IT201900002753A1 - Intraocular ophthalmic compositions for vitreo-retinal surgery - Google Patents
Intraocular ophthalmic compositions for vitreo-retinal surgery Download PDFInfo
- Publication number
- IT201900002753A1 IT201900002753A1 IT102019000002753A IT201900002753A IT201900002753A1 IT 201900002753 A1 IT201900002753 A1 IT 201900002753A1 IT 102019000002753 A IT102019000002753 A IT 102019000002753A IT 201900002753 A IT201900002753 A IT 201900002753A IT 201900002753 A1 IT201900002753 A1 IT 201900002753A1
- Authority
- IT
- Italy
- Prior art keywords
- intraocular ophthalmic
- intraocular
- retinal
- inflammatory
- group
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims description 60
- 238000001356 surgical procedure Methods 0.000 title claims description 8
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims description 28
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 28
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 24
- -1 polydimethylsiloxane Polymers 0.000 claims description 21
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 20
- 230000003078 antioxidant effect Effects 0.000 claims description 15
- 230000002207 retinal effect Effects 0.000 claims description 14
- 206010038848 Retinal detachment Diseases 0.000 claims description 11
- 230000004264 retinal detachment Effects 0.000 claims description 11
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 claims description 8
- 206010061218 Inflammation Diseases 0.000 claims description 7
- 230000004054 inflammatory process Effects 0.000 claims description 7
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 claims description 6
- 230000001804 emulsifying effect Effects 0.000 claims description 6
- UWEYRJFJVCLAGH-UHFFFAOYSA-N perfluorodecalin Chemical compound FC1(F)C(F)(F)C(F)(F)C(F)(F)C2(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C21F UWEYRJFJVCLAGH-UHFFFAOYSA-N 0.000 claims description 6
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 4
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 claims description 4
- 241000701022 Cytomegalovirus Species 0.000 claims description 4
- 208000001351 Epiretinal Membrane Diseases 0.000 claims description 4
- 208000010412 Glaucoma Diseases 0.000 claims description 4
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 claims description 4
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 claims description 4
- 208000031471 Macular fibrosis Diseases 0.000 claims description 4
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 claims description 4
- 206010064997 Necrotising retinitis Diseases 0.000 claims description 4
- 235000010385 ascorbyl palmitate Nutrition 0.000 claims description 4
- 229960002537 betamethasone Drugs 0.000 claims description 4
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 claims description 4
- 229960003957 dexamethasone Drugs 0.000 claims description 4
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims description 4
- 229960000890 hydrocortisone Drugs 0.000 claims description 4
- 229960004752 ketorolac Drugs 0.000 claims description 4
- OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 claims description 4
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 claims description 4
- 229960003987 melatonin Drugs 0.000 claims description 4
- 229960001002 nepafenac Drugs 0.000 claims description 4
- QEFAQIPZVLVERP-UHFFFAOYSA-N nepafenac Chemical compound NC(=O)CC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1N QEFAQIPZVLVERP-UHFFFAOYSA-N 0.000 claims description 4
- 229950007031 palmidrol Drugs 0.000 claims description 4
- HXYVTAGFYLMHSO-UHFFFAOYSA-N palmitoyl ethanolamide Chemical compound CCCCCCCCCCCCCCCC(=O)NCCO HXYVTAGFYLMHSO-UHFFFAOYSA-N 0.000 claims description 4
- YVBBRRALBYAZBM-UHFFFAOYSA-N perfluorooctane Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F YVBBRRALBYAZBM-UHFFFAOYSA-N 0.000 claims description 4
- 230000002062 proliferating effect Effects 0.000 claims description 4
- 230000035755 proliferation Effects 0.000 claims description 4
- KBPHJBAIARWVSC-XQIHNALSSA-N trans-lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C KBPHJBAIARWVSC-XQIHNALSSA-N 0.000 claims description 4
- DVSZKTAMJJTWFG-SKCDLICFSA-N (2e,4e,6e,8e,10e,12e)-docosa-2,4,6,8,10,12-hexaenoic acid Chemical compound CCCCCCCCC\C=C\C=C\C=C\C=C\C=C\C=C\C(O)=O DVSZKTAMJJTWFG-SKCDLICFSA-N 0.000 claims description 2
- JKQXZKUSFCKOGQ-JLGXGRJMSA-N (3R,3'R)-beta,beta-carotene-3,3'-diol Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C[C@@H](O)CC1(C)C JKQXZKUSFCKOGQ-JLGXGRJMSA-N 0.000 claims description 2
- GZJLLYHBALOKEX-UHFFFAOYSA-N 6-Ketone, O18-Me-Ussuriedine Natural products CC=CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O GZJLLYHBALOKEX-UHFFFAOYSA-N 0.000 claims description 2
- RZZPDXZPRHQOCG-OJAKKHQRSA-M CDP-choline(1-) Chemical compound O[C@@H]1[C@H](O)[C@@H](COP([O-])(=O)OP([O-])(=O)OCC[N+](C)(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 RZZPDXZPRHQOCG-OJAKKHQRSA-M 0.000 claims description 2
- 208000031969 Eye Hemorrhage Diseases 0.000 claims description 2
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 claims description 2
- 229930003316 Vitamin D Natural products 0.000 claims description 2
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 2
- 229930003427 Vitamin E Natural products 0.000 claims description 2
- 208000036866 Vitreoretinopathy Diseases 0.000 claims description 2
- JKQXZKUSFCKOGQ-LQFQNGICSA-N Z-zeaxanthin Natural products C([C@H](O)CC=1C)C(C)(C)C=1C=CC(C)=CC=CC(C)=CC=CC=C(C)C=CC=C(C)C=CC1=C(C)C[C@@H](O)CC1(C)C JKQXZKUSFCKOGQ-LQFQNGICSA-N 0.000 claims description 2
- QOPRSMDTRDMBNK-RNUUUQFGSA-N Zeaxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCC(O)C1(C)C)C=CC=C(/C)C=CC2=C(C)CC(O)CC2(C)C QOPRSMDTRDMBNK-RNUUUQFGSA-N 0.000 claims description 2
- JKQXZKUSFCKOGQ-LOFNIBRQSA-N all-trans-Zeaxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2=C(C)CC(O)CC2(C)C JKQXZKUSFCKOGQ-LOFNIBRQSA-N 0.000 claims description 2
- 229960001284 citicoline Drugs 0.000 claims description 2
- 235000020669 docosahexaenoic acid Nutrition 0.000 claims description 2
- KAUVQQXNCKESLC-UHFFFAOYSA-N docosahexaenoic acid (DHA) Natural products COC(=O)C(C)NOCC1=CC=CC=C1 KAUVQQXNCKESLC-UHFFFAOYSA-N 0.000 claims description 2
- 235000020664 gamma-linolenic acid Nutrition 0.000 claims description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 2
- 235000012680 lutein Nutrition 0.000 claims description 2
- 239000001656 lutein Substances 0.000 claims description 2
- KBPHJBAIARWVSC-RGZFRNHPSA-N lutein Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\[C@H]1C(C)=C[C@H](O)CC1(C)C KBPHJBAIARWVSC-RGZFRNHPSA-N 0.000 claims description 2
- 229960005375 lutein Drugs 0.000 claims description 2
- ORAKUVXRZWMARG-WZLJTJAWSA-N lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C ORAKUVXRZWMARG-WZLJTJAWSA-N 0.000 claims description 2
- 230000006785 proliferative vitreoretinopathy Effects 0.000 claims description 2
- 210000001525 retina Anatomy 0.000 claims description 2
- 229960003471 retinol Drugs 0.000 claims description 2
- 235000020944 retinol Nutrition 0.000 claims description 2
- 239000011607 retinol Substances 0.000 claims description 2
- 230000000472 traumatic effect Effects 0.000 claims description 2
- 235000019155 vitamin A Nutrition 0.000 claims description 2
- 239000011719 vitamin A Substances 0.000 claims description 2
- 235000019166 vitamin D Nutrition 0.000 claims description 2
- 239000011710 vitamin D Substances 0.000 claims description 2
- 150000003710 vitamin D derivatives Chemical class 0.000 claims description 2
- 235000019165 vitamin E Nutrition 0.000 claims description 2
- 229940046009 vitamin E Drugs 0.000 claims description 2
- 239000011709 vitamin E Substances 0.000 claims description 2
- 229940045997 vitamin a Drugs 0.000 claims description 2
- 229940046008 vitamin d Drugs 0.000 claims description 2
- FJHBOVDFOQMZRV-XQIHNALSSA-N xanthophyll Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C=C(C)C(O)CC2(C)C FJHBOVDFOQMZRV-XQIHNALSSA-N 0.000 claims description 2
- 235000010930 zeaxanthin Nutrition 0.000 claims description 2
- 239000001775 zeaxanthin Substances 0.000 claims description 2
- 229940043269 zeaxanthin Drugs 0.000 claims description 2
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 claims 2
- 235000020673 eicosapentaenoic acid Nutrition 0.000 claims 2
- 229960005135 eicosapentaenoic acid Drugs 0.000 claims 2
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 claims 2
- 238000009472 formulation Methods 0.000 description 25
- 239000000243 solution Substances 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 9
- 238000004945 emulsification Methods 0.000 description 9
- 102000053171 Glial Fibrillary Acidic Human genes 0.000 description 7
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 7
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 7
- 239000003963 antioxidant agent Substances 0.000 description 6
- 235000006708 antioxidants Nutrition 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- 230000007170 pathology Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000003556 assay Methods 0.000 description 4
- 206010012689 Diabetic retinopathy Diseases 0.000 description 3
- 239000000306 component Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 208000002367 Retinal Perforations Diseases 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 208000029233 macular holes Diseases 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 230000002497 edematous effect Effects 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 229920006158 high molecular weight polymer Polymers 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
Landscapes
- Prostheses (AREA)
- Materials For Medical Uses (AREA)
Description
Titolo: "Composizioni oftalmiche intraoculari per la chirurgia vitreo-retinica” Title: "Intraocular ophthalmic compositions for vitreo-retinal surgery"
DESCRIZIONE DESCRIPTION
Il polidimetilsilossano (PDMS), detto anche olio di silicone, e i perfluorocarburi (PFCL) vengono utilizzati nella chirurgia vitreo-retinica, come sostituti vitreali, nei casi di distacco di retina, retinopatia diabetica proliferante, etc. Polydimethylsiloxane (PDMS), also called silicone oil, and perfluorocarbons (PFCL) are used in vitreo-retinal surgery, as vitreous substitutes, in cases of retinal detachment, proliferating diabetic retinopathy, etc.
Queste soluzioni idrofobe, una volta, iniettate all’interno dell’occhio vengono rimosse subito, come nel caso particolare dei perfluorocarburi, o mantenute per mesi o settimane a diretto contatto con il tessuto retinico, come nel caso particolare del polidimetilsilossano, prima di essere rimosse chirurgicamente. These hydrophobic solutions, once injected into the eye, are removed immediately, as in the particular case of perfluorocarbons, or kept for months or weeks in direct contact with the retinal tissue, as in the particular case of polydimethylsiloxane, before being removed. surgically.
L’utilizzo clinico di questi endotamponanti vitreali è ormai conclamato e relativamente sicuro; tuttavia permangono delle forti criticità cliniche, rappresentate ad esempio: The clinical use of these vitreous endotamponants is now overt and relatively safe; however strong clinical criticalities remain, represented for example:
- dallo sviluppo di un’infiammazione e necrosi retinica - from the development of inflammation and retinal necrosis
- dalla proliferazione della membrana epi-retinica - from the proliferation of the epi-retinal membrane
- dal glaucoma secondario - from secondary glaucoma
- dall’emulsificazione delle soluzioni tamponanti (fortemente idrofobe) con i componenti idrofili di natura edematosa, che normalmente si formano in corso di chirurgia; con conseguente infiammazione intraoculare; (1) - from the emulsification of buffering solutions (strongly hydrophobic) with the hydrophilic components of an edematous nature, which are normally formed during surgery; resulting in intraocular inflammation; (1)
E’ stato già dimostrato (2) che, aggiungendo ad una soluzione di polidimetilsilossano, frazioni dello stesso polimero ad alto peso molecolare e, quindi, aumentando la viscosità estensionale, aumentava anche la resistenza all’emulsificazione; tuttavia, ciò non porta ad una infiammazione intraoculare meno intensa. It has already been shown (2) that, by adding fractions of the same high molecular weight polymer to a polydimethylsiloxane solution and, therefore, increasing the extensional viscosity, the resistance to emulsification also increased; however, this does not lead to less intense intraocular inflammation.
L’infiammazione intraoculare post-chirurgica, rimane infatti una complicanza molto frequente che potrebbe generare conseguenze cliniche anche molto severe per il paziente. Post-surgical intraocular inflammation remains a very frequent complication that could generate even very severe clinical consequences for the patient.
Riassunto dell’invenzione Summary of the invention
Gli autori della presente invenzione hanno sorprendentemente trovato come preparare una composizione a base di polidimetilsilossano e/o perfluorocarburi, che può essere impiegata nella chirurgia vitreo-retinica e per altre applicazioni oftalmiche e che supera gli inconvenienti delle soluzioni già note nell’arte. Oggetto dell’invenzione The authors of the present invention have surprisingly found how to prepare a composition based on polydimethylsiloxane and / or perfluorocarbons, which can be used in vitreo-retinal surgery and for other ophthalmic applications and which overcomes the drawbacks of the solutions already known in the art. Object of the invention
In un primo oggetto, la presente invenzione descrive composizioni oftalmiche intraoculari a base di polidimetilsilossano e/o perfluoricarburi. In a first object, the present invention describes intraocular ophthalmic compositions based on polydimethylsiloxane and / or perfluoricarbons.
In un secondo oggetto, le composizioni della presente invenzioni sono descritte per l’uso medico. In a second object, the compositions of the present inventions are described for medical use.
In un aspetto preferito, tali composizioni sono descritte per l’uso medico oftalmico intraoculare. In a preferred aspect, these compositions are described for intraocular ophthalmic medical use.
In un altro aspetto, le composizioni dell’invenzione sono descritte per l’uso medico nell’ambito della chirurgia vitreoretinica, come sostituti vitreali. In another aspect, the compositions of the invention are described for medical use in the field of vitreoretinal surgery, as vitreous substitutes.
In un altro oggetto, è descritto l’uso di polidimetilsilossani e/o polifluocarburi per ridurre la capacità emulsionante di soluzioni comprendenti tali polidimentilsilossani e/o polifluorocarburi con molecole naturali o di sintesi aventi attività anti-infiammatoria e/o antiossidante. In another object, the use of polydimethylsiloxanes and / or polyfluocarbons to reduce the emulsifying capacity of solutions comprising such polydimyl siloxanes and / or polyfluorocarbons with natural or synthetic molecules having anti-inflammatory and / or antioxidant activity is described.
In un altro oggetto è descritto un metodo per il trattamento di patologie oftalmiche che comprende l’impiego delle composizioni dell’invenzione. Another object describes a method for the treatment of ophthalmic pathologies which includes the use of the compositions of the invention.
In ancora un altro oggetto è descritto un metodo per la protezione fisica e biologica del tessuto retinico comprendente l’impiego delle composizioni dell’invenzione. Still another object describes a method for the physical and biological protection of the retinal tissue comprising the use of the compositions of the invention.
Breve descrizione delle figure Brief description of the figures
La figura 1 riporta i risultati dei saggi per determinare l’area di emulsificazione (%). Figure 1 reports the results of the assays to determine the emulsification area (%).
La figura 2 riporta i risultati di espressione di GFAP (%) nelle cellule retiniche. Figure 2 reports the GFAP (%) expression results in retinal cells.
La figura 3 riporta i risultati dei saggi di espressione di Ki67 (%) nelle cellule retiniche. Figure 3 reports the results of the Ki67 (%) expression assays in retinal cells.
La figura 4 riporta i risultati delle misure di tensione superficiale. Figure 4 reports the results of the surface tension measurements.
Descrizione dettagliata dell’invenzione Detailed description of the invention
In accordo con un primo oggetto dell’invenzione sono descritte preparazioni oftalmiche intraoculari a base di polidimentilsilossano e/o perfluorocarburi. In accordance with a first object of the invention, intraocular ophthalmic preparations based on polydimyl siloxane and / or perfluorocarbons are described.
In particolare, tali preparazioni sono in combinazione con sostanze endogene e/o esogene aventi proprietà antiossidante e/o antiinfiammatoria. In particular, these preparations are in combination with endogenous and / or exogenous substances having antioxidant and / or anti-inflammatory properties.
Per gli scopi della presente invenzione, le composizioni descritte comprendono circa 95-99% in peso di polidimetilsilossano e/o di perfluorocarburi. For the purposes of the present invention, the compositions described comprise about 95-99% by weight of polydimethylsiloxane and / or perfluorocarbons.
In un aspetto dell’invenzione, il polidimetilsilossano si caratterizza per un contenuto di oligosilossani ≤ 500 ppm. In one aspect of the invention, the polydimethylsiloxane is characterized by a content of oligosiloxanes ≤ 500 ppm.
Per gli scopi della presente invenzione, i perfluorocarburi sono scelti preferibilmente fra perfluoro-n-ottano (PF8) perfluorodecalina (PF10). For the purposes of the present invention, the perfluorocarbons are preferably selected from perfluoro-n-octane (PF8) perfluorodecaline (PF10).
Secondo uno aspetto dell’invenzione, il polidimetilsilossano e i perfluorocarburi possono essere contenuti nelle composizioni descritte preferibilmente in un rapporto di circa 9 a 1 e più preferibilmente di circa 7 a 3 rispetto al polidimetilsilossano. According to one aspect of the invention, the polydimethylsiloxane and the perfluorocarbons can be contained in the compositions described preferably in a ratio of about 9 to 1 and more preferably of about 7 to 3 with respect to the polydimethylsiloxane.
Per quanto riguarda le sostanze ad attività antiinfiammatoria ed antiossidante, queste possono essere sostanze naturali, eventualmente endogene, o di sintesi. As for the substances with anti-inflammatory and antioxidant activity, these can be natural, possibly endogenous, or synthetic substances.
Per gli scopi della presente invenzione, tali sostanze sono scelte nel gruppo che comprende: For the purposes of the present invention, such substances are selected from the group which includes:
- molecole naturali ad attività antiossidante e/o antinfiammatoria; - natural molecules with antioxidant and / or anti-inflammatory activity;
- molecole endogene ad attività antiossidante e/o antinfiammatoria; - endogenous molecules with antioxidant and / or anti-inflammatory activity;
- molecole di sintesi ad attività antinfiammatoria. - synthetic molecules with anti-inflammatory activity.
Per gli scopi della presente invenzione, le molecole naturali ad attività antiossidante e/o antinfiammatoria sono scelte nel gruppo che comprende: luteina, zeaxantina, ascorbil palmitato (AP), vitamina E, vitamina A (retinolo), acido docosaesanoico (DHA), acido eicosapentaenoico (EPA), acido γ-linolenico (GLA), vitamina D, citicolina. For the purposes of the present invention, the natural molecules with antioxidant and / or anti-inflammatory activity are selected from the group which includes: lutein, zeaxanthin, ascorbyl palmitate (AP), vitamin E, vitamin A (retinol), docosahexaenoic acid (DHA), acid eicosapentaenoic (EPA), γ-linolenic acid (GLA), vitamin D, citicoline.
Per gli scopi della presente invenzione, le molecole endogene ad attività antiossidante e/o antinfiammatoria sono scelte nel gruppo che comprende: palmitoiletanolamide (PEA), melatonina (MLT), cortisolo (CRT). For the purposes of the present invention, the endogenous molecules with antioxidant and / or anti-inflammatory activity are selected from the group which includes: palmitoylethanolamide (PEA), melatonin (MLT), cortisol (CRT).
Per gli scopi della presente invenzione, le molecole di sintesi ad attività antinfiammatoria sono scelte nel gruppo che comprende antiinfiammatori non-steroidei (FANS) e steroidei, come i glucocorticoidi. For the purposes of the present invention, the synthetic molecules with anti-inflammatory activity are selected from the group which includes non-steroidal anti-inflammatory drugs (NSAIDs) and steroids, such as glucocorticoids.
Più in particolare, tali molecole di sintesi ad attività antinfiammatoria sono scelte nel gruppo che comprende: desametasone (DES), betametasone (BET), nepafenac (NPF), ketorolac (KTR). More specifically, these synthetic molecules with anti-inflammatory activity are selected from the group that includes: dexamethasone (DES), betamethasone (BET), nepafenac (NPF), ketorolac (KTR).
In accordo con il secondo oggetto, le composizioni dell’invenzione sono descritte per l’uso medico. In accordance with the second object, the compositions of the invention are described for medical use.
Più in particolare, le composizioni dell’invenzione sono descritte per l’uso medico oftalmico medico oftalmico intraoculare. More specifically, the compositions of the invention are described for intraocular ophthalmic medical ophthalmic medical use.
In particolare, le composizioni descritte trovano impiego come sostituto vitreale (o come tamponanti endovitreali). In particular, the compositions described are used as a vitreous substitute (or as endovitreal buffering agents).
Più in particolare, le composizioni descritte trovano impiego nell’ambito della chirurgia vitreo-retinica. More specifically, the compositions described are used in the field of vitreoretinal surgery.
In un aspetto preferito, le composizioni dell’invenzione sono descritte per l’uso medico nel trattamento di patologie scelte nel gruppo che comprende: retinopatia diabetica, distacco retinico, foro macular idiopatico e altre complicanze derivanti dalla degenerazione del tessuto retinico. In a preferred aspect, the compositions of the invention are described for medical use in the treatment of pathologies chosen in the group which includes: diabetic retinopathy, retinal detachment, idiopathic macular hole and other complications deriving from retinal tissue degeneration.
Secondo altri aspetti dell’invenzione, le formulazioni dell’invenzione sono descritte per l’uso medico, in cui tali formulazioni sono iniettate all’interno della camera oculare per il trattamento del distacco retinico e/o la manipolazione della retina in corso di circostanze scelte nel gruppo che comprende, per esempio: According to other aspects of the invention, the formulations of the invention are described for medical use, wherein such formulations are injected into the ocular chamber for the treatment of retinal detachment and / or manipulation of the retina under selected circumstances. in the group which includes, for example:
- distacco di retina, - retinal detachment,
- distacco di retina con vitreoretinopatia proliferante, - retinal detachment with proliferating vitreoretinopathy,
- distacco di retina traumatico, - traumatic retinal detachment,
- ditacco di retina causato dal Citomegalovirus (CMV), - retinal heel caused by Cytomegalovirus (CMV),
- lussazione della lente, - dislocation of the lens,
- emoraggia intraoculare. - intraocular haemorrhage.
In particolare, tali soluzioni comprendono molecole naturali o di sintesi aventi attività anti-infiammatoria e/o antiossidante. In particular, such solutions comprise natural or synthetic molecules having anti-inflammatory and / or antioxidant activity.
Tali molecole aventi attività anti-infiammatori e/o antiossidante sono le molecole di origine naturale o sintetica sopra descritte. Such molecules having anti-inflammatory and / or antioxidant activities are the molecules of natural or synthetic origin described above.
In accordo con un altro oggetto è descritto un metodo per il trattamento di patologie oftalmiche che comprende l’impiego delle composizioni dell’invenzione. In accordance with another object, a method for the treatment of ophthalmic pathologies is described which includes the use of the compositions of the invention.
In particolare, tale metodo comprende la somministrazione intraoculare delle composizioni dell’invenzione. In particular, this method comprises the intraocular administration of the compositions of the invention.
Tali patologie oftalmiche sono in particolare scelte nel gruppo che comprende: retinopatia diabetica, distacco retinico, foro macular idiopatico e altre complicanze derivanti dalla degenerazione del tessuto retinico. These ophthalmic pathologies are in particular chosen in the group which includes: diabetic retinopathy, retinal detachment, idiopathic macular hole and other complications deriving from retinal tissue degeneration.
In tali patologie, le composizioni dell’invenzione trovano impiego come sostituto vitreale. In such pathologies, the compositions of the invention are used as a vitreous substitute.
Più in particolare, le composizioni descritte trovano impiego come tamponanti endovitreali. More particularly, the described compositions are used as endovitreal buffering agents.
In un altro oggetto è descritto un metodo per la protezione fisica e biologica del tessuto retinico comprendente l’impiego delle composizioni dell’invenzione. Another object describes a method for the physical and biological protection of the retinal tissue comprising the use of the compositions of the invention.
E’ stato inoltre osservato che le composizioni dell’invenzione sono in grado di limitare e/o ridurre lo sviluppo di infiammazioni o necrosi retinica, di limitare la proliferazione della membrana epi-retinica, il glaucoma secondario. It has also been observed that the compositions of the invention are able to limit and / or reduce the development of inflammation or retinal necrosis, to limit the proliferation of the epi-retinal membrane, secondary glaucoma.
In un altro oggetto, è descritto l’uso di polifluocarburi e/o polidimetilsilossani per ridurre la capacità emulsionante di soluzioni comprendenti tali polifluorocarburi e/o polidimentilsilossani. In another object, the use of polyfluocarbons and / or polydimethylsiloxanes to reduce the emulsifying capacity of solutions comprising such polyfluorocarbons and / or polydimethylsiloxanes is described.
Le formulazioni della presente invenzione sono state studiate fisicamente e biologicamente al fine di valutarne eventuali caratteristiche peculiari rispetto a prodotti già presenti sul mercato o, per alcuni parametri biologici, a soluzioni controllo essenzialmente soluzioni saline. The formulations of the present invention have been studied physically and biologically in order to evaluate any peculiar characteristics with respect to products already present on the market or, for some biological parameters, to control solutions essentially saline solutions.
La seguente tabella riporta alcuni esempi di formulazioni in accordo con la presente invenzione. The following table reports some examples of formulations according to the present invention.
In particolare, nelle formulazioni da F1 a F6, al PDMS avente un diverso peso molecolare (aventi comunque un contenuto di oligosilossani ≤ 500 ppm), al perfluoro-n-ottano o alla perfluorodecalina sono combinate sostanze naturali ad azione an tiossidante-antinfiammatoria secondo quanto sopra descritto. In particular, in the formulations F1 to F6, the PDMS having a different molecular weight (however having an oligosiloxane content ≤ 500 ppm), perfluoro-n-octane or perfluorodecaline are combined with natural substances with an antioxidant-anti-inflammatory action according to what described above.
Nelle seguenti formulazioni da F7 a F9 il polidimetilsilossano a diverso peso molecolare (aventi comunque un contenuto di oligosilossani ≤ 500 ppm) è combinato con perfluorocarburi e con sostanze endogene antiossidanti-antinfiammatorie. In the following formulations from F7 to F9 the polydimethylsiloxane of different molecular weight (however having an oligosiloxane content ≤ 500 ppm) is combined with perfluorocarbons and with endogenous antioxidant-anti-inflammatory substances.
Nelle seguenti formulazioni da F10 a F12 il polidimetilsilossano a diverso peso molecolare (aventi comunque un contenuto di oligosilossani ≤ 500 ppm) o i PFCL con molecole di sintesi ad attivi tà antinfiammatoria. In the following formulations from F10 to F12 the polydimethylsiloxane of different molecular weight (however having an oligosiloxane content ≤ 500 ppm) or the PFCL with synthetic molecules with anti-inflammatory activity.
Alcune delle formulazioni comprese tra F1 e F12 sono state successivamente caratterizzate fisicamente e biologicamente. Some of the formulations between F1 and F12 were subsequently physically and biologically characterized.
Per verificare le ridotte proprietà emulsionanti delle formulazioni dell’invenzione, sono state condotte delle prove di emulsificazione, ponendo in contatto le soluzioni di questa invenzione e soluzioni tensioattivate con Tween 80 (surfattante a base di polisorbato). To verify the reduced emulsifying properties of the formulations of the invention, emulsification tests were carried out, putting in contact the solutions of this invention and surfactant solutions with Tween 80 (surfactant based on polysorbate).
Le soluzioni controllo impiegate sono due: The control solutions used are two:
CTRL 1: Perfluorodecalina 100%. CTRL 1: Perfluorodecaline 100%.
CTRL2: PDMS 100%. CTRL2: PDMS 100%.
La capacità emulsionante è stata misurata adattando quanto già descritto in letteratura da Savion et al. (3)., 500 µl delle formulazioni F1-F12 sono state emulsionate con una soluzione acquosa contenente il 15% di Tween 80. Le soluzioni sono state pipettate in una cuvetta e sonicate per 30 secondi in un bagno acquoso a temperatura compresa tra 20-24°C. Le soluzioni sono state quindi centrifugate a 5000 g per 30 minuti. Dopo la centrifugazione, l’olio non emulsionato era in superficie, quello emulsionato era in mezzo e la componente acquosa era in basso. Le cuvette che erano state impiegate per la centrifuga venivano quindi fotografate al fine di calcolare l’area di emulsificazione mediante software ImageJ (Wayne Rasband, National Institute of Health, Bethesda, MD, http://rsb.info.nih.gov/ij/index.html). L’area di emulsificazione viene espressa in percentuale attraverso la formula: area di olio emulsionato (%) = (area di olio emulsionato X 100) / (area di olio non emulsionato area di olio emulsionato area della soluzione acquosa). The emulsifying capacity was measured by adapting what has already been described in the literature by Savion et al. (3)., 500 µl of the F1-F12 formulations were emulsified with an aqueous solution containing 15% Tween 80. The solutions were pipetted into a cuvette and sonicated for 30 seconds in an aqueous bath at a temperature between 20- 24 ° C. The solutions were then centrifuged at 5000 g for 30 minutes. After centrifugation, the non-emulsified oil was on the surface, the emulsified one was in the middle and the aqueous component was at the bottom. The cuvettes that had been used for the centrifuge were then photographed in order to calculate the emulsification area using ImageJ software (Wayne Rasband, National Institute of Health, Bethesda, MD, http://rsb.info.nih.gov/ij /index.html). The emulsification area is expressed as a percentage through the formula: area of emulsified oil (%) = (area of emulsified oil X 100) / (area of non-emulsified oil area of emulsified oil area of aqueous solution).
Nella seguente tabella sono riportate le percentuali (%) di area di emulsificazione (tabella 1 e figura 1). Si dimostra come le formulazioni della presente invenzione posseggono adeguate proprietà anti-emulsionanti. The following table shows the percentages (%) of emulsification area (table 1 and figure 1). It is shown how the formulations of the present invention possess adequate anti-emulsifying properties.
Tabella 1. Area di emulsificazione % Table 1. Emulsification area%
La figura 1 riporta i risultati dei saggi per determinare l’area di emulsificazione (%). Figure 1 reports the results of the assays to determine the emulsification area (%).
Le formulazioni oggetto della seguente invenzione sono state saggiate in vitro su cellule retiniche porcine al fine di valutarne la biocompatibilità e l’effetto protettivo dopo un determinato tempo di contatto. The formulations object of the following invention were tested in vitro on porcine retinal cells in order to evaluate their biocompatibility and protective effect after a certain contact time.
A tal proposito sono state eseguite delle prove di immunoistochimica valutando l’espressione di marker proteici: GFAP (glial fibrillary acidic protein) e Ki67 (antigene espresso nelle cellule in proliferazione). Le formulazioni oggetto dell’invenzione sono state testate rispetto a soluzioni contenenti solo PDMS o PFCL, considerate formulazioni controllo. In this regard, immunohistochemical tests were performed by evaluating the expression of protein markers: GFAP (glial fibrillary acidic protein) and Ki67 (antigen expressed in proliferating cells). The formulations object of the invention have been tested with respect to solutions containing only PDMS or PFCL, considered control formulations.
La liberazione di GFAP è stata utilizzata per quantificare il danno a carico delle cellule di Muller dopo il tempo di contatto con le soluzioni testate. GFAP release was used to quantify the damage to Muller cells after contact time with the tested solutions.
La liberazione di GFAP è stata rilevata nel 30-50% delle cellule retiniche poste a contatto con le soluzioni F1,F3,F4,F7,F8 ed F10 rispetto alle soluzioni contenenti soltanto PDMS (CTRL2) o perfluorodecalina (CTRL1) che mostravano il 70-75% di liberazione. GFAP release was detected in 30-50% of retinal cells placed in contact with solutions F1, F3, F4, F7, F8 and F10 compared to solutions containing only PDMS (CTRL2) or perfluorodecaline (CTRL1) which showed 70 -75% release.
La figura 2 riporta i risultati di espressione di GFAP (%) nelle cellule retiniche. Figure 2 reports the GFAP (%) expression results in retinal cells.
Ki67 è un marker utilizzato per la valutazione della proliferazione cellulare. Il 7-17% delle cellule poste a contatto con le formulazioni F1,F3,F4,F7,F8 e F10 mostravano espressione di Ki67 mentre i gruppi controllo PDMS (CTRL2) e perfluorodecalina (CTRL1) mostravano il 36-40% di espressione. Ki67 is a marker used for the assessment of cell proliferation. 7-17% of the cells placed in contact with the F1, F3, F4, F7, F8 and F10 formulations showed expression of Ki67 while the PDMS (CTRL2) and perfluorodecaline (CTRL1) control groups showed 36-40% expression.
Si nota inoltre, sorprendentemente, come l’espressione di GFAP delle formulazioni F3 e F7 che contengono molecole naturali ad attività antiossidante-antinfiammatoria sia molto bassa e comunque paragonabile a quella della formulazione F10, che invece contiene molecole di sintesi ad attività antinfiammatoria. We also note, surprisingly, how the GFAP expression of the F3 and F7 formulations which contain natural molecules with antioxidant-anti-inflammatory activity is very low and in any case comparable to that of the F10 formulation, which instead contains synthetic molecules with anti-inflammatory activity.
La figura 3 riporta i risultati dei saggi di espressione di Ki67 (%) nelle cellule retiniche. Figure 3 reports the results of the Ki67 (%) expression assays in retinal cells.
Anche per quel che riguarda l’espressione di Ki67 si nota come le formulazioni contenenti sostanze antiossidanti naturali abbiano un’azione protettiva paragonabile alle formulazioni contenenti molecole di sintesi ad azione antinfiammatoria molto potente. Also with regard to the expression of Ki67, it is noted that the formulations containing natural antioxidant substances have a protective action comparable to the formulations containing synthetic molecules with a very powerful anti-inflammatory action.
Sulle composizioni dell’invenzione contenenti PDMS sono state eseguite anche misure di tensione superficiale, i cui risultati sono riportati nella figura 4. Surface tension measurements were also performed on the compositions of the invention containing PDMS, the results of which are shown in Figure 4.
Le misure di tensione interfacciale sorprendentemente non hanno rilevato differenze significative tra la soluzione controllo PDMS 100% (CTRL 2) e le formulazioni testate contenenti PDMS 99,5% e componenti ad attività antiossidanti-antinfiammatoria 0,5% (F1, F2, F7 e F10). Interfacial tension measurements surprisingly did not reveal significant differences between the 100% PDMS control solution (CTRL 2) and the tested formulations containing 99.5% PDMS and components with 0.5% antioxidant-anti-inflammatory activity (F1, F2, F7 and F10).
Da quanto sopra descritto saranno immediatamente evidenti alla persona esperta nel settore i vantaggi offerti dalla presente invenzione. From what has been described above, the advantages offered by the present invention will be immediately apparent to the person skilled in the art.
Innanzitutto, con la presente domanda di brevetto vengono messe a disposizione delle formulazioni a base di polidimetilsilossano e/o di perfluorocarburi per l’uso oftalmico, in particolare come tamponanti endovitreali, insieme a molecole naturali e/o di sintesi, comunque facilmente reperibili dal punto di vista commerciali, che sono in grado di garantire protezione fisica e soprattutto una migliore protezione biologica del tessuto retinico. First of all, with this patent application, formulations based on polydimethylsiloxane and / or perfluorocarbons for ophthalmic use, in particular as endovitreal buffers, are made available, together with natural and / or synthetic molecules, however easily available from the point of commercial point of view, which are able to guarantee physical protection and above all a better biological protection of the retinal tissue.
E’ sorprendente come formulazioni contenenti molecole naturali ad attività antiossidante possano garantire una protezione fisica e biologica paragonabile o superiore a formulazioni contenenti molecole di sintesi ad attività antinfiammatoria. It is surprising how formulations containing natural molecules with antioxidant activity can guarantee physical and biological protection comparable or superior to formulations containing synthetic molecules with anti-inflammatory activity.
Inoltre, le formulazioni dell’invenzione hanno sorprendentemente dimostrato di avere basse proprietà emulsificanti. Furthermore, the formulations of the invention have surprisingly been shown to have low emulsifying properties.
Oltre a ciò, le formulazioni hanno dimostrato di limitare e/o ridurre lo sviluppo di infiammazioni o necrosi retinica, di limitare la proliferazione della membrana epi-retinica, il glaucoma secondario. In addition to this, the formulations have been shown to limit and / or reduce the development of inflammation or retinal necrosis, to limit the proliferation of the epi-retinal membrane, secondary glaucoma.
Bibliografia Bibliography
1. Ni C. et al., Intravitreous silicone injection. Histopathologic findings in a human eye after 12 years. Arch. Ophthalmol., 1983; 101:1399-1401 1. Ni C. et al., Intravitreous silicone injection. Histopathologic findings in a human eye after 12 years. Arch. Ophthalmol., 1983; 101: 1399-1401
2. Williams RL et al., Injectability of silicone oil-based tamponade agents, Br. J. Ophthalmol., 2011; 95:273-275 2. Williams RL et al., Injectability of silicone oil-based tamponade agents, Br. J. Ophthalmol., 2011; 95: 273-275
3. Savion N. et al., Role of blood components in ocular silicone oil emulsification. Studies on an in vitro model, IOVS, 1996; 37:2694-2699 3. Savion N. et al., Role of blood components in ocular silicone oil emulsification. Studies on an in vitro model, IOVS, 1996; 37: 2694-2699
Claims (12)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT102019000002753A IT201900002753A1 (en) | 2019-02-26 | 2019-02-26 | Intraocular ophthalmic compositions for vitreo-retinal surgery |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT102019000002753A IT201900002753A1 (en) | 2019-02-26 | 2019-02-26 | Intraocular ophthalmic compositions for vitreo-retinal surgery |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IT201900002753A1 true IT201900002753A1 (en) | 2020-08-26 |
Family
ID=66641299
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IT102019000002753A IT201900002753A1 (en) | 2019-02-26 | 2019-02-26 | Intraocular ophthalmic compositions for vitreo-retinal surgery |
Country Status (1)
| Country | Link |
|---|---|
| IT (1) | IT201900002753A1 (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5518731A (en) * | 1990-09-27 | 1996-05-21 | Allergan, Inc. | Nonaqueous fluorinated drug delivery vehicle suspensions |
| US20050288197A1 (en) * | 2004-06-08 | 2005-12-29 | Ocularis Pharma, Inc. | Silicone polymer topical eye compositions and methods of use |
| WO2018029476A1 (en) * | 2016-08-09 | 2018-02-15 | The University Of Liverpool | Ophthalmic compositions |
-
2019
- 2019-02-26 IT IT102019000002753A patent/IT201900002753A1/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5518731A (en) * | 1990-09-27 | 1996-05-21 | Allergan, Inc. | Nonaqueous fluorinated drug delivery vehicle suspensions |
| US20050288197A1 (en) * | 2004-06-08 | 2005-12-29 | Ocularis Pharma, Inc. | Silicone polymer topical eye compositions and methods of use |
| WO2018029476A1 (en) * | 2016-08-09 | 2018-02-15 | The University Of Liverpool | Ophthalmic compositions |
Non-Patent Citations (4)
| Title |
|---|
| NI C ET AL.: "silicone intravitreous injection. Histopathologic finding in a human eye after 12years", ARCH. OPHTHALMOL., vol. 101, 1983, pages 1399 - 1401 |
| SAVION N ET AL.: "Role of blood components in ocular silicone oil emulsification. Studies on an in vitro model", IOVS, vol. 37, 1996, pages 2694 - 2699 |
| WAYNE RASBAND, NATIONAL INSTITUTE OF HEALTH, Retrieved from the Internet <URL:http://rsb.info.nih.gov/ii/index.htmh> |
| WILLIAMS RL ET AL.: "injectability of silicone oil-based tamponade agents", BR. J. OPHTHALMOL., vol. 95, 2011, pages 273 - 275 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Richter et al. | Morphological changes in the anterior eye segment after long-term treatment with different receptor selective prostaglandin agonists and a prostamide | |
| Mackiewicz et al. | In vivo retinal tolerance of various heavy silicone oils | |
| Carino et al. | Topical tetracaine versus topical tetracaine plus intracameral lidocaine for cataract surgery | |
| KR20070094600A (en) | Therapeutic agent for ophthalmic diseases | |
| Sousa-Martins et al. | Use of lutein and zeaxanthin alone or combined with Brilliant Blue to identify intraocular structures intraoperatively | |
| Fukuda et al. | Morphologic and functional advantages of macular hole surgery with brilliant blue G-assisted internal limiting membrane peeling | |
| JP5712221B2 (en) | Treatment method for retinal diseases using intraocular tamponade | |
| JP2007308398A (en) | Eye drops and method for producing the same | |
| EP2696900A2 (en) | Dyes for membranes and biological structures | |
| Vasavada et al. | Corneal endothelial morphologic assessment in pediatric cataract surgery with intraocular lens implantation: a comparison of preoperative and early postoperative specular microscopy | |
| CN110013498A (en) | A kind of eye drops and preparation method thereof of hydrochloric olopatadine | |
| IT201900002753A1 (en) | Intraocular ophthalmic compositions for vitreo-retinal surgery | |
| Pastor et al. | Intravitreal silicone and fluorosilicone oils: pathologic findings in rabbit eyes | |
| Guo et al. | Antioxidant nanoemulsion loaded with latanoprost enables highly effective glaucoma treatment | |
| Tewari et al. | Macular hole closure with triamcinolone-assisted internal limiting membrane peeling | |
| Pereira et al. | Descemet membrane endothelial keratoplasty in children | |
| KR20160096376A (en) | Ophthalmic composition comprising hyaluronic acid, mineral oil and surfactants | |
| Zhao et al. | Comparative study of a modified sub-Tenon’s capsule injection of triamcinolone acetonide and the intravenous infusion of umbilical cord mesenchymal stem cells in retinitis pigmentosa combined with macular edema | |
| JP2021523222A (en) | Eye drops and methods for continuous delivery of the drug to the retina | |
| Rickmann et al. | Systemic curcumin-human serum albumin in proliferative vitreoretinal retinopathy: a pilot study | |
| Aggarwala | Hypertrophy of the Eye Focusing Ciliary Muscle in Glaucoma and Beneficial Effect of Nitric Oxide | |
| Soós | Investigation of the Emulsification of Silicone Oil used in Vitrectomy in the Presence of Hydrophilic Ophthalmic Media | |
| Aslıhan Kurt et al. | Heavy Silicone Oil as an Endotamponade in Recurrent or Complicated Retinal Detachment and Macular Hole. | |
| de Andrade Sobrinho et al. | Comparison of Cycloplegic and Manifest Refraction in Children and Adolescents | |
| JOONDEPH | Uses of visualization aids in vitreoretinal surgery |