JP2010530371A - 神経学的機能を増強するための作用物質、組成物および方法 - Google Patents
神経学的機能を増強するための作用物質、組成物および方法 Download PDFInfo
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| WO2011010682A1 (ja) * | 2009-07-24 | 2011-01-27 | 協和発酵キリン株式会社 | ステロール誘導体 |
| DK2806877T3 (da) | 2012-01-23 | 2019-11-04 | Sage Therapeutics Inc | Neuroaktive steroidformuleringer omfattende et kompleks af allopregnanolon og sulfobutylether beta-cyclodekstrin |
| CA2882708A1 (en) | 2012-08-21 | 2014-02-27 | Sage Therapeutics, Inc. | Methods of treating epilepsy or status epilepticus |
| EP2916846B1 (en) | 2012-11-09 | 2025-09-17 | Drawbridge Pharmaceuticals Pty Ltd | Neuroactive steroids and their use to facilitate neuroprotection |
| JP2016501876A (ja) | 2012-11-30 | 2016-01-21 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | ステロイドの抗痙攣活性 |
| JOP20200195A1 (ar) | 2014-09-08 | 2017-06-16 | Sage Therapeutics Inc | سترويدات وتركيبات نشطة عصبياً، واستخداماتها |
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| IL265225B (en) * | 2016-09-07 | 2022-08-01 | Glia Llc | Treatment of symptoms related to neurodegenerative disorders through pharmacological dermal activation of cranial nerves |
| CA3151334C (en) * | 2019-08-19 | 2024-04-09 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Topical neurosteroid formulations |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002506034A (ja) * | 1998-03-11 | 2002-02-26 | ベクストルム,トルビエーン | Cns疾患の治療におけるエピアロプレグナノロン |
| JP2004532796A (ja) * | 2000-10-11 | 2004-10-28 | エモリー ユニバーシティ | 外傷性中枢神経系損傷の処置のための方法 |
| WO2005009359A2 (en) * | 2003-07-15 | 2005-02-03 | Roberta Diaz Brinton | Agents, compositions and methods for enhancing neurological function |
| WO2006037016A2 (en) * | 2004-09-27 | 2006-04-06 | The Regents Of The University Of California | Novel therapy for treatment of chronic degenerative brain diseases and nervous system injury |
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| US4897388A (en) | 1988-12-20 | 1990-01-30 | Geriatric Research Institute, Inc. | Method of treating Alzheimer's disease |
| IL110309A0 (en) | 1993-07-15 | 1994-10-21 | Univ Kentucky Res Found | A method of protecting against neuron loss |
| US5939545A (en) | 1994-02-14 | 1999-08-17 | Cocensys, Inc. | Method, compositions, and compounds for allosteric modulation of the gaba receptor by members of the androstane and pregnane series |
| DE69634039T2 (de) | 1995-06-06 | 2005-12-08 | Euro-Celtique S.A. | Steroidderivate der Androstan- und der Pregnanreihe |
| US6552010B1 (en) | 1999-11-12 | 2003-04-22 | Genelabs Technologies, Inc. | Treatment of SLE with dehydroepiandrosterone |
| KR20070086866A (ko) | 2003-02-13 | 2007-08-27 | 화이자 프로덕츠 인크. | 항-인슐린양 성장인자 i 수용체 항체의 용도 |
| US20050020552A1 (en) | 2003-07-16 | 2005-01-27 | Chaim Aschkenasy | Pharmaceutical composition and method for transdermal drug delivery |
| US20070093460A1 (en) * | 2005-08-24 | 2007-04-26 | Morris David J | Methods of using selective 11beta-HSD inhibitors to treat gluocorticoid associated states |
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2008
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002506034A (ja) * | 1998-03-11 | 2002-02-26 | ベクストルム,トルビエーン | Cns疾患の治療におけるエピアロプレグナノロン |
| JP2004532796A (ja) * | 2000-10-11 | 2004-10-28 | エモリー ユニバーシティ | 外傷性中枢神経系損傷の処置のための方法 |
| WO2005009359A2 (en) * | 2003-07-15 | 2005-02-03 | Roberta Diaz Brinton | Agents, compositions and methods for enhancing neurological function |
| WO2006037016A2 (en) * | 2004-09-27 | 2006-04-06 | The Regents Of The University Of California | Novel therapy for treatment of chronic degenerative brain diseases and nervous system injury |
Non-Patent Citations (3)
| Title |
|---|
| JPN6013021963; BRINTON,R.D. et al: Current Alzheimer research Vol.3, No.1, 2006, p.11-7 * |
| JPN6013021965; BRINTON,R.D. et al: Current Alzheimer research Vol.3, No.3, 2006, p.185-90 * |
| JPN6013021967; DATABASE CAPLUS ON STN , 2006 * |
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| US20100105646A1 (en) | 2010-04-29 |
| EP2167098B1 (en) | 2018-09-05 |
| EP2167098A1 (en) | 2010-03-31 |
| US8969329B2 (en) | 2015-03-03 |
| WO2008154579A1 (en) | 2008-12-18 |
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