【摘要】 目的制备齐墩果酸静脉注射乳剂,初步考察齐墩果酸静脉注射乳剂在大鼠体内的药动学。方法采用高速分散法制备初乳,探头超声法制备终乳;透射电镜观察形态;大鼠尾静脉分别注射静脉乳剂和溶液剂,用反相高效液相色谱法测定不同时间血浆中齐墩果酸的浓度,采用3P97程序计算药动学参数,并进行统计学分析。结果制得的静脉注射乳剂为圆形或类圆形,离心稳定性系数为(44.1±1.2)%,平均粒径为(176.0±3.8)nm,Zeta电位为(-17.5±4.1)mV,含量为(87.8±1.8)%;静脉注射乳剂和溶液剂经大鼠尾静脉注射后,体内过程均为二室模型,t1/2α分别为(7.8±0.8)和(3.5±0.5)min;t1/2β分别为(308.1±22.8)和(146.3±11.6)min;AUC分别为(208.6±15.6)和(103.9±11.8)μg.min.mL-1,两种制剂的t1/2β和AUC0-t经方差分析后均存在显著性差异(P<0.05),静脉注射乳剂显著增加了齐墩果酸的AUC,延长了其在血液循环中的时间。结论制备的齐墩果酸静脉注射乳剂含量较高,粒度均匀;与溶液剂相比,乳剂静脉给药后,药动学参数发生了明显的改变。更多还原

【Abstract】 OBJECTIVE To prepare oleanolic acid intravenous emulsions and study its pharmacokinetics in rats.METHODS Oleanolic acid intravenous emulsion was prepared by two-step emulsification using high speed stirring-ultrasonic wave.The pharmaceutical properties including appearance,content,Ke,particle size,and Zeta potential were determined.Rats were i.v.injected with oleanolic acid intravenous emulsion or oleanolic acid solution via tail veins.The concentrations in rat plasma were assayed by high-performance liquid chromatography(HPLC).The pharmacokinetic parameters were computed by 3P97 program package.RESULTS The droplets of oleanolic acid intravenous emulsion were almost spherical,The mean diameter was(176.0±3.8) nm,and Zeta potential was(-17.5±4.1) mV.The content of oleanolic acid intravenous emulsions was(87.8±1.8)%.The plasma pharmacokinetic process of the oleanolic acid intravenous emulsions obeyed a two-compartment model.t1/2β of oleanolic acid intravenous emulsions was(308.1±22.8) min,and AUC was(208.6±15.6) μg·min·mL-1,obviously higher than control preparation.CONCLUSION The intravenous emulsion has high content and even diameter.Its pharmacokinetic property has significant change with improved bioavailability.更多还原