WO2006064825A1 - Agent therapeutique pour la secheresse oculaire - Google Patents
Agent therapeutique pour la secheresse oculaire Download PDFInfo
- Publication number
- WO2006064825A1 WO2006064825A1 PCT/JP2005/022913 JP2005022913W WO2006064825A1 WO 2006064825 A1 WO2006064825 A1 WO 2006064825A1 JP 2005022913 W JP2005022913 W JP 2005022913W WO 2006064825 A1 WO2006064825 A1 WO 2006064825A1
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- Prior art keywords
- dihydroxy
- group
- fluorophenyl
- dry eye
- hydroxy
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4433—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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 a therapeutic agent for dry eye comprising a statin compound as an active ingredient.
- the cornea is a transparent avascular tissue having a diameter of about 1 cm and a thickness of about 1 mm
- the conjunctiva is a mucous membrane covering the surface of the eyeball behind the cornea edge and the back of the eyelid. It is known that when the cornea and conjunctiva are damaged, visual function is seriously affected. Corneal and conjunctival damage associated with dry eye adversely affects the normal reconstruction of the corneal epithelium and conjunctival epithelium, and as a result, the structure and function of the corneal stroma and corneal endothelium can be impaired.
- Non-patent document 1 Non-patent document 2
- statin compounds are known to suppress the biosynthesis of blood cholesterol and are widely used as therapeutic agents for hyperlipidemia and the like.
- Patent Document 1 describes that statins such as atorvastatin, lovastatin, pravastatin, flupastatin, cerivastatin, and simpastatin are useful as immunomodulators, immune inhibitors, and anti-inflammatory agents.
- Patent Document 2 describes that statin compounds such as cerivastatin, atorvastatin, sympastatin, and pravastatin are useful as therapeutic agents for TNF_a related diseases such as inflammatory diseases and cardiovascular diseases.
- statin compounds have no reports on the pharmacological effects of statin compounds on keratoconjunctival diseases such as dry eye.
- Patent Document 1 Japanese Translation of Special Publication 2004-512278
- Patent Document 2 Japanese Patent Laid-Open No. 2001-294526
- Non-Patent Document 1 Eyesight, 46, 738-743 (1992)
- Non-Patent Document 2 Ophthalmic Surgery, 5, 719-727 (1992)
- statin compounds were conducted intensive research in order to search for new pharmaceutical uses of statin compounds.
- a corneal disorder healing efficacy test using a rat dry eye model (+)-(IS, 3R, 7S, 8S, 8aR) -3, 7 Dimethinole 1, 2, 3, 7, 8, 8a Hexahydro 8-
- a therapeutic agent for dry eye or a disease associated with dry eye comprising a compound represented by the following general formula (1) or a salt thereof as an active ingredient,
- A represents a lower alkylene group or a lower alkenylene group
- Ring X represents a non-aromatic ring or a nitrogen-containing aromatic heterocycle
- R 1 represents a hydrogen atom or a lower alkyl group
- R 2 represents a hydroxy group
- R 1 and R 2 may be condensed to form a rataton ring
- R 3 represents a hydrogen atom or a lower alkyl group
- R 4 is an optionally substituted lower alkyl group, cycloalkyl group, optionally substituted aryl group, hydroxy group or ester thereof, lower alkoxy group, carboxyl group or amide thereof, or lower alkyl An amino group or an amide thereof; m represents an integer of 0 to 4, and when m is 2 or more, each R 4 may be the same or different. )
- R 5 and R 6 are the same or different and each represents a hydrogen atom, a hydroxy group, a lower alkoxy group or a lower alkyl group;
- R 7 represents a hydroxy group or an ester thereof
- R 8 and R 11 are the same or different and each represents a hydrogen atom, a lower alkyl group or an aryl group which may have a substituent;
- R 9 and R 1Q are the same or different and each represents an optionally substituted aryl group, carboxy group or amide thereof;
- R 12 represents a hydrogen atom or a lower alkyl group
- R represents a hydrogen atom or a lower alkyl group
- R 14 represents a hydrogen atom or a lower alkyl group which may have a substituent
- R 15 represents an aryl group which may have a substituent
- R 16 and R 18 are the same or different and each represents a hydrogen atom, a lower alkyl group or an aryl group which may have a substituent;
- R 17 represents a lower alkylamino group or an amide thereof
- R 19 represents a hydrogen atom or a lower alkyl group
- R 2Q represents an aryl group which may have a substituent
- R 21 represents an aryl group which may have a substituent
- R 22 represents a cycloalkyl group before [1] or [2], or dry eye or a therapeutic agent for a disease associated with dry eye,
- the “lower alkylene group” refers to a linear or branched alkylene group having 1 to 8 carbon atoms.
- methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, heptamethylene, otatamethylene, methylmethylene, ethylmethylene group and the like can be mentioned.
- lower alkenylene group refers to a linear or branched alkenylene group having 2 to 8 carbon atoms.
- Non-aromatic ring means a monocyclic or bicyclic non-cyclic ring having 6 to 10 carbon atoms, and may contain:! To 2 double bonds in the ring.
- An aromatic hydrocarbon ring is shown.
- Nitrogen-containing aromatic heterocycle means:! ⁇ A single 4 to 9 carbon atom having 2 nitrogen atoms A cyclic or bicyclic aromatic heterocycle is shown.
- Examples include pyrrole, pyrazole, imidazole, pyridine, pyridazine, pyrimidine, pyrazine, quinoline, isoquinoline, phthalazine, cinnoline, quinazoline, quinoxaline, indole, isoindole, indazole, benzoimidazole ring, preferably pyrrole, Examples include pyridine, quinoline and indole rings.
- the "lower alkyl group” refers to a straight or branched alkyl group having from 6 to 6 carbon atoms. Examples thereof include methinole, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, se c-butinole, tert-butinole, n_pentinole, isopentinole, neopentinole, n_hexinole, isohexenole group and the like.
- the substituent of the "lower alkyl group optionally having substituent (s)" represents one or two groups selected from a hydroxy group and a lower alkoxy group.
- cycloalkyl group refers to a cycloalkyl having 3 to 8 carbon atoms.
- cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl group and the like can be mentioned.
- the "lower alkoxy group” refers to straight-chain or branched alkoxy having 1 to 6 carbon atoms. For example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, n-pentyloxy, n xyloxy groups and the like are shown.
- aryl group refers to a monocyclic or bicyclic aromatic hydrocarbon having 6 to 10 carbon atoms.
- a phenyl, a naphthyl group, etc. are mentioned,
- substituent of “optionally substituted aryl group” is 1 or 2 groups selected from a halogen atom and an alkyl group.
- Halogen atom refers to a fluorine, chlorine, bromine or iodine atom.
- Ester of hydroxy group refers to an ester composed of a hydroxy group and an aliphatic carboxylic acid.
- the aliphatic carboxylic acid refers to a straight-chain or branched monocarboxylic acid having 1 to 7 carbon atoms. Specific examples thereof include formic acid, acetic acid, propionic acid, butyric acid, valeric acid, 2-methylbutane. Examples include acid and 2,2_dimethylbutanoic acid.
- the “carboxy group amide” refers to an amide having a carboxy group and ammonia, a primary or secondary amine, and the like.
- the amine may be a lower alkylamine or an arylamine, and specific examples of the lower alkylamine include methylamine, ethylamine, ethylmethylamine, dimethylamine, jetylamine, dihexylamine and the like, and specific examples of the arylamine are ananiline, naphthylamine. Etc.
- lower anolenoquinamino group refers to a mono- or dialkylamino group in which a hydrogen atom of an amino group is substituted 1 or 2 with the lower alkyl group.
- Specific examples of the monoalkylamino group include methinoreamino, ethenoreamino, and ethylmethylamino.
- Specific examples of the dialkylamino group include dimethylenoamino, dimethylamino-containing dihexylamino, and the like.
- the "amide of a lower alkylamino group” refers to a sulfonic acid amide composed of a lower alkylamino group and an aliphatic sulfonic acid.
- the aliphatic sulfonic acid refers to a linear or branched monosulfonic acid having from 6 to 6 carbon atoms. Specific examples include methanesulfonic acid, ethanesulfonic acid, hexanesulfonic acid, 2-butanesulfonic acid and the like.
- Lataton ring refers to a 6-membered ⁇ -latathon ring.
- the “salt” in the present compound is not particularly limited as long as it is a pharmaceutically acceptable salt.
- an inorganic acid such as hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, phosphoric acid, etc.
- Salt acetic acid, fumaric acid, maleic acid, succinic acid, citrate, tartaric acid, adipic acid, darconic acid, darcoheptic acid, glucuronic acid, terephthalic acid, methanesulfonic acid, lactic acid, hippuric acid, 1, 2 —Ethane disulfonic acid, isethionic acid, ratatobionic acid, oleic acid, pamoic acid, polygalatathuronic acid, stearic acid, tannic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, ⁇ -tonoleenesulfonic acid, lauryl sulfate, methyl sulfate , Salts with organic acids such as naphthalene sulfonic acid and sulfosalicylic acid, quaternary ammonium salts with methyl bromide, methyl iodide, bromine ion, chlorine ion Salt
- the present compound may be in the form of a hydrate or a solvate.
- Preferable specific examples of the present compound include, for example, (+)-one (IS, 3R, 7S, 8S, 8aR) — 3, 7 Dimethinole 1, 2, 3, 7, 8, 8a Hexahydro 8— [2 — [(2R, 4R) — 4-hydroxy-6-oxotetrahydro-1 2H pyran-1-yl] ethyl] 1 naphthyl 2, 2-dimethylbutanoate (sympastatin), (+) — (3R, 5R) — 3, 5-Dihydroxy 1 7 — [(IS, 2S, 6S, 8S, 8aR) -1, 2, 6, 7, 8, 8a Hexahydro 1-6 Hydroxy 1 2-Methyl-8— [(2S) — 2-Methylbutyryloxy] 1 naphthyl] heptanoic acid (Pura / statin), (+) (IS, 3R, 7S, 8S, 8aR) -3, 7 Dimethinole 1,
- the disease associated with dry eye is not particularly limited as long as it is a disease associated with dry eye, such as corneal ulcer, punctate superficial keratopathy, corneal epithelial defect, conjunctival epithelial defect and the like.
- the therapeutic agent for dry eye or a disease associated with dry eye according to the present invention can be administered either orally or parenterally.
- Examples of the dosage form include eye drops, eye ointments, injections, tablets, capsules, granules, powders and the like, and eye drops are particularly preferable. These can be formulated using widely used techniques.
- eye drops include isotonic agents such as sodium chloride and concentrated glycerin, buffering agents such as sodium phosphate and sodium acetate, polyoxyethylene sorbitan monolate, polyoxyl stearate 40, polyoxyethylene hardened castor
- a surfactant such as oil, a stabilizer such as sodium quenate and sodium edetate, and a preservative such as benzalkonium chloride and paraben can be used as necessary. If the pH is within the range allowed for ophthalmic preparations, the range of 4-8 is preferred.
- An eye ointment can be prepared using a widely used base such as white petrolatum or liquid paraffin.
- Oral preparations such as tablets, capsules, granules, powders, etc. include bulking agents such as lactose, crystalline cellulose, starch, vegetable oil, lubricants such as magnesium stearate and talc, hydroxypropylcellulose, polybulurpyrrolidone, etc. 1J, carboxymethyl cellulose Calcium, low-substituted hydroxypropyl methylcellulose and other disintegrants, hydroxypropylmethylcellulose, macrogol, silicone resin, etc.
- a film agent such as a latin film can be added as necessary to prepare the film.
- the present invention also relates to a method for treating dry eye or a disease associated with dry eye, comprising administering an effective amount of the compound represented by the general formula (1) or a salt thereof to a patient.
- the dose of the active ingredient can be appropriately selected depending on the symptom, age, dosage form, etc.
- 0.0001-10% (wZv), preferably 0.001-3% (w / v) Do it one to several times.
- 0.1 to 5000 mg per day usually preferably 1 to 1000 mg should be administered once or divided into several doses.
- a dry eye model was prepared according to the method of Fujihara et al. (Invest. Ophthalmol. Vis. Sci 42 (1): 96-100 (2001)). After the dry eye model was prepared, corneal damage was scored according to the method of Murakami et al. (New Ophthalmology 21 (1): 87-90 (2004)), and the improvement rate of corneal damage after instillation of each statin compound was determined. Asked.
- test compound (compounds A to H) was instilled (instillation amount: 5 ⁇ L / time) as follows.
- a physiological phosphate buffer solution (PBS solution) of Compound A (0.02%) was instilled into both eyes 6 times a day for 14 days (4 eyes per group, 8 eyes).
- Compound G ophthalmic group Compound G (0.002%) in PBS was applied to both eyelids 6 times a day for 14 days (4 animals per group, 8 eyes) 0
- Improvement rate (%) ⁇ (control)-(this compound) ⁇ / disorder degree X 100
- the concentration becomes 0.001% (, 0.1% (w / v), 0.3% (w / v), 1.0% (w / v), 3. 0% (Yes.
- an ointment with a concentration of 1% (WZW) or 3% (wZw) can be prepared.
- an ointment with a concentration of 1% (w / w) or 3% (w / w) can be prepared.
- Each eye ointment can be prepared by using Compound C, Compound D, and Compounds F to H instead of Compound E.
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- Animal Behavior & Ethology (AREA)
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Abstract
Applications Claiming Priority (2)
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JP2004361554 | 2004-12-14 | ||
JP2004-361554 | 2004-12-14 |
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WO2006064825A1 true WO2006064825A1 (fr) | 2006-06-22 |
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PCT/JP2005/022913 WO2006064825A1 (fr) | 2004-12-14 | 2005-12-14 | Agent therapeutique pour la secheresse oculaire |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013113067A1 (fr) * | 2012-02-02 | 2013-08-08 | The University Of Sydney | Améliorations dans la stabilité du film lacrymal |
Citations (5)
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JP2000264847A (ja) * | 1999-01-12 | 2000-09-26 | Teruo Nishida | 角膜障害治療剤 |
WO2002030425A1 (fr) * | 2000-10-12 | 2002-04-18 | Nissan Chemical Industries, Ltd. | Medicaments pour la prevention ou le traitement de complications du diabete |
JP2002205944A (ja) * | 2000-11-08 | 2002-07-23 | Santen Pharmaceut Co Ltd | ファルネシル酢酸を有効成分とする角結膜疾患治療剤 |
JP2004149480A (ja) * | 2002-10-31 | 2004-05-27 | Saisentan Igaku Kenkyusho:Kk | 経口又は経皮投与用の眼科疾患治療剤 |
JP2005145961A (ja) * | 2003-10-24 | 2005-06-09 | Santen Pharmaceut Co Ltd | 角結膜障害の治療剤 |
-
2005
- 2005-12-14 WO PCT/JP2005/022913 patent/WO2006064825A1/fr active Application Filing
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2000264847A (ja) * | 1999-01-12 | 2000-09-26 | Teruo Nishida | 角膜障害治療剤 |
WO2002030425A1 (fr) * | 2000-10-12 | 2002-04-18 | Nissan Chemical Industries, Ltd. | Medicaments pour la prevention ou le traitement de complications du diabete |
JP2002205944A (ja) * | 2000-11-08 | 2002-07-23 | Santen Pharmaceut Co Ltd | ファルネシル酢酸を有効成分とする角結膜疾患治療剤 |
JP2004149480A (ja) * | 2002-10-31 | 2004-05-27 | Saisentan Igaku Kenkyusho:Kk | 経口又は経皮投与用の眼科疾患治療剤 |
JP2005145961A (ja) * | 2003-10-24 | 2005-06-09 | Santen Pharmaceut Co Ltd | 角結膜障害の治療剤 |
Non-Patent Citations (1)
Title |
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PARK H.-J. ET AL.: "3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Interfere With Angiogenesis by Inhibiting the Geranylgeranylation of RhoA", CIRCUL. RES., vol. 91, no. 2, 26 July 2002 (2002-07-26), pages 143 - 150, XP002997966 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013113067A1 (fr) * | 2012-02-02 | 2013-08-08 | The University Of Sydney | Améliorations dans la stabilité du film lacrymal |
AU2013214693B2 (en) * | 2012-02-02 | 2017-02-23 | Kenneth Gek-Jin OOI | Improvements in tear film stability |
AU2017204257B2 (en) * | 2012-02-02 | 2018-06-21 | Kenneth Gek-Jin Ooi | Improvements in tear film stability |
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