WO1994003167A1 - Cataract remedy - Google Patents
Cataract remedy Download PDFInfo
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- WO1994003167A1 WO1994003167A1 PCT/JP1993/001008 JP9301008W WO9403167A1 WO 1994003167 A1 WO1994003167 A1 WO 1994003167A1 JP 9301008 W JP9301008 W JP 9301008W WO 9403167 A1 WO9403167 A1 WO 9403167A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
Definitions
- the present invention relates to an anti-cataract agent comprising a compound represented by the following general formula [I], an intramolecular disulfide thereof, or a salt thereof as an active ingredient.
- a feature of the compound represented by the general formula [I], which is an active ingredient of the medicament of the present invention, is that the compound has an isobutanol group bonded to a sulfur atom via a methylene group.
- This compound and its disulfide compound have already been disclosed in JP-A-2-776 and JP-A-2-138271, and it is reported that the compound has a liver injury-suppressing action, an immunomodulatory action and a bile action. (JP-A-2-776, JP-A-2-138271, JP-A-3-227924). However, the application of these compounds to the field of ophthalmology has not yet been reported.
- cysteine derivatives having a structure partially similar to the compound represented by the general formula [I] on cataract has also been reported (JP-A-55-92315, JP-A-57-56454).
- this cysteine derivative does not have an isobutanol group bonded to a sulfur atom via a methylene group, which is a feature of the compound represented by the general formula [I].
- Cataract is a disease in which the lens becomes cloudy and causes loss of vision. They are classified into senile cataracts, diabetic cataracts, steroid cataracts, etc. according to their causes, but all are intractable diseases. Since the treatment of cataracts requires the administration of drugs over a long period of time, drugs are required to be highly safe as well as effective. Because of this, the effect --The development of highly safe and highly safe therapeutic drugs is desired.
- the present inventors have conducted intensive studies to find a compound that is highly effective against cataract and that is highly safe. As a result, the compound represented by the general formula [I] or its molecular disulfide meets this condition. Found to meet. Disclosure ⁇
- the present invention relates to an anti-cataract agent comprising a compound represented by the formula [I] or an intramolecular disulfide thereof, or a salt thereof (hereinafter, referred to as the present compound) as an active ingredient.
- the salt of CH 2 SHCH 2 SH compounds, sodium salts, potassium salts, calcium salts, and salts with inorganic or organic bases are pharmaceutically acceptable, such as Jechiru Amin salt.
- the present inventors have intensively studied to find a compound having a high effect on cataract and a high safety.
- the dose of the compound is not particularly limited as long as the effect is exerted, and is not particularly limited, but is 1 mg to 100 mg per day for oral preparations, and 0.1% to 5% for eye drops. Is preferably administered once to several times a day, and may be appropriately selected depending on symptoms, age, dosage form, and the like.
- oral preparations examples include tablets, granules, capsules, and the like
- eye drops examples include eye drops and ophthalmic solution B.
- Oral preparations may be prepared by adding necessary additives according to the dosage form. For example, a method described in JP-A Nos. 2-7-6 to 2-138271 may be used. In the case of eye drops, it may be prepared by adding an isotonic agent, a buffering agent, a stabilizing agent, an antiseptic agent, a pH adjusting agent and the like as needed.
- preparation examples of eye drops of the present compound are shown.
- HC hydrocortisone sodium succinate
- the opacity of the lens 48 hours after HC administration was determined according to the following criteria. Judgment criteria
- the degree of lens opacity was all III or higher, and those corresponding to IV and V accounted for 95% or more of the total.
- the experiment was performed by a delayed dermal antigen test using guinea pigs.
- test substance to physiological saline so that the concentration becomes 6 mg / ml, and adjust the pH to 7 with a 1N aqueous sodium hydroxide solution.
- This solution was mixed with an equal volume of Freund's complete adjuvant to prepare an emulsion.
- this emulsion was placed in the limb of the guinea pig on each limb. This was carried out by injecting 0.6 ml in the back of the neck subcutaneously by -m1. One week after the sensitization, 0.5 ml each of the same emulsion was administered to the subcutaneous region of the back of the neck and into the thigh muscle as a booster sensitization. After shaving the back of guinea pigs Bok from the additional sensitization in 2 weeks, physiological saline solution of the test substance (6mg / m l) was intracutaneously administered to the back skin by 0. 05M l. 24 hours after intradermal administration, its antigenicity was determined according to the following criteria. Judgment criteria
- Soil Redness of 5 mm or more and less than 10 mm
- the present invention provides an excellent therapeutic agent for cataract.
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Abstract
Description
一 _ 明 細 書 発 明 の 名 称 抗 白 内 障 斉 技 術 分 野 I. Name of the description of the invention The field of anti-cataract technology
本発明は下記一般式 [ I ] で示される化合物もしくはその分子内ジスルフィ ド、 またはそれらの塩類を有効成分とする抗白内障剤に関する。 The present invention relates to an anti-cataract agent comprising a compound represented by the following general formula [I], an intramolecular disulfide thereof, or a salt thereof as an active ingredient.
C H C H
CH3 - C - C 0 N H C H C 00 H [ I ] CH 3 -C-C 0 NHCHC 00 H [I]
I I C H2 S H C Hz S H IICH 2 SHCH z SH
背 景 技 術 Background technology
本発明医薬の有効成分である一般式 [ I ] で示される化合物の特徴は、 メチレ ン基を介して硫黄原子と結合したィソブタノィル基を有するところにある。 この 化合物およびそのジスルフィ ド体は既に特開平 2— 776ゃ特開平 2 - 1 382 7 1に開示されており、 その作用としては肝障害抑制作用、 免疫調節作用ゃ利胆 作用を有することが報告されている （特開平 2— 776、 特開平 2— 1 3827 1、 特開平 3— 227924) 。 しかしながら、 これらの化合物を眼科分野へと 応用することは未だ報告されていない。 A feature of the compound represented by the general formula [I], which is an active ingredient of the medicament of the present invention, is that the compound has an isobutanol group bonded to a sulfur atom via a methylene group. This compound and its disulfide compound have already been disclosed in JP-A-2-776 and JP-A-2-138271, and it is reported that the compound has a liver injury-suppressing action, an immunomodulatory action and a bile action. (JP-A-2-776, JP-A-2-138271, JP-A-3-227924). However, the application of these compounds to the field of ophthalmology has not yet been reported.
—方、 一般式 [ I ] で示される化合物と部分的に類似した構造を有するシステ ィン誘導体の白内障に対する効果も報告されている （特開昭 55 - 923 1 5, 特開昭 57 - 56454) 。 しかし、 このシスティン誘導体は、 一般式 [ I ] で 示される化合物の特徴であるメチレン基を介して硫黄原子と結合したィソブタノ ィル基を有しないものである。 On the other hand, the effect of cysteine derivatives having a structure partially similar to the compound represented by the general formula [I] on cataract has also been reported (JP-A-55-92315, JP-A-57-56454). ). However, this cysteine derivative does not have an isobutanol group bonded to a sulfur atom via a methylene group, which is a feature of the compound represented by the general formula [I].
白内障は水晶体が混濁し、 視力を失う疾患である。 その発症原因により、 老人 性白内障、 糖尿病性白内障、 ステロイ ド白内障等に分類されるが、 いずれも難治 性の疾患である。 白内障の治療には薬物を長期間にわたって投与する必要がある ことから、 薬物には効果とともに高い安全性が要求されている。 このため、 効果 - - が高くかつ安全性の高い'冶療薬の開発が望まれている。 Cataract is a disease in which the lens becomes cloudy and causes loss of vision. They are classified into senile cataracts, diabetic cataracts, steroid cataracts, etc. according to their causes, but all are intractable diseases. Since the treatment of cataracts requires the administration of drugs over a long period of time, drugs are required to be highly safe as well as effective. Because of this, the effect --The development of highly safe and highly safe therapeutic drugs is desired.
そ二で、 本発明者らは白内障に対して効果が高く、 しかも安全性の高い化合物 を見 出すべく鋭意検討した結果、 一般式 [ I ] で示される化合物もしくはその 分子 ジスルフィ ドがこの条件を満たすことを見い出した。 発 ^ の 開 示 The present inventors have conducted intensive studies to find a compound that is highly effective against cataract and that is highly safe. As a result, the compound represented by the general formula [I] or its molecular disulfide meets this condition. Found to meet. Disclosure ^
発明は一 式 [ I ] で示される化合物もしくはその分子内ジスルフィ ド、 ま たはそれらの塩類 （以下、 本化合物とする） を有効成分とする抗白内障剤に関す The present invention relates to an anti-cataract agent comprising a compound represented by the formula [I] or an intramolecular disulfide thereof, or a salt thereof (hereinafter, referred to as the present compound) as an active ingredient.
C H3 CH 3
I I
C H3 - C - CONHCHCO O H [ I ] CH 3 -C-CONHCHCO OH [I]
I i I i
C H2 S H C H2 S H 化合物の塩としては、 ナトリウム塩、 カリウム塩、 カルシウム塩、 ジェチル ァミン塩等の医薬として許容される無機または有機塩基との塩が挙げられる。 本発明者らは白内障に対して効果が高く、 しかも安全性の高い化合物を見い出 すべく鋭意検討した。 The salt of CH 2 SHCH 2 SH compounds, sodium salts, potassium salts, calcium salts, and salts with inorganic or organic bases are pharmaceutically acceptable, such as Jechiru Amin salt. The present inventors have intensively studied to find a compound having a high effect on cataract and a high safety.
白内障に対する薬物の効果を判定するには種々の方法が知られている力 実験 的白内障モデルである副腎皮質ホルモンにより惹起された鷄胚の白内障モデル （ 西郡等、 Exp Eye Res.， 36, 617- 622 (1983) )を用いて本化合物の効果を調べた。 詳細なデータについては薬理試験の項で述べるが、 副腎皮質ホルモンとしてコ ハク ¾ヒ ドロコルチゾンナトリゥムを用いて実験したところ、 本化合物投与群は コン 卜ロールと比較して水晶体の白濁を明らかに減少させた。 Various methods are known to determine the effects of drugs on cataracts. A cataract model of chicken embryos induced by adrenocortical hormone, an experimental cataract model (Nishigori et al., Exp Eye Res., 36, 617- 622 (1983)). Although detailed data will be described in the section on pharmacological tests, an experiment was performed using succinohydrocortisone sodium as an adrenocortical hormone. Reduced to.
次に、 その安全性を評価するために、 上記の鶏胚のモデルで確認したところ、 本化合物を投与しても 1例の死亡例もなく、 本化合物の安全性は極めて高いもの でめつ,こ。 Next, in order to evaluate its safety, it was confirmed in the chicken embryo model described above, and no single fatal case was observed after administration of this compound, indicating that the safety of this compound is extremely high. , This.
また、 含硫黄化合物を投与するとアレルギーを生ずる可能性があると言われて いることから、 モルモッ 卜を用いた遅延型皮^抗原性試験法により実験したとこ ろ、 ご、化合物はアレルギーが生じにくいことがわかつた。 一 一 Also, it is said that administration of sulfur-containing compounds may cause allergies. I can tell you. One one
^上の結果から、 白内障に対する効果が優れ、 しかも安全性が高い.という課題 が解決された。 ^ The above results have solved the problem of excellent effects on cataracts and high safety.
化合物の投与量はその効果が発揮される量であればよく、 特に限定する必要 はないが、 経口剤では 1 日あたり 1 m g〜 1 0 0 0 m g、 点眼剤では 0 . 〇 1〜 5 %の濃度のものを 1 日 1〜数回投与するのが好ましく、 症状、 年令、 剤型等に よって適宜選択すればよい。 The dose of the compound is not particularly limited as long as the effect is exerted, and is not particularly limited, but is 1 mg to 100 mg per day for oral preparations, and 0.1% to 5% for eye drops. Is preferably administered once to several times a day, and may be appropriately selected depending on symptoms, age, dosage form, and the like.
経口剤の種類としては、 錠剤、 顆粒剤、 カプセル剤などが挙げられ、 点眼剤と しては点眼液ゃ眼軟 Bが挙げられる。 経口剤は剤型に応じて必要な添加剤を加え ればよく、 例えば特開平 2 - 7了 6ゃ特開平 2 - 1 3 8 2 7 1に記載されている 方法を用いればよい。 点眼液の場合には、 等張化剤、 緩衝化剤、 安定化剤、 防腐 斉 、 P H調整剤等を必要に応じて加えて調製すればよい。 Examples of the type of oral preparation include tablets, granules, capsules, and the like, and examples of the eye drops include eye drops and ophthalmic solution B. Oral preparations may be prepared by adding necessary additives according to the dosage form. For example, a method described in JP-A Nos. 2-7-6 to 2-138271 may be used. In the case of eye drops, it may be prepared by adding an isotonic agent, a buffering agent, a stabilizing agent, an antiseptic agent, a pH adjusting agent and the like as needed.
実施例として本化合物の点眼剤の製剤例を示す。 As examples, preparation examples of eye drops of the present compound are shown.
[実施例] [Example]
処方 1 ( 1 0 0 m 1中） Formula 1 (in 100 m1)
本化合物 0 . 1 g 0.1 g of the present compound
塩化ナト リウム 0 . 9 g 0.9 g of sodium chloride
水酸化ナト リウム Sodium hydroxide
滅菌精製水 Sterile purified water
製法 Manufacturing method
滅菌精製水に本化合物と塩化ナト リゥムを加えた後、 水酸化ナ卜 リゥムを加え て p Hを 6 . 0に調整した。 同様の方法を用いて下記の処方の製剤を得た < After adding the present compound and sodium chloride to sterile purified water, the pH was adjusted to 6.0 by adding sodium hydroxide. Using the same method, the following formulation was obtained <
処方 2 ( 1 0 0 m 1中） Formula 2 (in 100 m1)
本化合物 1 · 0 g This compound 1.0 g
リ ン酸水素ニナト リウム 0 . 1 g 0.1 g of sodium sodium phosphate
水酸化ナト リウム Sodium hydroxide
滅菌精製水 一 一 処方 3 ( 1 00 m 1中: Sterile purified water Prescription 3 (1 00 m 1 in:
本化合物 0. 1 The present compound 0.1
塩化ナ ト リ ウム 0. 9 g 0.9 g of sodium chloride
メチルパラベン 0. 025 g Methyl paraben 0.025 g
プロピルパラベン 0. 0 1 5 g Propyl paraben 0.0 15 g
水酸化ナト リウム Sodium hydroxide
滅菌精製水 Sterile purified water
「薬理試験」 `` Pharmacological test ''
白内障に対する薬物の効果を調べる方法として、 副腎皮質ホルモンにより惹起 した鷄胚の白内障モデル （西郡等、 Exp Eye Res. , 36, 617-622 (1983) ) を用い る方法がある。 そこで、 本モデルを用いて本化合物の白内障に対する効果を調べ た。 As a method of examining the effect of drugs on cataract, there is a method using a cataract model of a chicken embryo induced by adrenocortical hormone (Nishigun et al., Exp Eye Res., 36, 617-622 (1983)). Therefore, the effect of the present compound on cataract was investigated using the present model.
(実験方法） (experimental method)
前述の論文に準じ、 コハク酸ヒ ドロコルチゾンナトリウム （以下 HCと略する ) で白内障を惹起 （投与量 0. S S umo lZe g g) した後、 本化合物 1 〇 1110 1を0. 2 m 1の 5 OmMの炭酸水素ナトリウム水溶液に溶解し、 H C投与 後 3時間と 1 0時間の 2回投与した。 コントロールには 50 mMの炭酸水素ナト リゥム水溶液 （ 0. 2m l ) を H C投与後 3時間と 1 0時間の 2回投与した。 After inducing cataract (dose 0. SS umo lZe gg) with hydrocortisone sodium succinate (hereinafter abbreviated as HC) according to the above-mentioned paper, the compound 1 〇 1110 1 was replaced with 0.2 ml 1 It was dissolved in an aqueous solution of OmM sodium bicarbonate and administered twice, 3 hours and 10 hours after HC administration. As a control, a 50 mM aqueous sodium hydrogen carbonate solution (0.2 ml) was administered twice, 3 hours and 10 hours after HC administration.
HC投与 48時間後における水晶体の混濁を、 下記の判定基準に従って判定し た。 判定基準 The opacity of the lens 48 hours after HC administration was determined according to the following criteria. Judgment criteria
I 水晶体に濁りが認められない I No turbidity in the lens
II かすかな不透明のリングがある II Has a faint opaque ring
III 明確な白濁リングがある III There is a clear cloudy ring
IV 白濁核質部中心にピンホールサイズの透明部分が残っている IV Pinhole-sized transparent part remains in the center of cloudy nucleoplasm
. V 核質部全体が白濁している (結果） V The entire nucleoplasm is cloudy (result)
得られた結果を表 1に示した The results obtained are shown in Table 1.
表 1 table 1
H Cのみを投与したコントロール群では、 水晶体の白濁の度合が全て III以上で あり、 特に IVと Vに該当するものが全体の 9 5 %以上になっている。 In the control group to which only HC was administered, the degree of lens opacity was all III or higher, and those corresponding to IV and V accounted for 95% or more of the total.
—方、 本化合物を投与した群ではコントロールと比較して明らかに水晶体の白 濁を抑制していた。 ' On the other hand, the group to which this compound was administered clearly suppressed the lens opacity as compared with the control. '
「安全性試験」 ' `` Safety test '' ''
1 ) 鶏胚の白内障モデルを用いた実験 1) Experiments using a cataract model of chicken embryo
本化合物である一般式 [ 1〗 で示される化合物および一般式 [ I ] で示される 化合物の分子内ジスルフィ ドを前記の鶏胚モデルに 1 O u m o 1投与 （4 0例ず つ） したところ、 1例の死亡例も観察されなかった。 When the intramolecular disulfide of the compound represented by the general formula [1〗] and the compound represented by the general formula [I] was administered to the chicken embryo model by 1 Oumo 1 (40 cases each), No deaths were observed.
2 ) 抗原性試験 2) Antigenicity test
モルモッ トを用いた遅延型皮^抗原性試験により実験を行なった。 The experiment was performed by a delayed dermal antigen test using guinea pigs.
(実験方法） (experimental method)
被験物質の濃度が 6 mg/ml となるように生理食塩液に加え、 1 N水酸化ナトリ ゥム水溶液で P Hを 7に調整する。 この溶液と等容量のフロイン ト完全アジュバ ン卜とを混合してェマルジヨンを作製した。 Add the test substance to physiological saline so that the concentration becomes 6 mg / ml, and adjust the pH to 7 with a 1N aqueous sodium hydroxide solution. This solution was mixed with an equal volume of Freund's complete adjuvant to prepare an emulsion.
初回感作は、 このェマルジヨンをモルモッ トの四肢の足踱内にそれぞれ 0 . 1 - ~ m 1ずつ、 首の後部皮下に 0. 6 m 1投与することにより行なった。 この感作を 行なってから 1週間後、 追加感作として同じエマルジョンを首の後部皮下と大腿 部筋肉内に各々 0. 5m lずつ投与した。 追加感作から 2週間目にモルモッ 卜の 背部を剃毛後、 被験物質の生理食塩液 （ 6mg/ml ) を 0. 05m lずつ背部皮膚 に皮内投与した。 皮内投与 24時間後に下記の基準に従って、 その抗原性を判定 した。 判定基準 For the first sensitization, this emulsion was placed in the limb of the guinea pig on each limb. This was carried out by injecting 0.6 ml in the back of the neck subcutaneously by -m1. One week after the sensitization, 0.5 ml each of the same emulsion was administered to the subcutaneous region of the back of the neck and into the thigh muscle as a booster sensitization. After shaving the back of guinea pigs Bok from the additional sensitization in 2 weeks, physiological saline solution of the test substance (6mg / m l) was intracutaneously administered to the back skin by 0. 05M l. 24 hours after intradermal administration, its antigenicity was determined according to the following criteria. Judgment criteria
- ：発赤が 5 mm未満のもの -: Redness less than 5 mm
土 ：発赤が 5 mm以上 1 0mm未満のもの Soil: Redness of 5 mm or more and less than 10 mm
+ ：発赤が 1 0 mm以上 1 5 mm未満のもの +: Redness of 10 mm or more and less than 15 mm
+ + ：発赤が 1 5 mm以上のもの ++: Redness of 15 mm or more
+++ ： 浮腫あるいは壊死を伴う発赤 +++: Redness with edema or necrosis
(糸吉不 ) (Itoyoshi Fu)
本化合物である一般式 [ I ] で示される化合物および一般式 [ I ] で示される 化合物の分子内ジスルフィ ドを被験物質として^験した結果、 いずれも 6例中 6 例が （一） であった。 上記の 2つの安全性の試験結果から、 本化合物の安全性が極めて高いことが確 認された。 産業上の利用可能性 As a result of a test using the compound represented by the general formula [I] and the intramolecular disulfide of the compound represented by the general formula [I] as test substances, 6 out of 6 cases were (1). Was. From the above two safety test results, it was confirmed that the safety of this compound was extremely high. Industrial applicability
本発明は優れた白内障の治療剤を提供するものである。 The present invention provides an excellent therapeutic agent for cataract.
Claims
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4247077A JP2843955B2 (en) | 1992-08-01 | 1992-08-01 | Anti-cataract agent |
| JP4/247077 | 1992-08-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1994003167A1 true WO1994003167A1 (en) | 1994-02-17 |
Family
ID=17158090
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP1993/001008 Ceased WO1994003167A1 (en) | 1992-08-01 | 1993-07-20 | Cataract remedy |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JP2843955B2 (en) |
| WO (1) | WO1994003167A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996040107A1 (en) * | 1995-06-07 | 1996-12-19 | Alcon Laboratories, Inc. | The use of n,n'-bis(mercaptoacetyl) hydrazine drivatives as anticataract agents |
| US6379664B1 (en) | 1998-09-29 | 2002-04-30 | Board Of Regents University Of Nebraska-Lincoln | Composition and method for the prevention and treatment of oxidative damage in ocular tissues |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU7049694A (en) * | 1993-06-14 | 1995-01-03 | Rambus Inc. | Method and apparatus for writing to memory components |
| US5670545A (en) * | 1996-02-09 | 1997-09-23 | Board Of Regents Of The University Of Colorado | Method for the treatment of ischemic disease and reperfusion injury and the prevention of the adverse effects of reactive oxygen species |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5592315A (en) * | 1979-01-05 | 1980-07-12 | Santen Pharmaceut Co Ltd | Remedy for cataract |
| JPS5756454A (en) * | 1980-09-20 | 1982-04-05 | Santen Pharmaceut Co Ltd | Disulfide type cysteine derivative |
| JPH02776A (en) * | 1988-01-25 | 1990-01-05 | Santen Pharmaceut Co Ltd | Cysteine-related compound |
| JPH02138271A (en) * | 1988-08-13 | 1990-05-28 | Santen Pharmaceut Co Ltd | Sulfur-containing cyclic compound |
-
1992
- 1992-08-01 JP JP4247077A patent/JP2843955B2/en not_active Expired - Lifetime
-
1993
- 1993-07-20 WO PCT/JP1993/001008 patent/WO1994003167A1/en not_active Ceased
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5592315A (en) * | 1979-01-05 | 1980-07-12 | Santen Pharmaceut Co Ltd | Remedy for cataract |
| JPS5756454A (en) * | 1980-09-20 | 1982-04-05 | Santen Pharmaceut Co Ltd | Disulfide type cysteine derivative |
| JPH02776A (en) * | 1988-01-25 | 1990-01-05 | Santen Pharmaceut Co Ltd | Cysteine-related compound |
| JPH02138271A (en) * | 1988-08-13 | 1990-05-28 | Santen Pharmaceut Co Ltd | Sulfur-containing cyclic compound |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996040107A1 (en) * | 1995-06-07 | 1996-12-19 | Alcon Laboratories, Inc. | The use of n,n'-bis(mercaptoacetyl) hydrazine drivatives as anticataract agents |
| US5686450A (en) * | 1995-06-07 | 1997-11-11 | Alcon Laboratories, Inc. | Use of N,N'-bis(mercaptoacetyl) hydrazine derivatives as anticataract agents |
| US5688828A (en) * | 1995-06-07 | 1997-11-18 | Alcon Laboratories, Inc. | Use of N,N'-bis(mercaptoacetyl) hydrazine derivatives as anticataract agents |
| US6379664B1 (en) | 1998-09-29 | 2002-04-30 | Board Of Regents University Of Nebraska-Lincoln | Composition and method for the prevention and treatment of oxidative damage in ocular tissues |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0656661A (en) | 1994-03-01 |
| JP2843955B2 (en) | 1999-01-06 |
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