JP2014515408A - 行動及び精神障害の治療のためのシロ−イノシトール - Google Patents
行動及び精神障害の治療のためのシロ−イノシトール Download PDFInfo
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| WO2014110277A1 (en) * | 2013-01-09 | 2014-07-17 | Elan Pharmaceuticals, Inc. | Methods of treating developmental and personality disorders |
| US11191735B2 (en) | 2015-03-13 | 2021-12-07 | Nutrition 21, Llc | Arginine silicate for periodontal disease |
| WO2017004226A1 (en) * | 2015-06-30 | 2017-01-05 | Jds Therepeutics, Llc | Arginine silicate inositol for improving cognitive function |
| WO2017029353A1 (en) * | 2015-08-20 | 2017-02-23 | Transition Therapeutics Ireland Limited | Treatment of behaviors in dementia patients |
| US20170135969A1 (en) | 2015-11-12 | 2017-05-18 | Jds Therapeutics, Llc | Topical arginine-silicate-inositol for wound healing |
| CN109890384A (zh) | 2016-09-01 | 2019-06-14 | Jds治疗有限公司 | 生物素镁组合物和使用方法 |
| MX2021005213A (es) | 2018-11-02 | 2021-09-08 | Nutrition 21 Llc | Composiciones que contienen complejos de silicato de arginina estabilizado con inositol y inositol para mejorar funciones cognitivas en jugadores de videojuegos. |
| MX2022006535A (es) * | 2019-12-02 | 2022-09-09 | Suven Life Sciences Ltd | Métodos para tratar síntomas de comportamiento y psicológicos en pacientes con demencia. |
| PL4069231T3 (pl) * | 2019-12-02 | 2025-09-08 | Suven Life Sciences Limited | Połączenia masupirdyny z donepezilem lub memantyną do leczenia obajwów behawioralnych i psychologicznych u pacjentów z demencją |
| IL294021A (en) | 2019-12-16 | 2022-08-01 | Nutrition 21 Llc | Methods of production of arginine-silicate complexes |
| JP2025530588A (ja) * | 2022-09-07 | 2025-09-16 | エアジェン ファーマ リミテッド | Ｓｃｙｌｌｏ－イノシトールとフラボンとの組み合わせ |
| CN115998724B (zh) * | 2023-03-28 | 2023-06-16 | 中国人民解放军军事科学院军事医学研究院 | 布洛芬在抗幻觉作用药物中的新用途 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007500205A (ja) * | 2003-05-29 | 2007-01-11 | イッサム リサーチ デベロップメント カンパニー オブ ザ ヘブリュー ユニバーシティー オブ エルサレム | 精神障害を治療するための２，２，３，３，テトラメチルシクロプロパンカルボン酸誘導体の使用 |
| JP2009529502A (ja) * | 2006-03-09 | 2009-08-20 | ワラタ ファーマシューティカルズ， インコーポレイテッド | タンパク質凝集の障害の処置のためのシクロヘキサン多価アルコール処方物 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7521481B2 (en) * | 2003-02-27 | 2009-04-21 | Mclaurin Joanne | Methods of preventing, treating and diagnosing disorders of protein aggregation |
| DK2058390T3 (da) | 2003-10-14 | 2013-05-06 | Hokko Chem Ind Co | Fremgangsmåde til fremstilling af scyllo-inositol |
| ZA200807993B (en) * | 2006-03-09 | 2010-02-24 | Waratah Pharmaceuticals Inc | A cyclohexane polyalcohol formulation for treatment of disorders of protein aggregation |
| EP2545023A4 (en) | 2010-02-15 | 2017-04-12 | Abbvie Inc. | Process for the preparation of scyllo-inositol |
| US20150306043A1 (en) * | 2012-09-28 | 2015-10-29 | Transition Therapeutics Ireland Limited | Combination treatments for bipolar disorders |
-
2012
- 2012-06-04 CA CA2837926A patent/CA2837926A1/en not_active Abandoned
- 2012-06-04 WO PCT/US2012/040789 patent/WO2012173808A1/en not_active Ceased
- 2012-06-04 RU RU2013154699/15A patent/RU2013154699A/ru not_active Application Discontinuation
- 2012-06-04 AU AU2012271068A patent/AU2012271068A1/en not_active Abandoned
- 2012-06-04 CN CN201280037339.8A patent/CN103906520A/zh active Pending
- 2012-06-04 KR KR1020147000006A patent/KR20140041670A/ko not_active Withdrawn
- 2012-06-04 JP JP2014513795A patent/JP2014515408A/ja active Pending
- 2012-06-04 BR BR112013031117A patent/BR112013031117A8/pt not_active IP Right Cessation
- 2012-06-04 EP EP12727719.2A patent/EP2714050A1/en not_active Withdrawn
- 2012-06-04 US US14/123,581 patent/US20140243422A1/en not_active Abandoned
-
2013
- 2013-11-27 IL IL229658A patent/IL229658A0/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007500205A (ja) * | 2003-05-29 | 2007-01-11 | イッサム リサーチ デベロップメント カンパニー オブ ザ ヘブリュー ユニバーシティー オブ エルサレム | 精神障害を治療するための２，２，３，３，テトラメチルシクロプロパンカルボン酸誘導体の使用 |
| JP2009529502A (ja) * | 2006-03-09 | 2009-08-20 | ワラタ ファーマシューティカルズ， インコーポレイテッド | タンパク質凝集の障害の処置のためのシクロヘキサン多価アルコール処方物 |
Non-Patent Citations (9)
| Title |
|---|
| JPN6016006995; ＥＭＢＯ Ｊ． ２０（１６）, 2001, ４４６７-４４７７ * |
| JPN6016006998; Ｊ． Ｍｏｌ． Ｍｅｄ． ８５, 2007, ６０３-６１１ * |
| JPN6016007002; Ｂｒａｉｎ Ｒｅｓｅａｒｃｈ ８８０, 2000, ８４-９１ * |
| JPN6016007005; 日薬理誌 １３０, 2007, ４６９-４７６ * |
| JPN6016007009; Ｍｏｌｅｃｕｌａｒ Ｐｓｙｃｈｉａｔｒｙ １４, 2009, ２６９-２７９ * |
| JPN6016007011; ＳＹＮＡＰＳＥ ６５, 20110601, １２８９-１２９７ * |
| JPN6016007013; ＢＩＯＣＨＥＭＩＣＡＬ ＡＮＤ ＢＩＯＰＨＹＳＩＣＡＬ ＲＥＳＥＡＲＣＨ ＣＯＭＭＵＮＩＣＡＴＩＯＮＳ １５３（１）, 1988, １２８-１３４ * |
| JPN6016007016; Ｃｏｃｈｒａｎｅ Ｄａｔａｂａｓｅ ｏｆ Ｓｙｓｔｅｍａｔｉｃ Ｒｅｖｉｅｗｓ Ｉｓｓｕｅ １, 2010, １-１７ * |
| JPN6016007019; Ｂｉｐｏｌａｒ Ｄｉｓｏｒｄｅｒｓ Ｖｏｌ．２， Ｉｓｓｕｅ １, 2000, ４７-５５ * |
Also Published As
| Publication number | Publication date |
|---|---|
| BR112013031117A8 (pt) | 2018-08-14 |
| BR112013031117A2 (pt) | 2018-06-19 |
| RU2013154699A (ru) | 2015-07-20 |
| KR20140041670A (ko) | 2014-04-04 |
| CA2837926A1 (en) | 2012-12-20 |
| IL229658A0 (en) | 2014-01-30 |
| WO2012173808A1 (en) | 2012-12-20 |
| EP2714050A1 (en) | 2014-04-09 |
| AU2012271068A1 (en) | 2013-12-19 |
| CN103906520A (zh) | 2014-07-02 |
| US20140243422A1 (en) | 2014-08-28 |
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