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Evaluation of anticoagulant behavior of thrombin-inhibiting polymer with fibrinolytic factor-binding sites and application for biomaterials

具有纤溶因子结合位点的凝血酶抑制聚合物的抗凝行为评价及其在生物材料中的应用

基本信息

批准号：
14580840
负责人：
SHIRAISHI Kohei
金额：
$ 0.64万
依托单位：
Kinki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

Novel polymers modified with zwitterionic L-serine or L-lysine in the side chain, poly-(O-methacryloyl-L-serine)[poly(SerMA)], poly(α-methacrylamide-L-lysine)[poly(α-LysMA)], and poly(ε-methacrylamide-L-lysine) [poly(ε-LysMA)] were prepared as a surface modifier for blood compatible biomaterials such as catheter, dialyzer and so forth, Tn this research, the evaluation of their blood compatibility has been investigated from the point of view of effects of zwitterionic polymers on the denaturation of serum proteins or platelets, on the inhibition of thrombin which plays a central role in the bloodclotting process, on the selective binding of plasminogen which is the primary zymogen in the fibrinolytic pathway, and on the enhancement of fibrinolytic activity of plasmin or plasminogen/tissue type plasminogen activator(t-PA). Poly(SerMA), poly(α-LysMA), and poly(ε-LysMA) showed the low interaction with albumin, γ-globulin, fibrinogen to prevent protein denaturation. Poly(α-LysMA) uncompetitively inhibits thrombin activity. The fibrinolytic activity by plasmin and plasminogen/t-PA, was enhanced in the presence of poly(α-LysMA) showing specific binding to plasminogen, no enhancement of their fibrinolytic activity was observed in the case of poly(SerMA) or poly(ε-LysMA). As a result ofmeasurements, it is considered that zwitterionic polymers having amino acid moiety, especially poly(α-LysMA) as a blood compatible material are applicable for use in the biomedical devices.

在侧链中用两性离子L-丝氨酸或L-赖氨酸修饰的新型聚合物，聚-（O-甲基丙烯酰-L-丝氨酸）[聚（SerMA）]，聚（α-甲基丙烯酰胺-L-赖氨酸）[聚（α-LysMA）]和聚制备了（ε-甲基丙烯酰胺-L-赖氨酸）[poly（ε-LysMA）]作为血液相容性生物材料的表面改性剂，从两性离子聚合物对血清蛋白或血小板变性，对在凝血过程中起中心作用的凝血酶的抑制，对纤溶酶原（纤溶途径中的主要酶原）的选择性结合，以及对纤溶酶或纤溶酶原/组织型纤溶酶原激活物（t-PA）的纤溶活性的增强。Poly（SerMA）、poly（α-LysMA）和poly（ε-LysMA）与白蛋白、γ-球蛋白、纤维蛋白原的相互作用较弱，可防止蛋白变性。聚（α-LysMA）非竞争性抑制凝血酶活性。纤溶酶和纤溶酶原/t-PA的纤溶活性在与纤溶酶原特异性结合的poly（α-LysMA）存在时增强，而poly（SerMA）和poly（ε-LysMA）对纤溶酶和纤溶酶原/t-PA的纤溶活性无增强作用。作为测量的结果，认为具有氨基酸部分的两性离子聚合物，特别是聚（α-LysMA）作为血液相容性材料适用于在生物医学装置中使用。