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积聚斑块，使动脉通路变窄，从而抑制血流。冠状动脉疾病是美国死亡率最高的疾病（五分之一的死亡）。这种疾病通常通过支架、植入式金属网管来治疗，支架可以扩大血管以促进血液流动。冠状动脉疾病治疗中一个未满足的重大需求是缺乏 X 射线可见的可吸收支架，该支架可以作为预防再狭窄的药物输送载体以及保持血管的临时机械支撑打开直至愈合稳定。此时的支架吸收将使患者从自然血管重建中获益最大。可吸收支架还可以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在扩张时能够发生显着的形状改变以扩大血管。 REVA 通过其获得专利的“滑动和锁定”支架设计消除了这个问题。 REVA 表明，这种设计中的支架即使由联合研究员 Kohn 教授发明的可吸收聚（DTE 碳酸盐）制成，也可以在体内动脉模型中发挥作用。第一阶段资助的目标是：(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既定工作台和体内性能标准。提出了三个具体目标：（AIM 1）基于现有可再吸收聚合物聚（DTE碳酸酯）的化学改性，通过可扩展的碘化和/或聚合方法合成一系列X射线可见聚合物； (AIM 2) 测试碘化聚合物并制造支架原型，以满足径向强度、展开和 X 射线可见性的必要临床标准； (AIM 3) 碘化聚合物的生物测试，以评估血细胞和蛋白质的相互作用、毒性，最重要的是，在预测动物模型中对不透射线的可吸收支架原型进行体内评估。第一阶段成功完成后，这项工作将在第二阶段与 REVA 单独的药物输送项目融合，并向商业产品迈进。可吸收支架代表着一个重大的商业机会。