FI120182B - Trombolyyttisesti aktiivisten proteiinien ja antikoagulanttien yhdistelmiä ja niiden käyttöjä - Google Patents
Trombolyyttisesti aktiivisten proteiinien ja antikoagulanttien yhdistelmiä ja niiden käyttöjä Download PDFInfo
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- FI120182B FI120182B FI963802A FI963802A FI120182B FI 120182 B FI120182 B FI 120182B FI 963802 A FI963802 A FI 963802A FI 963802 A FI963802 A FI 963802A FI 120182 B FI120182 B FI 120182B
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- heparin
- anticoagulant
- active protein
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- 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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Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/217,618 US5510330A (en) | 1994-03-25 | 1994-03-25 | Combinations of thrombolytically active proteins and non-heparin anticoagulants, and uses thereof. |
| US21761894 | 1994-03-25 | ||
| PCT/EP1995/001061 WO1995026202A1 (en) | 1994-03-25 | 1995-03-22 | Combinations of thrombolytically active proteins and anticoagulants, and uses thereof |
| EP9501061 | 1995-03-22 |
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| FI963802A0 FI963802A0 (fi) | 1996-09-24 |
| FI963802A FI963802A (fi) | 1996-09-24 |
| FI120182B true FI120182B (fi) | 2009-07-31 |
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| FI963802A FI120182B (fi) | 1994-03-25 | 1996-09-24 | Trombolyyttisesti aktiivisten proteiinien ja antikoagulanttien yhdistelmiä ja niiden käyttöjä |
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| EP (2) | EP0751785B2 (no) |
| JP (1) | JPH09510439A (no) |
| KR (1) | KR100366982B1 (no) |
| CN (1) | CN1090029C (no) |
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| NZ (1) | NZ282417A (no) |
| PL (1) | PL182165B1 (no) |
| RU (1) | RU2166326C2 (no) |
| UA (1) | UA41398C2 (no) |
| WO (1) | WO1995026202A1 (no) |
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| US7611533B2 (en) * | 1995-06-07 | 2009-11-03 | Cook Incorporated | Coated implantable medical device |
| US7550005B2 (en) * | 1995-06-07 | 2009-06-23 | Cook Incorporated | Coated implantable medical device |
| US7896914B2 (en) * | 1995-06-07 | 2011-03-01 | Cook Incorporated | Coated implantable medical device |
| US6774278B1 (en) * | 1995-06-07 | 2004-08-10 | Cook Incorporated | Coated implantable medical device |
| US7846202B2 (en) | 1995-06-07 | 2010-12-07 | Cook Incorporated | Coated implantable medical device |
| US20070203520A1 (en) * | 1995-06-07 | 2007-08-30 | Dennis Griffin | Endovascular filter |
| US7867275B2 (en) * | 1995-06-07 | 2011-01-11 | Cook Incorporated | Coated implantable medical device method |
| US5840733A (en) | 1996-07-01 | 1998-11-24 | Redcell, Canada, Inc. | Methods and compositions for producing novel conjugates of thrombin inhibitors and endogenous carriers resulting in anti-thrombins with extended lifetimes |
| US6010911A (en) * | 1997-04-30 | 2000-01-04 | Medtronic, Inc. | Apparatus for performing a heparin-independent high sensitivity platelet function evaluation technique |
| US6750201B1 (en) * | 1997-10-17 | 2004-06-15 | The Trustees Of The University Of Pennsylvania | Compositions and methods for promoting internalization and degradation of urokinase-type plasminogen activator |
| US6517814B2 (en) | 2001-01-09 | 2003-02-11 | Bristol-Myers Squibb Pharma Company | Macrocyclic chelants useful for metallopharmaceuticals |
| DE10115740A1 (de) * | 2001-03-26 | 2002-10-02 | Ulrich Speck | Zubereitung für die Restenoseprophylaxe |
| DE10153601A1 (de) * | 2001-11-02 | 2003-05-22 | Paion Gmbh | DSPA zur Behandlung von Schlaganfall |
| FI20020197A0 (fi) * | 2002-02-01 | 2002-02-01 | Orion Corp | Yhdistelmä akuutin myokardiilisen infarktin hoitoon |
| US7084118B2 (en) * | 2002-02-22 | 2006-08-01 | Genentech, Inc. | Combination treatment with t-PA variant and low molecular weight heparin |
| EP1521603B1 (en) * | 2002-07-12 | 2011-01-19 | Cook Incorporated | Coated medical device |
| DE10244847A1 (de) | 2002-09-20 | 2004-04-01 | Ulrich Prof. Dr. Speck | Medizinische Vorrichtung zur Arzneimittelabgabe |
| US7699966B2 (en) * | 2004-05-17 | 2010-04-20 | Medtronic, Inc. | Point of care heparin determination system |
| US20060222640A1 (en) * | 2005-03-29 | 2006-10-05 | Boehringer Ingelheim International Gmbh | New pharmaceutical compositions for treatment of thrombosis |
| TWI482628B (zh) * | 2007-10-18 | 2015-05-01 | Lundbeck & Co As H | 新穎之血栓溶解病患次群 |
| EP2231702A1 (en) * | 2007-12-21 | 2010-09-29 | Ifxa A/s | Protease inhibitor |
| BR112017008749A2 (pt) | 2014-11-03 | 2017-12-19 | Thrombolytic Science Llc | métodos e composições para trombólise segura e eficaz |
| KR20160094345A (ko) * | 2015-01-30 | 2016-08-09 | 고려대학교 산학협력단 | 베르베논 유도체를 포함하는 재관류 시술의 부작용을 감소 또는 예방하기 위한 조성물 |
| RU2622006C2 (ru) * | 2015-06-15 | 2017-06-08 | Федеральное государственное автономное образовательное учреждение высшего профессионального образования "Казанский (Приволжский) федеральный университет" (ФГАОУВПО КФУ) | Применение рекомбинантного штамма bacillus subtilis eo-11 вкпм в-11978 в качестве продуцента субтилизиноподобной протеиназы, вещества с тромболитическими и антикоагулянтными свойствами |
| CN105396127A (zh) * | 2015-11-13 | 2016-03-16 | 中国人民解放军第四军医大学 | 一种用于急性心肌梗死的冠状动脉溶栓剂 |
| WO2018232305A1 (en) * | 2017-06-16 | 2018-12-20 | Thrombolytic Science, Llc | Methods and compositions for thrombolysis |
| CN114292765B (zh) * | 2021-09-24 | 2023-04-07 | 江西康之康中药科技有限公司 | 枯草芽孢杆菌纳豆亚种r3及其在发酵水蛭低温干燥品中的应用 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8508717D0 (en) * | 1985-04-03 | 1985-05-09 | Beecham Group Plc | Composition |
| DK43387A (da) † | 1986-01-29 | 1987-07-30 | Beecham Group Plc | Fibrinolytisk enzym |
| US5084274A (en) * | 1987-11-17 | 1992-01-28 | Scripps Clinic And Research Foundation | Inhibition of arterial thrombotic occlusion or thromboembolism |
| DE3804600A1 (de) * | 1988-02-13 | 1989-08-24 | Basf Ag | Mischung aus einer thrombolytisch wirkenden und einer antithrombotischen substanz |
| GB8822147D0 (en) * | 1988-09-21 | 1988-10-26 | Ciba Geigy Ag | Pharmaceutically active combination |
| US5204323B1 (en) * | 1988-10-06 | 1995-07-18 | Ciba Geigy Corp | Hirudin antidotal compositions and methods |
| GB8826428D0 (en) * | 1988-11-11 | 1988-12-14 | Biopharm Ltd | Antithrombin |
| US4980165A (en) * | 1989-01-27 | 1990-12-25 | Genetics Institute, Inc. | Pharmaceutical formulations of plasminogen activator proteins |
| DE3903581A1 (de) * | 1989-02-07 | 1990-08-16 | Boehringer Mannheim Gmbh | Gewebs-plasminogenaktivator-derivat |
| CA2064231A1 (en) * | 1989-07-20 | 1991-01-21 | John M. Maraganore | Combinations and methods for treating or preventing thrombotic diseases |
| US5240913A (en) * | 1989-08-18 | 1993-08-31 | Biogen, Inc. | Inhibitors of thrombin |
| US5196404B1 (en) * | 1989-08-18 | 1996-09-10 | Biogen Inc | Inhibitors of thrombin |
| US5049132A (en) * | 1990-01-08 | 1991-09-17 | Cordis Corporation | Balloon catheter for delivering therapeutic agents |
| US5189019A (en) * | 1990-04-23 | 1993-02-23 | Merck & Co., Inc. | Antistasin derived anticoagulant protein |
| US5242810A (en) * | 1990-12-07 | 1993-09-07 | Biogen, Inc. | Bifunctional inhibitors of thrombin and platelet activation |
| US5242688A (en) * | 1990-12-24 | 1993-09-07 | Eli Lilly And Company | Method of treating thromboembolic disorders by administration of diglycosylated t-pa variants |
| WO1992018157A1 (de) † | 1991-04-16 | 1992-10-29 | Boehringer Mannheim Gmbh | Pharmazeutische verpackungseinheit enthaltend plasminogenaktivatoren zur mehrfachbolusgabe |
| DE10199044I2 (de) † | 1992-06-03 | 2006-02-09 | Genentech Inc | Varianten des Gewebeplasminogenaktivators mit verbesserter Therapeutischer wirkung |
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