneration, diabetic retinopathy, primary open-angle glaucoma, normal intraocular pressure glaucoma, primary closed Angular glaucoma, high intraocular pressure, uveitis, and intraocular infections. Preferred symptoms include uveitis, wet-dry senile macular degeneration (AMD), diabetic macular edema (DME), diabetic retinopathy (DR), and corneal mycosis. When a composition is said to be "consisting essentially of" a "component" of a particular component as shown, this may indicate that the composition is composed of or contains a specific component and one or Both of the plurality of non-specific components, a prerequisite is that one or more non-specific components do not render the composition unsuitable for its intended use. For example, with regard to such compositions containing a given active pharmaceutical ingredient suitable for treating the given symptoms, there may be the presence of one or more non-specific components, provided that the non-specific component does not render the composition unsuitable for treatment The symptoms. Generally, in a composition "consisting essentially of" a specific component shown, the total amount of any component other than the specific component based on the weight of the composition does not exceed 20% by weight, It is preferably not more than 10% by weight, more preferably not more than 5% by weight, and most preferably not more than 2% by weight. After the composition of the present invention is placed in a liquid medium, such as in a test tube or in vivo, the volume of the composition of the present invention decreases in size over time. After the composition of the present invention is placed in a liquid medium, the active pharmaceutical ingredient (such as sirolimus) in the composition of the present invention often does not precipitate. If the composition is used in the eye, it may be beneficial not to settle, as Shendian may interfere with vision. In some cases, it may be beneficial not to precipitate because the stimulus is minimized. It is surprising that it does not settle over time. The composition of the present invention can be contained in a vial. The volume of the composition contained in the vial can range, for example, from about 35 microliters to about 1000 microliters, such as about 40 microliters to about 900 microliters, about 45 microliters to about 800 microliters, and about 50 microliters to About 700 microliters, about 55 microliters to about 600 microliters, about 60 microliters to about 500 microliters, about 65 microliters to about 400 microliters, about 70 microliters to about 300 microliters, and about 75 microliters to About 200 microliters, about 80 microliters to about 100 microliters, and about 300 microliters to about 500 microliters. When used intraocularly, the composition of the present invention can be administered as a vitreous body and / or a subconjunctival reservoir. The composition is usually injected from a standard hypodermic syringe, catheter or trocar that has been pre-filled with the pharmaceutical composition. It is often preferable to use the smallest sized needle (i.e., the smallest diameter) or catheter for injection in the human or animal eye, subcutaneously, intramuscularly, intravascularly (high / low flow), intramyocardial, and extramural. Membrane, intratumoral or intracranial location, traumatic location, tight joint space or body cavity discomfort to the individual during injection. In some examples, administration comprises intravitreal injection and / or subconjunctival injection. Any needle or catheter size suitable for the injection site can be used. Size is usually better with higher gauges (for example to reduce pain or injury). However, excessively high gauges can cause complications such as prolonged injection time or increased injection force due to capillary action and / or viscosity. Hope to pass the range of 16 gauge and higher, 20 gauge and higher, 22 gauge and higher, 24 gauge and higher, 25 gauge and higher, 26 gauge and higher Higher, 27 gauge and higher, 28 gauge and higher, or 29 gauge and higher needle or catheter for injection of pharmaceutical composition. Needles or catheters are usually 34 gauges and smaller, 33 gauges and smaller, 32 gauges and smaller, 31 gauges and smaller, or 30 gauges and smaller. For example, the gauge can be in the range of 23 to 32, such as 27 to 30. When using a syringe, any needle length suitable for the injection site can be used. The needle is preferably long enough to allow the tip to effectively reach the target reservoir location. The needle is preferably short enough to allow an operator (such as a physician or nurse) to maintain control of the syringe and / or injection procedure. Needles for intraocular storage can be at least 0.5 cm, 1 cm, 1.5 cm, or 2 cm in length. Needles for intraocular storage can be up to 4 cm, 3 cm or 2.5 cm in length. Those skilled in the art can use this specification as a guide to determine the appropriate needle size (such as a gauge and / or length). The syringe should be made of a material that is compatible with the composition it contains. For example, the syringe may contain glass or a polymer (such as a cyclic olefin polymer, a cyclic olefin copolymer, and polypropylene). The syringe may contain a metal plunger, such as a stainless steel plunger. In some examples, the syringe is a Luer lock syringe. In some examples, the syringe is contained within a container, such as a box. The volume of the composition contained within the syringe can range, for example, from about 5 microliters to about 100 microliters, such as about 5 microliters to about 75 microliters, about 10 microliters to about 50 microliters, and about 15 microliters to About 40 microliters, and about 20 microliters to about 30 microliters. Accordingly, syringe volumes often range from about 5 microliters to about 100 microliters, about 10 microliters to about 75 microliters, about 15 microliters to about 50 microliters, and about 20 microliters to about 40 microliters. And may be less than about 50 microliters. Surprisingly, these small volumes can provide effective doses. The release profile and duration of the effect of the composition of the invention is surprising. In some examples, the amount of active pharmaceutical ingredient released within 3 months after administration is about 30% to about 70%, such as about 40% to about 60%, of the total amount of active pharmaceutical ingredient in the initially administered composition % Or about 50%. In some examples, when the composition is administered intraocularly to a human patient as a single dose, the median amount of the pharmaceutically active ingredient released from the composition is: (1) the composition at the time of administration 1 month after administration In the range of 1% to 20% or 2% to 15% of the total amount of the active pharmaceutical ingredients in the Chinese medicine; (2) 10% to 60% of the total amount of the active pharmaceutical ingredients in the composition at the time of administration 3 months after the administration % Or 20% to 50%; and (3) 30% to 100% or 40% to 90% of the total amount of the pharmaceutically active ingredient in the composition at the time of administration 6 months after the administration. In some examples, the release rate of the active pharmaceutical ingredient from the composition is in the range of about 1 microgram / day to about 30 micrograms / day, such as about 2 micrograms / day to about 20 micrograms / day or about 5 micrograms / day To about 15 μg / day. In the case of continuous administration of the depot-type blend of the present invention, there is no particular dose interval limitation as long as the interval is sufficient for the desired effect; however, it may be better to administer it at intervals of 3 days to 5 years , Such as once a month to once every 9 months, or once every 6 months to once every 8 months. For example, the composition can be once every 3 days, once every 5 days, once a week, once every 2 weeks, once a month, once every 2 months, once every 3 months, once every 4 months, once every 5 months, and once every 6 months , Once every 7 months, once every 8 months, once every 9 months, once a year, once every 2 years, once every 3 years, once every 4 years or once every 5 years, this interval may be better, and often Once every 2 months, once every 3 months, once every 4 months, once every 5 months, once every 6 months or once a year. In addition, the dose interval may be changed as appropriate. Examples The materials listed in the examples below are commercially available from a number of sources. Some market vendors are revealed in this article. Products are available from other market vendors. The possible market suppliers of the mentioned products are not intended to limit the invention in any way. Polymers (PLGA: initiated by dodecanol, L / G 85/15, MW 13.9KDa), (PLA: initiated by dodecanol, MW 13.9KDa), and (polycaprolactone PCL: initiated by dodecane Alcohol induced, MW 95.3KDa) was obtained on the market from Durect Corporation under the LACTEL brand. SAIB was obtained from Durect Corporation. Solvents include benzyl alcohol (BA), benzyl benzoate, propylene glycol, and dehydrated, 200 proof ethanol, USP grade, such as available from Spectrum Chemicals on the market. N-methyl-2-pyrrolidone (NMP) is commercially available from ISPs. Super-refined PEG 400-LQ- (MH) was obtained from Croda on the market, and DMSO (DMSO) was obtained from Gaylord on the market. Castor oil is commercially available from Spectrum Chemicals. KolliSolve® GTA (glyceryl triacetate) is commercially available from BASF, and 99% of triethyl citrate (TEC) is commercially available from Sigma Aldrich. High purity tributyl citrate (ATBC) NF, USP grade is commercially available from Mutchler Inc. Synperonic PE / F68-FL-CQ (poloxamer 188) is commercially available from Croda. Dulbecco's phosphate-buffered saline (PBS), hyaluronic acid (HA), and sodium lauryl sulfate (SDS), commercially available from Sigma-Aldrich, are used in the preparation of release media. Vitamin E (DL-α-tocopherol) is commercially available from BASF. Sirolimus is commercially available from Althea through Santen Pharmaceutical Company. Example 1 Referring to Tables 1 and 2 below, the solubility of sirolimus was tested in a solvent and a mixture of benzyl benzoate and ethanol at room temperature. Referring to Table 4 below, sirolimus (SRL) was dissolved in various solvents and tested for concentration after 8 days at room temperature. Protect the sample from light, but expose it to ambient humidity. Chemical stability test: Put about 2 ml of sirolimus blend in each 2 ml corrugated glass vial at ambient humidity and store at 5 ° C and 25 ° C to avoid exposure to light. The samples were analyzed by HPLC to determine the sirolimus concentration. The HPLC instruments and parameters are as follows: Mobile phase: A: 20 mM ammonium formate, pH 4.0 B: acetonitrile Detection: λ = 276 nm column temperature: 50 ° C Preparation of sirolimus solution blend: The polymer was dissolved in the solvent / solvent mixture at the weight ratio shown in Table 5 and mixed until homogeneous. SAIB was added to the polymer / solvent solution at the weight ratio shown in Table 5 and mixed at 50 ° C until a homogeneous solution was formed. Sirolimus was dissolved in each vehicle at a concentration of 3% to 5% by weight. In-tube drug release test: The sirolimus blend was injected at 50 to 100 microliters into 5 ml of release medium (including 0.1% SDS or 0.05% HA in PBS) equilibrated at 37 ° C. The sample was placed on a rotary shaker rotating at 30 rpm or 50 rpm at 37 ° C. At different points in time (eg, 1, 4, 8, 24 hours and up to 50 days for some blends), the entire release medium is sampled and replaced with freshly prepared release medium equilibrated at 37 ° C. Take care not to touch the depot drug during sampling. The samples were analyzed by HPLC to determine the sirolimus concentration. Results of Example 1: Solubility of sirolimus in aqueous media and solvents: The addition of 0.1% SDS enhances the aqueous solubility of sirolimus in PBS (Table 1). The solubility of sirolimus in benzyl benzoate / ethanol is greater than the solubility in benzyl benzoate or ethanol. As seen in Table 2, the highest solubility was observed at a benzyl benzoate / ethanol ratio of 7. Chemical stability of sirolimus in release test media and compatibility with solvents: Table 3 shows the stability in 0.1% SDS containing PBS used as a release medium for drug release tests. The solvent was tested for compatibility with sirolimus. Table 4 shows the recovery of sirolimus after storage in a solvent at room temperature. Evaluation of prototype blends: The sirolimus solution blends have low viscosity (can be injected through 27G and 30G needles). In an in-tube drug release test in PBS, 0.1% SDS showed that drug release was ≥50 days at 37 ° C (Figures 1a, 1b, and 1c) and 18 days in HA, Figure 2 (Test composition C115 only). In FIG. 1, the composition C105b uses vehicle V105, but has a sirolimus concentration of 4.5% by weight. The data in Table 6 indicate the stability of sirolimus in blends exposed to ambient humidity for at least 2 months at 25 ° C and 5 ° C, except for NMP-containing blends (C107, C108 and C110). Storage at 25 ° C and 5 ° C is a better condition for products on the market. With regard to the preferred composition of the present invention, it is not necessary to store the sirolimus blend under inert conditions and / or at sub-zero temperatures. The vehicles and pharmaceutical compositions shown in Tables 5 and 6 below were manufactured. Example 2 Preparation of sirolimus solution blend: Poloxamer 188 was dissolved in a mixture of benzyl benzoate and ethanol (weight ratio is shown in Table 8) and mixed until uniform. SAIB (weight ratio is shown in Table 8) was added and mixed at 50 ° C until a homogeneous solution was formed. After the solution was cooled, glycerol triacetate or triethyl acetoacetate (weight ratio is shown in Table 8) was added and mixed thoroughly. Sirolimus was dissolved in each vehicle at a weight of 3% to 4.5% by weight. Chemical stability test: Put about 2 ml of sirolimus blend in each 2 ml corrugated glass vial at ambient humidity and store at 5 ° C and 40 ° C to avoid exposure to light. Result of Example 2: In-tube test: The tested blend composition is shown in Table 9. Table 8 Vehicle composition containing poloxamer 188 Table 9 Blend composition containing poloxamer 188 Table 10 shows a comparison of chemical stability data for blends with and without poloxamer. Table 10 Chemical stability of sirolimus in solution blends after 2 weeks Example 3 Viscosity test: The viscosity of the vehicle was measured using a Brookfield DVIII + programmable rheometer. The measurement was performed using a cone plate with a CPE-52 spindle. Viscosity is measured using a Brinell TC-602D cooling bath / programmable controller maintained at 25 ± 0.5 ° C. Chemical stability test: Put about 2 ml of sirolimus blend in each 2 ml corrugated glass vial at ambient humidity and store at 5 ° C, 25 ° C and 40 ° C to avoid exposure to light. Preparation of the blend 1% poloxamer 188 was dissolved in a mixture of benzyl benzoate and ethanol (shown in Table 13) and mixed until homogeneous. Add SAIB (ratio shown in Table 13) and mix at 50 ° C until a homogeneous solution is formed. After the solution was cooled to room temperature, PEG 400 or tributyl acetoacetate (in the ratio shown in Table 13) was added and mixed thoroughly. Add Vitamin E and mix thoroughly. Add 3% sirolimus and stir until all is dissolved. The compositions shown in Table 11 were evaluated by viscosity, chemical stability, and sirolimus release (up to 24 hours) in an aqueous release medium. These compositions have a low viscosity as shown in Table 12. The chemical stability of the sirolimus blends after storage at 5 ° C, 25 ° C, and 40 ° C for 1 and 2 weeks is shown in Table 13. A summary of the chemical stability of the sirolimus blends after storage at 40 ° C for 2 weeks and the cumulative release of sirolimus% after 24 hours at 37 ° C in PBS with 0.1% SDS is shown in the table. 14 and Figure 3. When the amount of HVLCM increases, the viscosity of the composition generally increases. For example, when the amount of SAIB is increased from 1% to 49%, the viscosity of the composition is increased from 11 to 46 cP. The amount of HVLCM (such as SAIB) does not appear to have an effect on the chemical stability of sirolimus. The amount of HVLCM (e.g. SAIB) appears to have only a slight effect on the initial rate of drug (e.g. sirolimus) release. In the presence of ATBC, SAIB (1 to 10% by weight) appears to have little to no effect on chemical stability. A polymer (such as poloxamer) appears to reduce the initial release of a drug (such as sirolimus) in a test tube. Polymers (such as poloxamer) at 1% by weight do not appear to affect the viscosity of the composition. In ATBC-containing blends, 1% vitamin E in the presence of 1% poloxamer appears to have little or no effect on enhancing chemical stability. Among the chemical stability enhancers evaluated, tocopherols (such as vitamin E) appear to be the most effective chemical stability enhancers for sirolimus. Tocopherol in the presence of ATBC (with or without poloxamer) appears to enhance the stability of sirolimus. Increasing vitamin E from 1% to 10% by weight does not appear to significantly enhance chemical stability further. Example 4: In vivo PK study A pharmaceutical composition having the components and amounts shown in Table 15 was prepared. Male Japanese white rabbits were subjected to general anesthesia and then both eyes were anesthetized on the surface by administration of oxybuprocaine hydrochloride (0.5%) eye drops. Rabbits received a single binocular intravitreal injection of 20 or 30 microliters of the blend. Rabbits were euthanized 1 month, 2 months, 3 months, and 6 months after administration. The removed eyes were dissected and frozen at the same time, and the vitreous fluid and retinal-choroid were separated. The amount of sirolimus was determined using a combination of liquid chromatography and tandem mass spectrometry. The residual rate of sirolimus in vitreous fluid is shown in Table 16 (based on 4 to 6 eyes). Sirolimus concentrations in the retina-choroid are shown in Table 17 (based on 3 to 6 eyes). The remaining amount is provided as mean ± SD. Figures 4 and 5 show data on the amount of sirolimus remaining in the reservoir and the concentration of sirolimus in vitreous fluid over a 6-month period. The blends called C401 and C407 are made with the same components and their ratios on different occasions. As shown in Tables 16 and 17 and FIGS. 4 and 5, the release profiles of sirolimus in the blends C401 and C407 with a vehicle composed of SAIB, BB, and EtOH are variability. Example 5: In vivo PK study A pharmaceutical composition having the components and amounts shown in Table 18 was prepared. Male Japanese white rabbits were subjected to general anesthesia and then both eyes were anesthetized on the surface by administration of obucaine hydrochloride (0.5%) eye drops. Rabbits received a single binocular intravitreal injection of 20 or 30 microliters of the blend. Rabbits were euthanized 1 month, 2 months, 3 months, and 6 months after administration. The removed eyes were dissected and frozen at the same time, and the vitreous fluid and retinal-choroid were separated. The amount of sirolimus was determined using a combination of liquid chromatography and tandem mass spectrometry. Table 19 shows the residual rates of sirolimus in the intravitreal reservoir. Table 20 shows the sirolimus concentration in the retina / choroid. Amounts are expressed as mean ± SD (based on 2 to 4 eyes). Figures 6 and 7 show data on the amount of sirolimus remaining in the reservoir and the concentration of sirolimus in vitreous fluid over a 6-month period. Blood concentrations of sirolimus were measured at 30-day intervals. The results are shown in FIG. 8. Example 6: The solvents used in the in vivo PK research are as follows: SAIB and tributyl acetamyl citrate (such as available on the market from Sigma-Aldrich), benzyl benzoate and ethanol (99.5) (From Nacalai Tesque, Inc.), Vitamin E (such as Riken Vitamin from the market). Sirolimus is commercially available from a number of sources, including Santen Pharmaceutical Company. Preparation of sirolimus solution blend: Measure 240 mg of sirolimus into a standard bottle and add 4.4 ml of pre-mixed SD / BB / EtOH (10/40/5, v / v / v ), 3.6 ml of pre-mixed BB / EtOH (40/5, v / v) or 3.68 ml of pre-mixed VitE / BB / EtOH (1/40/5, v / v / v) and dissolve. Then, 3.6 ml, 4.4 ml, or 4.32 ml of tributyl acetamyl citrate were added and mixed to prepare SD / BB / EtOH / ATBC (10/40/5/45, v / v / v / v), Blend of BB / EtOH / ATBC (40/5/55, v / v / v) or VitE / BB / EtOH / ATBC (1/40/5/54, v / v / v / v). A control composition containing EtOH / PEG400 / SRL (4/92/4, w / w / w) was also prepared. The composition and dosage are shown in Table 21. Rabbit PK study after intravitreal injection of the sirolimus solution blend: Male Japanese white rabbits were under general anesthesia and then two eyes were administered to the surface by administering obucaine hydrochloride (0.5%) eye drops Get anesthesia. Rabbits received a single binocular intravitreal injection of 30 microliters of test blend or 20 microliters of 4% sirolimus in PEG400 / EtOH (94/2). Rabbits were euthanized 4 and 12 weeks after administration. The removed eyes were dissected and frozen while the vitreous fluid was separated. The amount of sirolimus in the vitreous is determined using a combination of liquid chromatography and tandem mass spectrometry. Table 22 shows the remaining doses in the intravitreal reservoir. Figure 9 shows data on the amount of sirolimus remaining in the reservoir over a 12-week period. Because the reservoir cannot be removed from the vitreous fluid alone, it is assumed in the present invention that the amount of sirolimus remaining in the reservoir is equal to the combined amount of sirolimus in the vitreous fluid and the reservoir. Example 7: Pharmaceutical composition The composition was prepared according to Tables 23a and 23b. The amount of the excipient is expressed in parts by weight. The pharmaceutical composition contains sirolimus at a concentration of 3 mg / ml. Example 8 Sustained-release evaluation test: The drug-sustaining release properties of the depot type blend of the present invention were evaluated. Preparation of test article: 240 mg of sirolimus was weighed into a standard bottle, and then dissolved and mixed by adding 0.8 ml of dimethyl sulfene and 7.2 ml of ethyl ethyl triethyl citrate, and then 0.20 μm A pore size filter was subjected to sterilization filtration to prepare a comparative composition blend C801. Weigh 240 mg of sirolimus into a standard bottle and then add 3.6 ml of benzyl benzoate / ethanol (40: 5 by volume) or 3.68 ml of vitamin E / benzyl benzoate / It was dissolved in ethanol (volume ratio of 1: 40: 5), 4.4 ml or 4.32 ml of tri-n-butyl citrate citrate was added and mixed, followed by sterilizing filtration through a filter with a pore size of 0.20 micrometer to prepare a blend C802 and C803. Rabbit pharmacokinetic evaluation: A Hamilton syringe equipped with a 30G needle was administered intravitreally to 0.03 ml of each of the albino rabbit's eyes, reservoir-type blends C801 (for comparison), C802, and C803. After 4 weeks and 12 weeks after the administration, sodium pentobarbital anesthetic administered intravenously was euthanized and the eyeballs were removed. The removed eyeballs were immediately frozen and the vitreous body was collected in a state containing a reservoir type blend. The sirolimus concentration in the vitreous body at each collection time point was measured using LC-MS / MS, and the amount of drug residue after administration was evaluated. Test results and considerations: The test results are shown in Table 24. Table 24 As shown in Table 24, only 10.0% of the administered sirolimus remained in 4 weeks after the administration of comparative blend C801; on the contrary, the remaining 71.1% of the administered blend C802 and 83.7% The amount of blend C803 administered. From the above results, it was confirmed that the depot-type blend of the present invention improves the sustained-release property. Example 9: Pharmaceutical composition and in vivo PK study composition were prepared according to Table 25. The amount of the excipient is expressed in parts by weight. The pharmaceutical composition contains a sirolimus concentration of 30 mg / g. Rabbit PK study after intravitreal injection of the sirolimus solution blend: Male Japanese white rabbits were under general anesthesia and then two eyes were administered to the surface by administering obucaine hydrochloride (0.5%) eye drops Get anesthesia. Rabbits received a single binocular intravitreal injection of 30 microliters of the test formulation. Rabbits were euthanized 4 and 12 weeks after administration. The removed eyes were dissected and frozen while the vitreous fluid was separated. The amount of sirolimus in the vitreous is determined using a combination of liquid chromatography and tandem mass spectrometry. Table 26 shows the remaining doses in the intravitreal reservoir. Figure 10 shows data concerning the amount of sirolimus remaining in the reservoirs over the 6 month period for the blends C901 to C905. As noted above, it is assumed in the present invention that the amount of sirolimus remaining in the reservoir is equal to the amount of sirolimus in the combined vitreous body fluid and the reservoir. Table 27 and Figure 11 show data on sirolimus concentrations in the retina-choroids involving the blends C901 to C905 over a 6-month period. The sirolimus blood concentrations of the blends C901 to C905 were measured at 30-day intervals. The results are shown in FIG. 12. Example 10: Pharmaceutical composition and in vivo PK study composition were prepared according to Table 28. The amount of the excipient is expressed in parts by weight. The pharmaceutical composition contains a sirolimus concentration of 30 mg / g. Rabbit PK study after intravitreal injection of the sirolimus solution blend: Male Japanese white rabbits were under general anesthesia and then two eyes were administered to the surface by administering obucaine hydrochloride (0.5%) eye drops Get anesthesia. Rabbits received a single binocular intravitreal injection of 30 microliters of the test formulation. Rabbits were euthanized 4 and 12 weeks after administration. The removed eyes were dissected and frozen while the vitreous fluid was separated. The amount of sirolimus in the vitreous is determined using a combination of liquid chromatography and tandem mass spectrometry. Table 29 shows the remaining doses in the intravitreal reservoir. Figure 13 shows data relating to the amount of sirolimus remaining in the reservoirs for the blends C906 to C909 over a 6 month period. As noted above, it is assumed in the present invention that the amount of sirolimus remaining in the reservoir is equal to the amount of sirolimus in the combined vitreous body fluid and the reservoir. Table 30 and Figure 14 show data on sirolimus concentrations in the retina-choroid over the 6-month period involving the blends C906 to C909. The sirolimus blood concentrations of the blends C906 to C909 were measured at 30-day intervals. The results are shown in FIG. 15. Example 11: Pharmaceutical compositions and in vivo PK study compositions were prepared according to Table 31. The amount of the excipient is expressed in parts by weight. The pharmaceutical composition contains a sirolimus concentration of 30 mg / g. Rabbit PK study after intravitreal injection of the sirolimus solution blend: Male Japanese white rabbits were under general anesthesia and then two eyes were administered to the surface by administering obucaine hydrochloride (0.5%) eye drops Get anesthesia. Rabbits received a single binocular intravitreal injection of 30 microliters of the test formulation. Rabbits were euthanized 4 and 12 weeks after administration. The removed eyes were dissected and frozen while the vitreous fluid was separated. The amount of sirolimus in the vitreous is determined using a combination of liquid chromatography and tandem mass spectrometry. Table 32 and Figure 16 show data related to the amount of sirolimus remaining in the vitreous fluid of the blends C907 to C909, C914 and C915 over a 6 month period. Table 33 and Figure 17 show data on sirolimus concentrations in the retina-choroids involving the blends C907 to C909, C914 and C915 over a 6 month period. Blood concentrations of sirolimus of the blends C907 to C909, C914 and C915 were measured at 30-day intervals. The results are shown in FIG. 18. Example 12: Pharmaceutical compositions and in vivo PK study compositions were prepared according to Table 34. The amount of the excipient is expressed in parts by weight. The pharmaceutical composition contains a sirolimus concentration of 30 mg / g. Rabbit PK study after intravitreal injection of the sirolimus solution blend: Male Japanese white rabbits were under general anesthesia and then two eyes were administered to the surface by administering obucaine hydrochloride (0.5%) eye drops Get anesthesia. Rabbits received a single binocular intravitreal injection of 30 microliters of the test formulation. Rabbits were euthanized 4 and 12 weeks after administration. The removed eyes were dissected and frozen while the vitreous fluid was separated. The amount of sirolimus in the vitreous is determined using a combination of liquid chromatography and tandem mass spectrometry. Table 35 and Figure 19 show data concerning the amount of sirolimus remaining in the vitreous fluid of blend C914 over a 6-month period. Table 36 and Figure 20 show data for sirolimus concentration in the retina-choroid over the 6-month period involving blend C914. Blood concentrations of sirolimus of blend C914 were measured at 30-day intervals. The results are shown in FIG. 21. Example 13 The composition is shown in Table 37. The amount of the excipient is expressed in parts by weight. The pharmaceutical composition contains a sirolimus concentration between 10 and 35 mg / g. Preparation of test items: Weigh benzyl benzoate, ethanol and tri-n-butyl acetoacetate into bottles and mix thoroughly. Add Vitamin E and mix. Add sirolimus at the concentration shown in Table 37, and stir the solution until everything is dissolved. The resulting solution was sterilized and filtered using a 0.2 micron pore size sterilizing filter. Rabbit PK study after intravitreal injection of sirolimus solution blends: Male Japanese white rabbits were under general anesthesia and then two eyes were administered to the surface by administering obucaine hydrochloride (0.4%) eye drops Get anesthesia. Rabbits received a single binocular intravitreal injection of 30 or 50 microliters of the test blend. Blood is collected via the ear arteries. Rabbits were euthanized 4 weeks after administration. The removed eyes were dissected and frozen at the same time, and the vitreous fluid and retinal-choroid were separated. The amount of sirolimus in vitreous fluid, retinal-choroid and whole blood was determined using a combination of liquid chromatography and tandem mass spectrometry. Table 38 shows data concerning the amount of sirolimus remaining in the vitreous fluid of the blends C1001 to C1006 over a 6-month period. Table 39 shows data related to sirolimus concentrations in the retina-choroid over the 6-month period involving the blends C1001 to C1006. The blood concentrations of sirolimus of the blends C1001 to C1006 were measured. The results are shown in Table 40. Example 14: Pharmaceutical composition The composition was prepared according to Table 41. The amount of the excipient is expressed in parts by weight. The pharmaceutical composition contains a sirolimus concentration of 30 mg / g. Example 15: Preparation of SAIB / Vitamin E Mix SAIB / Vitamin E Mix: SAIB was dissolved in Vitamin E (weight ratio shown in Table 42) and the mixture was mixed until homogeneous. Density test: About 2 ml of the mixture was poured into a densitometer and the density of the mixture was measured at 25 ° C. As shown in Table 42, the density is increased depending on the weight ratio of SAIB: vitamin E. In addition, the weight ratio of SAIB: vitamin E and the density at 25 ° C are linearly related, as shown in FIG. 22. According to the linear approximation formula, the density (at 25 ° C) = 0.0016 × (SAIB: weight ratio of vitamin E) +0.9445. When the density is 1, the weight ratio of SAIB: vitamin E is about 34.7%. Therefore, when the weight ratio of SAIB: vitamin E is less than about 34.7%, the mixture can float in water. The vitreous body fluid has a slightly higher density (about 1.0053 g / ml) than water and is usually at a body temperature (37 ° C) instead of 25 ° C. The depot-type blend of the present invention including SAIB and vitamin E is injected into a vitreous fluid and releases API and other excipients. At the end of the release time, the depot mainly consists of SAIB, Vitamin E and API, as almost all other excipients have been released. If the weight ratio of SAIB: vitamin E in the depot-type blend is less than about 38%, the depot can float in the vitreous humor, causing patient discomfort. Example 16: Fluocinolone Acetonide Blend The composition shown in Table 43 was prepared by adding 3% w / w of fluoxonol to the vehicle. The resulting blend was a solution with some excess solids. The excipient doses in Table 43 are expressed in parts by weight. In-tube release test of the floxacin blend: 50 microliters of the blend was injected into a 5 ml release medium (0.2% SDS-containing PBS equilibrated at 37 ° C) using a 1 ml EXEL syringe with a 23G needle. The sample was placed on a rotary shaker that was rotated at 50 rpm at 37 ° C. 4.5 ml of medium was drawn at each time point and replaced with fresh 4.5 ml of medium. Take care not to touch the depot drug during sampling. The samples were analyzed by HPLC to determine the concentration of fluoxlon. Samples were prepared in triplicate. The release profile of the floxacin blend is shown in FIG. 23. Example 17: Triamcinolone Blend The composition shown in Table 44 was prepared by adding 3% w / w triamcinolone to the vehicle. The resulting blend was a solution with some excess solids. The excipient doses in Table 44 are expressed in parts by weight. Intra-tube release test of triamcinolone blend: 50 microliters of the blend was injected into a 5 ml release medium (0.2% SDS-containing PBS equilibrated at 37 ° C) using a 1 ml EXEL syringe with a 23G needle. The sample was placed on a rotary shaker that was rotated at 50 rpm at 37 ° C. 4.5 ml of medium was drawn at each time point and replaced with fresh 4.5 ml of medium. Take care not to touch the depot drug during sampling. The samples were analyzed by HPLC to determine triamcinolone concentration. Samples were prepared in triplicate. The release profile of the triamcinolone blend is shown in Figure 24. Example 18: Ibuprofen Blend The composition shown in Table 45 was prepared by adding 3% w / w ibuprofen to the vehicle. The resulting blend was a clear solution. The excipient doses in Table 45 are expressed in parts by weight. In-tube release test of the ibuprofen blend: 50 microliters of the blend was injected into 5 ml of release medium (0.2% SDS-containing PBS equilibrated at 37 ° C) using a 1 ml EXEL syringe with a 23G needle. The sample was placed on a rotary shaker that was rotated at 50 rpm at 37 ° C. 4.5 ml of medium was drawn at each time point and replaced with fresh 4.5 ml of medium. Take care not to touch the depot drug during sampling. The samples were analyzed by HPLC to determine the ibuprofen concentration. Samples were prepared in triplicate. The release profile of the ibuprofen blend is shown in Figure 25. Example 19: Pharmaceutical composition The composition was prepared according to Tables 46 and 47. The component amount of the vehicle is expressed in parts by weight per 100 parts of the composition. All the compositions in Tables 46 and 47 have a sirolimus concentration of 30 mg / g. Example 20: Pharmaceutical composition and in vivo PK study composition were prepared according to Table 48. The component amount of the vehicle is expressed in parts by weight per 100 parts of the composition. All the compositions in Table 48 have a sirolimus concentration of 30 mg / g. Male Japanese white rabbits were given general anesthesia by intravenous injection of pentobarbital sodium, and then bucaine hydrochloride (0.4%) eye drops were topically administered to both eyes and anesthetized on the surface. Rabbits received a single binocular intravitreal injection of 10 or 30 microliters of the test formulation. Blood is collected via the ear arteries. Rabbits were euthanized 1 month after administration. The removed eyes were dissected and frozen at the same time, and the vitreous fluid and retinal-choroid were separated. Sirolimus in vitreous fluid, retinal-choroid and whole blood was quantified using a combination of liquid chromatography and tandem mass spectrometry. Table 49 and Figure 26 show data concerning the amount of sirolimus remaining in the vitreous fluid of the blends C1701 and C1711 over a period of 1 month. Table 50 shows data related to sirolimus concentrations of the blends C1701 and C1711 in the retina-choroid over a 1-month period. The sirolimus blood concentrations of the blends C1701 and C1702 were measured over 30 days. The results are shown in Figure 27. Example 21: The pharmaceutical composition and the in vivo PK study composition were prepared according to Table 51. The component amount of the vehicle is expressed in parts by weight per 100 parts of the composition. Male Japanese white rabbits were given general anesthesia by intravenous injection of pentobarbital sodium, and then bucaine hydrochloride (0.4%) eye drops were topically administered to both eyes and anesthetized on the surface. Rabbits received a single binocular intravitreal injection of 10 or 30 microliters of blends C2101 to 2108 or 20 microliters of blends C2109 and C2110. Blood is collected via the ear arteries. Rabbits were euthanized 1 month after administration. The removed eyes were dissected and frozen at the same time, and the vitreous fluid and retinal-choroid were separated. Sirolimus in vitreous fluid, retinal-choroid and whole blood was quantified using a combination of liquid chromatography and tandem mass spectrometry. Table 52 and Figure 28 show data concerning the amount of sirolimus remaining in the vitreous fluid of the blend shown in Table 51 over a period of 1 month. ND: below detection limit. Table 53 shows data concerning sirolimus concentrations in the retina-choroid over the 1-month period involving the blends shown in Table 51. ND: The sirolimus blood concentration of the blend shown in Table 51 below the detection limit was measured at 30-day intervals. The results are shown in FIG. 29. Example 22: Stability of sirolimus in water A composition was prepared according to Table 54. The amount of the excipient is expressed in parts by weight. The pharmaceutical composition contains a sirolimus concentration of 30 mg / g. 30 microliters of these compositions were poured into 4 ml of water filled in a glass vial. The samples were stored at 37 ° C and 60 ° C and removed over time. Specifically, 1 ml of water was taken as a water sample from the sample after storage. In addition, 7 ml of acetonitrile was added to the remaining 3 ml of water and the reservoir to dissolve the reservoir in the sample and adjust the volume to 10 ml. A sample of about 1 ml of the dissolved depot was taken as a mixture sample. The amount of sirolimus in these samples was determined using liquid chromatography, and the amount of sirolimus in the reservoir was determined based on the amount in the water sample and the mixture sample. Table 55 and Figure 30 show the amount of sirolimus remaining after storage at 60 ° C. Table 56 and Figure 31 show the amount of sirolimus remaining after storage at 37 ° C. All the compositions (drugs and vehicles) disclosed in the foregoing examples and directed throughout the present invention can be used in preclinical and / or clinical research, including in-vitro research, animal research, and / or clinical research Any of these studies may address, for example, properties (eg, drug release rate), pharmacokinetics, pharmacodynamics, toxicology, safety, and / or efficacy. The composition can be used therapeutically in humans (clinical use) or animals (veterinary use), humans or animals requiring such treatments.

圖1a、1b和1c顯示來自數種本發明組成物之試管內藥物釋放。 　　圖2顯示來自在0.05%玻尿酸(HA)介質中的本發明組成物之試管內藥物釋放。 　　圖3顯示在含有0.1% SDS之PBS介質中的西羅莫司調合物之累積釋放輪廓。 　　圖4顯示經6個月自本發明組成物之玻璃體內貯庫物獲得的剩餘在玻璃體液中的西羅莫司。 　　圖5顯示在兔子視網膜狀脈絡膜(RC)中的西羅莫司(6個月數據)。 　　圖6顯示剩餘在玻璃體液中的西羅莫司，如下文實施例5中更詳細的說明。 　　圖7顯示隨時間在RC中西羅莫司濃度，如下文實施例5中更詳細的說明。 　　圖8顯示在放入玻璃體內貯庫物後的西羅莫司血液濃度，如下文實施例5中更詳細的說明。 　　圖9顯示在玻璃體內貯庫物中的剩餘劑量。各點代表平均±SD(3-4個眼睛)。時間0為標稱值(100%)。 　　圖10顯示剩餘在玻璃體液中的西羅莫司，如下文實施例9中更詳細的說明。 　　圖11顯示隨時間在RC中西羅莫司濃度，如下文實施例9中更詳細的說明。 　　圖12顯示在放入玻璃體內貯庫物後的西羅莫司血液濃度，如下文實施例9中更詳細的說明。 　　圖13顯示剩餘在玻璃體液中的西羅莫司，如下文實施例10中更詳細的說明。 　　圖14顯示隨時間在RC中西羅莫司濃度，如下文實施例10中更詳細的說明。 　　圖15顯示在放入玻璃體內貯庫物後的西羅莫司血液濃度，如下文實施例10中更詳細的說明。 　　圖16顯示剩餘在玻璃體液中的西羅莫司，如下文實施例11中更詳細的說明。 　　圖17顯示隨時間在RC中西羅莫司濃度，如下文實施例11中更詳細的說明。 　　圖18顯示在放入玻璃體內貯庫物後的西羅莫司血液濃度，如下文實施例11中更詳細的說明。 　　圖19顯示剩餘在玻璃體液中的西羅莫司，如下文實施例12中更詳細的說明。 　　圖20顯示隨時間在RC中西羅莫司濃度，如下文實施例12中更詳細的說明。 　　圖21顯示在放入玻璃體內貯庫物後的西羅莫司血液濃度，如下文實施例12中更詳細的說明。 　　圖22繪製由SAIB及維生素E所組成之混合物在25℃下以SAIB：VE之重量比為函數之密度。 　　圖23顯示包含氟辛龍(fluocinolone)作為活性醫藥成分的本發明組成物之釋放輪廓。 　　圖24顯示包含曲安西龍(triamcinolone)作為活性醫藥成分的本發明組成物之釋放輪廓。 　　圖25顯示包含布洛芬(ibuprofen)作為活性醫藥成分的本發明組成物之釋放輪廓。 　　圖26顯示剩餘在玻璃體液中的西羅莫司，如下文實施例20中更詳細的說明。 　　圖27顯示在放入玻璃體內貯庫物後的西羅莫司血液濃度，如下文實施例20中更詳細的說明。 　　圖28顯示剩餘在玻璃體液中的西羅莫司，如下文實施例21中更詳細的說明。 　　圖29顯示在放入玻璃體內貯庫物後的西羅莫司血液濃度，如下文實施例21中更詳細的說明。 　　圖30顯示維生素E濃度對在60℃下儲存後剩餘的西羅莫司量之效應，如實施例22中更詳細的說明。 　　圖31顯示維生素E濃度對在37℃下儲存後剩餘的西羅莫司量效應，如實施例22中更詳細的說明。Figures 1a, 1b and 1c show the release of drug from a test tube from several compositions of the invention. Figure 2 shows the drug release from a test tube of a composition of the invention in 0.05% hyaluronic acid (HA) medium. Figure 3 shows the cumulative release profile of sirolimus blend in 0.1% SDS-containing PBS medium. Figure 4 shows sirolimus remaining in vitreous fluid obtained from the intravitreal reservoir of the composition of the present invention over 6 months. Figure 5 shows sirolimus in rabbit retinal choroid (RC) (6 months data). Figure 6 shows sirolimus remaining in the vitreous fluid, as explained in more detail in Example 5 below. Figure 7 shows the sirolimus concentration in RC over time, as explained in more detail in Example 5 below. Figure 8 shows the sirolimus blood concentration after being placed in the intravitreal reservoir, as explained in more detail in Example 5 below. Figure 9 shows the remaining dose in the intravitreal reservoir. Each point represents the mean ± SD (3-4 eyes). Time 0 is the nominal value (100%). Figure 10 shows sirolimus remaining in vitreous fluid, as explained in more detail in Example 9 below. Figure 11 shows the sirolimus concentration in RC over time, as explained in more detail in Example 9 below. Figure 12 shows the sirolimus blood concentration after being placed in the intravitreal reservoir, as explained in more detail in Example 9 below. Figure 13 shows sirolimus remaining in vitreous fluid, as explained in more detail in Example 10 below. Figure 14 shows the sirolimus concentration in RC over time, as explained in more detail in Example 10 below. Figure 15 shows the sirolimus blood concentration after being placed in the intravitreal reservoir, as explained in more detail in Example 10 below. Figure 16 shows sirolimus remaining in vitreous fluid, as explained in more detail in Example 11 below. Figure 17 shows the sirolimus concentration in RC over time, as explained in more detail in Example 11 below. Figure 18 shows the sirolimus blood concentration after being placed in the intravitreal reservoir, as explained in more detail in Example 11 below. Figure 19 shows sirolimus remaining in vitreous fluid, as explained in more detail in Example 12 below. Figure 20 shows the sirolimus concentration in RC over time, as explained in more detail in Example 12 below. Figure 21 shows the sirolimus blood concentration after being placed in the intravitreal reservoir, as explained in more detail in Example 12 below. Figure 22 plots the density of a mixture of SAIB and Vitamin E as a function of the weight ratio of SAIB: VE at 25 ° C. Figure 23 shows the release profile of the composition of the present invention containing fluocinolone as an active pharmaceutical ingredient. Figure 24 shows a release profile of a composition of the present invention containing triamcinolone as an active pharmaceutical ingredient. Figure 25 shows a release profile of a composition of the present invention containing ibuprofen as an active pharmaceutical ingredient. Figure 26 shows sirolimus remaining in vitreous fluid, as explained in more detail in Example 20 below. Figure 27 shows the sirolimus blood concentration after being placed in the intravitreal reservoir, as explained in more detail in Example 20 below. Figure 28 shows sirolimus remaining in vitreous fluid, as explained in more detail in Example 21 below. Figure 29 shows the sirolimus blood concentration after being placed in the intravitreal reservoir, as explained in more detail in Example 21 below. Figure 30 shows the effect of vitamin E concentration on the amount of sirolimus remaining after storage at 60 ° C, as explained in more detail in Example 22. Figure 31 shows the effect of vitamin E concentration on the amount of sirolimus remaining after storage at 37 ° C, as explained in more detail in Example 22.

Claims (54)

一種用於人類個體眼疾之治療方法的組成物，其中： 　　- 該組成物包含0.2至3.1重量%之西羅莫司(sirolimus)、0.9至1.1重量%之蔗糖乙酸酯異丁酸酯(SAIB)、43.4至45.0重量%之苯甲酸苯甲酯、4.7至5.1重量%之乙醇、46.2至48.0重量%之聚乙二醇及0.01至1.5重量%之維生素E；且 　　- 該方法包含將5至100微升體積的該組成物注射至個體的玻璃體中，隨後經至少1個月不投予另外的西羅莫司至該個體的該玻璃體中。A composition for the treatment of eye diseases in human individuals, wherein:-the composition comprises 0.2 to 3.1% by weight of sirolimus, 0.9 to 1.1% by weight of sucrose acetate isobutyrate (SAIB ), 43.4 to 45.0% by weight of benzyl benzoate, 4.7 to 5.1% by weight of ethanol, 46.2 to 48.0% by weight of polyethylene glycol, and 0.01 to 1.5% by weight of vitamin E; and-the method comprises A volume of 100 microliters of the composition was injected into the vitreous of the subject, and then no additional sirolimus was administered to the vitreous of the subject for at least 1 month. 根據申請專利範圍第1項之組成物，其中該組成物包含2.9至3.1重量%之西羅莫司。The composition according to item 1 of the patent application scope, wherein the composition comprises 2.9 to 3.1% by weight of sirolimus. 根據申請專利範圍第1或2項之組成物，其中該組成物包含43.4至44.2重量%之苯甲酸苯甲酯、4.7至4.9重量%之乙醇及46.2至47.0重量%之聚乙二醇。The composition according to item 1 or 2 of the scope of patent application, wherein the composition comprises 43.4 to 44.2% by weight of benzoic acid benzoate, 4.7 to 4.9% by weight of ethanol and 46.2 to 47.0% by weight of polyethylene glycol. 根據申請專利範圍第1或2項之組成物，其中該組成物包含0.02至1重量%之維生素E。The composition according to item 1 or 2 of the patent application scope, wherein the composition contains 0.02 to 1% by weight of vitamin E. 根據申請專利範圍第1或2項之組成物，其中該組成物包含少於1重量%之維生素E。The composition according to item 1 or 2 of the patent application scope, wherein the composition contains less than 1% by weight of vitamin E. 根據申請專利範圍第1或2項之組成物，其中該組成物包含0.5重量%或更少的維生素E。A composition according to item 1 or 2 of the scope of patent application, wherein the composition contains 0.5% by weight or less of vitamin E. 根據申請專利範圍第1或2項之組成物，其中該組成物包含少於0.1重量%之維生素E。The composition according to item 1 or 2 of the patent application scope, wherein the composition contains less than 0.1% by weight of vitamin E. 根據申請專利範圍第1或2項之組成物，其中該組成物包含0.02至0.09重量%之維生素E。The composition according to item 1 or 2 of the patent application scope, wherein the composition contains 0.02 to 0.09% by weight of vitamin E. 根據申請專利範圍第1或2項之組成物，其中該組成物包含約3重量%之西羅莫司、約1重量%之SAIB、約43.7重量%之苯甲酸苯甲酯、約4.8重量%之乙醇、約46.5重量%之聚乙二醇及約1重量%之維生素E。The composition according to item 1 or 2 of the scope of patent application, wherein the composition comprises about 3% by weight of sirolimus, about 1% by weight of SAIB, about 43.7% by weight of benzoic acid benzoate, and about 4.8% by weight Ethanol, about 46.5% by weight of polyethylene glycol and about 1% by weight of vitamin E. 根據申請專利範圍第1或2項之組成物，其中該聚乙二醇為PEG400。The composition according to item 1 or 2 of the patent application scope, wherein the polyethylene glycol is PEG400. 根據申請專利範圍第1或2項之組成物，其中該組成物基本上由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇、聚乙二醇及維生素E所組成。The composition according to item 1 or 2 of the scope of the patent application, wherein the composition is basically composed of sirolimus, SAIB, benzyl benzoate, ethanol, polyethylene glycol and vitamin E. 根據申請專利範圍第1或2項之組成物，其中該組成物係由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇、聚乙二醇及維生素E所組成。The composition according to item 1 or 2 of the scope of patent application, wherein the composition is composed of sirolimus, SAIB, benzyl benzoate, ethanol, polyethylene glycol and vitamin E. 根據申請專利範圍第1或2項之組成物，其中該方法包含將10微升至30微升體積的該組成物注射至個體的玻璃體中，隨後經至少1個月不投予另外的西羅莫司至該個體的該玻璃體中。A composition according to item 1 or 2 of the scope of patent application, wherein the method comprises injecting a volume of 10 to 30 microliters of the composition into the vitreous of an individual, and then not administering additional sirolide for at least 1 month Mousse into the vitreous of the individual. 根據申請專利範圍第1或2項之組成物，其中該方法包含將19微升或更少體積的該組成物注射至個體的玻璃體中，隨後經至少1個月不投予另外的西羅莫司至該個體的該玻璃體中。A composition according to item 1 or 2 of the scope of patent application, wherein the method comprises injecting 19 microliters or less of the composition into the vitreous of an individual, and then not administering another sirolimus for at least 1 month Into the vitreous body of the individual. 根據申請專利範圍第1或2項之組成物，其中該方法包含將51微升或更多體積的該組成物注射至個體的玻璃體中，隨後經至少1個月不投予另外的西羅莫司至該個體的該玻璃體中。A composition according to item 1 or 2 of the scope of the patent application, wherein the method comprises injecting 51 microliters or more of the composition into the vitreous body of an individual, followed by not administering additional sirolimus for at least 1 month Into the vitreous body of the individual. 根據申請專利範圍第1或2項之組成物，其中該眼疾為眼色素層炎、糖尿病黃斑部水腫或濕式老年性黃斑部退化。The composition according to item 1 or 2 of the scope of patent application, wherein the eye disease is uveitis, diabetic macular edema, or wet age-related macular degeneration. 根據申請專利範圍第16項之組成物，其中該眼疾為眼色素層炎。The composition according to item 16 of the application, wherein the eye disease is uveitis. 根據申請專利範圍第16項之組成物，其中該眼疾為糖尿病黃斑部水腫。The composition according to item 16 of the scope of patent application, wherein the eye disease is diabetic macular edema. 根據申請專利範圍第16項之組成物，其中該眼疾為濕式老年性黃斑部退化。The composition according to item 16 of the scope of patent application, wherein the eye disease is wet age-related macular degeneration. 根據申請專利範圍第1或2項之組成物，其中該方法包含將該體積的該組成物注射至個體的玻璃體中，隨後經至少2個月不投予另外的西羅莫司至該個體的該玻璃體中。A composition according to item 1 or 2 of the scope of patent application, wherein the method comprises injecting the volume of the composition into the vitreous body of an individual and subsequently not administering additional sirolimus to the individual's body for at least 2 months. The glass body. 根據申請專利範圍第1或2項之組成物，其中該方法包含將該體積的該組成物注射至個體的玻璃體中，隨後經至少3個月不投予另外的西羅莫司至該個體的該玻璃體中。A composition according to item 1 or 2 of the scope of patent application, wherein the method comprises injecting the volume of the composition into the vitreous body of an individual, and subsequently not administering additional sirolimus to the individual's body for at least 3 months. The glass body. 根據申請專利範圍第1或2項之組成物，其中所述將該體積的該組成物注射至個體的玻璃體中係在任何先前投予西羅莫司至該個體的該玻璃體中之後至少一個月發生。A composition according to item 1 or 2 of the scope of patent application, wherein said injecting the volume of the composition into the vitreous body of the subject is at least one month after any previously administered sirolimus into the vitreous body of the subject occur. 根據申請專利範圍第1或2項之組成物，其中所述將該體積的該組成物注射至個體的玻璃體中係在任何先前投予西羅莫司至該個體的該玻璃體中之後至少兩個月發生。A composition according to item 1 or claim 2, wherein said volume of said composition is injected into a vitreous body of an individual at least two after any previously administered sirolimus into the vitreous body of the individual Happened. 根據申請專利範圍第1或2項之組成物，其中所述將該體積的該組成物注射至個體的玻璃體中係在任何先前投予西羅莫司至該個體的該玻璃體中之後至少三個月發生。The composition according to item 1 or 2 of the scope of patent application, wherein said volume of the composition is injected into the vitreous body of the subject at least three times after any previously administered sirolimus into the vitreous body of the subject Happened. 根據申請專利範圍第1或2項之組成物，其中該方法包含注射呈一劑之該體積的該組成物。A composition according to item 1 or 2 of the scope of patent application, wherein the method comprises injecting the composition as a dose of the volume. 根據申請專利範圍第1或2項之組成物，其中該組成物係呈單位劑量型式(unit dose form)，該單位劑量型式含有單位劑量的該組成物，該單位劑量等於該方法中注射之該組成物的體積。The composition according to item 1 or 2 of the scope of patent application, wherein the composition is in a unit dose form, and the unit dose form contains a unit dose of the composition, and the unit dose is equal to the amount injected in the method. The volume of the composition. 根據申請專利範圍第26項之組成物，其中該單位劑量係容納在預填充之注射器內或適合於將該單位劑量轉移至注射器之容器中。A composition according to claim 26, wherein the unit dose is contained in a pre-filled syringe or a container suitable for transferring the unit dose to the syringe. 根據申請專利範圍第1或2項之組成物，其中該方法包含自具有下列特徵中之一或多者的注射器注射該體積的該組成物： 　　(a) 該注射器包含玻璃； 　　(b) 該注射器包含聚合物，其中該聚合物隨意地包含至少一種選自環狀烯烴聚合物、環狀烯烴共聚物和聚丙烯之成員； 　　(c) 該注射器包含金屬柱塞，其中該金屬柱塞隨意為不銹鋼柱塞；及 　　(d) 該注射器為魯爾鎖(leur-lock)注射器。A composition according to item 1 or 2 of the scope of patent application, wherein the method comprises injecting the volume of the composition from a syringe having one or more of the following characteristics: a (a) the syringe contains glass; (b) the syringe A polymer, wherein the polymer optionally comprises at least one member selected from the group consisting of a cyclic olefin polymer, a cyclic olefin copolymer, and polypropylene; (c) the syringe includes a metal plunger, wherein the metal plunger is optionally stainless steel Plunger; and (d) the syringe is a leur-lock syringe. 一種組成物，其 　　(i) 包含以A至I中任一者所示以重量計之量的西羅莫司、蔗糖乙酸酯異丁酸酯、苯甲酸苯甲酯、聚乙二醇、乙醇及維生素E：；或 　　(ii) 包含以J至T中任一者所示以重量計之量的西羅莫司、蔗糖乙酸酯異丁酸酯、苯甲酸苯甲酯、乙醇及維生素E：。A composition (i) comprising sirolimus, sucrose acetate isobutyrate, benzyl benzoate, polyethylene glycol, Ethanol and Vitamin E: ; Or (ii) contains sirolimus, sucrose acetate isobutyrate, benzyl benzoate, ethanol, and vitamin E in an amount by weight as shown in any of J to T: . 根據申請專利範圍第29項之組成物，其中該組成物包含2.9至3.1重量%之西羅莫司。The composition according to item 29 of the patent application scope, wherein the composition comprises 2.9 to 3.1% by weight of sirolimus. 根據申請專利範圍第29或30項之組成物，其中該組成物包含0.02至1重量%之維生素E。The composition according to claim 29 or 30, wherein the composition contains 0.02 to 1% by weight of vitamin E. 根據申請專利範圍第29或30項之組成物，其： 　　(i) 包含以A′至I′中任一者所示以重量計之大約量的西羅莫司、蔗糖乙酸酯異丁酸酯、苯甲酸苯甲酯、聚乙二醇、乙醇及維生素E： ；或 　　(ii) 包含以J′至T′中任一者所示以重量計之大約量的西羅莫司、蔗糖乙酸酯異丁酸酯、苯甲酸苯甲酯、乙醇及維生素E：。A composition according to item 29 or 30 of the scope of patent application, which: (i) contains an approximate amount by weight of sirolimus, sucrose acetate isobutyric acid shown by any of A ′ to I ′ Esters, benzyl benzoate, polyethylene glycol, ethanol and vitamin E: ; Or (ii) contains an approximate amount of sirolimus, sucrose acetate isobutyrate, benzyl benzoate, ethanol, and vitamin E by weight, shown in any of J 'to T': . 根據申請專利範圍第29或30項之組成物，其中該聚乙二醇為PEG400。The composition according to claim 29 or 30, wherein the polyethylene glycol is PEG400. 根據申請專利範圍第29或30項之組成物，其中該組成物(i)基本上由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇、聚乙二醇及維生素E所組成；而該組成物(ii)基本上由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇及維生素E所組成。The composition according to item 29 or 30 of the scope of application for patent, wherein the composition (i) is basically composed of sirolimus, SAIB, benzoic acid benzoate, ethanol, polyethylene glycol and vitamin E; and Composition (ii) is basically composed of sirolimus, SAIB, benzyl benzoate, ethanol, and vitamin E. 根據申請專利範圍第29或30項之組成物，其中該組成物(i)係由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇、聚乙二醇及維生素E所組成；而該組成物(ii)係由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇及維生素E所組成。A composition according to item 29 or 30 of the scope of application for patent, wherein the composition (i) is composed of sirolimus, SAIB, benzyl benzoate, ethanol, polyethylene glycol and vitamin E; and the composition Compound (ii) is composed of sirolimus, SAIB, benzyl benzoate, ethanol and vitamin E. 一種單位劑量型式(unit dose form)，其含有5微升至100微升體積之根據申請專利範圍第29至35項中任一項所定義之組成物的單位劑量。A unit dose form containing a unit dose of a composition as defined in any one of claims 29 to 35 in a volume of 5 to 100 microliters. 根據申請專利範圍第36項之單位劑量型式，其中該組成物的體積為10微升至30微升。The unit dosage form according to item 36 of the application, wherein the composition has a volume of 10 microliters to 30 microliters. 根據申請專利範圍第29或30項所定義之組成物，其係用於一種治療人類個體眼疾之方法。A composition as defined in item 29 or 30 of the scope of patent application, which is used for a method for treating eye diseases in human individuals. 根據申請專利範圍第38項之組成物，其中該方法包含將該組成物注射至個體的玻璃體中，隨後經至少1個月不投予另外的西羅莫司至該個體的該玻璃體中。A composition according to item 38 of the application, wherein the method comprises injecting the composition into the vitreous body of an individual and subsequently not administering additional sirolimus to the vitreous body of the individual for at least 1 month. 根據申請專利範圍第38項之組成物，其中該眼疾為眼色素層炎、糖尿病黃斑部水腫或濕式老年性黃斑部退化。The composition according to item 38 of the application, wherein the eye disease is uveitis, diabetic macular edema, or wet age-related macular degeneration. 一種組成物，其包含0.2至3.1重量%之西羅莫司、0.9至1.1重量%之蔗糖乙酸酯異丁酸酯(SAIB)、43.4至45.0重量%之苯甲酸苯甲酯、5.1至4.9重量%之乙醇、46.2至48.0重量%之聚乙二醇及至少0.01重量%但少於1重量%之維生素E。A composition comprising 0.2 to 3.1% by weight of sirolimus, 0.9 to 1.1% by weight of sucrose acetate isobutyrate (SAIB), 43.4 to 45.0% by weight of benzyl benzoate, 5.1 to 4.9 Weight percent ethanol, 46.2 to 48.0 weight percent polyethylene glycol and at least 0.01 weight percent but less than 1 weight percent vitamin E. 根據申請專利範圍第41項之組成物，其包含2.9至3.1重量%之西羅莫司。The composition according to item 41 of the scope of patent application, which comprises 2.9 to 3.1% by weight of sirolimus. 根據申請專利範圍第41或42項之組成物，其包含0.02至0.9重量%之維生素E。The composition according to item 41 or 42 of the patent application scope, which contains 0.02 to 0.9% by weight of vitamin E. 根據申請專利範圍第41或42項之組成物，其包含0.5重量%或更少的維生素E。A composition according to item 41 or 42 of the scope of patent application, which contains 0.5% by weight or less of vitamin E. 根據申請專利範圍第41或42項之組成物，其包含少於0.1重量%之維生素E。The composition according to item 41 or 42 of the scope of patent application, which contains less than 0.1% by weight of vitamin E. 根據申請專利範圍第41或42項之組成物，其包含0.02至0.09重量%之維生素E。The composition according to item 41 or 42 of the scope of patent application, which contains 0.02 to 0.09% by weight of vitamin E. 根據申請專利範圍第41或42項之組成物，其中該聚乙二醇為PEG400。The composition according to item 41 or 42 of the patent application scope, wherein the polyethylene glycol is PEG400. 根據申請專利範圍第41或42項之組成物，其中該組成物基本上由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇、聚乙二醇及維生素E所組成。The composition according to item 41 or 42 of the scope of application for patent, wherein the composition is basically composed of sirolimus, SAIB, benzyl benzoate, ethanol, polyethylene glycol and vitamin E. 根據申請專利範圍第41或42項之組成物，其中該組成物係由西羅莫司、SAIB、苯甲酸苯甲酯、乙醇、聚乙二醇及維生素E所組成。The composition according to item 41 or 42 of the scope of the applied patent, wherein the composition is composed of sirolimus, SAIB, benzyl benzoate, ethanol, polyethylene glycol and vitamin E. 一種單位劑量型式，其含有5微升至100微升體積之根據申請專利範圍第41至49項中任一項所定義之組成物的單位劑量。A unit dose type comprising a unit dose of a composition defined in any one of claims 41 to 49 in a volume ranging from 5 microliters to 100 microliters. 根據申請專利範圍第50項之單位劑量型式，其中該組成物的體積為10微升至30微升。The unit dosage form according to item 50 of the application, wherein the composition has a volume of 10 microliters to 30 microliters. 根據申請專利範圍第41或42項所定義之組成物，其係用於一種治療人類個體眼疾之方法。A composition as defined in item 41 or 42 of the scope of patent application, which is used for a method for treating eye diseases in human individuals. 根據申請專利範圍第52項之組成物，其中該方法包含將該組成物或單位劑量型式注射至個體的玻璃體中，隨後經至少1個月不投予另外的西羅莫司至該個體的該玻璃體中。A composition according to claim 52, wherein the method comprises injecting the composition or unit dosage form into the vitreous body of an individual, and subsequently not administering additional sirolimus to the individual's body for at least 1 month. In the vitreous. 根據申請專利範圍第52項之組成物，其中該眼疾為眼色素層炎、糖尿病黃斑部水腫或濕式老年性黃斑部退化。The composition according to claim 52, wherein the eye disease is uveitis, diabetic macular edema, or wet age-related macular degeneration.
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Family Cites Families (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4443340A (en) 1981-10-09 1984-04-17 Betz Laboratories, Inc. Control of iron induced fouling in water systems
JPH04230389A (en) 1990-07-16 1992-08-19 American Home Prod Corp Rapamycin derivative
US5023262A (en) 1990-08-14 1991-06-11 American Home Products Corporation Hydrogenated rapamycin derivatives
PT98990A (en) 1990-09-19 1992-08-31 American Home Prod PROCESS FOR THE PREPARATION OF CARBOXYLIC ACID ESTERS OF RAPAMICIN
US5120842A (en) 1991-04-01 1992-06-09 American Home Products Corporation Silyl ethers of rapamycin
US5120725A (en) 1991-05-29 1992-06-09 American Home Products Corporation Bicyclic rapamycins
US5120727A (en) 1991-05-29 1992-06-09 American Home Products Corporation Rapamycin dimers
KR970007322B1 (en) 1991-12-19 1997-05-07 미쓰이도오아쓰 가가쿠 가부시키가이샤 Polyhydroxy carboxylic acid and production thereof
US5177203A (en) 1992-03-05 1993-01-05 American Home Products Corporation Rapamycin 42-sulfonates and 42-(N-carboalkoxy) sulfamates useful as immunosuppressive agents
US5242910A (en) 1992-10-13 1993-09-07 The Procter & Gamble Company Sustained release compositions for treating periodontal disease
US5527907A (en) 1993-11-19 1996-06-18 Abbott Laboratories Macrolide immunomodulators
EP1006935B1 (en) * 1995-06-07 2005-01-26 Southern Biosystems, Inc. High viscosity liquid controlled delivery system
US7833543B2 (en) * 1995-06-07 2010-11-16 Durect Corporation High viscosity liquid controlled delivery system and medical or surgical device
US5747058A (en) 1995-06-07 1998-05-05 Southern Biosystems, Inc. High viscosity liquid controlled delivery system
US6015815A (en) 1997-09-26 2000-01-18 Abbott Laboratories Tetrazole-containing rapamycin analogs with shortened half-lives
US6890546B2 (en) 1998-09-24 2005-05-10 Abbott Laboratories Medical devices containing rapamycin analogs
US6376517B1 (en) 1998-08-14 2002-04-23 Gpi Nil Holdings, Inc. Pipecolic acid derivatives for vision and memory disorders
CN101137369A (en) * 2005-02-09 2008-03-05 马库赛特公司 Formulations for ocular treatment
BRPI0608152A2 (en) * 2005-02-09 2009-11-10 Macusight Inc eye care formulations
US8663639B2 (en) * 2005-02-09 2014-03-04 Santen Pharmaceutical Co., Ltd. Formulations for treating ocular diseases and conditions
US20070027105A1 (en) 2005-07-26 2007-02-01 Alza Corporation Peroxide removal from drug delivery vehicle
US8586103B2 (en) * 2008-02-08 2013-11-19 Foresee Pharmaceuticals, Llc Non-polymeric compositions for controlled drug delivery
KR20140015266A (en) * 2010-11-24 2014-02-06 듀렉트 코퍼레이션 Biodegradable drug delivery composition
JP2016175900A (en) * 2015-03-18 2016-10-06 参天製薬株式会社 Sustained-release pharmaceutical composition
JP7051721B2 (en) * 2016-06-30 2022-04-11 デュレクト コーポレーション Depot preparation

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