水飞蓟宾脂质微球的制备及在大鼠体内的药物动力学考察Physicochemical characteristic and pharmacokinetics of silybin lipid microsphere
刘晓亮,张宇,孙蕴哲,唐星
LIU Xiao-liang,ZHANG Yu,SUN Yun-zhe,TANG Xing (School of Pharmacy
摘要(Abstract)：
目的制备水飞蓟宾脂质微球并对其理化性质及大鼠体内药物动力学特征进行考察,为水飞蓟宾的临床应用提供理论依据。方法采用高压均质法制备水飞蓟宾脂质微球;分别采用动态光散射法、超速离心法考察制剂的粒径、zeta电位及药物的相分布;以自制水飞蓟宾溶液剂作为参比制剂,采用HPLC法考察大鼠体内药物动力学。结果制剂平均粒径约为192.4 nm,zeta电位为-24.56 mV,约77.5%的药物分布在油水界面膜上;40℃加速实验10 d,药物的相分布无变化;4℃留样观察6个月内稳定;水飞蓟宾脂质微球和溶液剂的药时过程均符合双隔室模型;非隔室模型分析结果表明,脂质微球和溶液剂的AUC0-t分别为(1.90±0.29)、(2.07±0.44)mg.h.L-1,两制剂药-时曲线相似。结论所制备的水飞蓟宾脂质微球性质稳定,大部分药物分布在油水界面膜上;脂质微球未改变药物在大鼠体内的药物动力学特征。
Objective To study the physicochemical characteristics and pharmacokinetics of silybin lipid microsphere.Methods Dynamic light scattering and ultracentrifugation were used to evaluate the physicochemical characters of the silybin loaded lipid microsphere,such as the particle size,zeta potential and the distribution of drug in aqueous phase,in oil phase and in the oil and water interface of lipid microsphere.The plasma concentration was determined by HPLC,compared with silybin solution at the same time.Results The mean diameter was about 192.4 nm.The zeta potential was-24.56 mV.Over 77.5% of the silybin was in the interfacial layer of lipid microsphere.The phase distribution had no significant change during the storage at 40 ℃ for 10 d.The lipid microsphere was stable during the storage at 4 ℃ for 6 months.The result of the plasma concentration showed that the silybin lipid microsphere and the reference silybin solution were of two compartments.The AUC0-t of silybin lipid microsphere and silybin solution were(1.90±0.29)and(2.07±0.44)mg·h·L-1,respectively.The two plasma concentration-time profiles were alike.Conclusions Stable silybin lipid microsphere is prepared;most of the drug is in the interface of silybin lipid microsphere and the character of silybin in vivo is not changed.
关键词(KeyWords)：
水飞蓟宾;脂质微球;相分布;药物动力学
silybin;lipid microsphere;phase distribution;pharmacokinetics
基金项目(Foundation):
作者(Author):
刘晓亮,张宇,孙蕴哲,唐星
LIU Xiao-liang,ZHANG Yu,SUN Yun-zhe,TANG Xing (School of Pharmacy
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