TW201815397A - Ophthalmic agent and ophthalmologic drug - Google Patents

Abstract

The present invention addresses the problem of providing an ophthalmic agent that can be used to ameliorate at least one symptom selected from the group consisting of: eye discharge, dull and heavy feeling, eyestrain, blurred vision, red eyes, photophobia, and itchy eyes. Provided is an ophthalmic agent containing (A) hydroxypropyl methylcellulose and (B) vitamin E.

Description

眼科用劑及眼科用藥Ophthalmic agents and ophthalmic drugs

本發明是有關於一種眼科用劑及眼科用藥。The invention relates to an ophthalmic agent and an ophthalmic agent.

眼脂（亦稱「眼屎」）的成因在於結膜炎症、眼表黏液物質（黏液素（mucin））的分泌過多。作為眼脂的來源的滲出液自擴張的結膜血管滲出，經由結膜上皮到達眼表。於其中混合黏液物質（黏液素）或上皮細胞而成者即為眼脂。黏液素由結膜杯狀細胞分泌，其主要功能在於協助淚液留存於眼表面、並且將來自外界之異物或細菌包裹而加以活化的防禦機制。自杯狀細胞的黏液素的分泌由副交感神經控制，因對眼表的刺激而分泌會變得過盛。通常情況下有時亦會於眼表出現眼脂，尤其於高溫環境下或起床時會分泌眼脂，此為正常的且常見的。Eye fat (also known as "eye feces") is caused by conjunctival inflammation and excessive secretion of mucous substances (mucin) on the surface of the eye. The exudate, which is the source of ocular fat, exudates from the dilated conjunctival blood vessels and reaches the ocular surface through the conjunctival epithelium. Eyelids are made by mixing mucus (mucin) or epithelial cells. Mucin is secreted by conjunctival goblet cells. Its main function is to help the tear fluid stay on the surface of the eye and envelop foreign bodies or bacteria from the outside to activate the defense mechanism. The secretion of mucin from goblet cells is controlled by parasympathetic nerves, and secretion becomes excessive due to irritation to the ocular surface. Under normal circumstances, ocular lipids sometimes appear on the ocular surface, especially in high temperature environments or when you get up, it is normal and common.

作為一般的眼脂的處置方法，建議用潔淨的紙巾、紗布、棉棒等擦除。但是，因物理性地進行去除，故有時會損傷眼表。另外，於非處方藥品製造銷售認可基準下的一般滴眼藥、人工淚液中，作為效能或效果，可不借助調配特定的有效成分而強調「眼睛模糊（眼脂多時等）」。因此，認為人工淚液是藉由滴入眼睛所帶來的沖洗效果來處置輕度的眼脂。但是，因為是滴入眼睛所帶來的沖洗效果，故作為重度的眼脂的處置而效果並不充分，有改善的餘地。As a general treatment method for eyelids, it is recommended to wipe with clean paper towels, gauze, cotton swabs, etc. However, since the removal is performed physically, the ocular surface may be damaged. In addition, in general eye drops and artificial tears that are approved for the manufacture and sale of over-the-counter medicines, it is possible to emphasize "eye blur (long-term eye fat, etc.)" as an effect or effect without blending specific active ingredients. Therefore, artificial tears are thought to treat mild eyelids by the flushing effect brought about by dripping into the eyes. However, because it is a rinsing effect brought by dripping into the eyes, the effect as a treatment for severe eye fat is insufficient, and there is room for improvement.

另外，關於鈍重感的原因，有起因於器質性疾病者、以及起因於心因性要素者。作為器質性疾病，有眼科疾病（調節性眼疲勞、眼肌性眼疲勞、青光眼、乾眼病（dry eye）等外眼部疾病，視神經疾病）以及顱內腫瘍等顱內疾病。作為處理方法，可列舉對作為原因的疾病進行治療，但迄今為止仍不知曉對鈍重感有效的對症療法。The causes of dullness include those caused by organic diseases and those caused by psychogenic factors. As organic diseases, there are ophthalmic diseases (external eye diseases such as accommodative eye fatigue, ocular muscle fatigue, glaucoma, dry eye, and optic nerve diseases), and intracranial diseases such as intracranial ulcers. Examples of the treatment method include treating a disease as a cause, but a symptomatic treatment effective for bluntness has not been known so far.

此外，近年來，於使用個人電腦等電子終端機（視訊顯示終端機（Video Display Terminal，VDT））的作業中維持注視顯示器的狀態，主訴眼睛乾澀（目澀）的患者或乾眼病的患者增加。所謂「乾眼病」，意指淚液減少或實質性異常其本身的情況、或因淚液的量或質的異常而引起角結膜障礙的狀態。作為自覺症狀，例如可列舉：眼疲勞、充血、乾燥感、異物感、模糊、羞明感、發癢、疼痛、遠近調節不良、眼脂･眼淚的多寡、鈍重感，是一種對日常生活帶來較大不便的疾病。鑒於上述狀況，提出了緩和乾眼症的技術（例如，參照專利文獻1～專利文獻3）。 乾眼症有許多方面，因此，期望一種可對應於各症狀的緩和且可簡便地利用的技術。 [現有技術文獻] [專利文獻]In addition, in recent years, the use of electronic terminals such as personal computers (Video Display Terminal (VDT)) to maintain the state of watching the monitor, complaints of dry eyes (eyes) or dry eye disease increased . The term "dry eye disease" refers to a condition in which the tear fluid is reduced or a substantial abnormality occurs, or the corneal and conjunctival disorders are caused by abnormalities in the quantity or quality of the tear fluid. Examples of subjective symptoms include eye fatigue, congestion, dryness, foreign body sensation, blurring, shame, itching, pain, poor distance adjustment, eyelids, tears, and dullness. Major inconvenience. In view of the above-mentioned circumstances, techniques for alleviating dry eye have been proposed (for example, refer to Patent Documents 1 to 3). There are many aspects of dry eye. Therefore, a technique that can alleviate the symptoms and can be easily used is desired. [Prior Art Literature] [Patent Literature]

專利文獻1：日本專利特開2015-160826號公報 專利文獻2：日本專利特開2012-077080號公報 專利文獻3：日本專利特開2010-120856號公報Patent Literature 1: Japanese Patent Laid-Open No. 2015-160826 Patent Literature 2: Japanese Patent Laid-Open No. 2012-077080 Patent Literature 3: Japanese Patent Laid-Open No. 2010-120856

[發明所欲解決之課題] 本發明的課題在於提供一種可用於改善選自由眼脂生成、鈍重感、眼疲勞、眼睛模糊、充血、羞明感、及眼睛發癢所組成的群組中的至少一種症狀的眼科用劑。 [解決課題之手段][Problems to be Solved by the Invention] An object of the present invention is to provide at least one selected from the group consisting of eye fat production, dullness, eye fatigue, blurred eyes, congestion, shame, and itchy eyes. A symptomatic ophthalmic preparation. [Means for solving problems]

本發明者等人關於上述課題進行了努力研究，結果發現，可藉由含有（A）羥丙基甲基纖維素（以下，本說明書中亦稱為「羥丙甲纖維素（hypromellose）」）及（B）維生素E類的眼科用劑來解決上述課題，從而完成了本發明。另外發現，藉由更含有（C）維生素A類的眼科用劑，所期望的效能進一步提高。 即，本發明者等人提供下述[1]～[12]。 [1] 一種眼脂生成防止劑，其含有：（A）羥丙基甲基纖維素及（B）維生素E類。 [2] 一種鈍重感抑制劑，其含有：（A）羥丙基甲基纖維素及（B）維生素E類。 [3] 一種眼疲勞緩和劑，其含有：（A）羥丙基甲基纖維素及（B）維生素E類。 [4] 一種眼睛模糊緩和劑，其含有：（A）羥丙基甲基纖維素及（B）維生素E類。 [5] 一種充血抑制劑，其含有：（A）羥丙基甲基纖維素及（B）維生素E類。 [6] 一種羞明感緩和劑，其含有：（A）羥丙基甲基纖維素及（B）維生素E類。 [7] 一種眼睛發癢抑制劑，其含有：（A）羥丙基甲基纖維素及（B）維生素E類。 [8] 如所述[1]～[7]中任一項所記載的藥劑，其更含有（C）維生素A類。 [9] 如所述[8]所記載的藥劑，其中所述（C）維生素A類的量為每100 mL容量的藥劑中5萬國際單位（I.U.）～50萬I.U.。 [10] 如所述[1]～[9]中任一項所記載的藥劑，其為乾眼症的治療用及預防用的至少任一者。 [11] 如所述[1]～[9]中任一項所記載的藥劑，其為眼睛乾澀症狀的治療用及預防用的至少任一者。 [12] 一種眼科用藥，其使用如所述[1]～[11]中任一項所記載的藥劑。 [發明的效果]The present inventors conducted diligent research on the above-mentioned problems, and as a result, they found that (A) hydroxypropyl methylcellulose (hereinafter, also referred to as "hypromellose" in this specification) And (B) vitamin E-based ophthalmic agents to solve the above-mentioned problems, and completed the present invention. In addition, it has been found that the desired efficacy is further improved by further containing (C) an ophthalmic agent of vitamin A type. That is, the present inventors and others provide the following [1] to [12]. [1] An agent for preventing lipogenesis, comprising: (A) hydroxypropyl methylcellulose and (B) vitamin E. [2] A dullness inhibitor, which contains: (A) hydroxypropyl methyl cellulose and (B) vitamin E. [3] An eye fatigue reliever containing: (A) hydroxypropyl methylcellulose and (B) vitamin E. [4] An eye blur reducing agent, which contains: (A) hydroxypropyl methylcellulose and (B) vitamin E. [5] A congestion inhibitor, comprising: (A) hydroxypropyl methylcellulose and (B) vitamin E. [6] A shame reliever, which contains: (A) hydroxypropyl methylcellulose and (B) vitamin E. [7] An itching suppressant for the eyes, comprising: (A) hydroxypropyl methylcellulose and (B) vitamin E. [8] The medicament according to any one of the above [1] to [7], further comprising (C) vitamin A. [9] The pharmaceutical agent according to [8], wherein the amount of the (C) vitamin A is 50,000 international units (I.U.) to 500,000 I.U. per 100 mL of the medicine. [10] The agent according to any one of the above [1] to [9], which is at least one of a therapeutic and preventive agent for dry eye. [11] The medicament according to any one of the above [1] to [9], which is at least any one for the treatment and prevention of dry eyes. [12] An ophthalmic drug using the medicament according to any one of [1] to [11]. [Effect of the invention]

根據本發明，可提供一種可用於改善選自由眼脂生成、鈍重感、眼疲勞、眼睛模糊、充血、羞明感、及眼睛發癢所組成的群組中的至少一種症狀的眼科用劑、及使用該眼科用劑的眼科用藥。According to the present invention, there can be provided an ophthalmic agent that can be used to improve at least one symptom selected from the group consisting of eye fat production, dullness, eye fatigue, blurry eyes, congestion, shame, and itchy eyes, and An ophthalmic agent using the ophthalmic agent.

以下，對於本發明結合其較佳的實施方式進行詳細說明。 再者，本說明書中，只要未另行記載，則各成分的濃度（W/V%）與「g/100 mL」為相同含義。Hereinafter, the present invention will be described in detail with reference to its preferred embodiments. In addition, in this specification, unless otherwise stated, the concentration (W / V%) of each component has the same meaning as "g / 100 mL".

本說明書中，所謂「維生素E類」，除生殖酚（tocopherol）、參雙鍵生殖酚（tocotrienol）等維生素E其本身以外，亦指維生素E的鹽、維生素E的衍生物。In the present specification, the "vitamin E" refers to vitamin E itself, as well as tocopherol and tocotrienol, as well as vitamin E salts and vitamin E derivatives.

本說明書中，所謂「維生素A類」，除維生素A其本身以外，亦指維生素A油等含維生素A的混合物、維生素A脂肪酸酯等維生素A衍生物。In the present specification, "vitamin A" refers to vitamin A-containing mixtures such as vitamin A oil and vitamin A derivatives such as vitamin A fatty acid esters, in addition to vitamin A itself.

本說明書中，所謂「眼科用劑」，是指含有（A）羥丙基甲基纖維素及（B）維生素E類，且用於選自由防止眼脂生成、抑制鈍重感、緩和眼疲勞、緩和眼睛模糊、抑制充血、緩和羞明感及抑制眼睛發癢所組成的群組中的至少一種症狀改善的藥劑。In the present specification, the "ophthalmic agent" means selected from the group consisting of (A) hydroxypropyl methylcellulose and (B) vitamin E, and is selected from the group consisting of prevention of eye fat, suppression of dullness, relief of eye fatigue, An agent that relieves at least one of the symptoms of the group consisting of blurring eyes, suppressing congestion, reducing shame, and suppressing itching of eyes.

本說明書中，所謂「眼科用藥」，是指以滴眼劑或洗眼劑等產品形態對眼科用劑進行了指定者。In the present specification, the "ophthalmic drug" refers to a person who specifies an ophthalmic agent in the form of a product such as an eye drop or an eye wash.

[1. 眼科用劑] 眼科用劑為含有（A）羥丙基甲基纖維素及（B）維生素E類者。另外，眼科用劑較佳為更含有（C）維生素A類。[1. Ophthalmic preparations] Ophthalmic preparations are those containing (A) hydroxypropyl methylcellulose and (B) vitamin E. The ophthalmic agent preferably further contains (C) vitamin As.

（A）成分單獨僅稍微發揮緩和眼睛模糊的效能（參照比較例2）。另外，（B）成分單獨僅稍微發揮緩和眼疲勞的效能（參照比較例3）。 相對於此，組合含有（A）成分及（B）成分的眼科用劑與單獨含有（A）成分或（B）成分時相比，不僅提高緩和眼睛模糊與緩和眼疲勞的效能，而且達成如下的（A）成分或（B）成分單獨完全未發揮效能的症狀的緩和：防止眼脂生成、抑制鈍重感、抑制充血、緩和羞明感、抑制眼睛發癢。 另外，眼科用劑藉由更含有（C）成分而可使上述症狀改善的效能更優異。(A) The component alone has only a slight effect of reducing eye blur (see Comparative Example 2). In addition, the component (B) alone exhibited only a slight effect of reducing eye fatigue (see Comparative Example 3). On the other hand, the combination of the ophthalmic agent containing the component (A) and the component (B), compared with the case of containing the component (A) or (B) alone, not only improves the effectiveness of reducing eye blur and eye fatigue, but also achieves (A) or (B) of the component is not effective at all in relieving symptoms: prevention of eye fat production, suppression of dullness, suppression of congestion, relief of shame, suppression of itchy eyes. The ophthalmic agent can further improve the above-mentioned symptoms by further containing the component (C).

就製劑的外觀穩定性的觀點而言，由[（A）成分（W/V%）]/[（B）成分（W/V%）]表示的、（A）成分與（B）成分的比率較佳為0.02～200，更佳為0.03～150，進而較佳為0.04～100。 另外，由[（B）成分（W/V%）]/[（C）成分（（萬單位）/100 mL）]表示的、（B）成分與（C）成分的比率較佳為0.00005～0.5，更佳為0.000075～0.4，進而較佳為0.0001～0.25。 進而，由[（A）成分（W/V%）]/[（C）成分（（萬單位）/100 mL）]表示的、（A）成分與（C）成分的比率較佳為0.0001～1，更佳為0.00015～0.75，進而較佳為0.0002～0.5。From the viewpoint of the appearance stability of the preparation, the (A) component and the (B) component represented by [(A) component (W / V%)] / [(B) component (W / V%)] The ratio is preferably 0.02 to 200, more preferably 0.03 to 150, and still more preferably 0.04 to 100. In addition, the ratio of the (B) component to the (C) component represented by [(B) component (W / V%)] / [(C) component ((ten thousand units) / 100 mL)] is preferably 0.00005 to 0.5, more preferably 0.000075 to 0.4, and still more preferably 0.0001 to 0.25. Furthermore, the ratio of (A) component to (C) component represented by [(A) component (W / V%)] / [(C) component ((ten thousand units) / 100 mL)] is preferably 0.0001 to 1, more preferably 0.00015 to 0.75, and still more preferably 0.0002 to 0.5.

眼科用劑於防止眼脂生成、抑制鈍重感、緩和眼疲勞、緩和眼睛模糊、抑制充血、緩和羞明感、抑制眼睛發癢的效能方面優異。因此，可有效用於眼睛乾澀（目澀）症狀或乾眼症的治療用及預防用的至少任一者。The ophthalmic agent is excellent in the effectiveness of preventing the formation of eye fat, suppressing dullness, alleviating eye fatigue, alleviating eye blur, suppressing congestion, alleviating shame, and itching of eyes. Therefore, it can be effectively used for at least one of the treatment and prevention of dry eye symptoms and dry eye symptoms.

[2. （A）羥丙基甲基纖維素（亦稱羥丙甲纖維素）] 關於（A）成分，已知先前於醫療用滴眼劑的製劑設計･製造中是作為黏稠化劑來調配，且以提高藥物的結膜囊內滯留性、提高藥效的持續性或眼內轉移性為目的而使用（參照一般社團法人 日本眼科用劑協會HP）。即，（A）成分對其他藥效成分的效能進行輔助。 另一方面，含有（A）成分的眼科用劑發揮抑制眼睛模糊此一先前未知曉的基於未知屬性的效能。[2. (A) Hydroxypropyl methylcellulose (also known as hypromellose)] About component (A), it has been known that it was used as a thickener in the formulation design and manufacturing of medical eye drops. It is formulated and used for the purpose of improving the retention of the drug in the conjunctival sac, the continuity of the drug effect, or the intraocular metastasis (refer to the Japan Society of Ophthalmic Agents HP). That is, the component (A) assists the efficacy of other medicinal ingredients. On the other hand, an ophthalmic agent containing the component (A) exerts an effect based on an unknown attribute that suppresses blurring of the eyes, which has not been previously known.

就進一步發揮所期望的效能的方面而言，羥丙甲纖維素的重量平均分子量的下限值較佳為1萬（g/mol）以上，更佳為3萬（g/mol）以上，進而較佳為5萬（g/mol）以上。 另一方面，就進一步防止滴入眼睛後的不清晰的方面而言，上限值較佳為80萬（g/mol）以下，更佳為60萬（g/mol）以下，進而較佳為40萬（g/mol）以下。 再者，羥丙甲纖維素的重量平均分子量可藉由凝膠滲透層析-多角度雷射光散射（gel permeation chromatography-multi angle laser light scatting，GPC-MALLS）系統而測定。更詳細而言，可於以下條件下測定。 [測定條件] 管柱：ShodEx SB-806MHQ（管柱溫度：40℃） 溶離液：0.1 mol/L（NANO3：1.0 mL/min） 溶媒：0.1 mol/L（NANO3） 注入量：200 μL [裝置] 送液泵：ShodEx DS-4（昭和電工公司製造） 光散射檢測器（MALLS）：DAWN DSP 懷雅特技術公司（WyAtt TEchonology Corportion） 濃度檢測器：ShodEx R1-71（昭和電工公司製造）The lower limit of the weight-average molecular weight of hypromellose is preferably 10,000 (g / mol) or more, and more preferably 30,000 (g / mol) or more, in terms of further exerting desired performance. It is preferably 50,000 (g / mol) or more. On the other hand, in terms of further preventing unclearness after dripping into the eyes, the upper limit value is preferably 800,000 (g / mol) or less, more preferably 600,000 (g / mol) or less, and even more preferably Below 400,000 (g / mol). Furthermore, the weight average molecular weight of hypromellose can be measured by a gel permeation chromatography-multi angle laser light scatting (GPC-MALLS) system. More specifically, it can be measured under the following conditions. [Measurement conditions] Column: ShodEx SB-806MHQ (column temperature: 40 ° C) Eluent: 0.1 mol / L (NANO3: 1.0 mL / min) Solvent: 0.1 mol / L (NANO3) Injection volume: 200 μL [Device Liquid delivery pump: ShodEx DS-4 (manufactured by Showa Denko) Light scattering detector (MALLS): DAWN DSP WyAtt TEchonology Corportion Concentration detector: ShodEx R1-71 (manufactured by Showa Denko)

作為（A）成分，可使用市售品。作為所述市售品，可列舉信越化學工業公司製造的「梅特勞斯（METOLOSE）60SH-4000（重量平均分子量 約30萬（g/mol））」或「梅特勞斯（METOLOSE）60SH-50（重量平均分子量 約7萬（g/mol））」等。 再者，（A）成分可單獨使用一種，亦可將具有不同的重量平均分子量的（A）成分以任意的比例組合使用兩種以上。As (A) component, a commercial item can be used. Examples of the commercially available product include "METOLOSE 60SH-4000 (weight average molecular weight approximately 300,000 (g / mol))" or "METOLOSE 60SH" manufactured by Shin-Etsu Chemical Industry Co., Ltd. -50 (weight average molecular weight about 70,000 (g / mol)) "and so on. Moreover, (A) component may be used individually by 1 type, and (A) component which has a different weight average molecular weight may be used combining two or more types by arbitrary ratios.

（A）成分的濃度的下限值較佳為0.01 W/V%以上，更佳為0.05 W/V%以上。藉由為所述範圍，可發揮所期望的效能。 另一方面，上限值較佳為1 W/V%以下，更佳為0.8 W/V%以下，進而較佳為0.7 W/V%以下。藉由為該範圍，可使得難以產生滴入眼睛後的不清晰。The lower limit of the concentration of the component (A) is preferably 0.01 W / V% or more, and more preferably 0.05 W / V% or more. By setting it as the range, desired performance can be exhibited. On the other hand, the upper limit value is preferably 1 W / V% or less, more preferably 0.8 W / V% or less, and still more preferably 0.7 W / V% or less. By setting it as this range, it becomes difficult to generate the blur after dripping into an eye.

[3. （B）維生素E類] 已知（B）成分起到血液流通促進作用或抗氧化作用，可用於白內障治療用的滴眼劑中。 另一方面，含有（B）成分的眼科用劑發揮抑制眼睛疲勞此一先前未知曉的基於未知屬性的效能。[3. (B) Vitamin E] It is known that the component (B) can promote blood circulation or antioxidant, and can be used in eye drops for cataract treatment. On the other hand, an ophthalmic agent containing the component (B) exhibits a previously unknown effect based on unknown properties, which suppresses eye fatigue.

（B）成分只要為可用於眼科製劑的成分，則可無特別限制地使用。作為（B）成分，較佳為生殖酚、參雙鍵生殖酚等維生素E、該些的鹽、衍生物（酯）。 作為維生素E，例如可列舉：d-α-生殖酚、dl-α-生殖酚、β-生殖酚、γ-生殖酚、δ-生殖酚。 作為維生素E鹽，只要為醫藥上、藥理學上（製藥上）或生理學上容許者，則無特別限制。例如，可列舉與有機鹼的鹽（例如，與甲基胺、三乙基胺、三乙醇胺、嗎啉、哌嗪、吡咯啶、三吡啶、甲吡啶等有機胺的鹽）、與無機鹼的鹽（例如：銨鹽；鈉、鉀等鹼金屬鹽；鈣、鎂等鹼土金屬鹽；鋁等金屬鹽）。 作為維生素E衍生物，例如可列舉：維生素E乙酸酯（乙酸生殖酚）、維生素E煙鹼酸酯、維生素E琥珀酸酯、維生素E蘇子油酸酯。該些中，較佳為乙酸生殖酚（乙酸d-α-生殖酚、乙酸dl-α-生殖酚等）。(B) A component can be used without a restriction | limiting as long as it is a component which can be used for an ophthalmic preparation. The component (B) is preferably vitamin E such as reproductive phenol and ginseng double bond reproductive phenol, and salts and derivatives thereof. Examples of vitamin E include d-α-tocopherol, dl-α-tocopherol, β-tocopherol, γ-tocopherol, and δ-tocopherol. The vitamin E salt is not particularly limited as long as it is medically, pharmacologically (pharmaceutically), or physiologically acceptable. Examples include salts with organic bases (for example, salts with organic amines such as methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, and methylpyridine), and salts with inorganic bases. Salts (for example: ammonium salts; alkali metal salts such as sodium and potassium; alkaline earth metal salts such as calcium and magnesium; metal salts such as aluminum). Examples of the vitamin E derivative include vitamin E acetate (reproductive acetic acid acetate), vitamin E nicotinate, vitamin E succinate, and vitamin E threonine oleate. Among these, tocopherol acetate (d-α-tocopheryl acetate, dl-α-tocopherol acetate, etc.) is preferred.

（B）成分例如可較佳地使用日本藥典收載品等。 再者，（B）成分可單獨使用一種，亦可將生殖酚、參雙鍵生殖酚、其鹽或衍生物等不同種類的（B）成分以任意的比例組合使用兩種以上。As the component (B), for example, a Japanese Pharmacopoeia contained product can be preferably used. Furthermore, the (B) component may be used alone, or two or more different types of the (B) component such as reproductive phenol, ginseng double bond reproductive phenol, salts or derivatives thereof may be used in combination at an arbitrary ratio.

（B）成分的濃度的下限值較佳為0.005 W/V%以上，更佳為0.01 W/V%以上。藉由所述範圍，可發揮所期望的效能。 另一方面，上限值較佳為0.5 W/V%以下，更佳為0.2 W/V%以下。藉由該範圍，可使（B）成分可溶化，可維持外觀穩定性。The lower limit value of the concentration of the component (B) is preferably 0.005 W / V% or more, and more preferably 0.01 W / V% or more. With this range, desired performance can be exhibited. On the other hand, the upper limit value is preferably 0.5 W / V% or less, and more preferably 0.2 W / V% or less. Within this range, the component (B) can be dissolved and the appearance stability can be maintained.

[4. （C）維生素A類] 已知（C）成分起到促進黏液素產生的作用、治癒角膜創傷的作用。因此，（C）成分用作對淚液黏液素層的修復及角結膜障礙的治療發揮效果的、有效用於乾眼病治療的藥物。 另一方面，於眼科用劑中，（C）成分發揮抑制鈍重感、或在對促進可成為眼脂生成的原因的黏液素的產生起作用的同時可防止眼脂生成此一先前未知曉的基於未知屬性的效能。[4. (C) Vitamin A] The component (C) is known to play a role in promoting mucin production and healing corneal trauma. Therefore, the component (C) is used as a drug effective for the treatment of dry eye disease, which is effective in repairing the tear mucin layer and treating corneal and conjunctival disorders. On the other hand, in ophthalmic preparations, the component (C) suppresses dullness or promotes the production of mucin, which can cause the formation of eye fat, while preventing the production of eye fat. Power based on unknown attributes.

（C）成分只要為可用於眼科製劑的成分，則可無特別限制地使用。作為（C）成分，例如可列舉：視網醇（retinol）、視網醛（retinal）、視網酸（retinoic acid）、該些的3-脫氫體等維生素A群；維生素A油等含維生素A的混合物；維生素A脂肪酸酯等維生素A衍生物。 作為維生素A衍生物，詳細而言，可列舉：視網醇棕櫚酸酯、視網醇乙酸酯等。 作為（C）成分，較佳為視網醇棕櫚酸酯、視網醇乙酸酯、視網酸。(C) A component can be used without a restriction | limiting as long as it is a component which can be used for an ophthalmic preparation. Examples of the component (C) include vitamin A groups such as retinol, retinal, retinoic acid, and 3-dehydrogen; and vitamin A oil and the like A mixture of vitamin A; vitamin A derivatives such as vitamin A fatty acid esters. Specific examples of the vitamin A derivative include retinol palmitate, retinol acetate, and the like. As component (C), retinol palmitate, retinol acetate, and retinoid are preferred.

作為（C）成分，可使用市售品。例如，關於視網醇棕櫚酸酯，市售有100萬I.U.～180萬I.U.的產品。更詳細而言，可列舉日本羅氏維生素（Roche･Vitamin･Japan）公司製造的「視網醇棕櫚酸酯（170萬I.U./g）」；日本帝斯曼營養公司（DSM Nutrition Japan）製造的「視網醇棕櫚酸酯（174萬I.U./g）」等。 再者，（C）成分可單獨使用一種，亦可將視網醇、視網醛、視網酸、視網醇棕櫚酸酯、視網醇乙酸酯等不同種類的（C）成分以任意的比例組合使用兩種以上。As (C) component, a commercial item can be used. For example, about 1 million I.U. to 1.8 million I.U. are commercially available as retinol palmitate. More specifically, "Retinyl Palmitate (1.7 million IU / g)" manufactured by Roche, Vitamin, Japan; "DSM Nutrition Japan" Retinol palmitate (1.74 million IU / g) "and so on. Furthermore, the component (C) may be used singly, or different types of (C) components such as retinol, retinol, retinoid, retinol palmitate, and retinol acetate may be used arbitrarily. The ratio is used in combination of two or more.

（C）成分的量由利用第十六修訂版日本藥典維生素A定量法等中記載的方法而求出的國際單位（I.U.）來定義。 相對於眼科用劑的容量100 mL，（C）成分的量的下限值較佳為1萬I.U.以上，更佳為5萬I.U.以上。藉由為所述範圍，可更進一步提高所期望的效能。 另一方面，相對於眼科用劑的容量100 mL，（C）成分的量的上限值較佳為100萬I.U.以下，更佳為50萬I.U.以下。藉由為所述範圍，可維持（C）成分的穩定性。(C) The amount of the component is defined by the international unit (I.U.) determined by a method described in the 16th revised edition of the Japanese Pharmacopoeia Vitamin A Quantitative Method. The lower limit of the amount of the component (C) is preferably 10,000 I.U. or more, more preferably 50,000 I.U. or more, with respect to the capacity of the ophthalmic agent 100 mL. By setting it as the range, desired performance can be further improved. On the other hand, the upper limit of the amount of the component (C) is preferably 1 million I.U. or less, more preferably 500,000 I.U. or less, with respect to the volume of the ophthalmic agent 100 mL. By setting it as the said range, stability of (C) component can be maintained.

[5. 其他成分] 於眼科用劑中，可與無損本發明的效果的範圍內適量地調配其他成分。作為其他成分，可列舉：界面活性劑、防腐劑、糖類、緩衝劑、pH調整劑、等張化劑、穩定化劑、多元醇、黏稠劑、清涼化劑、藥物等。該些成分可單獨調配一種或適宜組合調配兩種以上。[5. Other components] In the ophthalmic agent, other components can be blended in an appropriate amount within a range that does not impair the effects of the present invention. Examples of the other components include surfactants, preservatives, sugars, buffers, pH adjusters, isotonic agents, stabilizers, polyols, thickeners, cooling agents, and drugs. These components can be formulated alone or in a suitable combination.

＜界面活性劑＞ 於界面活性劑中，例如可列舉：聚氧乙烯聚氧丙烯二醇、聚氧乙烯氫化蓖麻油、聚氧乙烯山梨糖醇酐油酸酯等聚氧乙烯山梨糖醇酐脂肪酸酯等非離子界面活性劑；烷基二胺基乙基甘胺酸等甘胺酸型兩性界面活性劑。就本申請案的症狀改善的方面而言，較佳為聚氧乙烯聚氧丙烯二醇。 界面活性劑的濃度較佳為0.0001 W/V%～15 W/V%，更佳為0.005 W/V%～10 W/V%。但就眼刺激性的方面而言，界面活性劑的濃度較佳為稀薄，更佳為5 W/V%以下。<Surfactant> Examples of the surfactant include polyoxyethylene sorbitan fats such as polyoxyethylene polyoxypropylene glycol, polyoxyethylene hydrogenated castor oil, and polyoxyethylene sorbitan oleate. Nonionic surfactants such as acid esters; glycine type amphoteric surfactants such as alkyldiaminoethylglycine. In terms of improvement of the symptoms of the present application, polyoxyethylene polyoxypropylene glycol is preferred. The concentration of the surfactant is preferably 0.0001 W / V% to 15 W / V%, and more preferably 0.005 W / V% to 10 W / V%. However, in terms of eye irritation, the concentration of the surfactant is preferably thinner, more preferably 5 W / V% or less.

＜防腐劑＞ 作為防腐劑，例如可列舉：氯化苄烷銨（benzalkonium chloride）、氯化苯釷（benzethonium chloride）、山梨酸鉀等山梨酸或其鹽、對羥基苯甲酸酯（對羥苯甲酸甲酯、對羥苯甲酸乙酯、對羥苯甲酸丙酯等）、葡萄糖酸洛赫西定（chlorhexidine gluconate）、乙汞硫柳酸鈉（thimerosal）、苯基乙基醇、鹽酸烷基二胺基乙基甘胺酸、泊利氯銨（Polidronium chloride）、鹽酸聚鹽酸己雙胍（Polihexanide chloride）。 防腐劑的濃度較佳為0.00001 W/V%～5 W/V%，更佳為0.0001 W/V%～3 W/V%，進而較佳為0.001 W/V%～2 W/V%。<Preservatives> Examples of the preservatives include sorbic acid or a salt thereof such as benzalconium chloride, benzethonium chloride, and potassium sorbate, and parabens (parabens) Methyl benzoate, ethyl paraben, propyl paraben, etc.), chlorhexidine gluconate, thimerosal, phenylethyl alcohol, alkane hydrochloride Diaminoethylglycine, Polidronium chloride, Polyhexanide chloride. The concentration of the preservative is preferably 0.00001 W / V% to 5 W / V%, more preferably 0.0001 W / V% to 3 W / V%, and still more preferably 0.001 W / V% to 2 W / V%.

＜糖類＞ 作為糖類，可列舉：葡糖等葡萄糖（glucose）、環糊精、木糖醇、山梨糖醇、甘露糖醇等。再者，該些可為d體、l體或dl體的任一者。 糖類的濃度較佳為0.001 W/V%～5.0 W/V%。<Sugars> Examples of the saccharides include glucose such as glucose, cyclodextrin, xylitol, sorbitol, and mannitol. Furthermore, these may be any of d-body, l-body, or dl-body. The sugar concentration is preferably from 0.001 W / V% to 5.0 W / V%.

＜緩衝劑＞ 作為緩衝劑，例如可列舉：檸檬酸、檸檬酸鈉、硼酸、硼砂、磷酸、磷酸氫鈉、磷酸二氫鈉、冰醋酸、氨丁三醇（trometamol）、碳酸氫鈉等。 緩衝劑的濃度較佳為0.001 W/V%～5.0 W/V%。<Buffering agent> Examples of the buffering agent include citric acid, sodium citrate, boric acid, borax, phosphoric acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, glacial acetic acid, trometamol, and sodium bicarbonate. The concentration of the buffering agent is preferably from 0.001 W / V% to 5.0 W / V%.

＜pH調整劑＞ 作為pH調整劑，較佳為使用無機酸或無機鹼劑。作為無機酸，例如可列舉（稀）鹽酸。作為無機鹼劑，例如可列舉：氫氧化鈉、氫氧化鉀、碳酸鈉、碳酸氫鈉。其中，較佳為鹽酸、氫氧化鈉。 pH調整劑的濃度較佳為0.00001 W/V%～10 W/V%，更佳為0.0001 W/V%～5 W/V%，進而較佳為0.001 W/V%～3 W/V%。<PH adjuster> As a pH adjuster, it is preferable to use an inorganic acid or an inorganic alkali agent. Examples of the inorganic acid include (dilute) hydrochloric acid. Examples of the inorganic alkali agent include sodium hydroxide, potassium hydroxide, sodium carbonate, and sodium bicarbonate. Among these, hydrochloric acid and sodium hydroxide are preferred. The concentration of the pH adjuster is preferably 0.00001 W / V% to 10 W / V%, more preferably 0.0001 W / V% to 5 W / V%, and still more preferably 0.001 W / V% to 3 W / V%. .

＜等張化劑＞ 作為等張化劑，例如可列舉：氯化鈉、氯化鉀。 等張化劑的濃度較佳為0.001 W/V%～5 W/V%，更佳為0.01 W/V%～3 W/V%，進而較佳為0.1 W/V%～2 W/V%。<Isotonicity agent> Examples of the isotonicity agent include sodium chloride and potassium chloride. The concentration of the isotonicity agent is preferably 0.001 W / V% to 5 W / V%, more preferably 0.01 W / V% to 3 W / V%, and still more preferably 0.1 W / V% to 2 W / V. %.

＜穩定化劑＞ 作為穩定化劑，例如可列舉依地酸鈉、環糊精、亞硫酸鹽、二丁基羥基甲苯等。 穩定化劑的濃度較佳為0.001 W/V%～5.0 W/V%。<Stabilizer> Examples of the stabilizer include sodium edetate, cyclodextrin, sulfite, and dibutylhydroxytoluene. The concentration of the stabilizer is preferably from 0.001 W / V% to 5.0 W / V%.

＜多元醇＞ 作為多元醇，可列舉：甘油、丙二醇、丁二醇、聚乙二醇等。 於調配多元醇的情況下，就對製劑穩定性帶來影響的方面而言，多元醇的濃度較佳為0.001 W/V%～5.0 W/V%，更佳為0.001 W/V%～1 W/V%。<Polyol> Examples of the polyol include glycerol, propylene glycol, butylene glycol, and polyethylene glycol. In the case of blending a polyol, the concentration of the polyol is preferably from 0.001 W / V% to 5.0 W / V%, and more preferably from 0.001 W / V% to 1 in terms of affecting the stability of the formulation. W / V%.

＜黏稠劑＞ 作為黏稠劑，例如可列舉：聚乙烯吡咯啶酮、羥乙基纖維素、甲基纖維素、聚乙烯醇、玻尿酸鈉、軟骨素硫酸鈉、聚丙烯酸、羧基乙烯聚合物等。 於調配黏稠劑的情況下，黏稠劑的濃度較佳為0.001 W/V%～5.0 W/V%。<Viscosity> Examples of the viscosity include polyvinylpyrrolidone, hydroxyethyl cellulose, methyl cellulose, polyvinyl alcohol, sodium hyaluronate, sodium chondroitin sulfate, polyacrylic acid, and carboxyvinyl polymer. In the case of blending a viscosity agent, the concentration of the viscosity agent is preferably 0.001 W / V% to 5.0 W / V%.

＜清涼化劑＞ 作為清涼化劑，例如可列舉：薄荷醇、樟腦、冰片（borneol）、香葉醇（geraniol）、桉油醇、沈香醇等。 於調配清涼化劑的情況下，清涼化劑的濃度較佳為0.0001 W/V%～0.1 W/V%。<Cooling agent> Examples of the cooling agent include menthol, camphor, borneol, geraniol, eucalyptol, and linalool. In the case of blending a cooling agent, the concentration of the cooling agent is preferably 0.0001 W / V% to 0.1 W / V%.

＜藥物＞ 作為藥物（藥學性有效成分），例如可列舉：充血消除成分（例如，腎上腺素、鹽酸腎上腺素、麻黃素鹽酸鹽、鹽酸四氫唑啉、萘甲唑啉鹽酸鹽、萘甲唑啉硝酸鹽、去氫腎上腺素鹽酸鹽（phenylephrine hydrochloride）、dl-甲基麻黃素鹽酸鹽等）、消炎･收斂劑（例如，新斯狄格明甲基硫酸鹽（neostigmine methyl sulfate）、ε-胺基己酸、尿囊素、氯化小蘖鹼水合物（berberine chloride hydrate）、硫酸小蘖鹼水合物、薁磺酸鈉、甘草酸二鉀、硫酸鋅、乳酸鋅、溶菌酵素鹽酸鹽等）、抗組胺劑（例如，苯海拉明鹽酸鹽、氯菲安明馬來酸鹽等）、水溶性維生素類（黃素腺嘌呤二核苷酸鈉、氰鈷胺、吡哆醇鹽酸鹽、泛醇、泛酸鈣、泛酸鈉等）、胺基酸類（例如，L-天冬胺酸鉀、L-天冬胺酸鎂、L-天冬胺酸鉀･鎂（等量混合物）、胺基乙基磺酸等）、磺胺劑等。 於調配藥物的情況下，關於藥物的濃度，可選擇各藥物的有效的適應性量，就對眼的刺激性、製劑的穩定性等方面而言，較佳為0.001 W/V%～5.0 W/V%。<Drugs> Examples of drugs (pharmaceutically effective ingredients) include decongestant components (eg, adrenaline, epinephrine hydrochloride, ephedrine hydrochloride, tetrahydrozoline hydrochloride, naphthozoline hydrochloride, Naphthozoline nitrate, phenylephrine hydrochloride, dl-methylephedrine hydrochloride, etc.), anti-inflammatory astringent agents (eg, neostigmine methyl sulfate (neostigmine) methyl sulfate), ε-aminocaproic acid, allantoin, berberine chloride hydrate, berberine sulfate hydrate, sodium sulfonate, dipotassium glycyrrhizinate, zinc sulfate, zinc lactate , Lysozyme hydrochloride, etc.), antihistamines (for example, diphenhydramine hydrochloride, chlorpheniramine maleate, etc.), water-soluble vitamins (flavin adenine dinucleotide sodium, Cyanocobalamin, pyridoxine hydrochloride, panthenol, calcium pantothenate, sodium pantothenate, etc., amino acids (eg, potassium L-aspartate, magnesium L-aspartate, L-aspartate) Potassium, magnesium (equivalent mixture), amino ethyl sulfonic acid, etc.), sulfonamides, etc. In the case of formulating drugs, regarding the concentration of the drug, an effective adaptive amount of each drug can be selected. In terms of irritation to the eyes and stability of the preparation, it is preferably 0.001 W / V% to 5.0 W / V%.

[6. 製備方法] 關於眼科用劑的製備方法，並無特別限制。例如，可藉由以下方法獲得：使難溶於水的維生素A與維生素E藉由聚氧乙烯聚氧丙烯二醇而溶解於殺菌精製水中，接著，於加入羥丙甲纖維素、各調配成分後對pH進行調整。其後，可無菌填充於適當的容器、例如聚對苯二甲酸乙二酯製的容器等中。[6. Preparation method] There is no particular limitation on the preparation method of the ophthalmic agent. For example, it can be obtained by dissolving vitamin A and vitamin E, which are hardly soluble in water, with polyoxyethylene polyoxypropylene glycol in sterilized and purified water, and then adding hypromellose and each compounding component. The pH was then adjusted. Thereafter, it can be aseptically filled in an appropriate container, for example, a container made of polyethylene terephthalate.

眼科用劑的pH（20℃）較佳為4.0～9.0，更佳為5.0～8.0，進而較佳為6.0～8.0。 再者，pH是使用pH滲壓計（「HOSM-1」；東亞DKK公司製造）於20℃下測定而得的值。The pH (20 ° C) of the ophthalmic agent is preferably 4.0 to 9.0, more preferably 5.0 to 8.0, and even more preferably 6.0 to 8.0. The pH is a value measured at 20 ° C using a pH osmometer ("HOSM-1"; manufactured by Toya DKK).

眼科用劑的黏度較佳為2.5 mPa･s～120 mPa･s，更佳為6 mPa･s～60 mPa･s。再者，黏度測定可於20℃下使用E型黏度計（例如，威斯康克（VISCONIC）ELD-R，東京計器公司製造）來進行。The viscosity of the ophthalmic agent is preferably 2.5 mPa ･ s to 120 mPa ･ s, and more preferably 6 mPa ･ s to 60 mPa ･ s. The viscosity measurement can be performed at 20 ° C using an E-type viscometer (for example, VISCONIC ELD-R, manufactured by Tokyo Keiki Co., Ltd.).

容器的包裝較佳為氧吸附枕型包裝，而非聚乙烯、聚對苯二甲酸乙二酯等的枕型包裝。藉此，可進一步提高（C）成分的穩定性。 再者，所謂「氧吸附枕型包裝」，是指使用了氧吸收劑練合膜的枕，該氧吸收劑練合膜能夠積極地將殘存於枕內的氧及自外部侵入的氧除去。The packaging of the container is preferably an oxygen-adsorbed pillow-type packaging, rather than a pillow-type packaging such as polyethylene, polyethylene terephthalate, and the like. This can further improve the stability of the (C) component. In addition, the "oxygen pillow type packaging" refers to a pillow using an oxygen absorber kneading film, which can actively remove oxygen remaining in the pillow and oxygen invading from the outside.

[7. 用途製劑] 眼科用劑為具有選自由眼脂生成防止劑、鈍重感抑制劑、眼疲勞緩和劑、眼睛模糊緩和劑、充血抑制劑、羞明感緩和劑及眼睛發癢抑制劑所組成的群組中的至少一種效能的用途製劑。[7. Use preparations] The ophthalmic agent is selected from the group consisting of an eye fat production inhibitor, a dullness inhibitor, an eye fatigue reducer, an eye blur reducer, a congestion inhibitor, a shame reliever, and an eye itching inhibitor. At least one potent use formulation in the group.

＜眼脂＞ 眼脂的成因在於結膜炎症、眼表黏液物質（黏液素）的分泌過多。作為眼脂的來源的滲出液自擴張的結膜血管滲出，經由結膜上皮到達眼表。於其中混合黏液物質（黏液素）或上皮細胞而成者即為眼脂。黏液素由結膜杯狀細胞分泌，其主要功能在於協助淚液留存於眼表、並且將來自外界之異物或細菌包裹而加以活化的防禦機制。自杯狀細胞的黏液素的分泌由副交感神經控制，因對眼表的刺激而分泌會變得過盛。通常情況下有時亦會於眼表出現眼脂。尤其於高溫環境下或起床時會分泌眼脂，此為正常的且常見的。<Eyeslipids> Eyelids are caused by conjunctival inflammation and excessive secretion of ocular surface mucus (mucin). The exudate, which is the source of ocular fat, exudates from the dilated conjunctival blood vessels and reaches the ocular surface through the conjunctival epithelium. Eyelids are made by mixing mucus (mucin) or epithelial cells. Mucin is secreted by conjunctival goblet cells, and its main function is to help the tear fluid stay on the surface of the eye, and it is a defense mechanism that activates foreign bodies or bacteria from the outside. The secretion of mucin from goblet cells is controlled by parasympathetic nerves, and secretion becomes excessive due to irritation to the ocular surface. Under normal circumstances, eyelids sometimes appear on the ocular surface. Eye fat is secreted especially in high temperature environments or when getting up. This is normal and common.

作為一般的眼脂的處置方法，建議用潔淨的紙巾、紗布、棉棒等擦除。但是，因物理性地進行去除，故有時會損傷眼表。另外，於非處方藥品製造銷售認可基準下的一般滴眼藥、人工淚液中，作為效能或效果，可不借助調配特定的有效成分而強調「眼睛模糊（眼脂多時等）」。因此，藉由滴入眼睛所帶來的沖洗效果，輕度的眼脂得到處置。然而，作為產生眼睛乾澀症狀時或乾眼症等重度的眼脂的處置，其效果並不充分。As a general treatment method for eyelids, it is recommended to wipe with clean paper towels, gauze, cotton swabs, etc. However, since the removal is performed physically, the ocular surface may be damaged. In addition, in general eye drops and artificial tears that are approved for the manufacture and sale of over-the-counter medicines, it is possible to emphasize "eye blur (long-term eye fat, etc.)" as an effect or effect without blending specific active ingredients. Therefore, with the rinsing effect brought by dripping into the eyes, mild eye fat is treated. However, it is not effective as a treatment for severe eye fat such as dry eye symptoms or dry eye symptoms.

於本發明的眼脂生成防止劑中調配有羥丙甲纖維素與維生素E類，因此抑制「眼脂的生成」，進而藉由調配維生素A類，可提高效果。尤其於產生眼睛乾澀症狀時或乾眼病中的「重度的眼脂生成防止」中，可發揮優異的效能。Hypromellose and vitamin E are blended in the anti-lipid production preventing agent of the present invention, and therefore, the "eye fat" is suppressed, and the effect can be improved by blending vitamin A. In particular, it has excellent efficacy when it produces dry eyes or "severe prevention of eye fat production" in dry eye disease.

＜鈍重感＞ 所謂鈍重，是指眼睛感到沉重的情況。於鈍重感的原因中，有起因於器質性疾病者、以及起因於心因性要素者。作為器質性疾病，有眼科疾病（調節性眼疲勞、眼肌性眼疲勞、青光眼、乾眼病等外眼部疾病，視神經疾病）以及顱內腫瘍等顱內疾病。作為處理方法，可列舉對作為原因的疾病進行治療，但迄今為止仍不知曉對鈍重感有效的對症療法。<Dullness> Dullness refers to a condition in which the eyes feel heavy. The causes of dullness include those caused by organic diseases and those caused by psychogenic factors. Organic diseases include ophthalmic diseases (external eye diseases such as accommodative eye fatigue, ocular muscle fatigue, glaucoma, dry eye disease, and optic nerve disease) and intracranial diseases such as intracranial ulcers. Examples of the treatment method include treating a disease as a cause, but a symptomatic treatment effective for bluntness has not been known so far.

於本發明的鈍重感抑制劑中調配有羥丙甲纖維素與維生素E類，因此抑制「鈍重感」，進而藉由調配維生素A類，可提高效果。尤其於產生眼睛乾澀症狀時或乾眼病中的「鈍重感的抑制」中，可發揮優異的效能。Hypromellose and vitamin E are blended in the dullness suppressing agent of the present invention, so that the "bluntness" is suppressed, and the effect can be improved by blending vitamin A. In particular, it exhibits excellent performance when it produces dryness symptoms or "inhibition of dullness" in dry eye disease.

＜眼疲勞＞ 眼疲勞的原因可列舉：近視、散光、老花眼、乾眼病、青光眼等眼睛的病症；齲齒或牙周病、糖尿病等身體的病症；使用個人電腦或智慧型手機等的生活環境；精神壓力等多種因素，會產生眼睛疲憊等症狀。作為先前的處理方法，可列舉：調整眼鏡、對眼睛滴入維生素B12、對眼睛滴入調節賦活劑、或藉由反復進行熱/冷敷而促進血液循環的方法等。然而，對於先前的對眼睛進行的滴入而言，有效果並不充分的課題，對於反復進行熱/冷敷的方法而言，有並不簡便的課題。＜ Eye fatigue> Causes of eye fatigue include: eye disorders such as myopia, astigmatism, presbyopia, dry eye disease, glaucoma; physical disorders such as dental caries or periodontal disease, diabetes; living environment using a personal computer or smartphone; Many factors, such as mental stress, can cause symptoms such as eye fatigue. Examples of the previous treatment method include a method of adjusting glasses, instilling vitamin B12 into the eyes, adjusting an activator into the eyes, or promoting blood circulation by repeatedly applying hot / cold compresses. However, there is a problem that the previous dripping to the eyes is insufficient, and there is a problem that is inconvenient for a method of repeatedly performing hot / cold compressing.

於本發明的眼疲勞緩和劑中調配有羥丙甲纖維素與維生素E類，因此緩和「眼疲勞」，進而藉由調配維生素A類，可提高效果。尤其於產生眼睛乾澀症狀時或乾眼病中的「眼疲勞的緩和」中，可發揮優異的效能。Hypromellose and vitamin E are blended in the eye fatigue relieving agent of the present invention. Therefore, "eye fatigue" is relieved, and the effect can be improved by blending vitamin A. In particular, it has excellent performance when it produces dry eyes or "relief of eye fatigue" in dry eye disease.

＜眼睛模糊＞ 於眼睛模糊的原因中，有起因於器質性疾病者、以及起因於心因性要素者。作為器質性疾病，可列舉：淚液的異常、結膜炎、角膜炎、白內障、眼疲勞等。作為處理方法，可列舉對作為原因的疾病進行治療，但迄今為止仍不知曉對眼睛模糊有效的對症療法。＜ Fuzzy eyes ＞ The causes of blurred eyes include those caused by organic diseases and those caused by psychogenic factors. Examples of the organic diseases include tear fluid abnormalities, conjunctivitis, keratitis, cataracts, and eye fatigue. Examples of the treatment method include treating a disease that is a cause, but a symptomatic treatment effective for blurring eyes has not been known so far.

於本發明的眼睛模糊緩和劑中調配有羥丙甲纖維素與維生素E類，因此緩和「眼睛模糊」，進而藉由調配維生素A類，可提高效果。尤其於產生眼睛乾澀症狀時或乾眼病中的「眼睛模糊的緩和」中，可發揮優異的效能。Hypromellose and vitamin E are blended in the eye blur reducing agent of the present invention, so that "eye blur" is relieved, and by blending vitamin A, the effect can be improved. In particular, it can exert excellent performance in the case of dry eyes or "eye blur reduction" in dry eye disease.

＜充血＞ 關於充血的原因，自感染性充血至過敏性充血、外傷性充血而範圍廣泛。作為處理方法，可列舉給予抗過敏劑、洗眼、對眼周邊部的冷卻等，但除該些以外，迄今為止仍不知曉對充血有效的對症療法。<Congestion> The cause of congestion ranges from infectious congestion to allergic congestion and traumatic congestion. Examples of the treatment method include administration of an antiallergic agent, eye washing, and cooling of the peripheral part of the eye. However, other than these, no symptomatic treatment effective for congestion has been known so far.

於本發明的充血抑制劑中調配有羥丙甲纖維素與維生素E類，因此抑制「充血」，進而藉由調配維生素A類，可提高效果。尤其於產生眼睛乾澀症狀時或乾眼病中的「充血的抑制」中，可發揮優異的效能。Hypromellose and vitamin E are blended in the congestion inhibitor of the present invention, so that "hyperemia" is suppressed, and the effect can be improved by blending vitamin A. In particular, it exhibits excellent efficacy in the "suppression of hyperemia" when dry eye symptoms occur or in dry eye disease.

＜羞明感＞ 所謂羞明，是指感覺到光刺眼的情況。作為羞明感的原因之一，可列舉角膜的異常，其是在因乾眼病等而於角膜產生損傷時容易出現的症狀。因此，對於損傷前的症狀緩和而言滴眼劑有效，但對於損傷後的症狀緩和而言，需要使用考慮到了傷口的滴眼劑。<Shame sense> The so-called shame sense refers to a situation in which light is dazzling. One of the causes of shame feeling is abnormality of the cornea, which is a symptom that easily occurs when the cornea is damaged due to dry eye disease or the like. Therefore, eye drops are effective for alleviating symptoms before injury, but for alleviating symptoms after injury, it is necessary to use eye drops in consideration of wounds.

於本發明的羞明感緩和劑中調配有羥丙甲纖維素與維生素E類，因此緩和「羞明感」，進而藉由調配維生素A類，可提高效果。尤其於產生眼睛乾澀症狀時或乾眼病中的「羞明感的緩和」中，可發揮優異的效能。Hypromellose and vitamin E are blended in the shame-relieving agent of the present invention, so the "shame feeling" is relieved, and the effect can be improved by blending vitamin A. In particular, it has excellent performance when it produces dry eyes or "relaxation of shame" in dry eye disease.

＜眼睛發癢＞ 眼睛發癢的主要原因為過敏性結膜炎。於乾眼病中淚液會減少，因此眼表的黏液素所形成的防禦機制並不充分，故眼睛發癢成為容易產生的症狀。因此，於利用滴眼劑進行處理的情況下，理想的是添加帶來過敏症狀的緩和的成分，但如上所述，在因乾眼病而於角膜產生損傷的情況下，有時不期望使用該成分。<Itchy eyes> The main cause of itchy eyes is allergic conjunctivitis. In dry eye disease, tears are reduced, so the defense mechanism formed by ocular surface mucin is not sufficient, so itchy eyes become a prone symptom. Therefore, in the case of treatment with eye drops, it is desirable to add a component that relieves allergic symptoms, but as described above, in the case of damage to the cornea due to dry eye disease, it may not be desirable to use this ingredient.

於本發明的眼睛發癢抑制劑中調配有羥丙甲纖維素與維生素E類，因此抑制「眼睛發癢」，進而藉由調配維生素A類，可提高效果。尤其於產生眼睛乾澀症狀時或乾眼病中的「眼睛發癢的抑制」中，可發揮優異的效能。Hypromellose and vitamin E are blended in the eye itching inhibitor of the present invention, so that "itching of the eyes" is suppressed, and the effect can be improved by blending vitamin A. In particular, it exhibits excellent performance when it produces dry eyes or "inhibition of eye itch" in dry eye disease.

[8. 適用疾病] 眼科用劑對眼脂生成、鈍重感、眼疲勞、眼睛模糊、充血、羞明感、眼睛發癢的症狀發揮優異的改善效果，因此，尤其可較佳地用作眼睛乾澀症狀或乾眼病的治療用及預防用的至少任一者。[Applicable diseases] Ophthalmic agents exhibit excellent improvement effects on the symptoms of eye fat formation, dullness, eye fatigue, blurry eyes, congestion, shame, and itchy eyes. Therefore, they are particularly suitable for dry eyes At least one of treatment and prevention of symptoms or dry eye disease.

[9. 眼科用藥] 本發明的眼科用藥使用上述眼科用劑。 作為本發明的眼科用藥，例如可列舉：滴眼劑、洗眼劑、注射劑、貼敷劑、凝膠、***劑。其中，較佳為滴眼劑。再者，該些可使用該領域中通用的通常技術來製備。進而，除上述以外，本發明的眼科用藥亦可製成眼內植入用製劑或微球（microsphere）等經藥物遞輸系統（Drug Delivery System，DDS）化的製劑。[9. Ophthalmic Medicine] The ophthalmic medicine of the present invention uses the above-mentioned ophthalmic medicine. Examples of the ophthalmic agent of the present invention include eye drops, eye wash agents, injections, patches, gels, and inserts. Among them, eye drops are preferred. Furthermore, these can be prepared using common techniques commonly used in the art. Furthermore, in addition to the above, the ophthalmic drug of the present invention can also be made into a drug delivery system (DDS) preparation such as an intraocular implant preparation or a microsphere.

滴眼劑及洗眼劑例如可視需要自氯化鈉、氯化鉀、濃甘油等等張化劑；磷酸鈉、乙酸鈉、ε-胺基己酸等緩衝化劑；聚氧乙烯山梨糖醇酐單油酸酯、硬氧乙烯脂酸酯40、聚氧乙烯氫化蓖麻油等界面活性劑；檸檬酸鈉、依地酸鈉等穩定化劑；氯化苄烷銨、對羥苯甲酸酯類等防腐劑中進行選擇使用來製備。pH只要為眼科製劑所容許的範圍內即可，通常較佳為4～8的範圍內。Eye drops and eye wash agents can be selected from sodium chloride, potassium chloride, concentrated glycerin, and other tonicity agents; buffering agents such as sodium phosphate, sodium acetate, and ε-aminohexanoic acid; polyoxyethylene sorbitan Surfactants such as monooleate, stearate 40, polyoxyethylene hydrogenated castor oil; stabilizers such as sodium citrate, sodium edetate; benzyl ammonium chloride, parabens, etc. Preservatives are selected for use. The pH may be within a range allowable for an ophthalmic preparation, and is usually preferably within a range of 4 to 8.

注射劑例如可視需要自氯化鈉等等張化劑；磷酸鈉等緩衝化劑；聚氧乙烯山梨糖醇酐單油酸酯等界面活性劑；甲基纖維素等增黏劑中進行選擇使用來製備。Injectables such as tonicizers such as sodium chloride; buffering agents such as sodium phosphate; surfactants such as polyoxyethylene sorbitan monooleate; optional thickeners such as methyl cellulose preparation.

***劑可藉由將羥丙基纖維素、羧基乙烯聚合物、聚丙烯酸等生物分解性聚合物與眼科用劑一起粉碎混合，並對該粉末進行壓縮成型來製備。再者，視需要可使用賦形劑、結合劑、穩定化劑、pH調整劑等。The insert can be prepared by pulverizing and mixing a biodegradable polymer such as hydroxypropyl cellulose, carboxyvinyl polymer, polyacrylic acid and an ophthalmic agent, and compressing the powder. Furthermore, if necessary, an excipient, a binding agent, a stabilizer, a pH adjuster, and the like can be used.

眼內植入用製劑例如可使用聚乳酸、聚乙醇酸、乳酸･乙醇酸共聚物、羥丙基纖維素等生物分解性聚合物來製備。Preparations for intraocular implants can be prepared using, for example, biodegradable polymers such as polylactic acid, polyglycolic acid, lactic acid / glycolic acid copolymer, and hydroxypropyl cellulose.

本發明的眼科用藥的用法可根據劑型、應給予患者的症狀的輕重、年齡、體重等而適宜地改變。例如，於作為劑形而選擇滴眼劑的情況下，可以一次10 μL～50 μL，一天分1次～10次、較佳為一天分2次～8次、更佳為一天分4次～6次對眼睛進行局部給藥來使用。The usage of the ophthalmic drug of the present invention can be appropriately changed according to the dosage form, the severity of the symptoms to be given to the patient, age, weight, and the like. For example, when eye drops are selected as the dosage form, 10 μL to 50 μL at a time may be used once to 10 times a day, preferably 2 to 8 times a day, and more preferably 4 times a day to The eye was administered topically 6 times.

軟性隱形眼鏡（soft contact lens）、硬性隱形眼鏡（hard contact lens）配戴者處於眼表容易乾燥，因配戴而感到眼睛模糊，且與裸眼相比更容易充血的狀態。本發明的眼科用藥較佳為軟性隱形眼鏡、矽水凝膠隱形眼鏡、硬性隱形眼鏡、透氧性硬性隱形眼鏡配戴者用，尤其較佳為強烈感覺到乾燥的軟性隱形眼鏡、矽水凝膠隱形眼鏡配戴者用。 另外，軟性隱形眼鏡、硬性隱形眼鏡配戴者處於角膜容易受損的狀態，容易受到防腐劑的影響。就該方面而言，本發明的眼科用藥亦較佳為不含有防腐劑而設為不調配防腐劑。 軟性隱形眼鏡、硬性隱形眼鏡配戴者存在當配戴隱形眼鏡時損傷眼睛，或者隱形眼鏡作為誘因而感染細菌性或病毒性的結膜炎，容易產生眼脂的情況。另外，因配戴隱形眼鏡，眼睛表面的水分減少，容易感到眼睛乾澀症狀及乾眼病的發作或鈍重感。因此，本發明的眼科用藥較佳為適用於軟性隱形眼鏡或硬性隱形眼鏡配戴者用。 [實施例]The wearers of soft contact lenses and hard contact lenses are in a state where the surface of the eye is easy to dry, the eyes are blurred due to wearing, and the state is more congested than the naked eye. The ophthalmic drug of the present invention is preferably for wearers of soft contact lenses, silicon hydrogel contact lenses, hard contact lenses, oxygen-permeable hard contact lenses, and particularly preferably soft contact lenses that strongly sense dryness, and silicone hydrogel For contact lens wearers. In addition, wearers of soft contact lenses and hard contact lenses are in a state where the cornea is easily damaged, and are easily affected by preservatives. In this respect, it is also preferable that the ophthalmic drug of the present invention does not contain a preservative and is not formulated with a preservative. The wearers of soft contact lenses and hard contact lenses may damage the eyes when wearing contact lenses, or contact lenses may induce bacterial or viral conjunctivitis, which may easily cause eye fat. In addition, wearing contact lenses reduces water on the surface of the eyes, making it easy to feel dry eyes and the onset or dullness of dry eye disease. Therefore, it is preferable that the ophthalmic drug of the present invention is suitable for wearers of soft contact lenses or hard contact lenses. [Example]

以下，藉由實施例對本發明進行更詳細說明。以下的實施例為用以對本發明進行較佳說明者，而非限定本發明者。Hereinafter, the present invention will be described in more detail through examples. The following examples are intended to better illustrate the present invention, but not to limit the present invention.

[黏度（mPa･s）] 關於實施例及比較例中製備的眼科用劑，使用E型黏度計（「威斯康克（VISCONIC）ELD-R」，東京計器公司製造），於20℃下進行黏度測定。[Viscosity (mPa ･ s)] For the ophthalmic preparations prepared in the examples and comparative examples, an E-type viscometer ("VISCONIC ELD-R", manufactured by Tokyo Keiki Co., Ltd.) was used at 20 ° C. The viscosity was measured.

[自覺症狀的評價] 於具有眼睛乾澀症狀、符合乾眼病診斷基準（新眼科24（2）：181～184，2007年）者中，以具有「眼脂」、「鈍重感」、「眼疲勞（眼睛疲憊）」、「眼睛模糊」、「充血」、「羞明感」、「眼睛發癢」的自覺症狀的7名組員進行試驗。作為預觀察期而設定為兩週，於預觀察期中，以一次一滴･一天六次對眼睛滴入預觀察期用滴眼藥（人工淚液「我的眼淚（MY TEAR）滴眼液（千壽製藥製造）」）。關於在預觀察期中自覺症狀未改善的5名組員，以一次一滴（約50 μL）･一天六次、四週對眼睛滴入被試驗藥，對自覺症狀的改善效果進行調查。 於開始給予被試驗藥時及給予被試驗藥後四週時對自覺症狀（7個項目）進行評價。[Evaluation of Symptoms] Among those who have dry eyes and meet the diagnostic criteria for dry eye disease (new ophthalmology 24 (2): 181-184, 2007), they have "eye fat", "bluntness", and "eye fatigue" (Strained eyes), 7 eyes with the symptoms of "blurred eyes", "hyperemia", "shame", and "itchy eyes" were tested. The pre-observation period is set to two weeks. During the pre-observation period, the eye drops are instilled in the pre-observation period (artificial tears "My Tear (MY TEAR) eye drops (Qianju) Pharmaceutical manufacturing) "). About the five group members who did not improve their subjective symptoms during the pre-observation period, the test drug was dripped into the eyes one drop at a time (about 50 μL) six times a day, and the effect of improving the subjective symptoms was investigated. The subjective symptoms (7 items) were evaluated at the beginning of the test drug administration and four weeks after the test drug administration.

再者，將組員得分的評分方法記述於下述表1中。The scoring method for the team members' scores is described in Table 1 below.

[表1] [Table 1]

將自給予被試驗藥四週時的各自覺症狀的得分的評分值減去開始給予被試驗藥時的得分的評分值而得的值設為對象組員的得分的變化量，關於對象組員的得分的變化量除以5名組員而平均化後的值，以下述基準進行自覺症狀的評價。 優：於給予被試驗藥後四週時，自覺症狀的得分的變化量較開始給予被試驗藥時改善0.5分以上 良：於給予被試驗藥後四週時，自覺症狀的得分的變化量較開始給予被試驗藥時改善0.3分以上～未滿0.5分 可：於給予被試驗藥後四週時，自覺症狀的得分的變化量較開始給予被試驗藥時改善超過0分～未滿0.3分 不良：無改善效果A value obtained by subtracting a score value of a score at the start of administration of the test drug from a score value of the respective symptoms at the time of administration of the test drug was set as the amount of change in the score of the target group member. The amount of change was divided by 5 members and averaged, and the subjective symptoms were evaluated on the basis of the following criteria. Excellent: Four weeks after the test drug was given, the change in the score of the subjective symptoms was improved by more than 0.5 points compared with the time when the test drug was started. Good: Four weeks after the test drug was given, the change in the score of the subjective symptoms was higher than the start. When the test drug is improved by 0.3 points or more and less than 0.5 points, the change in the score of the subjective symptoms is improved by more than 0 points to less than 0.3 points when the test drug is administered. Improve effect

（比較例1） 將聚氧乙烯（200）聚氧丙烯（70）二醇1.0 g與氯化鈉0.9 g溶解於精製水中，製備眼科用劑（被試驗藥）100 mL。使用所製備的眼科用劑，進行自覺症狀的評價。將結果記載於表2中。(Comparative Example 1) 100 g of polyoxyethylene (200) polyoxypropylene (70) diol and 0.9 g of sodium chloride were dissolved in purified water to prepare an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 2.

（比較例2） 將羥丙甲纖維素0.15 g（信越化學工業公司製造，「梅特勞斯（METOLOSE）60SH-4000」）與聚氧乙烯（200）聚氧丙烯（70）二醇1.0 g以及氯化鈉0.9 g溶解於精製水中，製備眼科用劑（被試驗藥）100 mL。使用所製備的眼科用劑，進行自覺症狀的評價。將結果記載於表2中。(Comparative Example 2) 0.15 g of hypromellose ("METOLOSE 60SH-4000" manufactured by Shin-Etsu Chemical Co., Ltd.) and 1.0 g of polyoxyethylene (200) polyoxypropylene (70) glycol And 0.9 g of sodium chloride was dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 2.

（比較例3） 將乙酸d-α-生殖酚0.05 g（理研維生素公司製造，「理研乙酸酯α」）、將聚氧乙烯（200）聚氧丙烯（70）二醇1.0 g溶解於精製水中，然後將氯化鈉0.9 g溶解於精製水中，製備眼科用劑（被試驗藥）100 mL。使用所製備的眼科用劑，進行自覺症狀的評價。將結果記載於表2中。(Comparative Example 3) 0.05 g of d-α-reproductive acetic acid ("RIKEN acetate α" manufactured by Riken Vitamin Co.) and 1.0 g of polyoxyethylene (200) polyoxypropylene (70) diol were dissolved in a purified product In water, 0.9 g of sodium chloride was dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 2.

（實施例1） 將乙酸d-α-生殖酚0.05 g（理研維生素公司製造，「理研乙酸酯α」）藉由聚氧乙烯（200）聚氧丙烯（70）二醇1.0 g溶解於精製水中，然後將羥丙甲纖維素0.15 g（信越化學工業公司製造，「梅特勞斯（METOLOSE）60SH-4000」；重量平均分子量 約30萬）與氯化鈉0.9 g溶解於精製水中，製備眼科用劑（被試驗藥）100 mL。所製備的眼科用劑於20℃下的黏度為7 mPa･s，於20℃下的pH為7.1。使用所製備的眼科用劑，進行自覺症狀的評價。將結果記載於表2、表4中。(Example 1) 0.05 g of d-α-tocopherol acetate (manufactured by RIKEN Vitamin Co., Ltd., "RIKEN acetate α") was dissolved in 1.0 g of polyoxyethylene (200) polyoxypropylene (70) diol and refined In water, 0.15 g of hypromellose ("METOLOSE 60SH-4000" manufactured by Shin-Etsu Chemical Industry Co., Ltd .; weight average molecular weight about 300,000) and 0.9 g of sodium chloride were dissolved in purified water to prepare Ophthalmic agent (test drug) 100 mL. The viscosity of the prepared ophthalmic agent was 7 mPa 为 s at 20 ° C, and the pH was 7.1 at 20 ° C. The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are described in Tables 2 and 4.

（實施例2） 將乙酸d-α-生殖酚0.05 g（理研維生素公司製造，「理研乙酸酯α」）與視網醇棕櫚酸酯5萬I.U.（日本羅氏維生素（Roche･Vitamin･Japan）公司製造，「棕櫚酸視網醇酯」）藉由聚氧乙烯（200）聚氧丙烯（70）二醇1.0 g溶解於精製水中，然後將羥丙甲纖維素0.15 g（信越化學工業公司製造，「梅特勞斯（METOLOSE）60SH-4000」）與氯化鈉0.9 g溶解於精製水中，製備眼科用劑（被試驗藥）100 mL。所製備的眼科用劑於20℃下的黏度為7 mPa･s，於20℃下的pH為7.1。使用所製備的眼科用劑，進行自覺症狀的評價。將結果記載於表2～表5中。(Example 2) 0.05 g of d-α-tocopherol acetate (manufactured by RIKEN Vitamin Co., Ltd., "RIKEN acetate α") and 50,000 IU of retinol palmitate (RocheRoVitamin ･ Japan) Manufactured by the company, “Retinyl palmitate”) 1.0 g of polyoxyethylene (200) polyoxypropylene (70) diol was dissolved in purified water, and then 0.15 g of hypromellose (manufactured by Shin-Etsu Chemical Co., Ltd.) "METOLOSE 60SH-4000") and 0.9 g of sodium chloride were dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The viscosity of the prepared ophthalmic agent was 7 mPa 为 s at 20 ° C, and the pH was 7.1 at 20 ° C. The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are described in Tables 2 to 5.

[表2] [Table 2]

根據比較1的結果可知，不含有效成分的眼科用劑完全不會產生所期望的效能。另外，根據比較例2及比較例3的結果，關於單獨含有（A）成分或（B）成分的眼科用劑，僅輕微地觀察到緩和眼疲勞或緩和眼睛模糊的效能，且未觀察到其他自覺症狀的改善效果。 另一方面，根據實施例1的結果，含有（A）成分及（B）成分的本發明的眼科用劑與分別單獨含有的情況相比，不僅緩和眼疲勞或緩和眼睛模糊的效能提高，而且發揮完全未曾觀察到自覺症狀的改善的、所期望的抑制鈍重感、防止眼脂生成、抑制充血、緩和羞明感、抑制眼睛發癢的效能，尤其於眼疲勞（眼睛疲憊）的效能方面優異。另外，根據實施例2的結果，於更含有（C）成分的情況下，於維持緩和眼疲勞的效果的狀態下，緩和眼睛模糊、抑制鈍重感、防止眼脂生成、抑制充血、緩和羞明感、抑制眼睛發癢的效能均進一步優異。 根據該些結果可知，組合含有（A）成分與（B）成分的眼科用劑可作為用作眼睛模糊緩和劑、鈍重感抑制劑、眼脂生成防止劑、充血抑制劑、羞明感緩和劑、眼睛發癢抑制劑的用途製劑來加以利用。From the results of Comparative 1, it can be seen that the ophthalmic agent containing no active ingredient does not produce the desired efficacy at all. In addition, based on the results of Comparative Examples 2 and 3, with regard to ophthalmic agents containing the component (A) or component (B) alone, only the effect of reducing eye fatigue or reducing eye blur was slightly observed, and no other was observed. Amelioration of subjective symptoms. On the other hand, according to the results of Example 1, the ophthalmic agent of the present invention containing the component (A) and the component (B) has an improved effect of reducing eye fatigue or blurring the eyes, as compared with the case where it is contained alone. It exhibits the desired effects of suppressing dullness, preventing eye fat production, suppressing congestion, alleviating shame, and suppressing itching of the eyes, without any improvement in subjective symptoms being observed. It is particularly excellent in terms of eye fatigue (eye fatigue). In addition, according to the results of Example 2, when the component (C) is further contained, while maintaining the effect of alleviating eye fatigue, the eyes are relieved of blurring, bluntness is suppressed, eye fat is prevented, hyperemia is suppressed, and shame is relieved. , The effect of suppressing itching of the eyes is further excellent. From these results, it can be seen that an ophthalmic agent containing the component (A) and the component (B) can be used as an eye blur reducer, a dullness inhibitor, an eye fat production preventive agent, a congestion inhibitor, a shame reliever, A preparation for the use of an eye itch inhibitor.

（實施例3） 將乙酸d-α-生殖酚0.05 g（理研維生素公司製造，「理研乙酸酯α」）與視網醇棕櫚酸酯5萬I.U.（日本羅氏維生素（Roche･Vitamin･Japan）公司製造，「棕櫚酸視網醇酯」）藉由聚氧乙烯（200）聚氧丙烯（70）二醇1.0 g溶解於精製水中，然後將羥丙甲纖維素0.15 g（信越化學工業公司製造，「梅特勞斯（METOLOSE）60SH-50」；重量平均分子量 約7萬）與氯化鈉0.9 g溶解於精製水中，製備眼科用劑（被試驗藥）100 mL。使用所製備的眼科用劑，進行自覺症狀的評價。將結果記載於表3中。(Example 3) 0.05 g of d-α-reproductive acetic acid (manufactured by RIKEN Vitamin Co., Ltd., "RIKEN acetate α") and 50,000 IU of retinol palmitate (Roche ･ Vitamin ･ Japan) Manufactured by the company, “Retinyl palmitate”) 1.0 g of polyoxyethylene (200) polyoxypropylene (70) diol was dissolved in purified water, and then 0.15 g of hypromellose (manufactured by Shin-Etsu Chemical Co., Ltd.) "METOLOSE 60SH-50"; a weight-average molecular weight of about 70,000) and 0.9 g of sodium chloride were dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 3.

[表3] [table 3]

根據實施例2及實施例3的結果，使用重量平均分子量大的（A）成分的眼科用劑為防止眼脂生成、抑制鈍重感、抑制眼睛模糊、抑制眼睛發癢的效能優異者。Based on the results of Examples 2 and 3, the ophthalmic agent using the component (A) having a large weight average molecular weight is one having excellent efficacy in preventing the production of eye fat, suppressing dullness, suppressing blurring of the eyes, and suppressing itching of the eyes.

（實施例4） 將乙酸d-α-生殖酚0.05 g（理研維生素公司製造，「理研乙酸酯α」）與視網醇棕櫚酸酯3萬I.U.（日本羅氏維生素（Roche･Vitamin･Japan）公司製造，「棕櫚酸視網醇酯」）藉由聚氧乙烯（200）聚氧丙烯（70）二醇1.0 g溶解於精製水中，然後將羥丙甲纖維素0.15 g（信越化學工業公司製造，「梅特勞斯（METOLOSE）60SH-4000」）與氯化鈉0.9 g溶解於精製水中，製備眼科用劑（被試驗藥）100 mL。使用所製備的眼科用劑，進行自覺症狀的評價。將結果記載於表4中。(Example 4) 0.05 g of d-α-tocopherol acetate (manufactured by RIKEN Vitamin Co., Ltd., "RIKEN acetate α") and 30,000 IU of retinol palmitate (Roche ･ Vitamin ･ Japan) Manufactured by the company, “Retinyl palmitate”) 1.0 g of polyoxyethylene (200) polyoxypropylene (70) diol was dissolved in purified water, and then 0.15 g of hypromellose (manufactured by Shin-Etsu Chemical Co., Ltd.) "METOLOSE 60SH-4000") and 0.9 g of sodium chloride were dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 4.

（實施例5） 將乙酸d-α-生殖酚0.05 g（理研維生素公司製造，「理研乙酸酯α」）與視網醇棕櫚酸酯15萬I.U.（日本羅氏維生素（Roche･Vitamin･Japan）公司製造，「棕櫚酸視網醇酯」）藉由聚氧乙烯（200）聚氧丙烯（70）二醇3.0 g溶解於精製水中，然後將羥丙甲纖維素0.15 g（信越化學工業公司製造，「梅特勞斯（METOLOSE）60SH-4000」）與氯化鈉0.9 g溶解於精製水中，製備眼科用劑（被試驗藥）100 mL。使用所製備的眼科用劑，進行自覺症狀的評價。將結果記載於表4中。(Example 5) 0.05 g of d-α-reproductive acetic acid (manufactured by RIKEN Vitamin Co., Ltd., "RIKEN acetate α") and 150,000 IU of retinol palmitate (Roche ･ Vitamin ･ Japan) Manufactured by the company, "Retinyl palmitate") 3.0 g of polyoxyethylene (200) polyoxypropylene (70) diol was dissolved in purified water, and then 0.15 g of hypromellose (manufactured by Shin-Etsu Chemical Co. "METOLOSE 60SH-4000") and 0.9 g of sodium chloride were dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 4.

（實施例6） 將乙酸d-α-生殖酚0.05 g（理研維生素公司製造，「理研乙酸酯α」）與視網醇棕櫚酸酯30萬I.U.（日本羅氏維生素（Roche･Vitamin･Japan）公司製造，「棕櫚酸視網醇酯」）藉由聚氧乙烯（200）聚氧丙烯（70）二醇5.0 g溶解於精製水中，然後將羥丙甲纖維素0.15 g（信越化學工業公司製造，「梅特勞斯（METOLOSE）60SH-4000」）與氯化鈉0.9 g溶解於精製水中，製備眼科用劑（被試驗藥）100 mL。使用所製備的眼科用劑，進行自覺症狀的評價。將結果記載於表4中。(Example 6) 0.05 g of d-α-reproductive acetic acid (manufactured by RIKEN Vitamin Co., Ltd., "RIKEN acetate α") and 300,000 IU of retinol palmitate (Roche, Vitamin, Japan) Manufactured by the company, "Retinyl palmitate") 5.0 g of polyoxyethylene (200) polyoxypropylene (70) glycol was dissolved in purified water, and then 0.15 g of hypromellose (manufactured by Shin-Etsu Chemical Co. "METOLOSE 60SH-4000") and 0.9 g of sodium chloride were dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 4.

（實施例7） 將乙酸d-α-生殖酚0.05 g（理研維生素公司製造，「理研乙酸酯α」）與視網醇棕櫚酸酯50萬I.U.（日本羅氏維生素（Roche･Vitamin･Japan）公司製造，「棕櫚酸視網醇酯」）藉由聚氧乙烯（200）聚氧丙烯（70）二醇5.0 g溶解於精製水中，然後將羥丙甲纖維素0.15 g（信越化學工業公司製造，「梅特勞斯（METOLOSE）60SH-4000」）與氯化鈉0.9 g溶解於精製水中，製備眼科用劑（被試驗藥）100 mL。使用所製備的眼科用劑，進行自覺症狀的評價。將結果記載於表4中。(Example 7) 0.05 g of d-α-reproductive acetic acid (manufactured by RIKEN Vitamin Co., Ltd., “RIKEN acetate α”) and retinol palmitate 500,000 IU (Roche ･ Vitamin ita Japan) Manufactured by the company, "Retinyl palmitate") 5.0 g of polyoxyethylene (200) polyoxypropylene (70) glycol was dissolved in purified water, and then 0.15 g of hypromellose (manufactured by Shin-Etsu Chemical Co., Ltd.) "METOLOSE 60SH-4000") and 0.9 g of sodium chloride were dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 4.

[表4] [Table 4]

根據實施例1、實施例4的結果，若更含有3萬I.U.的（C）成分，則抑制充血與緩和眼睛發癢的效能得到改善。另外，根據實施例2、實施例5～實施例7的結果，若（C）成分的量為5萬I.U.以上，則防止眼脂生成、抑制鈍重感、緩和眼疲勞（眼睛疲憊）、緩和眼睛模糊、抑制充血、緩和羞明感、抑制眼睛發癢的效能均優異。 根據該些結果可知，於將除（A）成分與（B）成分以外更含有（C）成分的眼科用劑作為用作眼睛模糊緩和劑、鈍重感抑制劑、眼脂生成防止劑、充血抑制劑、羞明感緩和劑、眼睛發癢抑制劑的用途製劑來加以利用的情況下，（C）成分的量較佳為5萬I.U.以上。According to the results of Example 1 and Example 4, if the component (C) of 30,000 I.U. is further contained, the effect of suppressing hyperemia and alleviating eye itch is improved. In addition, according to the results of Example 2, Example 5 to Example 7, if the amount of the (C) component is 50,000 IU or more, the production of eye fat is prevented, the dullness is suppressed, the eye fatigue (eye fatigue) is relieved, and the eyes are relieved. It is excellent in blurring, suppressing congestion, alleviating shame, and suppressing itchy eyes. From these results, it can be seen that ophthalmic agents containing the component (C) in addition to the components (A) and (B) are used as an eye blur reducer, a dullness suppressor, an agent for preventing eye fat production, and a hyperemia inhibitor. In the case of using an agent, a stigma mitigating agent, or an eye itching inhibitor, the amount of the component (C) is preferably 50,000 IU or more.

（實施例8） 將乙酸d-α-生殖酚0.05 g（理研維生素公司製造，「理研乙酸酯α」）與視網醇棕櫚酸酯5萬I.U.（日本羅氏維生素（Roche･Vitamin･Japan）公司製造，「棕櫚酸視網醇酯」）藉由聚氧乙烯（200）聚氧丙烯（70）二醇0.2 g溶解於精製水中，然後將羥丙甲纖維素0.15 g（信越化學工業公司製造，「梅特勞斯（METOLOSE）60SH-4000」）與氯化鈉0.9 g溶解於精製水中，製備眼科用劑（被試驗藥）100 mL。使用所製備的眼科用劑，進行自覺症狀的評價。將結果記載於表5中。(Example 8) 0.05 g of d-α-reproductive acetic acid (manufactured by RIKEN Vitamin Co., Ltd., "RIKEN acetate α") and 50,000 IU of retinol palmitate (RocheitaVitamin ･ Japan) Manufactured by the company, "Retinyl palmitate" was dissolved in purified water with 0.2 g of polyoxyethylene (200) polyoxypropylene (70) diol, and then 0.15 g of hypromellose (manufactured by Shin-Etsu Chemical Industry Co., Ltd.) "METOLOSE 60SH-4000") and 0.9 g of sodium chloride were dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 5.

（實施例9） 將乙酸d-α-生殖酚0.05 g（理研維生素公司製造，「理研乙酸酯α」）與視網醇棕櫚酸酯5萬I.U.（日本羅氏維生素（Roche･Vitamin･Japan）公司製造，「棕櫚酸視網醇酯」）藉由聚氧乙烯（200）聚氧丙烯（70）二醇0.3 g溶解於精製水中，然後將羥丙甲纖維素0.15 g（信越化學工業公司製造，「梅特勞斯（METOLOSE）60SH-4000」）與氯化鈉0.9 g溶解於精製水中，製備眼科用劑（被試驗藥）100 mL。使用所製備的眼科用劑，進行自覺症狀的評價。將結果記載於表5中。(Example 9) 0.05 g of d-α-reproductive acetic acid (manufactured by RIKEN Vitamin Co., Ltd., "RIKEN acetate α") and 50,000 IU of retinol palmitate (Roche ･ Vitamin ･ Japan) Manufactured by the company, "Retinyl palmitate") 0.3 g of polyoxyethylene (200) polyoxypropylene (70) diol was dissolved in purified water, and then 0.15 g of hypromellose (manufactured by Shin-Etsu Chemical Co., Ltd.) "METOLOSE 60SH-4000") and 0.9 g of sodium chloride were dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 5.

（實施例10） 將乙酸d-α-生殖酚0.05 g（理研維生素公司製造，「理研乙酸酯α」）與視網醇棕櫚酸酯5萬I.U.（日本羅氏維生素（Roche･Vitamin･Japan）公司製造，「棕櫚酸視網醇酯」）藉由聚氧乙烯（200）聚氧丙烯（70）二醇0.4 g溶解於精製水中，然後將羥丙甲纖維素0.15 g（信越化學工業公司製造，「梅特勞斯（METOLOSE）60SH-4000」）與氯化鈉0.9 g溶解於精製水中，製備眼科用劑（被試驗藥）100 mL。使用所製備的眼科用劑，進行自覺症狀的評價。將結果記載於表5中。(Example 10) 0.05 g of d-α-reproductive acetic acid (manufactured by RIKEN Vitamin Co., Ltd., "RIKEN acetate α") and 50,000 IU of retinol palmitate (Roche, Vitamin, Japan) Manufactured by the company, "Retinyl palmitate" was dissolved in purified water with 0.4 g of polyoxyethylene (200) polyoxypropylene (70) diol, and then 0.15 g of hypromellose (manufactured by Shin-Etsu Chemical Co., Ltd.) "METOLOSE 60SH-4000") and 0.9 g of sodium chloride were dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 5.

[表5] [table 5]

若將聚氧乙烯（200）聚氧丙烯（70）二醇的量減少至0.2 W/V%，則緩和眼睛模糊的效能少許降低（參照實施例8）。另一方面，若聚氧乙烯（200）聚氧丙烯（70）二醇的量為0.3 W/V%以上，則防止眼脂生成、抑制鈍重感、緩和眼疲勞（眼睛疲憊）、緩和眼睛模糊、抑制充血、緩和羞明感、抑制眼睛發癢的效能均優異（參照實施例2、實施例9～實施例10）。When the amount of polyoxyethylene (200) polyoxypropylene (70) diol is reduced to 0.2 W / V%, the effect of reducing eye blur is slightly reduced (see Example 8). On the other hand, if the amount of polyoxyethylene (200) and polyoxypropylene (70) diol is 0.3 W / V% or more, it prevents the formation of eye fat, suppresses dullness, relieves eye fatigue (eye fatigue), and reduces eye blur. , The effect of suppressing congestion, alleviating shame, and suppressing itching of the eyes are excellent (refer to Example 2, Example 9 to Example 10).

以下記述將眼科用劑應用於本發明的眼科用藥時的處方例。 1.滴眼劑 [表6] The following describes prescription examples when an ophthalmic agent is applied to the ophthalmic agent of the present invention. 1. Eye drops [Table 6]

將表6中製備處方例1～處方例5的滴眼劑時使用的原料示於以下。 ･聚氧乙烯（200）聚氧丙烯（70）二醇： 「尤尼勞博（UNILUB）70DP-950B」，藥添規，日油公司製造，或者「勞托洛（Lutrol）F127」，藥添規，巴斯夫（BASF）公司製造 ･羥丙基甲基纖維素（羥丙甲纖維素）： 「梅特勞斯（METOLOSE）60SH-4000」，日本藥典，信越化學工業公司製造，重量平均分子量30萬（g/mol） ･單油酸聚氧乙烯（20）山梨糖醇酐（聚山梨糖醇酯80）：「萊奧道魯（Rheodol）TW-0120V」，日本藥典，花王公司製造 ･聚氧乙烯氫化蓖麻油60： 「HCO-60（醫藥用）」，藥添規，日光化學公司製造The raw materials used when preparing the eye drops of Formulation Examples 1 to 5 in Table 6 are shown below. ･ Polyoxyethylene (200) polyoxypropylene (70) diol: "UNILUB 70DP-950B", Yasushi Kiyoshi, manufactured by Nippon Oil Company, or "Lutrol F127", Yasushi Shiki , Basf (BASF) company made 纤维素 hydroxypropyl methylcellulose (hypromellose): "METOLOSE 60SH-4000", manufactured by the Japanese Pharmacopoeia, Shin-Etsu Chemical Industry Co., Ltd., weight average molecular weight 300,000 (G / mol) ･ Monooleic acid polyoxyethylene (20) Sorbitan (Polysorbate 80): "Reoodol TW-0120V", Japanese Pharmacopoeia, Kao Corporation ･ Polyoxygen Ethylene hydrogenated castor oil 60: "HCO-60 (for medical use)", medicinal supplement, manufactured by Nikko Chemical Co., Ltd.

[表7] [TABLE 7]

將表7中製備處方例6～處方例10的滴眼劑時使用的原料示於以下。 ･聚氧乙烯（200）聚氧丙烯（70）二醇： 「尤尼勞博（UNILUB）70DP-950B」，藥添規，日油公司製造，或者「勞托洛（Lutrol）F127」，藥添規，巴斯夫（BASF）公司製造 ･羥丙基甲基纖維素（羥丙甲纖維素）： 「梅特勞斯（METOLOSE）60SH-4000」，日本藥典，信越化學工業公司製造，重量平均分子量30萬（g/mol） ･單油酸聚氧乙烯（20）山梨糖醇酐（聚山梨糖醇酯80）：「萊奧道魯（Rheodol）TW-0120V」，日本藥典，花王公司製造 ･聚氧乙烯氫化蓖麻油60： 「HCO-60（醫藥用）」，藥添規，日光化學公司製造The raw materials used when preparing the eye drops of Formulation Examples 6 to 10 in Table 7 are shown below. ･ Polyoxyethylene (200) polyoxypropylene (70) diol: "UNILUB 70DP-950B", Yasushi Kiyoshi, manufactured by Nippon Oil Company, or "Lutrol F127", Yasushi Shiki , Basf (BASF) company made 纤维素 hydroxypropyl methylcellulose (hypromellose): "METOLOSE 60SH-4000", manufactured by the Japanese Pharmacopoeia, Shin-Etsu Chemical Industry Co., Ltd., weight average molecular weight 300,000 (G / mol) ･ Monooleic acid polyoxyethylene (20) Sorbitan (Polysorbate 80): "Reoodol TW-0120V", Japanese Pharmacopoeia, Kao Corporation ･ Polyoxygen Ethylene hydrogenated castor oil 60: "HCO-60 (for medical use)", medicinal supplement, manufactured by Nikko Chemical Co., Ltd.

2.洗眼劑 [表8] 2. Eyewash [Table 8]

將表8中製備處方例11～處方例13的洗眼劑時使用的原料示於以下。 ･聚氧乙烯（200）聚氧丙烯（70）二醇： 「尤尼勞博（UNILUB）70DP-950B」，藥添規，日油公司製造，或者「勞托洛（Lutrol）F127」，藥添規，巴斯夫（BASF）公司製造 ･羥丙基甲基纖維素（羥丙甲纖維素）： 「梅特勞斯（METOLOSE）60SH-4000」，日本藥典，信越化學工業公司製造，重量平均分子量30萬（g/mol） ･單油酸聚氧乙烯（20）山梨糖醇酐（聚山梨糖醇酯80）：「萊奧道魯（Rheodol）TW-0120V」，日本藥典，花王公司製造 ･聚氧乙烯氫化蓖麻油60： 「HCO-60（醫藥用）」，藥添規，日光化學公司製造The raw materials used in the preparation of the eye wash preparations of Formulation Examples 11 to 13 in Table 8 are shown below. ･ Polyoxyethylene (200) polyoxypropylene (70) diol: "UNILUB 70DP-950B", Yasushi Kiyoshi, manufactured by Nippon Oil Company, or "Lutrol F127", Yasushi Shiki , Basf (BASF) company made 纤维素 hydroxypropyl methylcellulose (hypromellose): "METOLOSE 60SH-4000", manufactured by the Japanese Pharmacopoeia, Shin-Etsu Chemical Industry Co., Ltd., weight average molecular weight 300,000 (G / mol) ･ Monooleic acid polyoxyethylene (20) Sorbitan (Polysorbate 80): "Reoodol TW-0120V", Japanese Pharmacopoeia, Kao Corporation ･ Polyoxygen Ethylene hydrogenated castor oil 60: "HCO-60 (for medical use)", medicinal supplement, manufactured by Nikko Chemical Co., Ltd.

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Claims (18)

一種眼脂生成防止劑，其含有：（A）羥丙基甲基纖維素及（B）維生素E類。An eye fat production preventing agent comprising: (A) hydroxypropyl methylcellulose and (B) vitamin E. 一種鈍重感抑制劑，其含有：（A）羥丙基甲基纖維素及（B）維生素E類。A dullness inhibitor, comprising: (A) hydroxypropyl methylcellulose and (B) vitamin E. 一種眼疲勞緩和劑，其含有：（A）羥丙基甲基纖維素及（B）維生素E類。An eye fatigue relieving agent comprising: (A) hydroxypropylmethyl cellulose and (B) vitamin E. 一種眼睛模糊緩和劑，其含有：（A）羥丙基甲基纖維素及（B）維生素E類。An eye blur reducing agent containing: (A) hydroxypropyl methyl cellulose and (B) vitamin E. 一種充血抑制劑，其含有：（A）羥丙基甲基纖維素及（B）維生素E類。A congestion inhibitor comprising: (A) hydroxypropyl methylcellulose and (B) vitamin E. 一種羞明感緩和劑，其含有：（A）羥丙基甲基纖維素及（B）維生素E類。A shame relief agent containing: (A) hydroxypropyl methyl cellulose and (B) vitamin E. 一種眼睛發癢抑制劑，其含有：（A）羥丙基甲基纖維素及（B）維生素E類。An eye itch inhibitor, comprising: (A) hydroxypropyl methylcellulose and (B) vitamin E. 如申請專利範圍第1項至第7項中任一項所述的藥劑，其更含有（C）維生素A類。The medicament according to any one of claims 1 to 7 of the scope of patent application, further comprising (C) vitamin A. 如申請專利範圍第8項所述的藥劑，其中所述（C）維生素A類的量為每100 mL容量的藥劑中5萬國際單位～50萬國際單位。The medicament according to item 8 of the scope of patent application, wherein the amount of (C) vitamin A is 50,000 to 500,000 international units per 100 mL of the medicament. 如申請專利範圍第1項至第7項中任一項所述的藥劑，其為乾眼症的治療用及預防用的至少任一者。The medicament according to any one of claims 1 to 7 of the scope of patent application, which is at least one of a treatment and a prevention for dry eye. 如申請專利範圍第8項所述的藥劑，其為乾眼症的治療用及預防用的至少任一者。The medicament according to item 8 of the scope of patent application, which is at least one of a treatment and a prevention for dry eye. 如申請專利範圍第9項所述的藥劑，其為乾眼症的治療用及預防用的至少任一者。The medicament according to item 9 of the scope of patent application, which is at least one of a treatment and a prevention for dry eye. 如申請專利範圍第1項至第7項中任一項所述的藥劑，其為眼睛乾澀症狀的治療用及預防用的至少任一者。The medicament according to any one of claims 1 to 7 of the scope of patent application, which is at least one of a treatment and a prevention for dry eyes. 如申請專利範圍第8項所述的藥劑，其為眼睛乾澀症狀的治療用及預防用的至少任一者。The medicament according to item 8 of the scope of patent application, which is at least one of treatment and prevention for dry eyes. 如申請專利範圍第9項所述的藥劑，其為眼睛乾澀症狀的治療用及預防用的至少任一者。The medicament according to item 9 of the scope of patent application, which is at least one of a treatment and a prevention for dry eyes. 一種眼科用藥，其使用如申請專利範圍第1項至第7項中任一項所述的藥劑。An ophthalmic drug using the medicament according to any one of claims 1 to 7 of the scope of patent application. 一種眼科用藥，其使用如申請專利範圍第8項所述的藥劑。An ophthalmic medicine using the medicine described in item 8 of the scope of patent application. 一種眼科用藥，其使用如申請專利範圍第9項所述的藥劑。An ophthalmic medicine using the medicine described in item 9 of the scope of patent application.