COVALENT SURFACE COATING WITH ANTITHROMBOTIC AGENTS

具有抗血栓剂的共价表面涂层

• 批准号: 3508717
• 负责人: DAVID L CLAPPER
• 金额: $ 14.81万
• 依托单位: SURMODICS, INC.
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-06-01 至 1993-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3508717
• 关键词: anticoagulants; antithrombogenic surface; binding proteins; biological models; biomaterial development /preparation; biomaterial interface interaction; blood chemistry; covalent bond; crosslink; dogs; heparin; hirudins; immune complex; implant; model design /development; plasminogen activator; prostaglandin analogs; streptokinase; thrombin; thrombosis; urokinase

The proposed Phase II research will develop coatings for implant devices that will greatly reduce thrombus formation upon contact with blood. The Phase I research developed procedures to immobilize hirudin onto polymers with: 1) a high retention of specific activity (one thrombin bound per two immobilized hirudin) and 2) a high loading density (sufficient hirudin was immobilized to bind and inactivate a monolayer of thrombin). Phase II will use proprietary BSI photochemistry to immobilize four classes of antithrombotic agents (hirudin, heparin, fibrinolytic enzymes, and prostaglandins) onto two implant device polymers (polyurethane and silicone rubber) and evaluate each in "side-by-side" blood compatibility assays. These agents immobilized individually and in combination will be evaluated for: 1) immobilized loading level, 2) ligand binding, 3) protease activity, 4) platelet binding and activation, and 5) thrombus formation. The assay media/systems will progress from: 1) buffers and plasma in static assays, to 2) whole blood in an in vitro recirculating loop, to 3) animal implants. The results are expected to demonstrate which agents or combinations of agents are most effective at inhibiting thrombus formation. Near the end of the project, additional devices of interest to potential Phase III partners will be coated with the most promising antithrombotic agents.

拟议的II期研究将开发植入设备的涂料 与血液接触后，这将大大减少血栓形成。这 I期研究开发了将Hirudin固定在 聚合物具有：1）高度保留特定活性（一个凝血酶 每两个固定的Hirudin绑定）和2）高负载密度 （将足够的海鲁丁固定以结合并灭活单层 凝血酶）。 第二阶段将使用专有BSI光化学 固定四类的抗血栓形成剂（Hirudin，肝素， 纤维蛋白水解酶和前列腺素） 聚合物（聚氨酯和硅橡胶），并评估 “并排”的血液兼容性测定。 这些固定和组合固定的试剂将是 评估：1）固定加载水平，2）配体结合，3） 蛋白酶活性，4）血小板结合和激活，5）血栓 形成。 测定媒体/系统将从：1）缓冲区和 静态测定中的等离子体，至2）体外再循环中的全血 循环，3）动物植入物。 结果预计将证明 哪些代理或代理的组合最有效地抑制 血栓形成。 在项目结束时，其他设备 潜在的第三阶段合作伙伴的兴趣将被覆盖最多 有希望的抗血栓形成剂。