新型改性聚碳酸亚丙酯的生物安全性评价及体内代谢分布研究

发布时间：2018-05-13 13:00

本文选题：聚碳酸亚丙酯 + 体内分布　；参考：《吉林大学》2013年博士论文

【摘要】：可降解生物医用高分子材料（Degradable mediacal biomaterial，DMB）的研发是生物医用高分子材料中最活跃与热门的研究领域之一，此类材料通过与活组织接触，可实现对疾病的诊断和治疗，及对组织和器官的替换或增进等功能。DMB在医学中的应用十分广泛，例如药物释放系统、手术缝合线、人造皮肤、骨科固定材料、血管移植与外科粘合剂等。DMB具有可降解、稳定性好、对环境的污染小以及成本低廉等特点，多年来各国科学家一直竞相开发并尝试应用于人体。与金属和陶瓷相比，DMB在性能和结构等方面与人体更接近，但是它对于生物体来说毕竟是异物，如果不具备良好的生物相容性，则会导致机体产生炎症、过敏或凝血等不良反应。除此之外，DMB如开发成体内医用制品，还应具备合适的仿生性能，以满足不同需求。聚碳酸亚丙酯（Poly(propylene carbonate），PPC）是由二氧化碳和环氧丙烷合成的高分子聚合物，降解产物为二氧化碳和水，可作为DMB原料。PPC虽具有良好的生物相容性和很低的氧透过率，但是由于其柔韧性较大，力学性能差等原因限制了多领域的应用。本研究前期工作中将聚碳酸亚丙酯（PPC）与β-羟基丁酸酯（PHB）按照80：20的比例进行改性与共混，研制出新型改性聚碳酸亚丙酯（M-PPC2），已在一定程度上提高PPC及M-PPC1（课题组前期材料，PPC:PHB=7:3）的力学及机械性能。本研究根据中华人民共和国国家标准GB/T16886中医疗器械生物学评价标准中的相关要求，选用细胞毒性实验、过敏实验、急性全身毒性实验、溶血实验、热原实验以及皮肤刺激实验对M-PPC2进行生物安全性评价。并以放射性同位素125I标记M-PPC2，以研究其在生物体内的分布及稳定性，并将125I标记后的M-PPC2长期植入家兔体内，研究其降解产物或中间产物在体内的代谢途径。结果表明：M-PPC2具有良好的生物安全性；M-PPC2具有良好的稳定性、材料短期大量入血后主要分布于肝脏；长期肌肉植入后M-PPC2可能的降解中间产物分布于肝脏，材料降解后较少经血液和尿液代谢。研究结果为M-PPC2作为DMB在医疗领域中更广泛的应用提供了基础研究数据。本研究的创新点在于： 1、首次对本课题组前期研制的M-PPC2的生物安全性进行研究，验证了该材料具有良好的生物安全性，可以作为生物医用材料。 2、首次进行了M-PPC2的体内分布及代谢研究，找到了M-PPC2的体内分布、代谢途径：M-PPC2的可能中间降解产物主要分布于肝脏，，材料降解后较少经血液和尿液代谢。
[Abstract]:The research and development of biodegradable mediacal biomaterial biomaterials is one of the most active and popular research fields in biomedical polymer materials. Through contact with living tissues, these materials can be used to diagnose and treat diseases. DMB is widely used in medicine, such as drug release system, surgical suture, artificial skin, orthopedic fixation materials, vascular graft and surgical adhesives. Because of its good stability, low environmental pollution and low cost, scientists all over the world have been competing to develop and apply it to human body for many years. Compared with metals and ceramics, DMB is more similar to human body in performance and structure, but it is a foreign body for organism after all. If it does not have good biocompatibility, it will lead to inflammation, allergies or blood clotting and other adverse reactions. In addition, if DMB is developed into medical products in vivo, it should also have suitable bionic properties to meet different requirements. Poly (propylene carbonate) is a polymer synthesized from carbon dioxide and propylene oxide. The degradation product is carbon dioxide and water, which can be used as raw material of DMB, although it has good biocompatibility and low oxygen permeability. However, due to its flexibility and poor mechanical properties, many applications are limited. In this study, poly-propylene carbonate (PPC) and 尾 -hydroxybutyrate (PHBB) were modified and blended at 80:20. A new modified poly (propylene carbonate) M-PPC _ (2) has been developed, which has improved the mechanical and mechanical properties of PPC and M-PPC _ (1) to some extent. In this study, according to the relevant requirements of the biological evaluation standard of medical devices in GB/T16886, the cytotoxicity test, allergy test, acute systemic toxicity test, hemolysis test were selected. The biosafety of M-PPC2 was evaluated by pyrogen test and skin stimulation test. M-PPC2 was labeled with radioisotope 125I to study the distribution and stability of M-PPC2, and the 125I-labeled M-PPC2 was implanted into rabbits for a long time to study the metabolic pathway of its degradation product or intermediate product in vivo. The results showed that the biological safety of% M-PPC2 was good, and M-PPC2 was mainly distributed in the liver after a large amount of blood injection, and the degradation intermediate product of M-PPC2 was distributed in the liver after long-term muscle implantation. After degradation, the materials were less metabolized by blood and urine. The results provide basic research data for the wider application of M-PPC2 as DMB in medical field. The innovations of this study are: 1. For the first time, the biosafety of M-PPC2 developed by our research group was studied for the first time, and it was proved that this material has good biological safety and can be used as biomedical material. 2. The distribution and metabolism of M-PPC2 in vivo were studied for the first time, and the distribution of M-PPC2 in vivo was found. The possible intermediate degradation product of the metabolic pathway: M-PPC2 was mainly distributed in the liver, and the material was less metabolized by blood and urine after degradation.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R318.08

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