【作者】 余兰；

【导师】 程已雪；

【作者基本信息】 武汉大学 ， 高分子化学与物理， 2005， 硕士

【摘要】 控制释放技术因其不需要频繁给药、能在较长时间内维持体内药物有效浓度、降低毒副作用而受到广泛关注。为了避免使用不方便的外科手术进行植入,可注射的、具有生物可降解性和生物相容性的聚合物微球成为较为理想的控制释放制剂形式。 本论文的第一章阐述了控制释放技术的概念、优点、分类、机理及常用的聚合物载体。介绍了微球药物控制释放系统的制备方法,以及聚ε-己内酯在药物控制释放领域的应用。 本研究主要分成两部分,第一部分的内容是合成了胆固醇封端的功能化ε-已内酯聚合物/寡聚物,以不同分子量的胆固醇封端的功能化ε-已内酯聚合物/寡聚物为载体、包载药物醋酸泼尼松,用熔融乳化法便利地制备了微球药物控制释放系统,微球的尺寸能够很好的控制。分别研究了微球药物控制释放系统在无酶情况下和有酶存在下的药物释放行为,并探讨了其药物控制释放机理。当无酶情况下,药物的释放行为由Fickican扩散机理控制;当假单胞菌脂肪酶存在下,药物的释放行为由Fickcan扩散和降解机理共同控制。释放曲线与经典的经验指数表达式非常吻合。 第二部分的研究内容是通过胆酸引发ε-已内酯的开环聚合,合成了一系列不同分子量的含胆酸结构的星型功能化聚ε-已内酯,并用核磁共振波谱、红外光谱、偏光显微镜对产物进行了表征。由于引入胆酸结构,一定分子量的产物在一定温度下呈现液晶态。研究功能化聚ε-已内酯的体外酶降解的结果表明,与线性聚ε-已内酯相比,胆酸结构的引入使功能化聚ε-已内酯的酶降解速率减慢。更多还原

【Abstract】 Controlled drug delivery technology has grown and diversified rapidly in recent years. Drug delivery systems (DDS) offer numerous advantages compared to conventional dosage forms, such as improved efficacy, reduced toxicity, and convenience. The delivery systems using macromolecules as drug carriers are the most important type of DDS. Of the different dosage forms reported, nanoparticles and microparticles attained much importance because their injectable property which can avoid the inconvenient surgical insertion of large implants.In the research background section of this thesis, we review the advantages, classification, mechanism and polymer matrices of drug delivery systems, the applications of poly (ε-caprolactone) (PCL) in drug controlled release field, and the preparation approaches of microsphere drug delivery systems.The research carried out is divided into two parts. In the first part, end-functionalized poly/oligo(ε-caprolactone)s were synthesized through the ring-opening polymerization of ε-caprolactone initiated by cholesterol with a hydroxyl group. Using the end-functionalized poly/oligo(ε-caprolactone)s with different molecular weights, the microsphere drug delivery systems with narrow size distributions were fabricated using a convenient melting-emulsion method. The drug release properties of microspheres were investigated with the presence of an enzyme, Pseudomonas cepacia lipase, as well as in the absence of the enzyme. The release profiles can be fitted nicely by the classical empirical exponential expression. Under the hydrolytic condition, the drug release is mainly controlled by Fickian diffusion, and the high molecular weight of the matrix results in a slower drug release rate. Under the enzymatic condition, the drug release is dominated by combined degradation and diffusion mechanism, and the high molecular weight sample exhibits a faster release rate which is mainly caused by the higher degradation rate of the sample with lower cholesteryl moiety content.In the second part, a series of star-like biodegradable polymers/oligomers based on ε-caprolactone (CL) containing cholic acid moieties were studied. The functionalized polymers/oligomers, CA-(CL)n, were synthesized through ring-opening polymerization initiated by cholic acid with hydroxyl groups. The functionalizedpolymers/oligomers were characterized by lK nuclear magnetic resonance spectroscopy (’H NMR), Fourier transform infrared (FTIR) and polarizing light microscopy (PLM). Incorporation of cholic acid moiety to the polymer chain results in liquid crystallinity for the resultant oligomers with particular molecular weights. The molecular weight of the CA-(CL)n polymers/oligomers can be controlled by adjusting the feed ratio of the initiator cholic acid to the monomer CL. The in vitro enzymatic degradation of CA-(CL)n polymers/oligomers was studied. Comparing with linear poly(s-caprolactone), incorporation of cholesteryl moiety to the polymer chain leads to a slower enzymatic degradation rate.更多还原