WO1998051313A1 - Remedes contre les yeux secs - Google Patents
Remedes contre les yeux secs Download PDFInfo
- Publication number
- WO1998051313A1 WO1998051313A1 PCT/JP1998/002080 JP9802080W WO9851313A1 WO 1998051313 A1 WO1998051313 A1 WO 1998051313A1 JP 9802080 W JP9802080 W JP 9802080W WO 9851313 A1 WO9851313 A1 WO 9851313A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- dry eye
- epithelial cells
- corneal epithelial
- emissions
- expression
- Prior art date
Links
Classifications
-
- 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
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
-
- 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
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to a therapeutic agent for dry eye comprising 1 ⁇ , 24-dihydroxybinane D as an active ingredient.
- Dry eye is a group of diseases that cause dry eye and cause abnormal corneal epithelium due to abnormal tears. Symptoms of dry eye patients include dry eye symptoms, conjunctival congestion, itching and foreign body sensation. Dry eye can cause visual impairment when severe, and it is recently said that dry eye also causes eye strain.
- the causes of the occurrence of dry eye are various, such as a decrease in tear secretion, a decrease in viscous components in tears, an excess of oily components, or a qualitative change in secretions, but many have not yet been elucidated.
- corneal epithelial cells have been reported in corneal epithelial cells of dry eye patients (Clinical Allergy,] J, 59-61 (1992)).
- corneal epithelial cells differentiate into keratinocytes, the cells originally possessed lose their normal functions. Keratinocytes are absent in normal human corneal epithelial cells, and keratinocytes may be involved in the development of dry eye.
- TG-I type I transdaltaminase has been added to human corneal epithelial cells.
- TG-I was reported to be expressed (Invest. Ophthalmol. Vis. Sci., 37, S355 (1996)).
- TG-I is an enzyme involved in the keratinization of keratinocytes, and its expression is an indicator of keratinocyte differentiation. Therefore, if the expression of TG-I in corneal epithelial cells of patients with dry eye can be suppressed, it is expected that the differentiation of keratinocytes in corneal epithelial cells will be suppressed, leading to treatment of dry eye. You.
- the active ingredient 1 ⁇ , 24-dihydroxyvitamin D 3 in the present invention is one of so-called active vitamins, and is a known compound described in JP-B-53-9222. It is. Its pharmaceutical uses include remedies for renal insufficiency and sickness (Japanese Patent Publication No. 53-31150, Japanese Patent Publication No. 53-31151), ischemic heart disease, brain A therapeutic agent for a disease involving tromboxane A 2 such as vascular disorder and bronchial asthma (Japanese Patent No. 2543632), and a therapeutic agent for chronic hepatitis (Japanese Patent Application Laid-Open No. Hei 3 — 504,249) ), And anti-inflammatory and antipyretic analgesics (Japanese Patent Publication No. 3-19207) are known.
- 24-Dihydroxyvitamine D 3 is a useful compound for various pharmaceutical uses as described above, but its new action And finding pharmaceutical applications are very interesting issues.
- the present inventors have proposed 1 ⁇ , 24 dihydroxyvititamin D. Intensive research result new was Do action of, 1 ⁇ , 2 4 - dihydric Dorokishibi evening Mi emissions 0 3 has been found and this suppresses the TG-I expression in the corneal epithelial cells. That, 1 alpha, 2 4 - dihydric Dorokishibita Mi emissions 0 3 suppresses the differentiation of keratinocytes in corneal epithelial cells, leading to finding useful as a dry eye treatment agent.
- the present invention 1 alpha, 2 4 - as an active ingredient dihydrazide Dorokishibita Mi emissions D 3, 1) dry eye treatment agent, 2) differentiation inhibiting agent in our Keru keratinocytes corneal epithelial cells, and 3) I type It relates to transglutaminase (TG-I) expression inhibitors, and their effects are described in detail in the pharmacological test section below.
- TG-I transglutaminase
- stereoisomer is present in 1 2 4 dihydric Dorokishibita Mi emissions 0 3 as an active ingredient of the present invention, they are all encompassed in the present invention.
- 1 ⁇ , 24 (R) -dihydroxyxivitamin D is particularly preferred. Is preferably used.
- the dosage form include tablets, capsules, granules, powders, injections, eye drops, eye ointments and the like, with eye drops being particularly preferred. These can be formulated using commonly used techniques.
- isotonic agents such as sodium chloride and concentrated glycerin
- buffering agents such as sodium phosphate and sodium acetate
- polyoxyethylene sorbitan monolate
- Surfactant, polyoxyl stearate 40, polyoxyethylene hydrogenated castor oil, etc., stabilizers such as sodium citrate, sodium edetate, chloride Formulations can be made using preservatives such as benzalconidum and paraben as needed.
- the pH should be within the range acceptable for ophthalmic preparations, but a range of 4 to 8 is preferred.
- bulking agents such as lactose, crystalline cellulose, starch, and vegetable oils, and lubricants such as magnesium stearate and talc
- Binders such as hydroxypropylcellulose and polyvinylpyrrolidone
- disintegrators such as calcium carboxymethylcellulose; low-substituted hydroxypropylmethylcellulose; hydroxypropylmethylcellulose; macrogol;
- a coating agent such as corn resin, a film agent such as a gelatin film, etc. may be added as needed.
- the dose can be appropriately selected depending on the symptoms, age, dosage form, etc., but if it is an eye drop, it is 0.001 to 1% (w / V), preferably 0.00001 to 0. 1% (WZV) should be instilled once or several times a day.
- w / V w / V
- WZV 0.00001 to 0. 1%
- 1% WZV
- it may be administered in an amount of 0.1 to 500 mg, preferably 1 to: LOOmg per day, in one or several divided doses.
- the concentration of 0000 001% (to w), 0.0 003% (/ V), 0.03% (w / v) 0.01% (w / v) , 0.03% (wZv) and 0.1% (w / v) eye drops can be prepared.
- a coating agent for example, a normal coating agent such as hydroxypropylmethylcellulose, macrogol, silicone resin, etc.
- TG-I Human corneal epithelial cells express TG-I, an enzyme involved in the proliferation of keratinocytes (Invest. Ophthalmol. Vis. Sci., 37, S355 (1996)). It is an indicator of the differentiation of transformed cells. Corneal epithelial cells in dry eye patients have keratinocytes due to abnormal differentiation (Arlergi's clinical study, 12, 59-61 (1992)), but suppress TG-I expression in corneal epithelial cells If this can be achieved, it is expected that the differentiation of keratinocytes in corneal epithelial cells will be suppressed, leading to treatment of dry eye.
- AMV Takara RNA-PCR kit
- the expression level of TG-ImRNA was calculated according to the following formula 1 so that the expression level in the control was 100.
- the present invention 1 alpha, 2 4 - dihydric Dorokishibita as a new medicinal use of Mi emissions D 3, 1 ⁇ , 2 4 - including dihydrazide Dorokishi Vita Mi emissions D 3 as an active ingredient, 1) dry eye
- the present invention provides a therapeutic agent, 2) an inhibitor of keratinocyte differentiation in corneal epithelial cells, and 3) an inhibitor of type I transglutaminase (TG-I) expression.
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- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP98919555A EP0998931A4 (en) | 1997-05-16 | 1998-05-12 | TREATMENT OF DRY EYES |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP9126759A JPH10316574A (ja) | 1997-05-16 | 1997-05-16 | ドライアイ治療剤 |
JP9/126759 | 1997-05-16 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1998051313A1 true WO1998051313A1 (fr) | 1998-11-19 |
Family
ID=14943228
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP1998/002080 WO1998051313A1 (fr) | 1997-05-16 | 1998-05-12 | Remedes contre les yeux secs |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP0998931A4 (ja) |
JP (1) | JPH10316574A (ja) |
WO (1) | WO1998051313A1 (ja) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0992242A1 (en) * | 1997-06-10 | 2000-04-12 | New Vision Co., Ltd. | Vitamin d-containing preventives and/or remedies for conjunctival/corneal xerosis |
US6187331B1 (en) | 1997-06-10 | 2001-02-13 | New Vision Co., Ltd. | Composition for prophylaxis and/or treatment of dry syndrome comprising vitamin D |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007133001A (ja) * | 2005-11-08 | 2007-05-31 | Seed Co Ltd | コンタクトレンズ用ケア用剤 |
US9877975B2 (en) | 2013-06-28 | 2018-01-30 | Keio University | Agent for treating meibomian gland dysfunction |
CN114126623A (zh) * | 2019-05-17 | 2022-03-01 | 宾夕法尼亚大学董事会 | 治疗肥胖和/或皮肤紊乱的方法和组合物 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996029079A1 (fr) * | 1995-03-20 | 1996-09-26 | Katsuhiko Mukai | Composition ophthamologique comprenant de la vitamine d activee |
WO1997018817A1 (fr) * | 1995-11-20 | 1997-05-29 | Kiyoshi Kita | Preparation externe contenant de la vitamine d ou de la vitamine k |
-
1997
- 1997-05-16 JP JP9126759A patent/JPH10316574A/ja active Pending
-
1998
- 1998-05-12 WO PCT/JP1998/002080 patent/WO1998051313A1/ja not_active Application Discontinuation
- 1998-05-12 EP EP98919555A patent/EP0998931A4/en not_active Withdrawn
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996029079A1 (fr) * | 1995-03-20 | 1996-09-26 | Katsuhiko Mukai | Composition ophthamologique comprenant de la vitamine d activee |
WO1997018817A1 (fr) * | 1995-11-20 | 1997-05-29 | Kiyoshi Kita | Preparation externe contenant de la vitamine d ou de la vitamine k |
Non-Patent Citations (2)
Title |
---|
MATSUNAGA T, ET AL.: "EFFECTS OF 1,24(R)-(OH)2D3 ON EPIDERMAL CELL DIFFERENTIATION IN MICE", YAKURI TO CHIRYO - JAPANESE PHARMACOLOGY AND THERAPEUTICS., RAIFU SAIENSU SHUPPAN, TOKYO., JP, vol. 21, no. 12, 1 January 1993 (1993-01-01), JP, pages 4573 - 4579, XP002917214, ISSN: 0386-3603 * |
SATO H., ET AL.: "TACALCITOL (1,24(OH)2D3, TV-O2) INHIBITS PHORBOL ESTER-INDUCED EPIDERMAL PROLIFERATION AND CUTANEOUS INFLAMMATION, AND INDUCES EPIDERMAL DIFFERENTIATION IN MICE.", ARCHIVES OF DERMATOLOGICAL RESEARCH., SPRINGER, INTERNATIONAL, BERLIN., DE, vol. 288., 1 January 1996 (1996-01-01), DE, pages 656 - 663., XP002914416, ISSN: 0340-3696, DOI: 10.1007/s004030050120 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0992242A1 (en) * | 1997-06-10 | 2000-04-12 | New Vision Co., Ltd. | Vitamin d-containing preventives and/or remedies for conjunctival/corneal xerosis |
EP0992242A4 (en) * | 1997-06-10 | 2000-05-10 | New Vision Co Ltd | PROPHYLACTIC AGENTS AND / OR REMEDIES CONTAINING VITAMIN D FOR PREVENTING AND / OR TREATING CONJUNCTIVAL / CORNEAL XEROSIS |
US6187331B1 (en) | 1997-06-10 | 2001-02-13 | New Vision Co., Ltd. | Composition for prophylaxis and/or treatment of dry syndrome comprising vitamin D |
US6410006B2 (en) | 1997-06-10 | 2002-06-25 | New Vision Co., Ltd. | Composition for prophylaxis and/or treatment of dry eye syndrome comprising vitamin D |
Also Published As
Publication number | Publication date |
---|---|
JPH10316574A (ja) | 1998-12-02 |
EP0998931A1 (en) | 2000-05-10 |
EP0998931A4 (en) | 2001-03-14 |
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