JP2010529128A - レット症候群および他の障害の処置 - Google Patents
レット症候群および他の障害の処置 Download PDFInfo
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
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- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014508744A (ja) * | 2011-01-27 | 2014-04-10 | ニューレン ファーマシューティカルズ リミテッド | グリシル−ｌ−２−メチルプロピル−ｌ−グルタミン酸を用いる自閉症スペクトラム障害の治療 |
| JP2016506380A (ja) * | 2012-11-28 | 2016-03-03 | ニューレン ファーマシューティカルズ リミテッド | グリシル−ｌ−２−メチルプロリル−ｌ−グルタミン酸を使用する自閉症スペクトラム障害の処置 |
| WO2021100614A1 (ja) * | 2019-11-19 | 2021-05-27 | 国立大学法人京都大学 | 大豆ペプチド及び／又はコラーゲンペプチド含有神経心理学的機能改善剤 |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20130066695A (ko) | 2004-08-23 | 2013-06-20 | 맨카인드 코포레이션 | 약물 전달용 디케토피페라진염, 디케토모르포린염 또는 디케토디옥산염 |
| MX373000B (es) | 2005-09-14 | 2020-05-21 | Mannkind Corp | Metodo para formulacion de farmaco basado en el aumento de la afinidad de agentes activos hacia las superficies de microparticulas cristalinas. |
| CA2650140A1 (en) * | 2006-04-14 | 2007-10-25 | Mriganka Sur | Identifying and modulating molecular pathways that mediate nervous system plasticity |
| TWI532497B (zh) | 2008-08-11 | 2016-05-11 | 曼凱公司 | 超快起作用胰島素之用途 |
| AU2010204995A1 (en) | 2009-01-16 | 2011-08-18 | Massachusetts Institute Of Technology | Diagnosis and treatment of autism spectrum disorders |
| EP2571515B1 (en) * | 2010-05-17 | 2016-11-30 | Icahn School of Medicine at Mount Sinai | Methods and assays for treating subjects with shank3 deletion, mutation or reduced expression |
| SG194034A1 (en) * | 2011-04-01 | 2013-11-29 | Mannkind Corp | Blister package for pharmaceutical cartridges |
| EP3628325A1 (en) * | 2011-07-22 | 2020-04-01 | The University of Chicago | Treatments for migraine and related disorders |
| MX2014004983A (es) | 2011-10-24 | 2014-09-22 | Mannkid Corp | Metodos y composiciones para tratar dolor. |
| ES2495266B8 (es) * | 2013-02-13 | 2015-11-12 | Consejo Superior De Investigaciones Científicas (Csic) | Uso de igf-1 como reactivo de diagnóstico y/o pronóstico precoz de la enfermedad de alzheimer |
| US10307464B2 (en) | 2014-03-28 | 2019-06-04 | Mannkind Corporation | Use of ultrarapid acting insulin |
| ES2927649T3 (es) | 2014-09-25 | 2022-11-08 | Cold Spring Harbor Laboratory | Tratamiento del síndrome de Rett |
| US10507196B2 (en) | 2016-01-26 | 2019-12-17 | Anavex Life Sciences Corp. | Neurodevelopmental disorder therapy |
| TWI601821B (zh) * | 2016-04-15 | 2017-10-11 | 中央研究院 | 治療神經發展性疾病 |
| WO2018217766A1 (en) | 2017-05-22 | 2018-11-29 | Whitehead Institute For Biomedical Research | Kcc2 expression enhancing compounds and uses thereof |
| CN108187031A (zh) * | 2018-02-11 | 2018-06-22 | 中国人民解放军第四军医大学 | rhIGF1在制备治疗脆性X综合征药物中的应用 |
| JP2022547948A (ja) | 2019-09-09 | 2022-11-16 | ザ・ユニバーシティ・オブ・シカゴ | 片頭痛の処置のための併用療法 |
| WO2022055045A1 (ko) * | 2020-09-08 | 2022-03-17 | 주식회사 선마린바이오테크 | 콜라게나제 저해 활성 펩타이드 유도체 및 이의 용도 |
| US20240148835A1 (en) * | 2021-01-28 | 2024-05-09 | University Of Florida Research Foundation, Incorporated | Treating disorders associated with dyrk1a dysfunction |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4411890A (en) | 1981-04-14 | 1983-10-25 | Beckman Instruments, Inc. | Synthetic peptides having pituitary growth hormone releasing activity |
| IL71991A (en) | 1983-06-06 | 1994-05-30 | Genentech Inc | Preparation of human FGI and FGE in their processed form through recombinant AND tranology in prokaryotes |
| DE68922602T2 (de) | 1988-01-28 | 1995-12-07 | Polygen Holding Corp | Polypeptide mit hormonwachstumsbefreiender wirkung. |
| AU628322B2 (en) | 1988-01-28 | 1992-09-17 | Eastman Kodak Company | Polypeptide compounds having growth hormone releasing activity |
| SE8803847A0 (sv) * | 1988-10-27 | 1990-04-28 | Kabigen Ab | Neuromodulerande peptid |
| US5093317A (en) * | 1989-06-05 | 1992-03-03 | Cephalon, Inc. | Treating disorders by application of insulin-like growth factor |
| DE69218948T2 (de) | 1991-08-01 | 1997-07-31 | Auckland Uniservices Ltd | IGF-I zur Verbesserung der neuronale Lage |
| US5861373A (en) * | 1991-08-01 | 1999-01-19 | Genentech, Inc | IGF-1 to improve the neural condition |
| US5420112A (en) | 1992-06-12 | 1995-05-30 | Lewis; Michael E. | Prevention and treatment of peripheral neuropathy |
| US5446024A (en) | 1993-12-17 | 1995-08-29 | Genentech, Inc. | Purification of insulin-like growth factor |
| WO1995017204A1 (en) | 1993-12-23 | 1995-06-29 | Auckland Uniservices Limited | Composition and methods to improve neural outcome |
| US5565428A (en) | 1995-05-22 | 1996-10-15 | Genentech, Inc. | Method of administration of IGF-I |
| US7074897B2 (en) | 1997-06-16 | 2006-07-11 | Genentech, Inc. | Pro943 polypeptides |
| US6358951B1 (en) | 1998-08-21 | 2002-03-19 | Pfizer Inc. | Growth hormone secretagogues |
| CN1261158C (zh) | 1998-09-03 | 2006-06-28 | 诺兰兹公司 | 生长激素在制备用于诱导神经保护作用的药剂中的应用 |
| PT1141014E (pt) | 1999-01-06 | 2005-04-29 | Genentech Inc | Variante mutante do factor de crescimento semelhante a insulina (igf-i) |
| EP1351976A2 (en) | 2000-08-24 | 2003-10-15 | Neuronz Limited | Gpe analogs |
| WO2002056873A2 (en) | 2000-12-22 | 2002-07-25 | Bayer Pharmaceuticals Corporation | 2-substituted dibenzo[a,e]1,2,3-triazolo[4,5-c][7]annulen-8-ones as growth hormone secretagogues |
| WO2002057241A1 (en) | 2000-12-22 | 2002-07-25 | Bayer Pharmaceuticals Corporation | 8-(AMINOALKOXYMINO)-8H-DIBENZO[a,e]TRIAZOLO[4,5-c]CYCLOHEPTENES AS GROWTH HORMONE SECRETAGOGUES |
| IL156435A0 (en) | 2001-02-09 | 2004-01-04 | Genentech Inc | Crystallization of igf-1 |
| US7863304B2 (en) | 2001-05-24 | 2011-01-04 | Neuren Pharmaceuticals Limited | Analogs of glycyl-prolyl-glutamate |
| ATE435852T1 (de) | 2001-05-24 | 2009-07-15 | Neuren Pharmaceuticals Ltd | Gpe-analoga und peptidomimetika |
| EP1648873A4 (en) | 2003-03-20 | 2008-06-25 | Neuren Pharmaceuticals Ltd | NEUROPROTECTIVE MACROCYLIC COMPOUNDS AND METHODS OF THEIR APPLICATION |
| US20050027110A1 (en) | 2003-07-24 | 2005-02-03 | Michael Russell | Drug delivery in the nervous system |
| DK2274978T3 (en) | 2003-09-12 | 2015-06-15 | Ipsen Biopharmaceuticals Inc | Methods of treating an insulin-like growth factor-I (IGF-I) deficiency |
| EP1684783A4 (en) | 2003-10-23 | 2009-07-08 | Neuren Pharmaceuticals Ltd | NEUROPROTECTIVE EFFECTS OF GLY-PRO-GLU AFTER INTRAVENOUS INFUSION |
| WO2006023530A2 (en) * | 2004-08-16 | 2006-03-02 | Massachusetts Institute Of Technology | Compositions and methods for enhancing structural and functional nervous system reorganization and recovery |
| JP2008511838A (ja) | 2004-08-30 | 2008-04-17 | テルシカ・インク | インシュリン様成長因子欠乏疾患の診断及び治療のための方法及び装置 |
| KR20060040550A (ko) | 2004-11-05 | 2006-05-10 | 마루이시세이야쿠가부시키가이샤 | 인슐린유사 성장인자-1 분비촉진제 |
| JP2008545752A (ja) | 2005-06-02 | 2008-12-18 | テルシカ インコーポレーティッド | 成長障害を処置するための方法 |
| CA2650140A1 (en) | 2006-04-14 | 2007-10-25 | Mriganka Sur | Identifying and modulating molecular pathways that mediate nervous system plasticity |
-
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Non-Patent Citations (4)
| Title |
|---|
| JPN6013009128; ＮＡＴＵＲＥ ＮＥＵＲＯＳＣＩＥＮＣＥ ＶＯＬ．９， ＮＯ．５, 200605, Ｐ．６６０-６６８ * |
| JPN6013009131; ＣＨＥＭＯＴＨＥＲＡＰＹ ＶＯＬ．５２, 2006, Ｐ．２７９-２８１ * |
| JPN6013009132; ＢＩＯＯＲＧＡＮＩＣ ＆ ＭＥＤＩＣＩＮＡＬ ＣＨＥＭＩＳＴＲＹ ＬＥＴＴＥＲＳ ＶＯＬ．１５, 2005, Ｐ．２２７９-２２８３ * |
| JPN6013009134; ＡＣＴＡ ＰＡＥＤＩＡＴＲ． ＶＯＬ．９０, 2001, Ｐ．１２５７-１２６１ * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014508744A (ja) * | 2011-01-27 | 2014-04-10 | ニューレン ファーマシューティカルズ リミテッド | グリシル−ｌ−２−メチルプロピル−ｌ−グルタミン酸を用いる自閉症スペクトラム障害の治療 |
| JP2016210808A (ja) * | 2011-01-27 | 2016-12-15 | ニューレン ファーマシューティカルズ リミテッド | グリシル−ｌ−２−メチルプロピル−ｌ−グルタミン酸を用いる自閉症スペクトラム障害の治療 |
| JP2018138606A (ja) * | 2011-01-27 | 2018-09-06 | ニューレン ファーマシューティカルズ リミテッド | グリシル−ｌ−２−メチルプロピル−ｌ−グルタミン酸を用いる自閉症スペクトラム障害の治療 |
| JP2016506380A (ja) * | 2012-11-28 | 2016-03-03 | ニューレン ファーマシューティカルズ リミテッド | グリシル−ｌ−２−メチルプロリル−ｌ−グルタミン酸を使用する自閉症スペクトラム障害の処置 |
| WO2021100614A1 (ja) * | 2019-11-19 | 2021-05-27 | 国立大学法人京都大学 | 大豆ペプチド及び／又はコラーゲンペプチド含有神経心理学的機能改善剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20120177630A1 (en) | 2012-07-12 |
| BRPI0812768A2 (pt) | 2014-12-02 |
| EP2164509A1 (en) | 2010-03-24 |
| AU2008262387A1 (en) | 2008-12-18 |
| WO2008153929A1 (en) | 2008-12-18 |
| US7994127B2 (en) | 2011-08-09 |
| CA2689549A1 (en) | 2008-12-18 |
| US20090099077A1 (en) | 2009-04-16 |
| CN101820896A (zh) | 2010-09-01 |
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