TWI819995B - 以加波沙朵（ｇａｂｏｘａｄｏｌ）治療發育障礙的方法 - Google Patents
以加波沙朵（ｇａｂｏｘａｄｏｌ）治療發育障礙的方法 Download PDFInfo
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| CN114072154B (zh) * | 2018-11-21 | 2024-03-08 | 塞迪戈Abc有限责任公司 | 用于治疗精神障碍的加波沙朵和锂的组合物 |
| MX2021005992A (es) | 2018-11-21 | 2021-09-14 | Certego Therapeutics Inc | Gaboxadol para reducir el riesgo de suicidio y para alivio rápido de la depresión. |
| JP2022514275A (ja) | 2018-12-17 | 2022-02-10 | オービッド・セラピューティクス・インコーポレイテッド | 非２４時間型睡眠覚醒障害の処置のためのガボキサドールの使用 |
| WO2020247127A1 (en) * | 2019-06-07 | 2020-12-10 | Paxmedica, Inc. | Compositions and methods for treating central nervous system disorders |
| JP2022540917A (ja) * | 2019-07-15 | 2022-09-20 | オービッド・セラピューティクス・インコーポレイテッド | 治療的処置のためのガボキサドール含有医薬製剤 |
| MX2022007715A (es) * | 2019-12-18 | 2022-07-19 | Ovid Therapeutics Inc | Gaboxadol para el tratamiento terapeutico del sindrome de delecion 1p36. |
| IL298334A (en) | 2020-05-20 | 2023-01-01 | Certego Therapeutics Inc | Ring deuterated gaboxadol and its use for the treatment of psychiatric disorders |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102137667A (zh) * | 2008-09-01 | 2011-07-27 | H.隆德贝克有限公司 | 包含加波沙朵和patl或oat抑制剂的药物组合物 |
Family Cites Families (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2830083A (en) | 1953-04-29 | 1958-04-08 | Allied Chem & Dye Corp | Production of aryloxy aliphatic carboxylic acids |
| US4084000A (en) | 1975-07-16 | 1978-04-11 | Nelson Research And Development Company | Method of treating schizophrenia |
| US4129652A (en) | 1976-08-16 | 1978-12-12 | Nelson Research & Development Company | Method for potentiating neuroleptic drugs |
| US4138484A (en) | 1976-08-16 | 1979-02-06 | Nelson Research & Development Company | Method for treating schizophrenia and method and composition for potentiating neuroleptic drugs |
| DK270278A (da) | 1977-06-20 | 1978-12-21 | Krogsgaard Larsen P | Cycliske aminosyrer |
| US4362731A (en) | 1980-09-01 | 1982-12-07 | Sandoz Ltd. | Myotonolytic use of 4,5,6,7-tetrahydroisoxazolo [5,4-c] pyridin-3-ol and derivatives thereof |
| US4353910A (en) | 1981-11-27 | 1982-10-12 | Kefalas A/S | Derivatives of 4,5,6,7-tetrahydroisoxazolo [5,4-c] pyridine-3-one, pharmaceutical compositions and methods of treatment |
| JPS61277618A (ja) | 1985-06-04 | 1986-12-08 | Suntory Ltd | 自閉症治療剤 |
| DE19525598C2 (de) | 1995-07-13 | 1997-09-25 | Max Planck Gesellschaft | Schlafmittel |
| DE19526864A1 (de) | 1995-07-22 | 1997-01-23 | Labtec Gmbh | Hormonpflaster |
| US6461644B1 (en) | 1996-03-25 | 2002-10-08 | Richard R. Jackson | Anesthetizing plastics, drug delivery plastics, and related medical products, systems and methods |
| US5948433A (en) | 1997-08-21 | 1999-09-07 | Bertek, Inc. | Transdermal patch |
| US7374779B2 (en) * | 1999-02-26 | 2008-05-20 | Lipocine, Inc. | Pharmaceutical formulations and systems for improved absorption and multistage release of active agents |
| AR031473A1 (es) | 2000-11-20 | 2003-09-24 | Lundbeck & Co As H | Intensificadores de gaba en el tratamiento de enfermedades relacionadas con una reducida actividad neuroesteroide |
| US20020082222A1 (en) * | 2000-11-30 | 2002-06-27 | Shapira Nathan Andrew | Treatments for neurogenetic disorders, impulse control disorder, and wound healing |
| US20020165217A1 (en) | 2001-05-01 | 2002-11-07 | Pfizer Inc. | Combination treatment for anxiety and depression |
| AU2002338855B2 (en) | 2001-05-21 | 2007-08-16 | H. Lundbeck A/S | Granular preparations of gaboxadol |
| US6676961B1 (en) | 2002-03-06 | 2004-01-13 | Automated Carrier Technologies, Inc. | Transdermal patch assembly |
| US20050234093A1 (en) | 2003-06-25 | 2005-10-20 | H. Lundbeck A/S | Treatment of depression and other affective disorders |
| MXPA05013016A (es) | 2003-06-25 | 2006-03-02 | Lundbeck & Co As H | Gaboxadol para el tratamiento de la depresion y otros trastornos afectivos. |
| WO2005023256A1 (en) | 2003-09-10 | 2005-03-17 | Merck Sharp & Dohme Limited | Use of gabaa receptor agonists for the treatment of hearing, vestibular and attention disorders, intention tremor and restless leg syndrome |
| TW200528098A (en) | 2003-12-18 | 2005-09-01 | Lundbeck & Co As H | Treatment of insomnia in human patients |
| US20050137222A1 (en) * | 2003-12-18 | 2005-06-23 | H. Lundbeck A/S | Treatment of insomnia in human patients |
| US20050215521A1 (en) | 2003-12-22 | 2005-09-29 | Karim Lalji | Modafinil combination therapy for improving sleep quality |
| GB0402118D0 (en) | 2004-01-30 | 2004-03-03 | Merck Sharp & Dohme | Polymorphic forms of a GABAA agonist |
| MXPA06011325A (es) | 2004-04-02 | 2006-12-15 | Lundbeck & Co As H | Tratamiento de la funcion respiratoria alterada con gaboxadol. |
| EA200601853A1 (ru) * | 2004-04-02 | 2007-02-27 | Х. Лундбекк А/С | Лечение нарушенной дыхательной функции |
| GB0417558D0 (en) * | 2004-08-06 | 2004-09-08 | Merck Sharp & Dohme | Novel combination therapy |
| DE102005020882A1 (de) | 2005-05-04 | 2006-11-09 | Dömling, Alexander, Dr. | Verwendung von Gaboxadol und Derivaten zur Behandlung von Kinase-induzierten Krankheiten |
| US20110046090A1 (en) | 2005-10-31 | 2011-02-24 | Braincells Inc. | Modulation of neurogenesis with gaba agents and gaba analogs |
| US20070112017A1 (en) * | 2005-10-31 | 2007-05-17 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| RS55585B1 (sr) * | 2006-11-22 | 2017-06-30 | Clinical Research Associates LLC | Postupci za lečenje daunovog sindroma, krhkog x sindroma i autizma |
| WO2008095221A1 (en) | 2007-02-07 | 2008-08-14 | Gosforth Centre (Holdings) Pty Ltd | Treatment of adhd |
| US20090269795A1 (en) | 2007-03-09 | 2009-10-29 | The Research Foundation Of State University Of New York | Mutant alpha4betadelta GABAA receptor and methods of treating anxiety or irritability |
| TW200920358A (en) | 2007-08-13 | 2009-05-16 | Lundbeck & Co As H | Method of treating stress-mediated depression |
| US20090048288A1 (en) | 2007-08-13 | 2009-02-19 | H. Lundbeck A/S | Method of treating stress-mediated depression |
| US20090143335A1 (en) * | 2007-10-29 | 2009-06-04 | H. Lundbeck A/S | Modified absorption formulation of gaboxadol |
| US20100286762A1 (en) | 2009-03-18 | 2010-11-11 | Musc Foundation For Research Development | Compositions and Methods for Ameliorating Clinical Electrical Disturbances |
| CN102147667A (zh) | 2010-02-08 | 2011-08-10 | 深圳富泰宏精密工业有限公司 | 触控笔 |
| WO2012050907A2 (en) | 2010-09-28 | 2012-04-19 | The Regents Of The University Of California | Gaba agonists in the treatment of disorders associated with metabolic syndrome and gaba combinations in treatment or prophylaxis of type i diabetes |
| US20130309306A1 (en) | 2010-12-01 | 2013-11-21 | The Regents Of The University Of California | Intrapulmonary benzodiazepine for the treatment and prevention of seizures |
| US9480695B2 (en) | 2011-09-29 | 2016-11-01 | The University Of Tokyo | Methods for inducing orexin neurons and agent for treating narcolepsy or eating disorder |
| EP3108876A1 (en) | 2011-10-13 | 2016-12-28 | Jaleva Pharmaceuticals LLC | Methods and compositions for rapid transbuccal delivery of active agents |
| 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 |
| US20150313913A1 (en) | 2013-02-05 | 2015-11-05 | University Of Washington Through Its Center For Commercialization | Positive allosteric modulators of the gaba-a receptor in the treatment of autism |
| PT3151832T (pt) * | 2014-06-06 | 2021-06-15 | Ovid Therapeutics Inc | Métodos para aumentar a inibição tónica e tratar a insónia secundária |
| JP6491679B2 (ja) | 2014-06-12 | 2019-03-27 | ファイザー・リミテッドＰｆｉｚｅｒ Ｌｉｍｉｔｅｄ | Ｇａｂａａ受容体活性のモジュレーターとしてのイミダゾピリダジン誘導体 |
| US20170348232A1 (en) | 2016-06-07 | 2017-12-07 | Ovid Therapeutics Inc. | Formulations of gaboxadol for treatment of angelman syndrome, fragile x syndrome and fragile x-associated tremor/ataxia syndrome |
| AU2016295138B2 (en) | 2015-07-17 | 2021-11-04 | Ovid Therapeutics Inc. | Methods of treating developmental disorders with gaboxadol |
| US9682069B2 (en) | 2015-07-17 | 2017-06-20 | Ovid Therapeutics Inc | Methods of treating Dravet syndrome |
| US9399034B1 (en) | 2015-08-11 | 2016-07-26 | Ovid Therapeutics Inc | Methods of sedation during critical care treatment |
| EP3334427A4 (en) | 2015-08-11 | 2019-02-06 | Ovid Therapeutics, Inc. | METHOD OF SUSPENSION AND PARENTERAL FORMULATION FOR USE IN INTENSIVE TREATMENT |
| US9351968B1 (en) | 2015-09-09 | 2016-05-31 | Ovid Therapeutics Inc | Methods of treating developmental disorders using pipradrol |
| FI3364993T3 (fi) | 2015-10-22 | 2023-01-13 | Menetelmiä angelmanin oireyhtymän hoitamiseksi | |
| WO2017205606A1 (en) | 2016-05-26 | 2017-11-30 | Ovid Therapeutics Inc. | Methods of treating behavioral syndromes using pipradrol |
| US20180042903A1 (en) | 2016-08-11 | 2018-02-15 | Ovid Therapeutics Inc. | Methods and compositions for treatment of epileptic disorders |
| CN110225754A (zh) | 2016-11-22 | 2019-09-10 | 奥维德医疗公司 | 用氟吡汀治疗发育障碍和/或癫痫发作紊乱的方法 |
| US10071083B2 (en) | 2017-02-03 | 2018-09-11 | Ovid Therapeutics Inc | Use of gaboxadol in the treatment of tinnitus |
-
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-
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-
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- 2022-11-04 US US17/981,148 patent/US12465597B2/en active Active
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102137667A (zh) * | 2008-09-01 | 2011-07-27 | H.隆德贝克有限公司 | 包含加波沙朵和patl或oat抑制剂的药物组合物 |
Non-Patent Citations (2)
| Title |
|---|
| 期刊 K EGAWA, et al., "Decreased tonic inhibition in cerebellar granule cells causes motor dysfunction in a mouse model of Angelman Syndrome", Sci Transl Med, 2012, 4(163)： 163ra157.; * |
| 期刊 R LOZANO, et al., "Modulation of the GABAergic pathway for the treatment of fragile X syndrome", Neuropsychiatric Disease and Treatment, 2014, 10： 1769~1779. * |
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