脂肪族聚碳酸酯涂层支架的制备和性能研究

发布时间：2019-05-20 15:25

【摘要】：经皮冠状动脉介入治疗(PCI)在三十余年时间里,历经了单纯的球囊扩张、金属裸支架(BMS)到药物洗脱支架(DES)三次飞跃。DES可以将一定负荷剂量的药物直接带到病变血管部位,使再狭窄率降低到10%以下。DES是在金属支架表面覆有一层或两层稳定聚合物涂层,以完成带药和释药的目的,聚合物和支架一样永久留存在血管中。DES的永久聚合物涂层可能是导致血管延迟愈合和(极)晚期支架内血栓的重要原因,因此发展对血管壁低毒的新型支架是当前研究热点。可降解聚合物涂层DES是研究趋势之一。可降解聚合物作为DES的药物载体,在完成其任务后,逐渐降解为小分子,避免了永久聚合物对血管壁的长期刺激。本文实验选择表面溶蚀降解方式的脂肪族聚碳酸酯(APC)作为支架的可降解聚合物涂层材料,将其和雷帕霉素的溶液直接涂覆到316L不锈钢支架上制备DES。论文的主要内容和结果包括： 1.研究了316L不锈钢支架表面处理和DES喷涂工艺,确定了合适的工艺参数；然后讨论了手动浸涂和自动喷涂两种涂层方法对涂层性能的影响,并从理论上分析了产生不同影响的原因。 2.研究了脂肪族聚碳酸酯在PBS模拟体液中的质量丢失率和吸水率,根据实验结果优选聚碳酸亚乙酯(PEC)和聚碳酸亚丙亚乙酯(PPEC)作为支架涂层材料；然后从细胞毒性试验、溶血试验和部分凝血激活酶时间试验初步证明,PEC和PPEC具有优良的生物相容性。 3.用戊二酸锌催化合成了PPEC,并深入研究了PEC和PPEC作为冠脉支架涂层材料的可行性,实验结果证明,脂肪族聚碳酸酯载药涂层支架具有广阔的应用前景。 4.详细考察了屏蔽层、药物梯度、载体种类、载体和药物的比例以及释放介质对DES药物释放的影响,明确了涂层药物释放模式及其控制因素,优化了可降解药物载体和DES的设计。
[Abstract]:Percutaneous coronary intervention for (PCI) has undergone simple balloon dilatation for more than 30 years. Three leaps from bare metal stent (BMS) to drug-eluting stent (DES). Des can bring a certain dose of drugs directly to the lesion vessel. Reduce the restenosis rate to less than 10%. Des is coated with one or two layers of stable polymer coating on the surface of the metal stent for the purpose of drug delivery and release. Polymers remain in blood vessels as permanently as stents. The permanent polymer coating of des may be an important cause of delayed healing of blood vessels and thrombus in (polar) late stents, so the development of novel stents with low toxicity to vascular wall is a hot research topic at present. Degradable polymer coating DES is one of the research trends. As the drug carrier of DES, degradable polymer gradually degrades to small molecule after completing its task, which avoids the long-term stimulation of permanent polymer to vascular wall. In this paper, aliphatic polycarbonate (APC) with surface dissolution and degradation was selected as the degradable polymer coating material of the scaffold, and the DES. was prepared by coating it directly with rapamicin solution on 316L stainless steel scaffold. The main contents and results of the paper include: 1. The surface treatment and DES spraying process of 316L stainless steel support were studied, and the suitable process parameters were determined. Then the effects of manual dipping and automatic spraying on the properties of the coating are discussed, and the reasons for the different effects are analyzed theoretically. 2. The mass loss rate and water absorption rate of aliphatic polycarbonate in PBS simulated body fluid were studied. according to the experimental results, polyethyl carbonate (PEC) and polypropylidene carbonate (PPEC) were selected as scaffolding coating materials. Then the cytotoxicity test, hemolysis test and partial coagulation activating enzyme time test showed that PEC and PPEC had excellent biocompatibility. 3. PPEC, was synthesized catalyzed by zinc glutarate and the feasibility of PEC and PPEC as coronary stent coating materials was deeply studied. the experimental results show that aliphatic polycarbonate coated stents have broad application prospects. 4. The effects of shielding layer, drug gradient, carrier type, ratio of carrier to drug and release medium on DES drug release were investigated in detail. The coated drug release mode and its control factors were clarified, and the design of degradable drug carrier and DES was optimized.
【学位授予单位】：钢铁研究总院
【学位级别】：博士
【学位授予年份】：2012
【分类号】：TH789

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