亮丙瑞林缓释微球的研究

目的 :制备收率及包封率高、可持续释药 3mo的亮丙瑞林微球。方法 :以生物可降解聚合物聚乳酸 (PLA)为载体 ,采用W /O/W复乳 液中干燥法制备缓释亮丙瑞林微球 ,以包封率及收率为指标 ,用正交设计对微球处方工艺进行优化 ,并考察微球的体外释放及体内药效。结果 :经优化得到的亮丙瑞林微球收率及包封率分别为 6 8%和 6 5 %。在选择的释放条件下 ,至 10 5d时 ,累积释放 88%。给予成熟雄性大鼠 10 0 μg·kg- 1·d- 1单剂量皮下注射 ,12h内出现睾酮迅速升高 ,3d内降至 0 .1μg·L- 1以下 ,并维持低睾酮水平 10 5d。结论 :制备的亮丙瑞林微球能产生持续长时间的缓释作用

Study on sustained-release leuprorelin microspheres

AIM: To prepare leuprorelin microspheres with high recovery and entrapment efficiency which can release for 3 mo. METHODS: The microspheres containing leuprorelin were prepared by W/O/W multiple emulsion-in liquid evaporation process in which in biodegradable poly(lactic acid)(PLA) was used as carrier material. L 9(3 4) orthogonal experiment design was utilized to optimize the formulas and preparation condition. The in vitro release and in vivo pharmacodynamics of the microspheres were studied. RESULTS: The recovery and entrapment efficiency of the mirospheres was 68 % and 65 %, respectively. Under the release condition, cumulative release rate was 88 % by the end of 105 d. After a single injection (sc) of leuprorelin microspheres at the dose of 100 μg·kg -1·d -1, the levels of testosterone elevated fast within 12 h, declined under 0.1 μg·L -1 in 3 d and the low levels of testosterone maintained for 105 d. CONCLUSION: This prepared leuprorelin microspheres can provide long-time sustained-release effects.