Reduction of Tunneled Dialysis Catheter Dysfunction Via Long Term Nitric Oxide Re

描述(申请人提供)：我们提出了一种新颖且价格具有竞争力的隧道透析导管(TDC)，该导管由专利聚合物配方制成，可通过长期释放一氧化氮(NO)有效地减少TDC功能障碍，特别是在动静脉瘘成熟期的血液透析和TDC依赖患者。对用于制备现有商业TDC的聚合物材料进行的初步研究表明，建议的装置将具有：(A)杀菌作用(B)抗血小板/抗血栓形成和(C)抗平滑肌细胞增殖活性，以靶向TDC功能障碍的所有当前效应臂：感染、血栓形成/纤维蛋白鞘形成和中心静脉狭窄。此外，预计该设备的保质期可以远远超过史无前例的37℃下的2-4个月(已经证明)，同时在体温(37℃)下保持3-4周以上的抗TDC功能障碍。目前，超过80%(88,200)的血液透析(HD)患者开始使用TDC进行HD，TDC的总体患病率超过20%。在2010年，有83,000名病人因与贸发局有关的菌血症或败血症而入院，而每一宗与中心线相关的血液医院感染，均会增加约47,000元的护理费用及增加14.6天的住院时间。目前的肝素、银包被或抗生素包被的tDCs要么价格昂贵、无效，要么在长期使用后出现机械故障。拟议中的装置将在美国进行加工和组装，成本几乎是目前肝素或银涂层tDC的一半，并可能对开始使用TDC的HD患者死亡率增加5倍产生重大临床影响，而不是房室瘘或移植物。为了继续开发我们的产品，我们建议：(1)体外检测用于有效防止生物被膜(金黄色葡萄球菌和表皮葡萄球菌)的11.5Fr卡宾/聚氨酯原型双腔导管的NO释放谱和生物活性；(2)优化聚合物配方，以便在适当灭菌的同时保持抗菌和抗血栓性能，以便在保质期3个月内保持抗菌和抗血栓性能；(3)通过猪模型获得体内“原则证明”的了解，以评估该产品在感染、血栓形成和降低CVS方面的临床有效性。在本地NO输送和释放方面处于世界领先地位的著名学术实验室(Meyerhoff实验室)和具有大型动物专业知识的创新、多产的转化研究团队(Roy-Chaudhury博士的透析血管通路研究组)之间的这种合作方式将有效地将技术、业务和临床需求结合在一起，为贸发局问题开发创新解决方案。这项技术已经由Biocrede Inc.通过密歇根大学的技术转移办公室选择。

DESCRIPTION (provided by applicant): We propose a novel and price competitive Tunneled Dialysis Catheter (TDC) made from a proprietary polymeric formulation to effectively reduce TDC dysfunction via long-term nitric oxide (NO) release, particularly during the period of AVF maturation in incident hemodialysis and TDC dependent patients. Preliminary studies with polymer materials used to prepare existing commercial TDCs, suggests that the proposed device will possess: (a) microbicidal (b) anti-platelet/anti-thrombosis and (c) anti-smooth-muscle cell-proliferation activities to target all the current effector arms of TDC dysfunction: infection thrombosis/fibrin sheath formation, and central venous stenosis. In addition, it is anticipated tha the device's shelf life can be extended well beyond the unprecedented 2-4 months at 37?C (already demonstrated) while maintaining anti-TDC dysfunction properties for over 3-4 weeks at body temperatures (37?C). Currently, over 80% (88,200) of incident hemodialysis (HD) patients start HD using a TDC, and the overall prevalence rate of TDCs is over 20%. In 2010, 83,000 patients were admitted to hospitals for TDC related bacteremia or sepsis, and each central line-associated bloodstream nosocomial infection adds ca. $47,000 to the cost of care and a 14.6 d increase in length of stay. Current heparin, silver impregnated, or antibiotic coated TDCs are either expensive, non-effective, or suffer from mechanical breakdown after prolonged use. The proposed device will be processed and assembled in the US at almost half the cost of current heparin or silver coated TDCs, and potentially have a significant clinical impact on the 5 fold increase in mortality in patients starting HD with a TDC as opposed to an AV fistula or graft. To continue the development of our product, we propose: (1) to examine in vitro NO release profiles and biological activity of dual lumen 11.5Fr carbosil/polyurethane prototype dual lumen catheters for effective biofilm prevention (Staphylococcus aureus, and Staphylococcus epidermidis); (2) to optimize the polymeric formulation to allow for 3 months of shelf life after proper sterilization while maintaining antimicrobial and antithrombotic properties; and (3) to obtain an in vivo "proof-of-principle" understanding to gauge the product's clinical effectiveness in terms of infection, thrombosis and CVS reduction using a pig model. This combined collaborative approach between a respected academic laboratory which is a world leader in the local delivery and release of NO (Meyerhoff laboratory) and an innovative and productive translational research group with large animal expertise (Dr. Roy-Chaudhury's Dialysis Vascular Access Research Group) will effectively bring the technology, business, and clinical needs together, to develop an innovative solution to the TDC problem. This technology has been optioned by Biocrede Inc. via the Office of Tech Transfer at the University of Michigan.