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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A—HUMAN NECESSITIES
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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
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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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
- C07K14/64—Relaxins
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Cardiology (AREA)
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- Pulmonology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Plant Substances (AREA)
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| US12788908P | 2008-05-16 | 2008-05-16 | |
| US61/127,889 | 2008-05-16 | ||
| 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 |
Related Child Applications (1)
| 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 (enExample) | 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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| Application Number | Title | Priority Date | Filing Date |
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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 |
Country Status (10)
| Country | Link |
|---|---|
| US (3) | US20110144019A1 (enExample) |
| EP (2) | EP3150219A1 (enExample) |
| JP (3) | JP2011520917A (enExample) |
| CN (2) | CN104815319A (enExample) |
| AU (1) | AU2009246112B2 (enExample) |
| BR (1) | BRPI0912559A2 (enExample) |
| CA (1) | CA2724535A1 (enExample) |
| MX (2) | MX2010012502A (enExample) |
| RU (1) | RU2512933C2 (enExample) |
| WO (1) | WO2009140657A2 (enExample) |
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 |
|---|---|---|---|---|
| CA2724540C (en) | 2008-05-16 | 2014-07-08 | Corthera, Inc. | Treating dyspnea associated with acute heart failure with relaxin |
| BR112012022654A2 (pt) | 2010-03-10 | 2016-11-01 | Univ Florida | modulação de aquaporinas com relaxina |
| US20130336979A1 (en) * | 2010-12-01 | 2013-12-19 | Fatima Smih | Diagnostic and treatment of chronic heart failure |
| MX2014000316A (es) * | 2011-07-08 | 2014-02-19 | Bayer Ip Gmbh | Proteinas de fusion liberadoras de relaxina y usos de las mismas. |
| 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 |
| EP2814513B1 (en) | 2012-02-14 | 2017-12-20 | The Regents of The University of California | Systemic delivery and regulated expression of paracrine genes for cardiovascular diseases and other conditions |
| HK1211594A1 (en) * | 2013-11-07 | 2016-05-27 | 上海恒瑞医药有限公司 | Human relaxin analogue, pharmaceutical composition of same, and pharmaceutical application of same |
| US10500227B2 (en) * | 2014-12-03 | 2019-12-10 | University Of Cincinnati | Bioactive gas-encapsulated echogenic liposomes and methods for treating cardiovascular disease |
| DK3387019T3 (da) | 2015-12-09 | 2022-01-10 | Scripps Research Inst | Relaxin-immunoglobulinfusionsproteiner og anvendelsesfremgangsmåder |
| MX2019008449A (es) | 2017-02-08 | 2019-09-09 | Bristol Myers Squibb Co | Polipetidos de relaxina modificada que comprenden un mejorador farmacocinetico y sus usos. |
| 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 |
| US12226455B2 (en) | 2019-11-16 | 2025-02-18 | Relaxera Pharmazeutische Gmbh & Co. Kg | Medical composition for treating cardiac wasting and cachexia |
| EP4192580A4 (en) * | 2020-08-05 | 2025-06-18 | AskBio Inc. | Methods for treating heart disease and congestive heart failure and administration of AAV vectors |
| 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 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US20080077025A1 (en) * | 2005-07-11 | 2008-03-27 | Leticia Delgado-Herrera | Methods for determining how to treat congestive heart failure |
| WO2009007848A2 (en) | 2007-07-12 | 2009-01-15 | Compugen Ltd. | Bioactive peptides and method of using same |
| CA2724540C (en) * | 2008-05-16 | 2014-07-08 | Corthera, Inc. | Treating dyspnea associated with acute heart failure with relaxin |
-
2009
- 2009-05-15 CN CN201510202983.1A patent/CN104815319A/zh active Pending
- 2009-05-15 WO PCT/US2009/044247 patent/WO2009140657A2/en not_active Ceased
- 2009-05-15 EP EP16174665.6A patent/EP3150219A1/en not_active Withdrawn
- 2009-05-15 MX MX2010012502A patent/MX2010012502A/es active IP Right Grant
- 2009-05-15 AU AU2009246112A patent/AU2009246112B2/en not_active Ceased
- 2009-05-15 RU RU2010151470/14A patent/RU2512933C2/ru not_active IP Right Cessation
- 2009-05-15 CA CA2724535A patent/CA2724535A1/en not_active Abandoned
- 2009-05-15 JP JP2011509781A patent/JP2011520917A/ja not_active Withdrawn
- 2009-05-15 BR BRPI0912559A patent/BRPI0912559A2/pt not_active Application Discontinuation
- 2009-05-15 EP EP09747738A patent/EP2288366A4/en not_active Ceased
- 2009-05-15 CN CN2009801176516A patent/CN102026649A/zh active Pending
- 2009-05-15 MX MX2012010249A patent/MX336145B/es unknown
- 2009-05-15 US US12/992,667 patent/US20110144019A1/en not_active Abandoned
-
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
-
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 |
|---|---|
| US20160287672A1 (en) | 2016-10-06 |
| BRPI0912559A2 (pt) | 2015-10-13 |
| MX336145B (es) | 2016-01-08 |
| EP2288366A2 (en) | 2011-03-02 |
| RU2512933C2 (ru) | 2014-04-10 |
| EP2288366A4 (en) | 2012-05-02 |
| US20140005112A1 (en) | 2014-01-02 |
| CN104815319A (zh) | 2015-08-05 |
| AU2009246112A1 (en) | 2009-11-19 |
| EP3150219A1 (en) | 2017-04-05 |
| CN102026649A (zh) | 2011-04-20 |
| RU2010151470A (ru) | 2012-06-27 |
| CA2724535A1 (en) | 2009-11-19 |
| JP2017061453A (ja) | 2017-03-30 |
| US20110144019A1 (en) | 2011-06-16 |
| MX2010012502A (es) | 2011-04-11 |
| JP2014237648A (ja) | 2014-12-18 |
| AU2009246112B2 (en) | 2013-05-02 |
| WO2009140657A2 (en) | 2009-11-19 |
| WO2009140657A3 (en) | 2010-01-07 |
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