JP2007534699A - 高眼圧症及び緑内障の治療ためのスタチン - Google Patents
高眼圧症及び緑内障の治療ためのスタチン Download PDFInfo
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- JP2007534699A JP2007534699A JP2007509736A JP2007509736A JP2007534699A JP 2007534699 A JP2007534699 A JP 2007534699A JP 2007509736 A JP2007509736 A JP 2007509736A JP 2007509736 A JP2007509736 A JP 2007509736A JP 2007534699 A JP2007534699 A JP 2007534699A
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| WO2007070866A2 (en) * | 2005-12-16 | 2007-06-21 | Alcon, Inc. | Control of intraocular pressure using alk5 modulation agents |
| PL2018153T3 (pl) | 2006-04-26 | 2012-09-28 | Rosemont Pharmaceuticals Ltd | Ciekłe kompozycje doustne |
| ES2330184B1 (es) * | 2008-06-03 | 2010-07-05 | Neuron Biopharma, S.A. | Uso de estatinas como anticonvulsivantes, antiepilepticos y neuroprotectores. |
| US20110293549A1 (en) | 2009-02-03 | 2011-12-01 | Athena Cosmetics, Inc. | Composition, method and kit for enhancing hair |
| US8299079B2 (en) | 2009-05-22 | 2012-10-30 | Kaufman Herbert E | Preparations and methods for ameliorating or reducing presbyopia |
| CN102093984B (zh) * | 2010-11-23 | 2012-07-04 | 清华大学 | 一种杂合酶P450sca2-BMR及其编码基因与应用 |
| CN104902892A (zh) | 2012-02-02 | 2015-09-09 | 悉尼大学 | 泪液膜稳定性的改进 |
| GB201611782D0 (en) * | 2016-07-06 | 2016-08-17 | Optibiotix Ltd | Composition |
| US10696638B2 (en) | 2017-12-26 | 2020-06-30 | Industrial Technology Research Institute | Compounds for inhibiting AGC kinase and pharmaceutical compositions comprising the same |
| WO2025147589A1 (en) * | 2024-01-05 | 2025-07-10 | Osanni Bio, Inc. | Implants, compositions, and methods for treating retinal diseases and disorders |
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| FR2534580A1 (fr) * | 1982-10-13 | 1984-04-20 | Synthelabo | Derives de phenyl-1 piperidino-2 propanol, leur preparation, et medicaments qui les contiennent |
| FR2585708B1 (fr) * | 1985-07-31 | 1989-07-07 | Sanofi Sa | Derives aminoalcools peptidiques inhibiteurs de la resine et des proteases acides, leur procede de preparation et leur application en therapeutique |
| US5151444B1 (en) * | 1987-09-18 | 1999-07-06 | R Tech Ueno Ltd | Ocular hypotensive agents |
| US5296504A (en) * | 1988-09-06 | 1994-03-22 | Kabi Pharmacia | Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension |
| ES2213504T1 (es) * | 1988-09-06 | 2004-09-01 | Pfizer Health Ab | Derivados de prostaglandina para el tratamiento del glaucoma o hipertension ocular. |
| FR2647675B1 (fr) * | 1989-06-05 | 1994-05-20 | Sanofi | Utilisation d'un derive de la statine dans le traitement des affections oculaires |
| JPH04243835A (ja) * | 1990-08-29 | 1992-08-31 | Pfizer Inc | 高眼圧症又は緑内障治療用薬剤組成物及び治療方法 |
| US5352708A (en) * | 1992-09-21 | 1994-10-04 | Allergan, Inc. | Non-acidic cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents |
| US5510383A (en) * | 1993-08-03 | 1996-04-23 | Alcon Laboratories, Inc. | Use of cloprostenol, fluprostenol and their salts and esters to treat glaucoma and ocular hypertension |
| US5599535A (en) * | 1995-06-07 | 1997-02-04 | Regents Of The University Of California | Methods for the cyto-protection of the trabecular meshwork |
| US6586425B2 (en) * | 1996-02-21 | 2003-07-01 | Wisconsin Alumni Research Foundation | Cytoskeletal active agents for glaucoma therapy |
| US6569461B1 (en) * | 1999-03-08 | 2003-05-27 | Merck & Co., Inc. | Dihydroxy open-acid and salts of HMG-CoA reductase inhibitors |
| EP1322306A2 (en) * | 2000-09-19 | 2003-07-02 | NovImmune S.A. | Use of statins (hmg-coa reductase inhibitors) for the preparation of medicament as a novel type of immunomodulator, immunosuppressor and anti-inflammatory agent |
| US20030065020A1 (en) * | 2001-07-13 | 2003-04-03 | Catharine Gale | Treatment of macular degeneration |
| US20030195167A1 (en) * | 2002-04-15 | 2003-10-16 | Kowa Co., Ltd. | PTX3-gene expression inhibitor |
| 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 |
| US20040248972A1 (en) * | 2003-05-16 | 2004-12-09 | Ambit Biosciences Corporation | Compounds and uses thereof |
| CA2523808A1 (en) * | 2003-05-16 | 2004-12-23 | Ambit Biosciences Corporation | Pyrrole compounds and uses thereof |
| US20060241122A1 (en) * | 2003-05-30 | 2006-10-26 | Lee Margaret S | Combination therapy for the treatment of neoplasms |
| US20090202524A1 (en) * | 2007-10-31 | 2009-08-13 | Alcon Research, Ltd. | Pai-1 expression and activity inhibitors for the treatment of ocular disorders |
-
2005
- 2005-04-25 AU AU2005237543A patent/AU2005237543B2/en not_active Ceased
- 2005-04-25 SI SI200530460T patent/SI1740164T1/sl unknown
- 2005-04-25 ES ES05738648T patent/ES2311986T3/es not_active Expired - Lifetime
- 2005-04-25 CN CN2005800130061A patent/CN1946384B/zh not_active Expired - Fee Related
- 2005-04-25 WO PCT/US2005/014255 patent/WO2005105069A1/en not_active Ceased
- 2005-04-25 BR BRPI0510245-6A patent/BRPI0510245A/pt not_active IP Right Cessation
- 2005-04-25 KR KR1020117018000A patent/KR20110091600A/ko not_active Withdrawn
- 2005-04-25 MX MXPA06012225A patent/MXPA06012225A/es active IP Right Grant
- 2005-04-25 ZA ZA200607988A patent/ZA200607988B/xx unknown
- 2005-04-25 JP JP2007509736A patent/JP2007534699A/ja active Pending
- 2005-04-25 DK DK05738648T patent/DK1740164T3/da active
- 2005-04-25 PT PT05738648T patent/PT1740164E/pt unknown
- 2005-04-25 AT AT05738648T patent/ATE404189T1/de active
- 2005-04-25 PL PL05738648T patent/PL1740164T3/pl unknown
- 2005-04-25 EP EP05738648A patent/EP1740164B1/en not_active Expired - Lifetime
- 2005-04-25 US US11/114,512 patent/US20050239871A1/en not_active Abandoned
- 2005-04-25 DE DE602005008935T patent/DE602005008935D1/de not_active Expired - Lifetime
- 2005-04-25 CA CA002560167A patent/CA2560167A1/en not_active Abandoned
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2006
- 2006-11-15 KR KR1020067023958A patent/KR101071192B1/ko not_active Expired - Fee Related
-
2008
- 2008-11-07 CY CY20081101271T patent/CY1108490T1/el unknown
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2010
- 2010-11-08 US US12/941,639 patent/US20110098314A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007512347A (ja) * | 2003-11-26 | 2007-05-17 | デューク・ユニバーシティー | 緑内障を予防するかまたは治療する方法 |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011518828A (ja) * | 2008-04-26 | 2011-06-30 | アルコン リサーチ， リミテッド | 眼球障害の処置のためのｐａｉ−１の発現および活性インヒビター |
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|---|---|
| AU2005237543A1 (en) | 2005-11-10 |
| US20050239871A1 (en) | 2005-10-27 |
| SI1740164T1 (sl) | 2009-02-28 |
| EP1740164A1 (en) | 2007-01-10 |
| PT1740164E (pt) | 2008-10-21 |
| KR20110091600A (ko) | 2011-08-11 |
| CY1108490T1 (el) | 2014-04-09 |
| ATE404189T1 (de) | 2008-08-15 |
| KR20070007932A (ko) | 2007-01-16 |
| CN1946384A (zh) | 2007-04-11 |
| CN1946384B (zh) | 2011-04-20 |
| HK1102913A1 (en) | 2007-12-07 |
| WO2005105069A1 (en) | 2005-11-10 |
| CA2560167A1 (en) | 2005-11-10 |
| US20110098314A1 (en) | 2011-04-28 |
| ZA200607988B (en) | 2007-12-27 |
| DK1740164T3 (da) | 2008-11-10 |
| PL1740164T3 (pl) | 2009-01-30 |
| ES2311986T3 (es) | 2009-02-16 |
| BRPI0510245A (pt) | 2007-10-23 |
| DE602005008935D1 (de) | 2008-09-25 |
| KR101071192B1 (ko) | 2011-10-10 |
| AU2005237543B2 (en) | 2011-02-10 |
| EP1740164B1 (en) | 2008-08-13 |
| MXPA06012225A (es) | 2007-01-31 |
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