【作者】 李涛；

【导师】 郝红；

【作者基本信息】 西北大学 ， 化学工艺， 2008， 硕士

【摘要】 聚乳酸（PLA）是性能优异的生物医用高分子材料,但是在使用过程中,存在着一定的局限性。例如PLA降解的中间产物乳酸在体内会引起无菌炎症,可产生不良反应;PLA化学结构中缺乏反应性官能基团,亲水性很差,降解周期不确定等等。为了改善聚（L-乳酸）（PLLA）的性能,本文以L-乳酸和壳聚糖（CS）为原料,将含亲水基团的碱性聚电解质CS与PLLA共聚,一方面改变PLLA的结晶性和亲水性,另一方面由于电荷的存在而改善其组织相容性及细胞亲和性。另外,采用溶剂挥发法,将PLLA接枝CS共聚物（PLCS）制备成载药微球,并与PLLA微球作比较,考察它们的载药释药性能,主要围绕以下几个方面进行研究和讨论:首先,通过单因素和正交实验,考察各因素对产物PLCS的影响。实验结果表明:原料配比（-NH₂:LA）、催化剂用量（DCC:DMAP:LA）、乳酸反应浓度、反应时间这4个因素对PLCS质量影响较显著。优选后的制备工艺条件为:原料配比为1:15,催化剂用量为1:0.053:1,乳酸反应浓度为1.88mol/L,反应时间为24h。通过最佳工艺条件制备的产物PLCS收率最高,接触角较小。其次,制备盐酸乌拉地尔PLLA微球、盐酸乌拉地尔PLCS微球,考察载药微球的性质。实验表明,相同投药比前提下,在有机相中加无水乙醇与不加无水乙醇所制得的PLCS微球的药物包封率均大于PLLA微球的药物包封率。盐酸乌拉地尔PLLA、PLCS微球表面光滑圆整,分散性良好无粘连且粒径分布集中。最后,采用恒温振荡法考察载药微球的体外释药特性,实验表明盐酸乌拉地尔PLLA微球、盐酸乌拉地尔PLCS微球以及包裹CS膜的盐酸乌拉地尔PLLA微球均具有缓释作用,其释药动力学模型均满足Higuchi模型。PLCS载药微球较PLLA载药微球以及包裹CS膜的PLLA载药微球的释药速度快,达到最大药物累积释放率的时间较短。更多还原

【Abstract】 Polylactic acid (PLA) is a high performance biomedical polymer material, but there are also some limitations in use. For example, intermediate product of PLA degradation is lactic acid, which will cause aseptic inflammation in the body, resulting in adverse reactions; chemical structure of PLA is lack of reactive functional groups; its hydrophilic is poor, and its degradation cycle is uncertain.In order to improve performance of poly(L-lactic acid) (PLLA), we taken L-lactic acid and chitosan (CS) as raw materials in this dissertation. CS, a kind of alkaline polyelectrolyte containing hydrophilic group, and PLLA were copolymerized through the role of efficient catalysts. Grafting copolymers of PLLA and CS (PLCS) were prepared to microspheres by the solvent evaporation method, and PLCS microspheres were compared with PLLA microspheres. The results of the research were expanded at the following points:First, the influence factors in the progress of preparing PLCS were studied according to monofactor method and multifactor orthogonalizing design method.The ratio of raw materials (-NH2: LA), the amount of catalyst (DCC:DMAP:LA), the reaction concentration of lactic acid and reaction time could affect PLCS characterize in evidence. The optimum preparation condition was: the ratio of raw materials was 1:15, the amount of catalyst was 1:0.053:1, the reaction concentration of lactic acid was 1.88mol/L, the reaction time was 24h. The copolymer prepared by the optimun preparation method was high yield and its contact angle was small.Second, we prepared Urapidil Hydrochloride-PLLA microspheres and Urapidil Hydrochloride-PLCS microspheres, and researched the characteristics of them. The result showed that, under the condition of the same dosing ratio, the drag loading efficiency of PLCS microspheres was always more than it of PLLA microspheres whether ethanol was added to organic phase or not. Urapidil Hydrochloride-PLLA microspheres and Urapidil Hydrochloride-PLCS microspheres were smooth, regular in morphology, good decentralization, and both of their average particle sizes were narrow size distribution.Third, in vitro release of Urapidil Hydrochloride from microspheres was performed by oscillating in constant temperature. The release study indicated that the Urapidil Hydrochloride-PLLA microspheres, Urapidil Hydrochloride-PLCS microspheres and coating CS on Urapidil Hydrochloride-PLLA microspheres exhibited sustained-release capacity, and the kinetics of all these microspheres in vitro release could be described by Higuchi equation. PLCS microspheres released the drug faster than PLLA microspheres and coating CS on PLLA microspheres. The time of maximum cumulative drug release rate of PLCS microspheres was shorter than that of another two kinds of microspheres.更多还原