JPH0611704B2 - Eye drops for corneal disease treatment - Google Patents
Eye drops for corneal disease treatmentInfo
- Publication number
- JPH0611704B2 JPH0611704B2 JP1011497A JP1149789A JPH0611704B2 JP H0611704 B2 JPH0611704 B2 JP H0611704B2 JP 1011497 A JP1011497 A JP 1011497A JP 1149789 A JP1149789 A JP 1149789A JP H0611704 B2 JPH0611704 B2 JP H0611704B2
- Authority
- JP
- Japan
- Prior art keywords
- corneal
- glutathione
- eye drops
- oxidized glutathione
- eye drop
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Description
【発明の詳細な説明】 「産業上の利用分野」 本発明は酸化型グルタチオンまたはその塩類を主成分と
する角膜疾患治療用点眼剤に関する。DETAILED DESCRIPTION OF THE INVENTION "Industrial field of application" The present invention relates to an eye drop for treating corneal diseases, which comprises oxidized glutathione or a salt thereof as a main component.
「従来技術、発明が解決しようとする課題および課題を
解決するための手段」 還元型グルタチオンはＳＨ酵素系を介して組織内呼吸の
円滑な運転に関与しているが、角膜潰瘍、角膜上皮剥
離、角膜炎などの角膜疾患時にその濃度が減少すること
が知られている。（あたらしい眼科２，２１（１９８
５）） そこで、これらの角膜疾患に対し、還元型グルタチオン
点眼剤を用いてグルタチオンを補給し、角膜上皮組織の
修復を促進する方法が行なわれている。"Prior Art, Problems to be Solved by the Invention and Means for Solving the Problems" Reduced glutathione is involved in smooth driving of tissue respiration through SH enzyme system, but corneal ulcer and corneal epithelial detachment It is known that its concentration decreases during corneal diseases such as keratitis. (New ophthalmology 2 , 21 (198
5)) Therefore, for these corneal diseases, a method of replenishing glutathione with a reduced glutathione eye drop to promote the repair of corneal epithelial tissue is used.
ところが、還元型グルタチオンは製剤中での安定性が悪
く、点眼剤では使用時に還元型グルタチオンの錠剤や顆
粒を溶解して用いなければならなかった。However, reduced glutathione has poor stability in the preparation, and therefore, it has been necessary to dissolve the reduced glutathione tablets or granules for use in eye drops.
このことから、角膜疾患の治療に有用で、かつ安定性に
優れた点眼剤を検討する必要があった。Therefore, it was necessary to study eye drops that are useful for the treatment of corneal diseases and have excellent stability.
そこで、本発明者らはこの問題について鋭意検討した結
果、酸化型グルタチオン点眼剤が創傷治癒促進作用を有
しており、角膜潰瘍等の角膜疾患に有用であることを見
い出した。又、酸化型グルタチオン点眼剤は安定性の点
において、還元型グルタチオンよりもはるかに優れてい
ることを見い出した。Therefore, as a result of diligent studies on this problem, the present inventors have found that oxidized glutathione eye drops have a wound healing promoting action and are useful for corneal diseases such as corneal ulcers. Further, they have found that oxidized glutathione eye drops are far superior to reduced glutathione in stability.
「発明の開示」 本発明は酸化型グルタチオンまたはその塩類（以下酸化
型グルタチオンと総称する）を主成分とする角膜疾患治
療用点眼剤に関する。[Disclosure of the Invention] The present invention relates to an eye drop for treating corneal diseases, which contains oxidized glutathione or salts thereof (hereinafter collectively referred to as oxidized glutathione) as a main component.
上記の塩としては医薬として許容されるものであればよ
く、例えばナトリウム、カリウム、カルシウム、マグネ
シウムなどの金属塩や有機アミン塩などが含まれる。The above-mentioned salts may be pharmaceutically acceptable salts, and include, for example, metal salts of sodium, potassium, calcium, magnesium and the like, organic amine salts and the like.
又、本発明でいう角膜疾患とは角膜潰瘍、角膜上皮剥
離、角膜炎などをいう。Further, the corneal disease as referred to in the present invention refers to corneal ulcer, corneal epithelial detachment, keratitis and the like.
還元型グルタチオンはＳＨ酵素系を介して組織内呼吸の
円滑な運転に関与しているが、角膜潰瘍、角膜上皮剥
離、角膜炎などの角膜疾患時にその濃度が減少すること
が知られている。（あたらしい眼科２，２１（１９８
５）） そこで、これらの角膜疾患に対し、還元型グルタチオン
点眼剤を用いてグルタチオンを補給し、角膜上皮組織の
修復を促進する方法が行なわれている。Although reduced glutathione is involved in smooth operation of tissue respiration through the SH enzyme system, its concentration is known to decrease during corneal diseases such as corneal ulcer, corneal epithelial detachment, and keratitis. (New ophthalmology 2 , 21 (198
5)) Therefore, for these corneal diseases, a method of replenishing glutathione with a reduced glutathione eye drop to promote the repair of corneal epithelial tissue is used.
ところが、還元型グルタチオンは製剤中での安定性が悪
く、点眼剤では使用時に還元型グルタチオンの錠剤や顆
粒を溶解して用いなければならなかった。However, reduced glutathione has poor stability in the preparation, and therefore, it has been necessary to dissolve the reduced glutathione tablets or granules for use in eye drops.
このことから、角膜疾患の治療に有用で、かつ安定性に
優れた点眼剤を検討する必要があった。Therefore, it was necessary to study eye drops that are useful for the treatment of corneal diseases and have excellent stability.
そこで、本発明者らはこの問題について鋭意検討を行な
った。その結果、酸化型グルタチオン点眼剤が創傷治癒
促進作用を有しており、角膜潰瘍等の角膜疾患に有用で
あることを見い出した。Therefore, the present inventors have diligently studied this problem. As a result, they have found that oxidized glutathione eye drops have a wound healing promoting action and are useful for corneal diseases such as corneal ulcers.
酸化型グルタチオンは２分子の還元型グルタチオンの−
ＳＨ基が酸化されて−Ｓ−Ｓ−結合した化合物である
が、眼疾患に対する酸化型グルタチオンの作用について
は知られておらず、酸化型グルタチオンが角膜疾患に有
効である事を本発明で初めて明らかにしたものである。Oxidized glutathione is equivalent to two molecules of reduced glutathione.
It is a compound in which the SH group is oxidized and is -SS-bonded, but the action of oxidized glutathione on eye diseases is not known, and it is the first time in the present invention that oxidized glutathione is effective for corneal diseases. It was made clear.
本発明者らは角膜疾患の治療剤として酸化型グルタチオ
ンの点眼剤を用いることを検討し、その有用性の指標と
して酸化型グルタチオンの角膜創傷治癒促進効果につい
て調べた。詳しくは薬理試験の項で述べるが、酸化型グ
ルタチオンを含有する本発明点眼剤は、対象の基剤と比
較して明らかに角膜創傷治癒促進作用を有しており、角
膜疾患の治療剤として有用であることが明らかとなっ
た。The present inventors examined the use of oxidized glutathione eye drops as a therapeutic agent for corneal diseases, and examined the effect of oxidized glutathione on promoting corneal wound healing as an index of its usefulness. As will be described in detail in the section of pharmacological test, the eye drop of the present invention containing oxidized glutathione clearly has a corneal wound healing promoting action as compared with the target base, and is useful as a therapeutic agent for corneal diseases. It became clear that
又、本発明点眼剤は安定性試験の項で述べるように非常
に安定であり、還元型グルタチオンの水溶液を室温１ヶ
月保存したものの定量値が約９０％となり組成に変化を
きたすのに対し、同じ条件で本発明点眼剤を保存したも
のの定量値はほとんど低下しておらず、組成の変化は認
められなかった。Further, the eye drop of the present invention is very stable as described in the section of stability test, and the quantitative value of the aqueous solution of reduced glutathione stored at room temperature for 1 month becomes about 90%, and the composition changes. Although the eye drop of the present invention was stored under the same conditions, the quantitative value was hardly reduced, and no change in composition was observed.
以上のように、本発明点眼剤は角膜創傷治癒促進作用を
有し、かつ安定性にも優れたものである。As described above, the eye drop of the present invention has a corneal wound healing promoting action and is also excellent in stability.
本発明点眼剤の酸化型グルタチオンの濃度はその効果が
発揮できるものであればよく、0.5〜５％のものが好ま
しいが、症状、年令などによって適宜選択すればよい。The concentration of oxidized glutathione in the eye drop of the present invention may be such that the effect can be exerted, and is preferably 0.5 to 5%, but may be appropriately selected depending on the symptoms, age and the like.
ｐＨは眼科製剤に許容される範囲内にあればよいが、４
〜７の範囲が好ましい。The pH may be within the range acceptable for ophthalmic preparations, but 4
The range of -7 is preferable.
本製剤には点眼剤として通常に用いられる添加物、例え
ばパラオキシ安息香酸エステル、塩化ベンザルコニウム
などの防腐剤、塩化ナトリウム、グリセリン、マンニト
ールなどの等張化剤、ε−アミノカプロン酸、酢酸ナト
リウム、リン酸ナトリウムなどの緩衝化剤、エデト酸ナ
トリウムなどの安定化剤、ポリビニルアルコールなどの
粘稠化剤、希塩酸、水酸化ナトリウムなどのｐＨ調節剤
等を必要に応じて用いることができる。Additives usually used as eye drops in this preparation, for example, paraoxybenzoic acid ester, preservatives such as benzalkonium chloride, isotonic agents such as sodium chloride, glycerin, mannitol, ε-aminocaproic acid, sodium acetate, A buffering agent such as sodium phosphate, a stabilizer such as sodium edetate, a thickening agent such as polyvinyl alcohol, a pH adjusting agent such as dilute hydrochloric acid or sodium hydroxide, and the like can be used as necessary.
このようにして得れた点眼剤は、通常１回１滴〜数滴、
１日１回〜数回投与することができる。The eye drop thus obtained is usually one drop to several drops at a time,
It can be administered once to several times a day.
尚、本発明点眼剤の剤型は点眼液、眼軟膏のいずれでも
よい。以下に実施例としてその製剤例をあげる。The dosage form of the eye drop of the present invention may be either an eye drop or an eye ointment. The formulation examples are given below as examples.
「実施例」 実施例１（点眼液） 処方１ １００ｍ中 酸化型グルタチオン 2.0ｇ ε−アミノカプロン酸 0.2ｇ 塩化ナトリウム 0.6ｇ 塩化ベンザルコニウム 0.005ｇ 水酸化ナトリウム 適量 滅菌精製水 〃 製法 滅菌精製水８０ｍに酸化型グルタチオン、ε−アミノ
カプロン酸、塩化ナトリウム、塩化ベンザルコニウムを
加えて溶解した後、水酸化ナトリウムを用いてpHを5.0
に調節する。滅菌精製水を加えて全量を１００ｍとす
る。"Example" Example 1 (ophthalmic solution) Formulation 1 In 100 m Oxidized glutathione 2.0 g ε-aminocaproic acid 0.2 g Sodium chloride 0.6 g Benzalkonium chloride 0.005 g Sodium hydroxide suitable amount Sterile purified water 〃 Manufacturing method Sterile purified water 80 m Oxidized glutathione, ε-aminocaproic acid, sodium chloride and benzalkonium chloride were added and dissolved, and the pH was adjusted to 5.0 with sodium hydroxide.
Adjust to. Add sterile purified water to bring the total volume to 100 m.
上記の同様の方法を用いて処方２〜４の点眼液を調製し
た。Ophthalmic solutions of Formulations 2 to 4 were prepared using the same method as described above.
処方２ １００ｍ中 （pH６．０） 酸化型グルタチオン 2.0ｇ 酢酸ナトリウム 0.2ｇ 塩化ナトリウム 0.6ｇ 塩化ベンザルコニウム 0.005ｇ エデト酸ナトリウム 0.01ｇ 希塩酸もしくは水酸化ナトリウム 適量 滅菌精製水 〃 処方３ １００ｍ中 （pH5.0） 酸化型グルタチオン 2.0ｇ 酢酸ナトリウム 0.2ｇ グリセリン 2.0ｇ パラオキシ安息香酸メチル 0.005ｇ パラオキシ安息香酸プロピル 0.01ｇ 水酸化ナトリウムもしくは希塩酸 適量 滅菌精製水 〃 処方４ １００ｍ中 （pH5.2） 酸化型グルタチオン 2.0ｇ ポリビニルアルコール 1.0ｇ マンニトール 3.5ｇ 塩化ベンザルコニウム 0.005ｇ 水酸化ナトリウム 適量 滅菌精製水 〃 実施例２ 処方５（眼軟膏） １００ｇ中 酸化型グルタチオン 2.0ｇ 流動パラフィン １０ｇ 白色ワセリン ８８ｇ 製法 流動パラフィンの中に酸化型グルタチオンを加えて分散
させる。これを８０℃に熱した白色パラフィン中に加
え、脱気しながらゆっくりと攪拌し室温まで冷却する。Formulation 2 100 m (pH 6.0) Oxidized glutathione 2.0 g Sodium acetate 0.2 g Sodium chloride 0.6 g Benzalkonium chloride 0.005 g Sodium edetate 0.01 g Dilute hydrochloric acid or sodium hydroxide Suitable amount Sterilized purified water 〃 Formula 3 100 m (pH 5. 0) Oxidized glutathione 2.0g Sodium acetate 0.2g Glycerin 2.0g Methyl paraoxybenzoate 0.005g Propyl paraoxybenzoate 0.01g Sodium hydroxide or dilute hydrochloric acid Appropriate amount of sterilized purified water 〃 Formula 4 100m (pH5.2) Oxidized glutathione 2.0g Polyvinyl alcohol 1.0 g Mannitol 3.5 g Benzalkonium chloride 0.005 g Sodium hydroxide A suitable amount of sterile purified water Example 2 Formulation 5 (eye ointment) in 100 g Oxidized glutathione 2.0 g Liquid paraffin 10 g White petrolatum 88 g Manufacturing method Oxidized in liquid paraffin Type glutathione is added and dispersed. This is added to white paraffin heated to 80 ° C., slowly stirred while being deaerated, and cooled to room temperature.
安定性試験 本発明点眼剤の安定性を調べるため、ｐＨを６に調整し
た２％の酸化型グルタチオン水溶液と還元型グルタチオ
ン水溶液を作り、室温で１ケ月間保存した後、その残存
率を測定した。Stability test In order to investigate the stability of the eye drop of the present invention, a 2% aqueous solution of oxidized glutathione and an aqueous solution of reduced glutathione adjusted to pH 6 were prepared and stored at room temperature for 1 month, and the residual rate was measured. .
その結果、還元型グルタチオン水溶液の残存率が約９０
％であつたのに対して、酸化型グルタチオン水溶液では
残存率の低下はほとんど認められなかった。As a result, the residual rate of the reduced glutathione aqueous solution was about 90.
%, On the other hand, almost no decrease in the residual rate was observed in the oxidized glutathione aqueous solution.
このことから本発明点眼剤が還元型グルタチオン点眼剤
に比べて安定性がはるかに優れていることがわかる。From this, it is understood that the eye drop of the present invention is far superior in stability to the reduced glutathione eye drop.
薬理試験 角膜疾患の治療剤としての有用性を検討するため、本発
明点眼剤の角膜創傷治癒促進作用について調べた。薬物
の角膜創傷治癒促進作用を調べる方法としては、ｎ−ヘ
プタノールを用いた角膜上皮剥離法が知られているので
この方法を用いた。Pharmacological test In order to examine the usefulness as a therapeutic agent for corneal diseases, the corneal wound healing promoting action of the eye drop of the present invention was investigated. As a method for investigating the corneal wound healing promoting action of a drug, a corneal epithelial detachment method using n-heptanol is known, and thus this method was used.
（実験方法） 実験はCintronらの方法（Ophthalmic Res.，１１，９０
（１９７９））を用いて行なった。酸化型グルタチオン
を生理食塩液（0.9％塩化ナトリウム液）に溶かし、pH
6.0に調製したものをウサギの角膜上皮剥離後、１回１
滴、１日４回点眼した。創傷面積を測定することにより
角膜創傷治癒促進作用を調べた。尚、対照として生理食
塩液を用いた。(Experimental method) The experiment was performed by the method of Cintron et al. (Ophthalmic Res., 11 , 90)
(1979)). Dissolve oxidized glutathione in physiological saline (0.9% sodium chloride solution) and adjust to pH.
Prepared in 6.0, and after exfoliating rabbit corneal epithelium 1
Drops were applied 4 times a day. The corneal wound healing promoting effect was examined by measuring the wound area. A physiological saline solution was used as a control.
（実験結果） 点眼直前の創傷面積を１００％として各時間での創傷面
積を表に示した。(Experimental Results) The wound area immediately before instillation was set as 100%, and the wound area at each time is shown in the table.
「発明の効果」 表に示されているように本発明点眼剤を点眼したものは
明らかに対照群よりも創傷面積が小さく、創傷治癒の促
進作用が認められた。 "Effect of the invention" As shown in the table, the eye drops of the present invention had a smaller wound area than the control group, and the effect of promoting wound healing was recognized.
この結果から、本発明点眼剤が角膜炎などの角膜疾患治
療剤として有用であることが示された。From these results, it was shown that the eye drop of the present invention is useful as a therapeutic agent for corneal diseases such as keratitis.
Claims (1)
分とする角膜疾患治療用点眼剤。1. An eye drop for treating corneal diseases, which comprises oxidized glutathione or a salt thereof as a main component.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1011497A JPH0611704B2 (en) | 1989-01-19 | 1989-01-19 | Eye drops for corneal disease treatment |
| KR1019890011003A KR960013437B1 (en) | 1988-08-05 | 1989-08-01 | Oxidized glutathion eye-drops |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1011497A JPH0611704B2 (en) | 1989-01-19 | 1989-01-19 | Eye drops for corneal disease treatment |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02193931A JPH02193931A (en) | 1990-07-31 |
| JPH0611704B2 true JPH0611704B2 (en) | 1994-02-16 |
Family
ID=11779666
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1011497A Expired - Lifetime JPH0611704B2 (en) | 1988-08-05 | 1989-01-19 | Eye drops for corneal disease treatment |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0611704B2 (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA927277B (en) * | 1991-10-02 | 1993-05-19 | Boston Ocular Res | Dry eye treatment process and solution. |
| ES2136557B1 (en) * | 1997-08-22 | 2000-07-01 | Martinez Parra Aurelio Juan | PRODUCT FOR TREATMENT OF DRY KERATITIS. |
| IT1298758B1 (en) * | 1998-03-19 | 2000-02-02 | Angelini Ricerche Spa | WETTING AND LUBRICANT SOLUTION FOR OPHTHALMIC USE |
| US20070142267A1 (en) | 1998-11-23 | 2007-06-21 | Novelos Therapeutics, Inc. | Methods for production of the oxidized glutathione composite with CIS-diamminedichloroplatinum and pharmaceutical compositions based thereof regulating metabolism, proliferation, differentiation and apoptotic mechanisms for normal and transformed cells |
| AU5109400A (en) * | 1999-06-14 | 2001-01-02 | Advanced Medicine Research Institute | Therapeutic compositions for ophthalmic use and therapeutic compositions for brain central lesions |
| JP5542511B2 (en) * | 2010-04-14 | 2014-07-09 | ロート製薬株式会社 | Contact lens ophthalmic composition |
| JP2011221464A (en) * | 2010-04-14 | 2011-11-04 | Rohto Pharmaceut Co Ltd | Ophthalmologic composition for contact lens |
-
1989
- 1989-01-19 JP JP1011497A patent/JPH0611704B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH02193931A (en) | 1990-07-31 |
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