JP2011515471A - 急性心筋梗塞を処置するための方法 - Google Patents
急性心筋梗塞を処置するための方法 Download PDFInfo
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4833—Thrombin (3.4.21.5)
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
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- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US7083708P | 2008-03-26 | 2008-03-26 | |
| US61/070,837 | 2008-03-26 | ||
| US13795308P | 2008-08-05 | 2008-08-05 | |
| US61/137,953 | 2008-08-05 | ||
| PCT/US2009/001954 WO2009142679A2 (en) | 2008-03-26 | 2009-03-26 | Methods for treating acute myocardial infarction |
Publications (2)
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| JP2011515471A true JP2011515471A (ja) | 2011-05-19 |
| JP2011515471A5 JP2011515471A5 (enExample) | 2012-05-24 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2011501845A Pending JP2011515471A (ja) | 2008-03-26 | 2009-03-26 | 急性心筋梗塞を処置するための方法 |
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| US (1) | US20110105400A1 (enExample) |
| EP (1) | EP2268304A2 (enExample) |
| JP (1) | JP2011515471A (enExample) |
| CA (1) | CA2719940A1 (enExample) |
| WO (1) | WO2009142679A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016535059A (ja) * | 2013-08-19 | 2016-11-10 | クラウス・マイケル・シュミット | 臓器保護のための液体麻酔薬と組み合わせた非麻酔性保護ガス |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2009229395A1 (en) | 2008-03-26 | 2009-10-01 | The Board Of Regents, The University Of Texas System | Method of treating degenerative diseases |
| US10220078B2 (en) | 2014-06-11 | 2019-03-05 | The Board Of Regents Of The University Of Texas System | Methods of using thrombin derivatives to treat medulloblastoma |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004502739A (ja) * | 2000-07-12 | 2004-01-29 | ザ ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム | トロンビン由来ペプチドを使用した治療法 |
| JP2005519066A (ja) * | 2002-01-16 | 2005-06-30 | ザ ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム | 心臓組織修復を促進するためのトロンビン由来ペプチド |
| JP2006510620A (ja) * | 2002-11-18 | 2006-03-30 | ザ・スクリプス・リサーチ・インステイチユート | 心筋梗塞の治療方法 |
| JP2006523685A (ja) * | 2003-04-17 | 2006-10-19 | シグマ−タウ・インドゥストリエ・ファルマチェウチケ・リウニテ・ソシエタ・ペル・アチオニ | 循環器疾患の治療のためのｌ−カルニチンの使用 |
| JP2007277264A (ja) * | 1995-06-07 | 2007-10-25 | Ortho Pharmaceutical Corp | エリトロポエチン受容体に結合する化合物およびペプチド |
| JP2007532483A (ja) * | 2004-03-15 | 2007-11-15 | ザ・スクリプス・リサーチ・インステイチユート | 心筋梗塞の治療方法 |
| WO2008036387A2 (en) * | 2006-09-22 | 2008-03-27 | Orthologic Corp. | Method of treating endothelial dysfunction |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5352664A (en) * | 1986-10-31 | 1994-10-04 | Board Of Regents, The University Of Texas System | Thrombin derived polypeptides; compositions and methods for use |
| US6630572B1 (en) * | 1986-10-31 | 2003-10-07 | The Board Of Regents, University Of Texas Syatems | Thrombin derived polypeptides: compositions and methods for use |
| US5244460A (en) * | 1991-11-27 | 1993-09-14 | The United States Of America As Represented By The Department Of Health And Human Services | Method to foster myocardial blood vessel growth and improve blood flow to the heart |
| WO1997015598A1 (fr) * | 1995-10-24 | 1997-05-01 | Juridical Foundation The Chemo-Sero-Therapeutic Research Institute | Nouveau peptide |
| US5912229A (en) * | 1996-03-01 | 1999-06-15 | Novo Nordisk Als | Use of a pharmaceutical composition comprising an appetite-suppressing peptide |
| US6197751B1 (en) * | 1997-11-10 | 2001-03-06 | The United States Of America As Represented By The Department Of Health And Human Services | Thymosin α1 promotes tissue repair, angiogenesis and cell migration |
| US6033436A (en) * | 1998-02-17 | 2000-03-07 | Md3, Inc. | Expandable stent |
| JP2002527401A (ja) * | 1998-10-13 | 2002-08-27 | カイロン コーポレイション | Ｆｇｆの脈管形成的に有効な単位用量および投与方法 |
| US6363938B2 (en) * | 1998-12-22 | 2002-04-02 | Angiotrax, Inc. | Methods and apparatus for perfusing tissue and/or stimulating revascularization and tissue growth |
| US20020063763A1 (en) * | 2000-11-29 | 2002-05-30 | Mantell David Allen | Apparatus and method for removing air bubbles from an ink jet printhead |
| EP1301196B1 (en) * | 2000-07-19 | 2003-11-26 | The Board of Regents, The University of Texas System | Stimulation of bone growth with thrombin peptide derivatives |
| CN1458974A (zh) * | 2000-07-20 | 2003-11-26 | 德克萨斯系统大学董事会 | 用非蛋白质水解激活的凝血酶受体的激动剂刺激软骨生长 |
| JP4192093B2 (ja) * | 2001-07-27 | 2008-12-03 | ザ ボード オブ リージェンツ オブ ザ ユニバーシティ オブ テキサス システム | 慢性皮膚潰瘍の治癒を促進する方法 |
| WO2004014937A2 (en) * | 2002-07-02 | 2004-02-19 | The Board Of Regents, The University Of Texas System | Thrombin peptide derivatives |
| CA2491135A1 (en) * | 2002-07-02 | 2004-01-15 | The Board Of Regents, The University Of Texas System | Thrombin peptide derivative dimers |
| PL1559431T3 (pl) * | 2003-12-31 | 2007-10-31 | Orthologic Corp | Kompozycja farmaceutyczna dla pochodnych peptydu trombiny |
| AU2006259408A1 (en) * | 2005-06-17 | 2006-12-28 | Genentech, Inc. | Use of VEGF for wound healing |
| EP2155234A1 (en) * | 2007-04-10 | 2010-02-24 | The Board of Regents,The University of Texas System | Combination therapy for chronic dermal ulcers |
| EP2155236A1 (en) * | 2007-04-10 | 2010-02-24 | The Board of Regents,The University of Texas System | Combination therapy for cardiac revascularization and cardiac repair |
| AU2009229399A1 (en) * | 2008-03-26 | 2009-10-01 | Orthologic Corp. | Thrombin derived peptides for smooth muscle relaxation |
-
2009
- 2009-03-26 EP EP09750910A patent/EP2268304A2/en not_active Withdrawn
- 2009-03-26 JP JP2011501845A patent/JP2011515471A/ja active Pending
- 2009-03-26 US US12/934,585 patent/US20110105400A1/en not_active Abandoned
- 2009-03-26 WO PCT/US2009/001954 patent/WO2009142679A2/en not_active Ceased
- 2009-03-26 CA CA2719940A patent/CA2719940A1/en not_active Abandoned
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007277264A (ja) * | 1995-06-07 | 2007-10-25 | Ortho Pharmaceutical Corp | エリトロポエチン受容体に結合する化合物およびペプチド |
| JP2004502739A (ja) * | 2000-07-12 | 2004-01-29 | ザ ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム | トロンビン由来ペプチドを使用した治療法 |
| JP2005519066A (ja) * | 2002-01-16 | 2005-06-30 | ザ ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム | 心臓組織修復を促進するためのトロンビン由来ペプチド |
| JP2006510620A (ja) * | 2002-11-18 | 2006-03-30 | ザ・スクリプス・リサーチ・インステイチユート | 心筋梗塞の治療方法 |
| JP2006523685A (ja) * | 2003-04-17 | 2006-10-19 | シグマ−タウ・インドゥストリエ・ファルマチェウチケ・リウニテ・ソシエタ・ペル・アチオニ | 循環器疾患の治療のためのｌ−カルニチンの使用 |
| JP2007532483A (ja) * | 2004-03-15 | 2007-11-15 | ザ・スクリプス・リサーチ・インステイチユート | 心筋梗塞の治療方法 |
| WO2008036387A2 (en) * | 2006-09-22 | 2008-03-27 | Orthologic Corp. | Method of treating endothelial dysfunction |
Non-Patent Citations (3)
| Title |
|---|
| JPN6008008187; Ｇｅｎｅｒａｌ Ｐｈａｒｍａｃｏｌｏｇｙ （２０００）， Ｖｏｌ．３５， Ｎｏ．５， ｐ．２４９-２５４ * |
| JPN6013043254; 竹村元三他、医学のあゆみ，ｖｏｌ．２０５，ｐ．７９９-８０３（２００３） * |
| JPN6013043258; 冨原均他、医学のあゆみ，ｖｏｌ．１６７，ｐ．５４６-５５０（１９９３） * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016535059A (ja) * | 2013-08-19 | 2016-11-10 | クラウス・マイケル・シュミット | 臓器保護のための液体麻酔薬と組み合わせた非麻酔性保護ガス |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2009249629A1 (en) | 2009-11-26 |
| WO2009142679A3 (en) | 2010-01-14 |
| EP2268304A2 (en) | 2011-01-05 |
| WO2009142679A2 (en) | 2009-11-26 |
| CA2719940A1 (en) | 2009-11-26 |
| US20110105400A1 (en) | 2011-05-05 |
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