RU2734632C2 - Составы разагилина с пролонгированным высвобождением и их применение - Google Patents
Составы разагилина с пролонгированным высвобождением и их применение Download PDFInfo
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- RU2734632C2 RU2734632C2 RU2016141314A RU2016141314A RU2734632C2 RU 2734632 C2 RU2734632 C2 RU 2734632C2 RU 2016141314 A RU2016141314 A RU 2016141314A RU 2016141314 A RU2016141314 A RU 2016141314A RU 2734632 C2 RU2734632 C2 RU 2734632C2
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- salt
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- rasagiline
- aminoindane
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| CN103316026B (zh) | 2012-03-23 | 2016-05-11 | 中国人民解放军军事医学科学院毒物药物研究所 | 含芬特明和托吡酯的联合产品及其制备方法 |
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| CA3064006C (en) * | 2017-05-19 | 2025-09-16 | Biscayne Neurotherapeutics Inc | Modified release pharmaceutical compositions of huperzine and methods of using the same |
| CN107049985B (zh) * | 2017-06-07 | 2020-06-19 | 广州帝奇医药技术有限公司 | 一种抗帕金森病药物的长效缓释制剂及其制备方法 |
| US11717501B2 (en) * | 2018-04-25 | 2023-08-08 | Neurocentria, Inc. | Magnesium threonate compositions and uses thereof |
| KR20220015437A (ko) * | 2019-05-31 | 2022-02-08 | 데날리 테라퓨틱스 인크. | 피리미디닐아미노-피라졸 화합물의 변형 방출 제제, 및 치료 방법 |
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| CN118680910B (zh) * | 2024-08-26 | 2024-12-03 | 山东齐都药业有限公司 | 用于缓释递送雷沙吉兰甲磺酸盐的药物组合物及其制备方法和应用 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2001614C1 (ru) * | 1990-01-03 | 1993-10-30 | Тева Фармасьютикал Индастриз Лтд. (Il) | R (+)-N-Пропаргил-1-аминоиндан и его фармацевтически пригодные кислотно-аддитивные соли и фармацевтическа композици , обладающа ингибирующей B-форму фермента моноаминооксидазы активностью |
| WO2005072705A1 (en) * | 2004-01-29 | 2005-08-11 | Neuromolecular, Inc. | Combination of a nmda receptor antagonist and a mao-inhibitor or a gadpf-inhibitor for the treatment of central nervous system-related conditions |
| WO2006014973A2 (en) * | 2004-07-26 | 2006-02-09 | Teva Pharmaceutical Industries, Ltd. | Pharmaceutical dosage forms including rasagiline |
| RU2325152C2 (ru) * | 2001-07-04 | 2008-05-27 | Сан Фармасьютикл Индастриз Лимитид | Удерживаемая в желудке система регулируемой доставки лекарственного средства |
| RU2379029C1 (ru) * | 2006-03-06 | 2010-01-20 | Чунцин Фармасьютикл Рисерч Инститьют Ко., Лтд. | Трансдермальный пластырь, содержащий разагилин, для лечения или профилактики заболеваний нервной системы и способ его приготовления |
| WO2010007181A2 (en) * | 2008-07-18 | 2010-01-21 | Medichem, S.A. | New salt forms of an aminoindan derivative |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4166452A (en) | 1976-05-03 | 1979-09-04 | Generales Constantine D J Jr | Apparatus for testing human responses to stimuli |
| US4256108A (en) | 1977-04-07 | 1981-03-17 | Alza Corporation | Microporous-semipermeable laminated osmotic system |
| US4265874A (en) | 1980-04-25 | 1981-05-05 | Alza Corporation | Method of delivering drug with aid of effervescent activity generated in environment of use |
| US4415547A (en) * | 1982-06-14 | 1983-11-15 | Sterling Drug Inc. | Sustained-release pharmaceutical tablet and process for preparation thereof |
| US4861800A (en) | 1987-08-18 | 1989-08-29 | Buyske Donald A | Method for administering the drug deprenyl so as to minimize the danger of side effects |
| HU208484B (en) | 1988-08-17 | 1993-11-29 | Chinoin Gyogyszer Es Vegyeszet | Process for producing pharmaceutical composition containing acid additional salt of selegilin as active component for treating schisofrenia |
| US5744500A (en) | 1990-01-03 | 1998-04-28 | Teva Pharmaceutical Industries, Ltd. | Use of R-enantiomer of N-propargyl-1-aminoindan, salts, and compositions thereof |
| US5225446A (en) | 1990-08-31 | 1993-07-06 | Deprenyl Animal Health, Inc. | Use of 1-deprenyl for retention of specific physiological functions |
| CA2039194C (en) | 1990-08-31 | 1997-01-28 | Norton W. Milgram | Uses of l-deprenyl and compositions for same |
| US5151449A (en) | 1990-08-31 | 1992-09-29 | Deprenyl Animal Health, Inc. | Use of L-deprenyl for retention of specific physiological functions |
| US5192808A (en) | 1990-08-31 | 1993-03-09 | Deprenyl Animal Health, Inc. | Therapeutic effect of L-deprenyl in the management of pituitary-dependent hyperadrenocorticism (cushing's disease) |
| US5169868A (en) | 1991-03-01 | 1992-12-08 | University Of Saskatchewan | Aliphatic propargylamines as specific mao-b inhibitors |
| WO1992017169A1 (en) | 1991-04-04 | 1992-10-15 | The University Of Toronto Innovations Foundation | Use of deprenyl to maintain, prevent loss, or recover nerve cell function |
| WO1992021333A2 (en) | 1991-05-24 | 1992-12-10 | Pharmavene, Inc. | Treatment of drug withdrawal symptoms and drug craving with type b monoamine oxidase inhibitors |
| IL99759A (en) | 1991-10-16 | 1997-06-10 | Teva Pharma | Mono-fluorinated derivatives of n-propargyl-1-aminoindan, their preparation and pharmaceutical compositions containing them |
| US5242950A (en) | 1992-04-23 | 1993-09-07 | Somerset Pharmaceuticals, Inc. | Treatment of macular degeneration |
| JP2916978B2 (ja) * | 1993-08-25 | 1999-07-05 | エスエス製薬株式会社 | 放出開始制御型製剤 |
| IL111240A (en) * | 1993-10-18 | 2001-10-31 | Teva Pharma | Salts of r(+) - enantiomers of n- propargyl-1-aminoindan and pharmaceutical compositions comprising them |
| US6348208B1 (en) | 1995-01-13 | 2002-02-19 | Somerset Pharmaceuticals, Inc. | Methods and pharmaceutical compositions employing desmethylselegiline |
| PE57198A1 (es) * | 1996-03-25 | 1998-10-10 | American Home Prod | Formula de liberacion prolongada |
| IL118836A (en) | 1996-07-11 | 2001-01-11 | Teva Pharma | Pharmaceutical compositions comprising s-(-)-n-propargyl-1-aminoindan |
| US6251938B1 (en) | 1996-12-18 | 2001-06-26 | Teva Pharmaceutical Industries, Ltd., | Phenylethylamine derivatives |
| HU229507B1 (en) | 1996-12-18 | 2014-01-28 | Technion Res & Dev Foundation | 1,2,3,4-tetrahydro-amino-naphtalenyl- and aminoindan derivatives and pharmaceutical compositions comprising them |
| US5840979A (en) | 1997-07-14 | 1998-11-24 | University Of Saskatchewan | Aliphatic propargylamines as cellular rescue agents |
| PL353180A1 (en) | 1999-04-29 | 2003-11-03 | Merck Patent Gmbh | Glycine cleavage system inhibitors as potential antipsychotics |
| US20040076668A1 (en) | 2002-07-03 | 2004-04-22 | Pfizer Inc. | Controlled-release pharmaceutical formulations |
| WO2004045515A2 (en) * | 2002-11-15 | 2004-06-03 | Teva Pharmaceutical Industries, Ltd. | Use of rasagiline with or without riluzole to treat amyotrophic lateral sclerosis |
| AR055070A1 (es) * | 2005-06-29 | 2007-08-01 | Panacea Biotec Ltd | Una composicion farmaceutica de liberacion sostenida, proceso para la preparacion de dicha composicion, metodo para la utilizacion de la misma y su uso |
| WO2007016284A2 (en) * | 2005-07-28 | 2007-02-08 | Shire Llc | Pharmaceutical formulations/composition of guanfacine suitable for single dose form adminstration daily |
| EP1909767A2 (en) * | 2005-07-28 | 2008-04-16 | Supernus Pharmaceuticals, Inc. | Modified release tablet formulations with enhanced mechanical properties |
| CN101486655A (zh) | 2008-01-17 | 2009-07-22 | 美德(江西)生物科技有限公司 | 甲磺酸雷沙吉兰晶形及其制备方法 |
| NZ590291A (en) | 2008-06-06 | 2013-11-29 | Pharma Two B Ltd | Pharmaceutical compositions for treatment of parkinson's disease |
| EP2285214B1 (en) | 2008-06-10 | 2012-05-16 | Teva Pharmaceutical Industries Ltd. | Rasagiline soft gelatin capsules |
| EP2218444A3 (en) | 2009-01-23 | 2010-08-25 | Teva Pharmaceutical Industries, Ltd. | Delayed release rasagiline formulation |
| KR101791715B1 (ko) * | 2010-02-03 | 2017-10-30 | 파마 투 비 엘티디 | 라사길린의 연장 방출 제형 및 그 용도 |
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- 2018-11-20 JP JP2018216973A patent/JP6770564B2/ja active Active
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Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2001614C1 (ru) * | 1990-01-03 | 1993-10-30 | Тева Фармасьютикал Индастриз Лтд. (Il) | R (+)-N-Пропаргил-1-аминоиндан и его фармацевтически пригодные кислотно-аддитивные соли и фармацевтическа композици , обладающа ингибирующей B-форму фермента моноаминооксидазы активностью |
| RU2325152C2 (ru) * | 2001-07-04 | 2008-05-27 | Сан Фармасьютикл Индастриз Лимитид | Удерживаемая в желудке система регулируемой доставки лекарственного средства |
| WO2005072705A1 (en) * | 2004-01-29 | 2005-08-11 | Neuromolecular, Inc. | Combination of a nmda receptor antagonist and a mao-inhibitor or a gadpf-inhibitor for the treatment of central nervous system-related conditions |
| WO2006014973A2 (en) * | 2004-07-26 | 2006-02-09 | Teva Pharmaceutical Industries, Ltd. | Pharmaceutical dosage forms including rasagiline |
| RU2379029C1 (ru) * | 2006-03-06 | 2010-01-20 | Чунцин Фармасьютикл Рисерч Инститьют Ко., Лтд. | Трансдермальный пластырь, содержащий разагилин, для лечения или профилактики заболеваний нервной системы и способ его приготовления |
| WO2010007181A2 (en) * | 2008-07-18 | 2010-01-21 | Medichem, S.A. | New salt forms of an aminoindan derivative |
Non-Patent Citations (2)
| Title |
|---|
| ХАРЕНКО А.В. и др. Основные факторы, контролирующие кинетику высвобождения теофиллина из полимерных композиций на основе интерполимерных комплексов. Проблемы качества лекарственных средств. НПО "Биотехнология" М., 1991, с. * |
| ХАРЕНКО А.В. и др. Основные факторы, контролирующие кинетику высвобождения теофиллина из полимерных композиций на основе интерполимерных комплексов. Проблемы качества лекарственных средств. НПО "Биотехнология" М., 1991, с. 37-38. * |
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