Radio-opaque Resorbable Stents

描述（由申请人提供）： 心脏上的冠状动脉经常积聚斑块，使动脉通路变窄，从而抑制血液流动。冠状动脉疾病占美国死亡率最高（1/5死亡）。这种疾病通常用支架治疗，支架是一种可植入的金属网状管，可以扩大血管使血液流动。在冠状动脉疾病的治疗中，一个显著的未满足的需求是缺乏X射线可见的可吸收支架，其可以用作药物递送载体以防止再狭窄以及临时机械支撑以保持血管开放直到愈合稳定。此时支架吸收将使患者从自然血管重建中获益最大。可吸收支架还将消除与金属支架相关的患者再治疗并发症。金属支架设计需要在扩张时能够发生显着形状改变的材料，以扩大血管。REVA已经消除了这个问题，他们的专利“滑动和锁定”支架设计。REVA已经表明，这种设计的支架即使由共同研究者Kohn教授发明的可吸收聚（DTE碳酸酯）制成，也可以在体内动脉模型中发挥作用。该1期资助的目的是：（i）证明使用新型聚碳酸酯和REVA专有的滑动锁定支架设计制造X射线可见（“碘化”）可吸收支架的可行性，以及（ii）证明这些支架符合X射线可视化、机械支架功能和血管生物相容性的规定实验室和体内性能标准。提出了三个具体目标：（目的1）基于现有的可吸收聚合物聚乙烯的化学改性，合成一系列X射线可见聚合物（AIM 2）测试碘化聚合物和制造支架原型，以满足径向强度、展开和X射线可见性的必要临床标准;和（AIM 3）碘化聚合物的生物学测试，以评估血细胞和蛋白质的相互作用、毒性，以及最重要的是，在预测动物模型中对不透射线的可再吸收支架原型进行体内评价。在第一阶段成功完成后，这项工作将在第二阶段与REVA的单独药物输送计划汇合，并向商业产品发展。可吸收支架代表了一个主要的商业机会。

DESCRIPTION (provided by applicant): Coronary arteries on the heart often buildup plaque that narrows the pathway of the artery which inhibits blood flow. Coronary artery disease accounts for the greatest mortality in the USA (1 in 5 deaths). This disease is frequently treated with stents, implantable metal mesh tubes that enlarge the vessel for blood to flow. A significant unmet need in the treatment of coronary artery disease is the lack of an X-ray visible, resorbable stent that can serve as a drug-delivery vehicle for the prevention of re-narrowing as well as a temporary mechanical support to keep the vessel open until healing stabilizes. Stent resorption at this point would allow the maximum patient benefit of natural vascular reconstruction. A resorbable stent would also eliminate patient re-treatment complications associated with metal stents. Metal stent designs require materials that can undergo significant shape alterations when expanded in order to enlarge the vessel. REVA has eliminated this problem with their patented "slide and lock" stent design. REVA has shown that stents in this design can function in an in vivo artery model even when fabricated from resorbable poly(DTE carbonate), invented by the co-investigator Professor Kohn. The objectives of this Phase 1 grant are to: (i) demonstrate the feasibility of fabricating X-ray visible ("iodinated"), resorbable stents using new polycarbonates and REVA's proprietary slide-and-lock stent design, and (ii) show that these stents meet defined bench and in vivo performance criteria for x-ray visualization, mechanical stent function and vascular biocompatibility. Three specific aims are proposed: (AIM 1) synthesis of a family of X-ray visible polymers based on the chemical modification of an existing, resorbable polymer, poly(DTE carbonate) through scaleable iodination and/or polymerization methods; (AIM 2) testing of iodinated polymers and fabrication of stent prototypes to meet necessary clinical criteria for radial strength, deployment and X-ray visibility; and, (AIM 3) biological testing of iodinated polymers to assess blood cell and protein interactions, toxicity and, most importantly, an in vivo evaluation of radio-opaque resorbable stent prototypes in a predictive animal model. Upon successful completion of Phase 1, this work will converge in Phase II with REVA's separate drug delivery program and advance toward commercial products. A resorbable stent represents a major commercial opportunity.