丙氨瑞林生物可降解缓释微球注射剂的研究

Studies on Biodegradable Sustained- Release Alarelin Microspheres Injection

以生物可降解聚合物聚乳酸/羟乙酸为载体,采用改良的复乳-液中蒸发法制备缓释丙氨瑞林微球注射剂,包封率为99.5%,平均体积径为91.36μm,收率大于95%。在37°C、pH7.0的生理等渗缓冲液中,微球首日释药14.3%,后以平均2.2%/d的速度释药5周,符合零级模式(r=0.994)。大鼠皮下注射微球后,首日释药15.1%,后以平均2.3%/d的速度释药5周,体内释药与体外释放间相关性良好(r=0.979)。雌性大鼠动情周期与子宫内膜异位模型试验表明,单剂量注射微球(释药速度为100μg·kg-1·d-1)后的疗效与每天给予同等剂量的常规溶液剂无显著差异。

Injectable sustained- release alarelin( LHRH- A) microspheres were prepared by double emulsion- in liquid evaporation process,using biodegradable poly lactic- co- glycolic acid as carrier.The entrapment efficiency was99.5 % ,mean particle size91 . 36μm and the yield above95 % .In p H7.0 physiological isotonic buffer solution,after1 4 .3% of LHRH- A was released first day,the microspheres released at rate of 2 .2 % per day for more than 35 d( r=0 .994 ) .After sc microspheres at rat,1 5 .1 % of LHRH- A was released first day,then 2 .3% per day for 5 weeks,the correlation between in vitro and in vivo releases was good ( r=0 .979) .It was shown at female rat estrous cycle and endometriosis model that a single injection of LHRH- A microspheres at the dose of 1 0 0 μg· kg-1· d-1showed the same effectiveness as the routine injection given daily of the same dose.