【作者】 邱海霞；

【导师】 田景振；

【作者基本信息】 山东中医药大学 ， 中药学， 2003， 硕士

【摘要】 本论文采用溶剂挥发法制备5-氟尿嘧啶聚乳酸微球（5-FU-PLA-MS）。在单因素考察的基础上，通过正交设计考察不同因素对载药量及包封率的影响，优化筛选处方和工艺的最佳条件，并对制得的微球进行形态考察、体外释放、稳定性、微球皮下埋植的局部刺激性及生物相容性、家兔体内药物动力学等方面进行考察。 制得的5-FU-PLA-MS外观呈白色，流动性好。光学显微镜下观察为圆整微球，电镜下观察，表面有细小孔隙；测得微球算术平均粒径为80μm，在40～120μm范围内达92.5％，平均载药量10.44％，包封率为73.1％。 采用恒温振荡法考察微球体外释药特性，微球体外释药符合双相动力学方程，回归方程为：1-Q=0.216exp（-0.084t）+0.74exp（-0.0014t），释药机理为融蚀和扩散；原料药体外释药符合一级动力学方程，回归方程为：ln（1-Q）=-0.281-0.685t。 初步稳定性考察结果表明，微球需在≤25℃条件下贮存。⁶⁰Co辐射灭菌是微球灭菌的好方法。 氟尿嘧啶制成聚乳酸微球后，其体内消除半衰期明显延长T_1/2为103.15h，而注射液的T_1/2仅为0.57h。微球组清除率明显降低，AUC明显增加，5-氟尿嘧啶聚乳酸微球体外各时间的累积释药百分率Y和体内相应时间的吸收分数X呈明显的正相关。结果显示，玻璃体内植入氟尿嘧啶聚乳酸微球治疗PVR安全、有效。更多还原

【Abstract】 PLA microspheres were prepared by solvent evaporation method. In order to gain the best parameters for preparing microspheres, the influences of different factors on average drug loading and average incorporation efficiency of microspheres were evaluated by orthogonal-designing method using L9(34) table.In the study, we have evaluated the physicochemical properties of the microspheres. The micropheres with good fluidity and the surface morphology of it was observed by EPMA. Examination using EPMA showed spherical particles with many little pores. The average particle size was 80um with 92.5% of the micdrospheres being in the range of 40-120μm. The average drug loading and the average incorporation efficiency were 10.44%, 73.1% respectively.In vitro release of 5-FU from microspheres was performed by oscillating in constant temperature method. The 5-FU from microspheres in vitro could be described by double phase dynamic model and could be described by the following equation: l-Q=0.216exp(-0.084t)+0.74exp(-0.0014t), The release mechanism was erosion and diffusion. The 5-FU stuff release profile in vitro could be described by first order dynamic model and could be expressed by the following equation: ln(1-Q)=-0.281 -0.685t .Experiment in vitro indicate that the 5-FU-PLA-MS have a good sustained release efficacy.The microspheres were stable in ≤25℃. 60Co radiation has no effect on surface morphology and the content of 5-FU.The microspheres were administeres into the vitreous cavity of rabbits to study the kinetics in the eyes and the tolerance of ocular tissues. Compared with 5-FU injection, the T1/2 of 5-FU-PLA-MS was significantly higher from 0.57h to 103.15h.These results suggested that 5-FU-PLA-MS had no effect in the ocular tissues. 5-FU-PLA-MS could be used as a controlled drug in the vitreous.更多还原