【作者】 孟琳；

【导师】 田景振；

【作者基本信息】 山东中医药大学 ， 中药学， 2010， 硕士

【摘要】 本文采用经改进的O/W型乳化溶剂挥发法制备汉防己甲素联合5-氟尿嘧啶聚乳酸微球(TET联合5-Fu-PLA-MS)。在单因素考察的基础上,通过正交实验对处方进行优化,筛选出最佳制备工艺及处方。在此基础上,对制备的微球进行形态学、体外释药、初步稳定性、小鼠皮下埋植组织相容性及家兔体内毒性、药效学研究。按本实验筛选的最佳工艺及处方制备的TET联合5-Fu-PLA-MS分散性及流动性好,在光学显微镜下观察,微球成球性好,外观圆整,表面较光滑,微球粒径分布狭窄,处于50-80μm的微球占89.5%,平均粒径为(63.4±2.04)μm,扫描电镜下观看球表面有微孔。5-Fu载药量、包封率分别为(6.37±0.189)%、(57.30±1.687)%,TET载药量、包封率分别为(2.54±0.115)%、(46.29±1.089)%,符合本研究的要求。体外释药符合Higuchi动力学方程,具有良好的缓释特征。初步稳定性试验结果表明TET联合5-FU-PLA-MS的化学稳定性好。60Co灭菌是微球灭菌的好方法。动物体内试验表明,所制备的TET联合5-Fu-PLA-MS组织相容性好,进行玻璃体腔埋植可安全、有效地防治实验性外伤增殖性玻璃体视网膜病变(PVR)。更多还原

【Abstract】 In the article, tetrandrine(TET) and 5-fluorouracil(5-Fu) microspheres (MS) were prepared by improved emulsify-solvent evaporation method with polylactic acid (PLA) being used as carriermaterials. On the basis of single factor investigation, use the orthogonal experiment to optimize the best prescription in order to gain the best technics and prescription for preparing microspheres. And then study the shape characteristics, the release features in vitro, the preliminary stability, the histocompatibility, the toxicity and pharmacodynamics in vivo of mice.The TET and 5-Fu-PLA-MS prepared according to the optimized technics and prescription have good dispersity and fluidity. Observed by EPMA, the ballability of it is good, the appearance is rounded and the surface is smooth. Observed by SEM, the surface of spherical particles have pores. The size distribution of microspheres is narrow. The average particle size was about 63.4μn with 89.5% of the microspheres being in the range of 50～80μm. The average drug loading and encapsulation efficiency of 5-Fu were (6.37±0.189)%, (57.30±1.687)%respectively, and that of TET were (2.54±0.115)%, (46.29±1.089)%. respectively. In vitro release of 5-Fu and TET from microspheres could be described by Higuchi model and had a good sustained release characteristic. the preliminary stability test indicate that the chemical stability of The TET and 5-Fu-PLA-MS is good.60Co radiation has no effect on the surface morphology and the content of 5-Fu and TET. Experiments in mice showed that the histocompatibility of TET and 5-Fu-PLA-MS is good.The microspheres administered into vitreous cavity of rabbits could prevent and treat experimental traumatic proliferative vitreoretinopathy safely and effectively.更多还原