几种缓释药用载体材料的合成及性能的分析研究.pdfVIP

摘 要 药物控制释放是目前国内外药剂领域的一个重要研究课题，现已有多种高分子 材料被引入药物控制释放体系。药物载体是药物释放体系的重要组成部分，也是影 响药效的主要因素。在过去的二十年中，聚酯类和聚酸酐类材料因其可降解性及低 毒性广泛用于化疗剂、抗生素药物、麻醉剂和多肽等药物的控释载体。 本文主要合成了三种不同的聚合物体系，研究了其体外降解与释药性能。取得 以下主要结果。 1. 选用长链脂肪二酸酐、富马酸和一缩二乙二醇熔融缩聚，得到了三个系列 的不饱和聚酯，并对它们进行了结构表征，考察了聚合物的疏水性、双键含量和分 子量等多种因素对它们的降解与释药性能的影响。结果表明所合成的这类聚合物具 有生物可降解性和较好的释药性能，而且随疏水性单体含量、不饱和键以及分子量 的增加，降解和释药速率减慢。 2. 选用1,6-己二醇、丁二酸酐和十二烷二酸为主要原料，先制备了二丁二酸己 二醇单酯单体，再采用熔融聚合的方法与十二烷二酸酐共聚得到了一系列组成不同 的聚酯酸酐，对它们进行了结构表征，并研究了其体外降解与释药性能。结果显示， 所合成的聚酯酸酐熔点较低，体外降解与释药曲线都符合一级动力学方程。 3. 选择甘氨酸、马来酸酐和一缩二乙二醇为原料，熔融缩聚合成了一系列的聚 酯酰胺。通过对聚合物吸水率的研究发现，影响吸水率的因素一是聚合物中一缩二 乙二醇的含量，随醇含量的增加，吸水率增加；二是聚合物固化时，所用的交联剂 的量，随交联剂用量的加大，吸水率下降。 关键词：聚酯; 聚酯酸酐; 聚酯酰胺; 熔融缩聚; 生物可降解; 药物缓释 I Abstract In recent years, the study of controlled release of drugs from around the world has been become an important field in medicine. Nowadays, a lot of macromolecule materials have been synthesized for drug controlled release. Drug carrier is an important composition of the drug release system, and the primary influencing factor of drug efficiency. In the past two decades, polyesters and polyanhydrides materials with biodegradation and low toxicity as drug carriers have been extensively investigated for the controlled delivery of a number of drugs, such as chemotherapeutics, antibiotics, anesthetics and polypeptides. In this paper, three kinds of polymers were synthesized. The polymers’ degradation and drug delivery were studied in vitro. The main results are as follows: Three kinds of unsaturated polyester from the fatty anhydride, fumaric acid and diethylene glycol were successfully prepared by melt polycondensation and