尼尔雌醇皮埋剂的研制及体内外释放实验  

Preparation of nylestriol implants and investigation of release test in vivo and in vitro

作　　者：刘石平[1] 廖二元[1] 伍汉文[1] 伍贤平[1] 邓小戈[1] 陈海林 陈良康 

机构地区：[1]湖南医科大学附属二院代谢内分泌研究所,长沙410011 [2]上海计划生育研究所

出　　处：《中国骨质疏松杂志》2001年第1期68-69,共2页Chinese Journal of Osteoporosis

基　　金：卫生部重点学科建设项目

摘　　要：目的　研制尼尔雌醇皮埋剂 ,了解其体内、体外释药行为 ,为长期雌激素替代治疗防治绝经后骨质疏松提供一种新的选择。方法　首先制成尼尔雌醇皮埋剂 ;接着建立其体外药物释放体系及药物体外释放量的反相高效液相色谱 (RP HPLC)的检测方法 ;同时将尼尔雌醇皮埋剂植入SD大鼠体内 ,于植入后 4、5、8个月取出 ,用剩余药量推算体内释药量 ;最后对体内、外累积释放量(Q)与时间 (t)进行线性回归分析并绘制尼尔雌醇皮埋剂体外释放曲线和体内、外Q t曲线。　结果　尼尔雌醇皮埋剂体外释放最初 1周释放量较大 ,之后平稳释放 ,Q和t线性相关良好 (r=0 996 ,P =0 0 0 0 ) ,平均体外释放量为 33 0 5 6 6 μg 日·支 ;体内释放实验中Q和t也呈良好的线性相关 (r=0 985 ,P =0 0 15 ) ,平均体内释放量为 19 6 5 μg 日·支。 结论　 (1)尼尔雌醇皮埋剂体外释放在最初 1周存在爆破效应 ,之后符合零级动力学释放 ;其在体内释放也符合零级动力学释放 ,尼尔雌醇皮埋剂有可能达到长效控释的目的。 (2 )NYL皮埋剂周期性或持续性加用孕激素可能成为长期雌激素替代治疗防治绝经后骨质疏松的一种新的选择。Objectives\ To prepare nylestriol implant and investigate its release characteristics in vivo and in vitro in order to provide a new choice for estrogen replacement therapy(ERT) of postmenopausal osteoporosis. Methods\ Nylestriol implants in the form of Norplant implants were prepared.Their release system in vitro and method of reverse phase high performance liquid chromatography(RP\|HPLC) for the determination of release quantities in vitro were established. At the same time, the release quantities of nylestriol implants in SD rats were computed according to the residual drug in the implants.Finally,the relations of accumulative release quantities of nylestriol implants in vivo and in vitro and release time were analyzed by linear regression analysis;in addition,release curve in vitro and accumulating release quantities\|time(Q\|t) curve in vivo and in vitro were plotted. Results\ The release quantities of nylestriol implant were greater in the first week,then kept steady.The linear correlation of accumulative release quantities(Q\|μg) in vitro with release time(t\|day) was high(r=0\^996,P=\^000),and the average release quantity in vitro was 33\^0566 μg/day·rod.The linear correlation of accumulative release quantities(Q\|mg) in vivo with release time(t\|month) was also good(r=0 985,P=0\^015),and the average release quantity in vivo was 19\^65 μg/day·rod. Conclusion\ (1)Nylestriol implants have blast effects in the first week of release in vitro, and then tend to be in line with zero dynamic release;and their release in vivo in SD rats also conforms to zero clynamic release,the implants being long\|acting and release\|controlled.(2)Periodic or continuous addition of progestin to nylestriol implant provides a new choice for ERT if needed for a long time.\;

关 键 词：尼尔雌醇皮埋剂 研制 药物体外释放实验 药物体内释放实验 骨质疏松 

分 类 号：R681.02[医药卫生—骨科学]