公开(公告)号：US06297023B1

公开(公告)日：2001-10-02

申请号：US08300447

申请日：1994-09-02

申请人： Jan McDonagh ,  Myoung H. Lee ,  Marcin J. Mankowski

发明人： Jan McDonagh ,  Myoung H. Lee ,  Marcin J. Mankowski

IPC分类号： C12Q156

CPC分类号： C12Q1/56 ,  G01N2333/8132 ,  G01N2333/968 ,  G01N2333/9726

摘要： The invention is based upon the discovery that PAI-1 activity of a sample can be measured with sensitivity and correlation to in vivo activity without the use of standard curves. The assay determines the PAI-1 activity of a sample upon utilizing the second order rate equation for the reaction of PAI-1 and t-PA, as measured by their activities, in that sample.

摘要翻译： 本发明基于以下发现：样品的PAI-1活性可以灵敏度测量并且与体内活性相关而不使用标准曲线。 该测定法通过利用PAI-1和t-PA的反应的二阶速率方程式（通过其活性测量）来确定样品的PAI-1活性。

公开(公告)号：US5637299A

公开(公告)日：1997-06-10

申请号：US461172

申请日：1995-06-05

申请人： Jan McDonagh ,  Myoung H. Lee

发明人： Jan McDonagh ,  Myoung H. Lee

IPC分类号： A61K38/16 ,  A61K38/48 ,  A61K38/49 ,  C12N9/64 ,  C12N9/68

CPC分类号： A61K38/484 ,  A61K38/166 ,  A61K38/49

摘要： This invention provides an improved method for enhancing the activity of thrombolytic agents, including t-PA, scu-PA, tcu-PA, streptokinase, acylated plasminogen-streptokinase activator complex (APSAC), mixtures of these, and other activators of plasminogen. The enhancement method comprises supplementation of plasma plasminogen levels with deglycosylated forms of glu- and lys-plasminogen. Deglycosylated plasminogen refers herein to glu- or lys-plasminogen 2 having a single oligosaccharide chain at Thr.sub.345, plasminogens having a single oligosaccharide chain at Asn.sub.288, and unglycosylated forms of plasminogen. The work described herein shows that a less glycosylated form of plasminogen (glu-plasminogen 2) has a higher affinity for fibrin clots than a more glycosylated plasminogen (glu-plasminogen 1). Based on this work, it is believed that glycosylation of plasminogen inhibits binding of plasminogen to fibrin clots, perhaps due to steric hindrance, and further, that deglycosylated forms of plasminogen may be more effective enhancers of scu-PA in thrombolytic therapy than fully glycosylated forms of plasminogen. Improved enhancement of the activity of thrombolytic agents allows the use of lower therapeutic doses and thus, is expected to relieve some of the bleeding and other side effects of thrombolytic therapy.

摘要翻译： 本发明提供了一种增强溶栓剂（包括t-PA，scu-PA，tcu-PA，链激酶，酰化纤溶酶原 - 链激酶激活剂复合物（APSAC））及其混合物和纤溶酶原激活剂的活性的改进方法。 增强方法包括用去糖基化形式的葡萄糖和溶血纤溶酶原补充血浆纤溶酶原水平。 糖基化纤维蛋白溶酶原是指在Thr345具有单个寡糖链的葡糖或溶酶体纤溶酶原2，在Asn288具有单个寡糖链的纤溶酶原和未糖基化形式的纤溶酶原。 本文所述的工作表明，较多糖基化的纤溶酶原（glu-plasminogen 1），较少的糖基化形式的纤溶酶原（glu-plasminogen 2）对纤维蛋白凝块具有更高的亲和力。 基于这项工作，据信纤维蛋白溶酶原的糖基化抑制纤维蛋白溶酶原与纤维蛋白凝块的结合，这可能是由于空间位阻引起的，此外，溶纤溶酶原的去糖基化形式可能是完全糖基化形式的溶栓治疗中scu-PA的更有效的增强剂 的纤溶酶原。 改善溶栓剂活性的增强使得可以使用较低的治疗剂量，因此预期可以缓解溶栓治疗的一些出血和其它副作用。