Radio-opaque Resorbable Stents

不透射线的可吸收支架

• 批准号: 6739292
• 负责人: JOAN K ZELTINGER
• 金额: $ 15万
• 依托单位: REVA MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6739292
• 关键词: DNA damage; X ray; biodegradable product; bioimaging /biomedical imaging; biomaterial compatibility; blood cells; blood proteins; blood vessel prosthesis; chemical structure; chemical synthesis; cytotoxicity; high performance liquid chromatography; immunofluorescence technique; infrared spectrometry; iodination; nuclear magnetic resonance spectroscopy; polymerization; polymers; swine; technology /technique development; thrombosis

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.

描述（由申请人提供）： 心脏上的冠状动脉经常会积聚斑块，从而缩小了抑制血液流动的动脉途径。冠状动脉疾病是美国最大的死亡率（五分之一的死亡）。该疾病经常用支架，可植入的金属网管处理，以扩大血管以流动血液。治疗冠状动脉疾病的重要需求是缺乏可见的，可吸收的支架，该支架可以用作预防重新进行的药物交付的车辆以及临时机械支撑，无法保持容器打开，直到恢复稳定。在这一点上，支架吸收将允许天然血管重建的最大益处。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。金属支架设计需要材料，可以在扩展时会进行显着的形状改变，以扩大容器。 Reva通过获得专利的“幻灯片和锁”支架设计消除了这个问题。 Reva表明，即使由共同投资者Kohn发明的可吸收性聚（DTE碳酸盐）制造，该设计中的支架也可以在体内动脉模型中起作用。该第1阶段赠款的目标是：（i）证明可见X射线的可行性（“碘化”），使用新的聚碳酸酯和Reva的专有滑动支架的可吸收支架，（ii）表明，这些支架符合定义的基准和X射线式的X射线型X射线式X射线效率，机械化功能，机械化功能，机械化功能和脉络化功能。提出了三个具体目的：（目标1）基于现有的可吸收聚合物，聚（DTE碳酸盐）通过可缩放的碘化和/或聚合方法的化学修饰，合成了X射线可见聚合物家族； （目标2）测试碘化聚合物和支架原型的制造，以满足径向强度，部署和X射线可见性的必要临床标准； （AIM 3）对碘化聚合物的生物学测试，以评估血细胞和蛋白质相互作用，毒性，最重要的是，在预测动物模型中对放射性可分离的可分离支架原型进行体内评估。成功完成第一阶段后，这项工作将与Reva独立的药物输送计划相聚并融入商业产品。可吸收支架代表了主要的商业机会。