KR102410503B1 - 안구 장애를 치료하기 위한 옥시메타졸린 조성물 및 방법 - Google Patents
안구 장애를 치료하기 위한 옥시메타졸린 조성물 및 방법 Download PDFInfo
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- KR102410503B1 KR102410503B1 KR1020200050837A KR20200050837A KR102410503B1 KR 102410503 B1 KR102410503 B1 KR 102410503B1 KR 1020200050837 A KR1020200050837 A KR 1020200050837A KR 20200050837 A KR20200050837 A KR 20200050837A KR 102410503 B1 KR102410503 B1 KR 102410503B1
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| KR1020220072209A Active KR102663319B1 (ko) | 2019-05-06 | 2022-06-14 | 안구 장애를 치료하기 위한 옥시메타졸린 조성물 및 방법 |
| KR1020240057166A Active KR102859351B1 (ko) | 2019-05-06 | 2024-04-29 | 안구 장애를 치료하기 위한 옥시메타졸린 조성물 및 방법 |
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| KR1020240057166A Active KR102859351B1 (ko) | 2019-05-06 | 2024-04-29 | 안구 장애를 치료하기 위한 옥시메타졸린 조성물 및 방법 |
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| US20120225918A1 (en) * | 2011-03-03 | 2012-09-06 | Voom, Llc | Compositions and Methods for Non-Surgical Treatment of Ptosis |
| US10814001B1 (en) * | 2019-05-06 | 2020-10-27 | Rvl Pharmaceuticals, Inc. | Oxymetazoline compositions |
| US20240156786A1 (en) | 2021-03-03 | 2024-05-16 | Voom, Llc | Compositions and methods for treatment of blepharitis |
| WO2023079427A1 (en) * | 2021-11-03 | 2023-05-11 | Avaca Pharma Private Limited | Ophthalmic compositions and methods thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009114521A1 (en) * | 2008-03-11 | 2009-09-17 | Alcon Research, Ltd. | Low viscosity, highly flocculated triamcinolone acetonide suspensions for intravitreal injection |
| WO2010141831A1 (en) * | 2009-06-05 | 2010-12-09 | Aciex Therapeutics, Inc. | Ophthalmic formulations, methods of manufacture, and methods of using same |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE51421B1 (en) | 1980-08-01 | 1986-12-24 | Smith & Nephew Ass | Ophthalmic compositions containing triamterene |
| US5459133A (en) | 1992-06-05 | 1995-10-17 | Telor Ophthalmic Pharmaceuticals, Inc. | Methods and products for treating presbyopia |
| US5888493A (en) | 1996-12-05 | 1999-03-30 | Sawaya; Assad S. | Ophthalmic aqueous gel formulation and related methods |
| DE10337186A1 (de) * | 2003-08-13 | 2005-03-17 | Merck Patent Gmbh | Wässrige Wirkstoff-Lösung |
| US7812049B2 (en) | 2004-01-22 | 2010-10-12 | Vicept Therapeutics, Inc. | Method and therapeutic/cosmetic topical compositions for the treatment of rosacea and skin erythema using α1-adrenoceptor agonists |
| JP2006131628A (ja) * | 2004-10-08 | 2006-05-25 | Rohto Pharmaceut Co Ltd | オキシメタゾリン含有水性組成物 |
| US8758816B2 (en) | 2004-11-24 | 2014-06-24 | Meda Pharmaceuticals Inc. | Compositions comprising azelastine and methods of use thereof |
| TWI454286B (zh) | 2006-03-17 | 2014-10-01 | Johnson & Johnson Vision Care | 安定氧化性不安定組合物之方法 |
| CA2650592A1 (en) | 2006-04-26 | 2007-11-08 | Aciex, Inc. | Compositions for the treatment and prevention of eyelid swelling |
| US8466203B2 (en) * | 2006-12-06 | 2013-06-18 | David Choohyun Paik | Method of stabilizing human eye tissue by reaction with nitrite and related agents such as nitro compounds |
| MX2010006932A (es) * | 2007-12-21 | 2010-10-05 | Schering Plough Healthcare | Aumento de la fotoestabilizacion de la oximetazolina. |
| US20120082625A1 (en) | 2010-09-28 | 2012-04-05 | Michael Graeber | Combination treatment for rosacea |
| WO2012063237A2 (en) * | 2010-11-08 | 2012-05-18 | Healor Ltd. | Buffered ophthalmic compositions and methods of use thereof |
| CA2819633C (en) | 2010-12-03 | 2019-04-23 | Allergan, Inc. | Pharmaceutical cream compositions and methods of use |
| US20120225918A1 (en) | 2011-03-03 | 2012-09-06 | Voom, Llc | Compositions and Methods for Non-Surgical Treatment of Ptosis |
| JP2015518006A (ja) | 2012-05-25 | 2015-06-25 | エクスクリア インコーポレイテッド | キシリトール系の抗粘膜組成物及び関連する方法並びに組成物 |
| UA119324C2 (uk) | 2013-04-02 | 2019-06-10 | Теміс Медікер Лімітед | Композиції фармацевтично активних речовин, що містять моноетиловий ефір діетиленгліколю або інші алкільні похідні |
| WO2015040086A1 (en) | 2013-09-18 | 2015-03-26 | Mycronic AB | Method, system and device for handling pallets in an smt system |
| WO2015191917A1 (en) | 2014-06-11 | 2015-12-17 | Allergan, Inc. | Stabilized oxymetazoline formulations and their uses |
| US11052094B2 (en) | 2015-05-29 | 2021-07-06 | Sydnexis, Inc. | D2O stabilized pharmaceutical formulations |
| US20170312335A1 (en) * | 2015-12-30 | 2017-11-02 | Lubris Llc | Topical use of prg4 for treatment of allergy and symptoms of inflammation |
| CN115006537A (zh) | 2016-01-26 | 2022-09-06 | 利维申制药有限公司 | α-肾上腺素能药剂的组合物和用途 |
| CN105997856A (zh) * | 2016-06-24 | 2016-10-12 | 魏威 | 盐酸羟甲唑啉滴眼液及其制备方法 |
| US11246816B2 (en) | 2016-06-30 | 2022-02-15 | The Procter And Gamble Company | Shampoo compositions comprising a chelant |
| US10814001B1 (en) | 2019-05-06 | 2020-10-27 | Rvl Pharmaceuticals, Inc. | Oxymetazoline compositions |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009114521A1 (en) * | 2008-03-11 | 2009-09-17 | Alcon Research, Ltd. | Low viscosity, highly flocculated triamcinolone acetonide suspensions for intravitreal injection |
| WO2010141831A1 (en) * | 2009-06-05 | 2010-12-09 | Aciex Therapeutics, Inc. | Ophthalmic formulations, methods of manufacture, and methods of using same |
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