CA2280089C - Compositions and methods for reducing ocular hypertension - Google Patents
Compositions and methods for reducing ocular hypertension Download PDFInfo
- Publication number
- CA2280089C CA2280089C CA002280089A CA2280089A CA2280089C CA 2280089 C CA2280089 C CA 2280089C CA 002280089 A CA002280089 A CA 002280089A CA 2280089 A CA2280089 A CA 2280089A CA 2280089 C CA2280089 C CA 2280089C
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- preservative
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- weight percent
- composition
- ophthalmic
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- WGJJROVFWIXTPA-OALUTQOASA-N prostanoic acid Chemical compound CCCCCCCC[C@H]1CCC[C@@H]1CCCCCCC(O)=O WGJJROVFWIXTPA-OALUTQOASA-N 0.000 description 1
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Classifications
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
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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
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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
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
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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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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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
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Ophthalmology & Optometry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US81922197A | 1997-03-17 | 1997-03-17 | |
| US08/819,221 | 1997-03-17 | ||
| PCT/EP1998/001483 WO1998041208A1 (en) | 1997-03-17 | 1998-03-13 | Compositions and methods for reducing ocular hypertension |
Publications (2)
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|---|---|
| CA2280089A1 CA2280089A1 (en) | 1998-09-24 |
| CA2280089C true CA2280089C (en) | 2009-03-03 |
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|---|---|---|---|
| CA002280089A Expired - Fee Related CA2280089C (en) | 1997-03-17 | 1998-03-13 | Compositions and methods for reducing ocular hypertension |
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| IL (1) | IL131041A0 (enExample) |
| MY (1) | MY122237A (enExample) |
| NO (1) | NO327713B1 (enExample) |
| NZ (1) | NZ337322A (enExample) |
| PE (1) | PE61899A1 (enExample) |
| PL (1) | PL197509B1 (enExample) |
| PT (1) | PT969846E (enExample) |
| RU (1) | RU2197970C2 (enExample) |
| SI (1) | SI0969846T2 (enExample) |
| TW (1) | TW527187B (enExample) |
| UA (1) | UA63938C2 (enExample) |
| WO (1) | WO1998041208A1 (enExample) |
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| US6011062A (en) * | 1994-12-22 | 2000-01-04 | Alcon Laboratories, Inc. | Storage-stable prostaglandin compositions |
| AR002194A1 (es) * | 1997-03-17 | 1998-01-07 | Sanchez Reynaldo Alemany | Instrumento computarizado para el analisis del movimiento. |
| US6187818B1 (en) | 1998-06-17 | 2001-02-13 | Pharmacia & Upjohn Company | Prostaglandins formulation and process |
| JP4880808B2 (ja) * | 1999-11-15 | 2012-02-22 | 久光製薬株式会社 | 人工涙液型点眼剤組成物 |
| JP4000505B2 (ja) | 1999-12-01 | 2007-10-31 | 第一三共株式会社 | 緑内障を治療するための併用剤 |
| CA2422031C (en) * | 2000-09-13 | 2011-11-15 | Santen Pharmaceutical Co., Ltd. | Ophthalmic solutions comprising difluoroprostaglandin f2 alpha |
| WO2002045748A1 (en) * | 2000-12-05 | 2002-06-13 | Sankyo Company, Limited | Ocular tension-lowering compositions for topical administration |
| US20020198209A1 (en) * | 2001-05-03 | 2002-12-26 | Allergan Sales Inc. | Compositions having enhanced pharmacokinetic characteristics |
| US7074827B2 (en) | 2002-10-24 | 2006-07-11 | Sucampo Ag (Usa) Inc. | Method for treating ocular hypertension and glaucoma |
| RU2266572C1 (ru) * | 2004-03-17 | 2005-12-20 | Российский государственный медицинский университет | Способ моделирования злокачественной артериальной гипертонии |
| CA2558135C (en) * | 2004-03-18 | 2012-08-14 | R-Tech Ueno, Ltd. | Aqueous composition comprising thiazole derivative |
| US8569367B2 (en) * | 2004-11-16 | 2013-10-29 | Allergan, Inc. | Ophthalmic compositions and methods for treating eyes |
| GB0501192D0 (en) * | 2005-01-20 | 2005-03-02 | Resolution Chemicals Ltd | Stable prostaglandin-containing compositions |
| US7851504B2 (en) * | 2005-03-16 | 2010-12-14 | Allergan, Inc. | Enhanced bimatoprost ophthalmic solution |
| DE202005005094U1 (de) * | 2005-03-31 | 2005-07-28 | Dr. Gerhard Mann Chem.-Pharm. Fabrik Gmbh | Ophthalmische Zusammensetzung |
| EP1916002B1 (en) * | 2005-08-02 | 2014-03-05 | Santen Pharmaceutical Co., Ltd. | Method for prevention of degradation of thermally unstable substance |
| JP5252787B2 (ja) * | 2005-08-02 | 2013-07-31 | 参天製薬株式会社 | 熱的に不安定な薬物の分解抑制方法 |
| JP2007099647A (ja) * | 2005-09-30 | 2007-04-19 | Kobayashi Pharmaceut Co Ltd | 粘膜適用組成物 |
| US8168206B1 (en) | 2005-10-06 | 2012-05-01 | Allergan, Inc. | Animal protein-free pharmaceutical compositions |
| BRPI0708891A2 (pt) * | 2006-03-13 | 2011-06-28 | R Tech Ueno Ltd | composição aquosa |
| US8466174B2 (en) * | 2006-03-17 | 2013-06-18 | Johnson & Johnson Vision Care, Inc. | Methods for stabilizing oxidatively unstable compositions |
| JP2010508306A (ja) * | 2006-10-31 | 2010-03-18 | アルコン リサーチ， リミテッド | 眼障害を治療するためのｐａｉ−１結合調節因子 |
| WO2008096804A1 (ja) * | 2007-02-07 | 2008-08-14 | Teika Pharmaceutical Co., Ltd. | ラタノプロスト含有点眼剤 |
| JP2009073788A (ja) * | 2007-09-21 | 2009-04-09 | Teika Seiyaku Kk | イソプロピルウノプロストン含有眼用組成物 |
| BRPI0819081A8 (pt) * | 2007-10-08 | 2016-08-30 | Fovea Pharmaceuticals Sa | Formulação oftálmica aquosa, processo para preparar a mesma, e, método para inibir, tratar ou prevenir doenças oculares e doença ou condição relacionada, em um paciente em necessidade de tal tratamento |
| TWI544927B (zh) | 2008-03-17 | 2016-08-11 | 愛爾康研究有限公司 | 具有低濃度的表面活性劑以促進治療劑之生物可利用性的藥學組成物 |
| CN101959500A (zh) * | 2008-03-17 | 2011-01-26 | 爱尔康研究有限公司 | 包含硼酸类化合物-多元醇络合物的水性药物组合物 |
| EP2127638A1 (en) | 2008-05-30 | 2009-12-02 | Santen Pharmaceutical Co., Ltd | Method and composition for treating ocular hypertension and glaucoma |
| RU2402316C2 (ru) * | 2009-01-11 | 2010-10-27 | Пшеничников Виталий Георгиевич | Фармацевтическая антиглаукомная композиция |
| US8952051B2 (en) * | 2009-11-05 | 2015-02-10 | Allergan, Inc. | Ophthalmic formulations containing substituted gamma lactams and methods for use thereof |
| CA2830896A1 (en) * | 2011-04-12 | 2012-10-18 | Yukihiko Mashima | Aqueous ophthalmic composition |
| US20130029919A1 (en) | 2011-07-26 | 2013-01-31 | Allergan, Inc. | Two part formulation system for opthalmic delivery |
| EP2567689A1 (en) | 2011-09-12 | 2013-03-13 | Visiotact Pharma | Ophthtalmic compositions comprising prostaglandin F2 alpha derivatives and hyaluronic acid |
| US8957048B2 (en) | 2011-10-06 | 2015-02-17 | Allergan, Inc. | Compositions for the treatment of dry eye |
| SG11201403013VA (en) | 2011-12-07 | 2014-07-30 | Allergan Inc | Efficient lipid delivery to human tear film using a salt-sensitive emulsion system |
| US9907826B2 (en) | 2011-12-07 | 2018-03-06 | Allergan, Inc. | Efficient lipid delivery to human tear film using a salt-sensitive emulsion system |
| UA121399C2 (uk) | 2014-11-25 | 2020-05-25 | Аллерган, Інк. | Стабілізовані композиції для офтальмологічного застосування, які містять омега-3-кислоти |
| WO2020061550A1 (en) * | 2018-09-21 | 2020-03-26 | Aufbau Medical Innovations Limited | Compositions and methods for glaucoma |
| BR112021020425A2 (pt) | 2019-04-12 | 2021-12-14 | Ecolab Usa Inc | Composições de limpeza multiuso concentrada e pronta para uso, e, métodos para limpar uma superfície e de fabricação da composição de limpeza multiuso |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2059058T3 (es) * | 1990-05-22 | 1994-11-01 | R Tech Ueno Ltd | Combinacion sinergica para uso oftalmico. |
| IE920397A1 (en) * | 1991-02-07 | 1992-08-12 | Allergan Inc | 2-decarboxyl-2-hydroxyalkyl-5-trans prostaglandin f¹derivatives |
| US5767154A (en) * | 1991-02-07 | 1998-06-16 | Allergan | 5-trans-prostaglandins of the F series and their use as ocular hypotensives |
| EP0708646A1 (en) * | 1994-05-06 | 1996-05-01 | Alcon Laboratories, Inc. | Use of vitamin e tocopheryl derivatives in ophthalmic compositions |
| US5631287A (en) † | 1994-12-22 | 1997-05-20 | Alcon Laboratories, Inc. | Storage-stable prostaglandin compositions |
| US5558876A (en) * | 1995-03-29 | 1996-09-24 | Alcon Laboratories, Inc. | Topical ophthalmic acidic drug formulations |
| AR002194A1 (es) * | 1997-03-17 | 1998-01-07 | Sanchez Reynaldo Alemany | Instrumento computarizado para el analisis del movimiento. |
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