川芎嗪棕榈酸酯亚微乳的制备及其药动学与脑靶向性的评价  

Preparation of tetramethylpyrazine palmitate lipid emulsion and its pharmacokinetics and brain targeting performance

作　　者：李茜[1] 王珍珍[1] 于小月[1] 曹然[1] 王银艳[1] 毛声俊[1] 

机构地区：[1]四川大学华西药学院靶向药物及释药系统教育部重点实验室,四川成都610041

出　　处：《华西药学杂志》2013年第3期249-252,共4页West China Journal of Pharmaceutical Sciences

基　　金：国家重大新药创制科技重大专项课题靶向释药系统与新制剂技术平台的建设(编号:2009ZX09310-002)

摘　　要：目的制备2-羟甲基-3,5,6-三甲基吡嗪棕榈酸酯(HTMPP)亚微乳,并考察其在小鼠体内的药动学及脑靶向性。方法采用星点设计-效应面法优选处方,高压均质法制备HTMPP亚微乳,HPLC法测定2-羟甲基-3,5,6-三甲基吡嗪(HTMP)的含量,DAS 2.0软件计算药动学参数。结果制备的亚微乳平均粒径为253.2±0.26 nm,HTMPP亚微乳在血浆中的t1/2为18.58 min,为磷酸川芎嗪(TMPP)注射液的1.83倍,AUC(0-∞)为745.96 mg.L-1.min-1,为TMPP注射液的1.43倍(P<0.01);其在脑中的AUC(0-∞)为632.31 mg.L-1.min-1,为TMPP注射液的1.43倍(P<0.01)。结论以HTMP计,HTMPP亚微乳与TMPP注射液相比,生物半衰期显著延长,具有较强的脑靶向性。OBJECTIVE To prepare the 2-Hydroxymethyl-3,5,6-trimethyl pyrazine palmitate（HTMPP） lipid emulsion and investigate the pharmacokinetics and its brain targeting performance in mice.METHODS HTMPP lipid emulsion was prepared by high-pressure homogeneous technique.Central composite design surface methodology was applied to optimize the lipid emulsion formulation.The concentration of drug in mice plasma and brain was determined by HPLC,and the parameters were calculated with DAS 2.0.RESULTS The mean diameter of lipid emulsion was 253.2±0.26 nm.The pharmacokinetic parameters of HTMPP lipid emulsion were 18.58 min for t1/2 and 745.96 mg·L^-1·min^-1 for AUC（0-∞） in plasma,and in brain,the AUC（0-∞） was 632.31 mg·L^-1·min^-1.The pharmacokinetic parameters of tetramethylpyrazine phosphate（TMPP） injection were 10.16 min for t1/2 and 522.03 mg·L^-1·min^-1 for AUC（0-∞） in plasma,and in brain,the AUC（0-∞） was 440.89 mg·L^-1·min^-1.CONCLUSION Compared with TMPP injection,the prepared HTMPP lipid emulsion prolonged the t1/2 and improved the brain targeting ability by determining the concentration of HTMP.

关 键 词：川芎嗪 2-羟甲基-3 5 6-三甲基吡嗪棕榈酸酯 亚微乳 星点设计 药动学 脑靶向 

分 类 号：R94[医药卫生—药剂学]