Nonthrombogenic, Antiseptic Nitric Oxide Releasing Catheters

描述（由申请人提供）：本项目将重点关注无血栓形成、抗菌一氧化氮（NO）释放导管的制备和评价。该SBIR的第1阶段将：1）开发独特的NO分泌导管（14-20号）; 2）在家兔和绵羊模型中进行测试，以评估血栓形成和细菌粘附;第2阶段将扩大生产规模，并评估毒性，为人体试验做准备。这项研究的基本原理是模拟内皮的功能。正常内皮释放的低水平NO抑制血小板粘附和活化，从而防止血栓形成。此外，已经表明低剂量的NO表现出显著的杀菌活性。因此，分泌NO的导管的制备将解决危重患者护理中的两个长期存在的问题。在过去的10年里，密歇根大学（U of M）的实验室已经开发出了采用新型二醇二氮烯鎓型NO供体的基本NO释放聚合物技术。该技术的成功应用已经包括开发用于体外循环装置的抗血小板涂层和制备具有更好分析性能的生物相容性更好的植入式化学传感器。通过与一直致力于这项技术的密歇根大学研究团队的合作，MC 3现在打算开发和测试以受控速率释放NO的导管，以防止血栓形成和感染，这是与导管使用相关的两个主要问题。 公共卫生相关性：凝血和感染是血管内（IV）导管的主要问题。正常的血管分泌一种叫做一氧化氮的化学物质，可以防止这些问题。这项研究将开发14-20号导管，分泌一氧化氮，降低凝血和感染的风险。

DESCRIPTION (provided by applicant): This project will focus on the preparation and evaluation of nonthrombogenic, antibacterial nitric oxide (NO) releasing catheters. Phase 1 of this SBIR will: 1) develop unique NO secreting catheters (14-20 gauge); 2) test them in rabbit and sheep models to evaluate thrombogenicity and bacterial adherence; Phase 2 will scale up manufacturing and evaluate toxicity in preparation for human trials. The rationale for this research is to mimic the function of the endothelium. Low levels of NO released by the normal endothelium inhibit platelet adhesion and activation, thus preventing thrombus formation. Further, it has been shown that NO at low doses exhibits significant bactericidal activity. Hence, the preparation of catheters that secrete NO will solve two longstanding problems in the care of critically ill patients. The basic NO release polymer technology that employs novel diazeniumdiolate type NO donors has been developed in laboratories at the University of Michigan (U of M) over the past 10 years. Successful applications of this technology have already included the development of anti-platelet coatings for extracorporeal circulation devices and the preparation more biocompatible implantable chemical sensors with improved analytical performance. Via collaboration with the research team at the U of M that has been working on this technology, MC3 now intends to develop and test catheters that release NO at controlled rates in order to prevent thrombosis and infection, two major problems associated with the use of catheters. PUBLIC HEALTH RELEVANCE: Clotting and infection is a major problem in intravascular (IV) catheters. Normal blood vessels secrete a chemical called nitric oxide which prevents these problems. This research will develop 14-20 gauge catheters which secrete nitric oxide, decreasing the risk of clotting and infection.