Herpetrione纳米混悬剂的制备及药动学初步研究  

Preparation of Herpetrione Nanosuspensions and Preliminary Study on Its Pharmacokinetics

作　　者：郭静静[1,2] 李仙义[3] 袁海龙[1] 吕俊兰[1,2] 付珊珊[1,2] 靳世英[1,2] 靳士晓[1,2] 

机构地区：[1]解放军第三〇二医院,北京100039 [2]成都中医药大学药学院,成都611730 [3]中国人民解放军总后勤部卫生部药品仪器检验所,北京100071

出　　处：《中国药学杂志》2012年第24期2004-2007,共4页Chinese Pharmaceutical Journal

基　　金：国家新药创制重大专项(2009ZX09103-349);北京市自然科学基金资助项目(7122176);国家教育部留学归国人员科研启动基金(20101561)

摘　　要：目的本实验制备了herpetrione纳米混悬剂(PEDX-NS),并进行了大鼠体内药动学研究。方法采用高压均质法制备herpetrione纳米混悬剂,考察纳米混悬剂的形态及粒径分布。以herpetrione(PEDX)为指标成分,采用HPLC测定大鼠灌胃给药后的血药浓度,用DAS2.0药动学软件计算药动学参数。结果制得的纳米混悬剂呈不规则球形,平均粒径为(238.6±1.9)nm,多分散度指数为(0.183±0.017)。herpetrione在大鼠体内动力学行为符合二室模型。herpetrione纳米混悬剂药-时曲线下面积(AUC)为25.19μg.h.mL-1,达峰浓度(ρmax)为11.64μg.mL-1,与参比药herpetrione普通混悬剂(PEDX-S)相比,分别提高了2.47倍和2.63倍(P<0.01)。结论高压均质法制备herpetrione纳米混悬剂工艺简单可行,herpetrione纳米混悬剂能显著提高药物体内生物利用度。OBJECTIVE To prepare herpetrione nanosuspension（PEDX-NS）and evaluate its pharmaeokinetics in rats. METHODS PEDX-NS was prepared by high pressure homogenization technology, and its morphology and mean diameter were determined. An HPLC method was employed to determine the concentration of herpetrione （PEDX） , the index component of PEDX-NS, in plasma, and the bioavailability of the nanosuspension was compared with the reference formulation after oral administration in Wistar rats. RESULTS The particles in the nanosuspension observed by scanning electron microscopy were irregular spheres, and the mean particle size of PEDX-NS was（238.6 ±1.9）nm. Its pharmacokinetic process calculated with DAS2.0 software was fitted to a two-compartment model. The AUC was 25.19 μg · h · mL^-1 and the pmaxWaS 11. 64 μg · mL^-1 , which were 2. 47 and 2. 63 times of the reference formulation, respectively（P 〈0. 01）. CONCLUSION It is feasible to prepare PEDX-NS by high pressure homogenization technology, and PEDX-NS can improve the bioavailability of PEDX notablely.

关 键 词：herpetrione 纳米混悬剂 药动学 高压均质法 

分 类 号：R944[医药卫生—药剂学] R969.1[医药卫生—药学]