JP2005516911A5 - - Google Patents
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- JP2005516911A5 JP2005516911A5 JP2003550756A JP2003550756A JP2005516911A5 JP 2005516911 A5 JP2005516911 A5 JP 2005516911A5 JP 2003550756 A JP2003550756 A JP 2003550756A JP 2003550756 A JP2003550756 A JP 2003550756A JP 2005516911 A5 JP2005516911 A5 JP 2005516911A5
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- JP
- Japan
- Prior art keywords
- pramipexole
- mpp
- composition
- caspase
- ppx
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2432527T3 (es) * | 2001-12-11 | 2013-12-04 | University Of Virginia Patent Foundation | Uso de pramipexol para tratar la esclerosis lateral amiotrófica |
| US20060281797A1 (en) * | 2001-12-11 | 2006-12-14 | University Of Virginia Patent Foundation | Neurorestoration with R(+) Pramipexole |
| WO2007022182A1 (en) * | 2005-08-15 | 2007-02-22 | University Of Virginia Patent Foundation | Neurorestoration with r(+) pramipexole |
| US20080262053A1 (en) * | 2005-10-18 | 2008-10-23 | Juergen Reess | Use of Pramipexole for Treating Moderate to Severe Restless Legs Syndrome (Rls) |
| WO2007121188A2 (en) * | 2006-04-10 | 2007-10-25 | Knopp Neurosciences, Inc. | Compositions and methods of using r(+) pramipexole |
| US8518926B2 (en) | 2006-04-10 | 2013-08-27 | Knopp Neurosciences, Inc. | Compositions and methods of using (R)-pramipexole |
| ES2379117T3 (es) * | 2006-05-16 | 2012-04-20 | Knopp Neurosciences, Inc. | Composiciones de R(+) y S(-) pramipexol y métodos de utilización de las mismas |
| EP2497473A1 (en) * | 2006-05-16 | 2012-09-12 | Knopp Neurosciences, Inc. | Therapeutically effective amounts of R(+) and S(-) pramipexole for use in the treatment of Parkinson's disease and pharmaceutical compositions thereof |
| AU2016210640B2 (en) * | 2006-12-14 | 2018-02-22 | Knopp Biosciences Llc | Compositions and methods of using (r)-pramipexole |
| DK2101766T3 (en) * | 2006-12-14 | 2017-01-16 | Knopp Biosciences Llc | Compositions and Methods for Using (R) -Pramipexole |
| AU2013209376B2 (en) * | 2006-12-14 | 2016-05-05 | Knopp Biosciences Llc | Compositions and methods of using (r)-pramipexole |
| US8524695B2 (en) * | 2006-12-14 | 2013-09-03 | Knopp Neurosciences, Inc. | Modified release formulations of (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine and methods of using the same |
| CA2681110A1 (en) * | 2007-03-14 | 2008-09-18 | Knopp Neurosciences, Inc. | Synthesis of chirally purified substituted benzothiazole diamines |
| JP2010521493A (ja) * | 2007-03-14 | 2010-06-24 | ノップ ニューロサイエンシーズ、インク． | （６ｒ）−４，５，６，７−テトラヒドロ−ｎ６−プロピル−２，６−ベンゾチアゾール−ジアミンの放出調節製剤およびそれらの使用方法 |
| GB0811642D0 (en) * | 2008-06-25 | 2008-07-30 | Univ Edinburgh | Assay |
| KR20110071064A (ko) * | 2008-08-19 | 2011-06-28 | 크놉 뉴로사이언시스 인코포레이티드 | (ｒ)-프라미펙솔을 사용하는 조성물 및 방법 |
| RU2012101792A (ru) * | 2009-06-19 | 2013-07-27 | Нопп Ньюросайенсиз, Инк. | Композиции и способы для лечения бокового амиотрофического склероза |
| WO2013096816A1 (en) | 2011-12-22 | 2013-06-27 | Biogen Idec Ma Inc. | Improved synthesis of amine substituted 4,5,6,7-tetrahydrobenzothiazole compounds |
| EP2887954B1 (en) | 2012-08-23 | 2020-05-06 | Susan Marie Metcalfe | Neurotherapeutic nanoparticle compositions |
| US10874669B2 (en) | 2012-11-29 | 2020-12-29 | Wayne State University | Neuroprotective agents for treatment of neurodegenerative diseases |
| WO2014085600A1 (en) * | 2012-11-29 | 2014-06-05 | Wayne State University | Neuroprotective agents for treatment of neurodegenerative diseases |
| US9662313B2 (en) | 2013-02-28 | 2017-05-30 | Knopp Biosciences Llc | Compositions and methods for treating amyotrophic lateral sclerosis in responders |
| US9468630B2 (en) | 2013-07-12 | 2016-10-18 | Knopp Biosciences Llc | Compositions and methods for treating conditions related to increased eosinophils |
| EP3838271B1 (en) | 2013-07-12 | 2025-09-03 | Areteia Therapeutics, Inc. | Treating elevated levels of eosinophils and/or basophils |
| ES2813674T3 (es) | 2013-08-13 | 2021-03-24 | Knopp Biosciences Llc | Composiciones y métodos para el tratamiento de trastornos de células plasmáticas y trastornos prolinfocíticos de células b |
| CA2921381A1 (en) | 2013-08-13 | 2015-02-19 | Knopp Biosciences Llc | Compositions and methods for treating chronic urticaria |
| WO2019049145A1 (en) | 2017-09-11 | 2019-03-14 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | COMPOSITIONS AND METHODS FOR NASAL BRAIN MEDICATION ADMINISTRATION FOR SYSTEMIC EFFECT |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US560420A (en) | 1896-05-19 | Steam and oil separator | ||
| DE3447075A1 (de) * | 1984-12-22 | 1986-07-03 | Dr. Karl Thomae Gmbh, 7950 Biberach | Tetrahydro-benzthiazole, deren herstellung und deren verwendung als zwischenprodukte oder als arzneimittel |
| ATE45735T1 (de) * | 1984-12-22 | 1989-09-15 | Thomae Gmbh Dr K | Tetrahydro-benzthiazole, deren herstellung und deren verwendung als zwischenprodukte oder als arnzneimittel. |
| DE3937271A1 (de) | 1989-11-09 | 1991-05-16 | Boehringer Ingelheim Kg | Transdermale applikation von 2-amino-6-n-propylamino-4,5,6,7-tetrahydrobenzothiazol |
| FR2688138B1 (fr) * | 1992-03-06 | 1995-05-05 | Rhone Poulenc Rorer Sa | Application de l'amino-2 trifluoromethoxy-6 benzothiazole pour obtenir un medicament destine au traitement de la sclerose laterale amyotrophique. |
| US5650420A (en) * | 1994-12-15 | 1997-07-22 | Pharmacia & Upjohn Company | Pramipexole as a neuroprotective agent |
| US6156777A (en) | 1994-12-15 | 2000-12-05 | Pharmacia & Upjohn Company | Use of pramipexole as a neuroprotective agent |
| JP3468526B2 (ja) * | 1995-10-26 | 2003-11-17 | サノフィーサンテラボ | 筋萎縮性側索硬化症治療薬調製のための１−（２−ナフタ−２−イルエチル）−４−（３−トリフルオロメチルフェニル）−１，２，３，６−テトラヒドロピリジンの使用 |
| GB9705428D0 (en) * | 1997-03-15 | 1997-04-30 | Knoll Ag | Therapeutic agents |
| US6197339B1 (en) * | 1997-09-30 | 2001-03-06 | Pharmacia & Upjohn Company | Sustained release tablet formulation to treat Parkinson's disease |
| PE20000728A1 (es) * | 1998-06-26 | 2000-08-21 | Cocensys Inc | Heterociclos 4-bencil piperidina alquilsulfoxido y su uso como antagonistas receptores subtipo-selectivo nmda |
| DE19830201A1 (de) * | 1998-07-07 | 2000-01-13 | Boehringer Ingelheim Pharma | Mittel mit antidepressiver Wirkung |
| WO2000006162A1 (de) * | 1998-07-27 | 2000-02-10 | Boehringer Ingelheim Pharma Kg | Mittel mit antidepressiver wirkung, mit pramipexol und einem weiteren antidepressivum |
| EP1126826B3 (en) * | 1998-11-02 | 2019-05-15 | Alkermes Pharma Ireland Limited | Multiparticulate modified release composition of methylphenidate |
| DE19938825A1 (de) | 1999-08-19 | 2001-04-26 | Boehringer Ingelheim Pharma | Wirkstoffkombination mit Clonidin |
| AU7620600A (en) | 1999-09-30 | 2001-04-30 | General Hospital Corporation, The | Use of pramipexole as a treatment for cocaine craving |
| PE20011074A1 (es) | 2000-02-23 | 2001-10-04 | Upjohn Co | Uso de pramipexol en el tratamiento de trastornos de adiccion |
| AU2001278875B2 (en) * | 2000-07-06 | 2007-06-07 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Tetrahydrobenzothiazole analogues as neuroprotective agents |
| DE10037619A1 (de) * | 2000-08-02 | 2002-02-14 | Daimler Chrysler Ag | Anordnung von Bedienelementen |
| ES2187249B1 (es) * | 2000-09-18 | 2004-09-16 | Synthon Bv | Procedimiento para la preparacion de 2-amino-6-(alquil)amino-4,5,6,7-tetrahidrobenzotiazoles. |
| AU2001296703A1 (en) * | 2000-10-06 | 2002-04-15 | Xenoport, Inc. | Bile acid prodrugs of l-dopa and their use in the sustained treatment of parkinsonism |
| DE10137082A1 (de) * | 2001-07-28 | 2003-02-13 | Hexal Ag | Matrixkontrolliertes transdermales therapeutisches System zur Anwendung von Pramiprexol und Ropinirol |
| ES2432527T3 (es) * | 2001-12-11 | 2013-12-04 | University Of Virginia Patent Foundation | Uso de pramipexol para tratar la esclerosis lateral amiotrófica |
| US20060281797A1 (en) * | 2001-12-11 | 2006-12-14 | University Of Virginia Patent Foundation | Neurorestoration with R(+) Pramipexole |
| WO2003077902A1 (en) * | 2002-02-19 | 2003-09-25 | Xenoport, Inc. | Methods for synthesis of prodrugs from 1-acyl-alkyl derivatives and compositions thereof |
| US20050226926A1 (en) * | 2002-07-25 | 2005-10-13 | Pfizer Inc | Sustained-release tablet composition of pramipexole |
| SI1610791T1 (sl) * | 2003-03-31 | 2011-05-31 | Titan Pharmaceuticals Inc | Implantibilna polimerna naprava za zadržano sproščanje dopaminskega agonista |
| WO2005010011A2 (en) * | 2003-07-15 | 2005-02-03 | Xenoport, Inc. | Methods of synthesis of acyloxyalkyl compounds |
| EA200700388A1 (ru) * | 2004-08-13 | 2007-08-31 | Бёрингер Ингельхайм Интернациональ Гмбх | Композиция пеллеты пролонгированного высвобождения, содержащая прамипексол или его фармацевтически приемлемую соль, способ её изготовления и её применение |
| TW200616604A (en) * | 2004-08-26 | 2006-06-01 | Nicholas Piramal India Ltd | Nitric oxide releasing prodrugs containing bio-cleavable linker |
| WO2007022182A1 (en) * | 2005-08-15 | 2007-02-22 | University Of Virginia Patent Foundation | Neurorestoration with r(+) pramipexole |
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- 2002-12-02 WO PCT/US2002/039970 patent/WO2003049705A2/en not_active Ceased
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- 2002-12-02 EP EP10009931A patent/EP2305252A1/en not_active Ceased
- 2002-12-02 KR KR10-2004-7008931A patent/KR20040066890A/ko not_active Withdrawn
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2006
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2009
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2010
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2011
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