公开(公告)号：EP0735050A3

公开(公告)日：1997-01-22

申请号：EP96302311.4

申请日：1996-04-01

申请人： HAMILTON CIVIC HOSPITALS RESEARCH DEVELOPMENT, INC.

发明人： Weitz, Jeffrey I. ,  Hirsh, Jack ,  Young, Edward

IPC分类号： C08B37/10 ,  A61K31/725

CPC分类号： C08B37/0078

摘要： The present invention provides compositions for inactivating thrombin bound to fibrin within a thrombus or clot, whereby the ability of clot-bound thrombin to catalytically promote further clot accretion is substantially diminished or eliminated. The compositions of the present invention are particularly useful for preventing thrombosis in the circuit of cardiac bypass apparatus and in patients undergoing renal dialysis, and for treating patients suffering from or at risk of suffering from thrombus-related cardiovascular conditions, such as unstable angina, acute myocardial infarction (heart attack), cerebrovascular accidents (stroke), pulmonary embolism, deep vein thrombosis, arterial thrombosis, etc . The compositions comprise agents which activate heparin cofactor II mediated inhibition of thrombin and having minimal affinity for antitrhombin III. Preferred agents are low molecular weight heparin preparations (MW of 3,000-8,000) prepared by depolymerising heparin using nitrous acid, oxidising the resultant product with periodate and reducing it with borohydride. The product has its non-sulphated uronic acid residues in open ring form and it substantially free of aldehyde groups.

公开(公告)号：EP0735050A2

公开(公告)日：1996-10-02

申请号：EP96302311.4

申请日：1996-04-01

申请人： HAMILTON CIVIC HOSPITALS RESEARCH DEVELOPMENT, INC.

发明人： Weitz, Jeffrey I. ,  Hirsh, Jack ,  Young, Edward

IPC分类号： C08B37/10 ,  A61K31/725

CPC分类号： C08B37/0078

摘要： The present invention provides compositions for inactivating thrombin bound to fibrin within a thrombus or clot, whereby the ability of clot-bound thrombin to catalytically promote further clot accretion is substantially diminished or eliminated. The compositions of the present invention are particularly useful for preventing thrombosis in the circuit of cardiac bypass apparatus and in patients undergoing renal dialysis, and for treating patients suffering from or at risk of suffering from thrombus-related cardiovascular conditions, such as unstable angina, acute myocardial infarction (heart attack), cerebrovascular accidents (stroke), pulmonary embolism, deep vein thrombosis, arterial thrombosis, etc .
The compositions comprise agents which activate heparin cofactor II mediated inhibition of thrombin and having minimal affinity for antitrhombin III. Preferred agents are low molecular weight heparin preparations (MW of 3,000-8,000) prepared by depolymerising heparin using nitrous acid, oxidising the resultant product with periodate and reducing it with borohydride. The product has its non-sulphated uronic acid residues in open ring form and it substantially free of aldehyde groups.

摘要翻译： 本发明提供用于灭活血栓或凝块内与纤维蛋白结合的凝血酶的组合物，从而基本上减少或消除凝块结合的凝血酶催化促进进一步凝块增生的能力。 本发明的组合物特别可用于预防心脏旁路装置和经历肾透析的患者的血液循环中的血栓形成，并且用于治疗患有血栓相关心血管疾病或患有血栓相关心血管病症的患者，例如不稳定型心绞痛，急性 心肌梗塞（心脏病发作），脑血管意外（脑卒中），肺栓塞，深静脉血栓形成，动脉血栓形成等。该组合物包含激活肝素辅因子II介导的凝血酶抑制并对抗菱形素III具有最小亲和力的试剂。 优选的药剂是通过使用亚硝酸解聚肝素制备的低分子量肝素制剂（3,000-8,000的MW），用高碘酸盐氧化所得产物并用硼氢化钠还原。 该产品具有开环形式的非硫酸化的糖醛酸残基且基本上不含醛基。

公开(公告)号：EP0735050B1

公开(公告)日：2002-09-25

申请号：EP96302311.4

申请日：1996-04-01

申请人： HAMILTON CIVIC HOSPITALS RESEARCH DEVELOPMENT, INC.

发明人： Weitz, Jeffrey I. ,  Hirsh, Jack ,  Young, Edward

IPC分类号： C08B37/10 ,  A61K31/727

CPC分类号： C08B37/0078