JP2011520917A - 慢性心不全の治療方法 - Google Patents
慢性心不全の治療方法 Download PDFInfo
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- JP2011520917A JP2011520917A JP2011509781A JP2011509781A JP2011520917A JP 2011520917 A JP2011520917 A JP 2011520917A JP 2011509781 A JP2011509781 A JP 2011509781A JP 2011509781 A JP2011509781 A JP 2011509781A JP 2011520917 A JP2011520917 A JP 2011520917A
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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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- A—HUMAN NECESSITIES
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P7/10—Antioedematous agents; Diuretics
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
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Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
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- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US19054508P | 2008-08-28 | 2008-08-28 | |
| US61/190,545 | 2008-08-28 | ||
| US20124008P | 2008-12-08 | 2008-12-08 | |
| US61/201,240 | 2008-12-08 | ||
| PCT/US2009/044247 WO2009140657A2 (en) | 2008-05-16 | 2009-05-15 | Method of treating chronic heart failure |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014129744A Division JP2014237648A (ja) | 2008-05-16 | 2014-06-25 | 慢性心不全の治療方法 |
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| JP2011520917A true JP2011520917A (ja) | 2011-07-21 |
| JP2011520917A5 JP2011520917A5 (cg-RX-API-DMAC10.html) | 2012-05-24 |
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| JP2011509781A Withdrawn JP2011520917A (ja) | 2008-05-16 | 2009-05-15 | 慢性心不全の治療方法 |
| JP2014129744A Withdrawn JP2014237648A (ja) | 2008-05-16 | 2014-06-25 | 慢性心不全の治療方法 |
| JP2016190522A Pending JP2017061453A (ja) | 2008-05-16 | 2016-09-29 | 慢性心不全の治療方法 |
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| JP2014129744A Withdrawn JP2014237648A (ja) | 2008-05-16 | 2014-06-25 | 慢性心不全の治療方法 |
| JP2016190522A Pending JP2017061453A (ja) | 2008-05-16 | 2016-09-29 | 慢性心不全の治療方法 |
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| Country | Link |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016505065A (ja) * | 2013-01-25 | 2016-02-18 | カーディオレンティス リミテッド | 心血管症候の治療方法 |
| JP2022507693A (ja) * | 2018-11-20 | 2022-01-18 | ウニベルジテート ハイデルベルク | 心不全の治療及び予防における使用のためのリラキシン受容体１ |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8415301B2 (en) | 2008-05-16 | 2013-04-09 | Corthera, Inc. | Method of treating dyspnea associated with acute heart failure by administering H2 relaxin |
| KR101800040B1 (ko) | 2010-03-10 | 2017-11-21 | 유니버시티 오브 플로리다 리서치 파운데이션, 인코포레이티드 | 릴랙신을 사용한 아쿠아포린의 조절 |
| WO2012072681A1 (en) * | 2010-12-01 | 2012-06-07 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Diagnostic and treatment of chronic heart failure |
| AU2012283235A1 (en) * | 2011-07-08 | 2014-01-09 | Bayer Intellectual Property Gmbh | Fusion proteins releasing Relaxin and uses thereof |
| AU2012291972B2 (en) * | 2011-08-04 | 2017-03-09 | Pharis Biotec Gmbh | Process for preparing human relaxin-2 |
| WO2013033324A2 (en) | 2011-08-31 | 2013-03-07 | University Of Florida Research Foundation, Inc. | Materials and methods for modulating activity of bone marrow derived cells |
| US20140364334A1 (en) * | 2011-12-21 | 2014-12-11 | Nuclea Biotechnologies, Inc. | Congestive heart failure biomarkers |
| JP6562632B2 (ja) | 2012-02-14 | 2019-08-21 | 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 | 心血管疾患および他の状態のためのパラクリン遺伝子の全身送達および制御された発現 |
| KR20160071472A (ko) * | 2013-11-07 | 2016-06-21 | 샹하이 헨그루이 파마수티컬 컴퍼니 리미티드 | 인간 릴렉신 유사체, 이의 약제학적 조성물 및 이의 약제학적 적용 |
| US10500227B2 (en) * | 2014-12-03 | 2019-12-10 | University Of Cincinnati | Bioactive gas-encapsulated echogenic liposomes and methods for treating cardiovascular disease |
| US11161891B2 (en) | 2015-12-09 | 2021-11-02 | The Scripps Research Institute | Relaxin immunoglobulin fusion proteins and methods of use |
| SG10201912034UA (en) | 2017-02-08 | 2020-02-27 | Bristol Myers Squibb Co | Modified relaxin polypeptides comprising a pharmacokinetic enhancer and uses thereof |
| CN107335051A (zh) * | 2017-08-18 | 2017-11-10 | 温州医科大学附属第医院 | 一种保护慢性心衰肾功能的药物组合物 |
| EP4058048A1 (en) * | 2019-11-16 | 2022-09-21 | Relaxera Pharmazeutische Gesellschaft mbH & Co. KG | Medical composition for treating cardiac wasting and cachexia |
| CN116406297A (zh) * | 2020-08-05 | 2023-07-07 | 阿斯克肋匹奥生物制药公司 | 治疗心脏疾患和充血性心力衰竭以及施用aav载体的方法 |
| RU2748529C1 (ru) * | 2020-09-01 | 2021-05-26 | Федеральное государственное бюджетное учреждение "Национальный медицинский исследовательский центр кардиологии" Министерства здравоохранения Российской Федерации (ФГБУ "НМИЦ кардиологии" Минздрава России) | Способ определения этиологии хронической сердечной недостаточности |
| IL321288A (en) * | 2022-12-09 | 2025-08-01 | Astrazeneca Ab | Dosing regimens using fusions of relaxin heterodimers |
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| US5023321A (en) | 1982-12-13 | 1991-06-11 | Howard Florey Institute Of Experimental Physiology & Medicine | Molecular cloning and characterization of a further gene sequence coding for human relaxin |
| US5166191A (en) * | 1991-08-19 | 1992-11-24 | Genentech, Inc. | Use of relaxin in cardiovascular therapy |
| CA2165781C (en) | 1993-06-21 | 2007-02-13 | Tim Breece | Process for producing relaxin |
| US5811395A (en) | 1995-06-07 | 1998-09-22 | Medical University Of South Carolina | Relaxin analogs and derivatives methods and uses thereof |
| RU2213559C2 (ru) * | 2000-01-26 | 2003-10-10 | Тюменская государственная медицинская академия | Способ лечения больных хронической сердечной недостаточностью на фоне ишемической болезни сердца |
| DE10155843A1 (de) * | 2000-11-16 | 2003-01-30 | Immundiagnostik Ag | Verfahren zur Prognose und Diagnose von Herzinsuffizienz |
| US20050113286A1 (en) * | 2002-03-18 | 2005-05-26 | Schreiner George F. | Methods for treating congestive heart failure |
| EP1729817B1 (en) * | 2004-03-30 | 2014-03-05 | Industry-Academic Cooperation Foundation | Gene delivery system containing relaxin gene and pharmaceutical composition using relaxin |
| WO2007008907A2 (en) * | 2005-07-11 | 2007-01-18 | Abbott Laboratories | Methods for determining how to treat congestive heart failure |
| CA2693651A1 (en) | 2007-07-12 | 2009-01-15 | Ronen Shemesh | Bioactive peptides and method of using same |
| US8415301B2 (en) * | 2008-05-16 | 2013-04-09 | Corthera, Inc. | Method of treating dyspnea associated with acute heart failure by administering H2 relaxin |
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- 2009-05-15 US US12/992,667 patent/US20110144019A1/en not_active Abandoned
- 2009-05-15 CN CN2009801176516A patent/CN102026649A/zh active Pending
- 2009-05-15 CA CA2724535A patent/CA2724535A1/en not_active Abandoned
- 2009-05-15 WO PCT/US2009/044247 patent/WO2009140657A2/en not_active Ceased
- 2009-05-15 JP JP2011509781A patent/JP2011520917A/ja not_active Withdrawn
- 2009-05-15 MX MX2012010249A patent/MX336145B/es unknown
- 2009-05-15 BR BRPI0912559A patent/BRPI0912559A2/pt not_active Application Discontinuation
- 2009-05-15 CN CN201510202983.1A patent/CN104815319A/zh active Pending
- 2009-05-15 EP EP09747738A patent/EP2288366A4/en not_active Ceased
- 2009-05-15 MX MX2010012502A patent/MX2010012502A/es active IP Right Grant
-
2013
- 2013-07-11 US US13/939,648 patent/US20140005112A1/en not_active Abandoned
-
2014
- 2014-06-25 JP JP2014129744A patent/JP2014237648A/ja not_active Withdrawn
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2016
- 2016-04-25 US US15/137,054 patent/US20160287672A1/en not_active Abandoned
- 2016-09-29 JP JP2016190522A patent/JP2017061453A/ja active Pending
Non-Patent Citations (10)
| Title |
|---|
| JPN6013038308; Ｅｎｄｏｃｒｉｎｏｌｏｇｙ Ｖｏｌ．１４５，Ｎｏ．９, 2004, ｐ４１２５-４１３３ * |
| JPN6013038310; Ａｎｎａｌｓ ｏｆ ｔｈｅ Ｎｅｗ Ｙｏｒｋ Ａｃａｄｅｍｙ ｏｆ Ｓｃｉｅｎｃｅｓ Ｖｏｌ．１０４１, 2005, ｐ１９０-１９３ * |
| JPN6013038311; Ｃｅｌｌｕｌａｒ ａｎｄ Ｍｏｌｅｃｕｌａｒ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｖｏｌ．６４，Ｎｏ．１２, 2007, ｐ１５３９-１５５７ * |
| JPN6013038313; Ｃｉｒｃｕｌａｔｉｏｎ Ｒｅｓｅａｒｃｈ Ｖｏｌ．９２，Ｎｏ．１, 2003, ｐ３２-４０ * |
| JPN6013038316; 分子心血管病 Ｖｏｌ．６，Ｎｏ．３, 2005, ｐ２９３-２９７ * |
| JPN6013038318; Ａｎｇｉｏｔｅｎｓｉｎ Ｒｅｓｅａｒｃｈ Ｖｏｌ．２，Ｎｏ．３, 2005, ｐ１９９-２０３ * |
| JPN6013038321; Ａｎｇｉｏｔｅｎｓｉｎ Ｒｅｓｅａｒｃｈ Ｖｏｌ．２，Ｎｏ．３, 2005, ｐ２３２-２３７ * |
| JPN6013038323; 日本薬理学雑誌 Ｖｏｌ．１２１，Ｎｏ．２, 2003, ｐ９１-１０１ * |
| JPN6013038325; メルクマニュアル 第１８版 日本語版 , 20070425, ｐ６８６-６９７, 日経ＢＰ社 * |
| JPN6013038328; Ｔ． Ｄｓｃｈｉｅｔｚｉｇ ｅｔ ａｌ．: Ｅｕｒｏｐｅａｎ Ｊｏｕｒｎａｌ ｏｆ Ｈｅａｒｔ Ｆａｉｌｕｒｅ Ｓｕｐｐｌｅｍｅｎｔｓ Ｖｏｌ．６，Ｎｏ．Ｓｕｐｐｌ．, 200706, ｐ９０ * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016505065A (ja) * | 2013-01-25 | 2016-02-18 | カーディオレンティス リミテッド | 心血管症候の治療方法 |
| JP2022507693A (ja) * | 2018-11-20 | 2022-01-18 | ウニベルジテート ハイデルベルク | 心不全の治療及び予防における使用のためのリラキシン受容体１ |
| JP7541003B2 (ja) | 2018-11-20 | 2024-08-27 | ウニベルジテート ハイデルベルク | 心不全の治療及び予防における使用のためのリラキシン受容体１ |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009140657A3 (en) | 2010-01-07 |
| JP2017061453A (ja) | 2017-03-30 |
| US20140005112A1 (en) | 2014-01-02 |
| AU2009246112A1 (en) | 2009-11-19 |
| EP3150219A1 (en) | 2017-04-05 |
| CN102026649A (zh) | 2011-04-20 |
| RU2512933C2 (ru) | 2014-04-10 |
| AU2009246112B2 (en) | 2013-05-02 |
| EP2288366A4 (en) | 2012-05-02 |
| CN104815319A (zh) | 2015-08-05 |
| CA2724535A1 (en) | 2009-11-19 |
| MX336145B (es) | 2016-01-08 |
| WO2009140657A2 (en) | 2009-11-19 |
| US20110144019A1 (en) | 2011-06-16 |
| US20160287672A1 (en) | 2016-10-06 |
| EP2288366A2 (en) | 2011-03-02 |
| BRPI0912559A2 (pt) | 2015-10-13 |
| RU2010151470A (ru) | 2012-06-27 |
| MX2010012502A (es) | 2011-04-11 |
| JP2014237648A (ja) | 2014-12-18 |
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