汉防己甲素联合5-氟尿嘧啶聚乳酸微球的制备及防治增殖性玻璃体视网膜病变的基础研究

发布时间：2018-10-26 11:14

【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)。
[Abstract]:Tetrandrine combined with 5-fluorouracil polylactic acid microspheres (TET combined with 5-Fu-PLA-MS) were prepared by modified O / W emulsion solvent volatilization method. On the basis of single factor investigation, the formulation was optimized by orthogonal experiment, and the optimum preparation technology and prescription were screened out. On this basis, morphology, drug release in vitro, preliminary stability, histocompatibility of subcutaneous implantation in mice, in vivo toxicity and pharmacodynamics of the prepared microspheres were studied. According to the optimum technology and prescription, the TET and 5-Fu-PLA-MS prepared by this experiment have good dispersion and fluidity. Under optical microscope, the microspheres have good sphericity, round appearance, smooth surface and narrow particle size distribution. The average diameter of microspheres was (63.4 卤2.04) 渭 m. The micropores were observed under scanning electron microscope (SEM). The encapsulation efficiency of 5-Fu was (6.37 卤0.189)% and (57.30 卤1.687)%, respectively. The entrapment efficiency of TET was (2.54 卤0.115)% and (46.29 卤1.089)%, respectively. The drug release in vitro accords with Higuchi kinetic equation and has good sustained release characteristics. The results of preliminary stability test showed that TET combined with 5-FU-PLA-MS had good chemical stability and that 60Co sterilization was a good method for microsphere sterilization. The results of animal experiments in vivo showed that the prepared TET combined with 5-Fu-PLA-MS had good histocompatibility, and the implantation of vitreous cavity was safe and effective in preventing and treating experimental traumatic proliferative vitreoretinopathy (PVR).
【学位授予单位】：山东中医药大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R774.1

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