热毒宁注射液与栀子苷单体在大鼠体内的药动学比较  

Comparison of Pharmacokinetics between Reduning Injection and Geniposide Monomer in Rats in vivo

作　　者：郑卫华[1] 王艳娟[1,2] 梁佳佳[1] 杨丽娜[1] 张丽丽[1] 萧伟[2] 付小环[2] 李发美[1] 熊志立[1] 

机构地区：[1]沈阳药科大学药学院,沈阳110016 [2]江苏康缘药业股份有限公司,江苏连云港222001

出　　处：《中国实验方剂学杂志》2014年第3期95-99,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：中国博士后科学基金项目(2013M541256);辽宁省博士启动基金项目(20131111);国家"重大新药创制"项目(2011ZX09304;2013ZX09402203)

摘　　要：目的：建立RP．HPLC测定大鼠血浆中栀子苷质量浓度的方法，比较热毒宁注射液中栀子苷与栀子苷单体在大鼠体内的药动学特点。方法：将12只雄性sD大鼠随机等分成2组，分别尾静脉注射热毒宁注射液和栀子苷单体，于不同时间点眼眶采血，以紫丁香苷为内标，血浆用乙腈沉淀蛋白，流动相乙腈-水（14：86），经AgelaC18色谱柱（4．6mm×150mm，5μm）分离，检测波长238nm，采用PhoenixTM。WinNonlin6．1软件计算药动学参数。结果：栀子苷在0．100～120mg·L-1线性关系良好（r=0．9987），定量下限0．100mg·L-1，低、中、高质量浓度的血浆样品的提取回收率分别为（85．94-1．7）％，（96．6±2．3）％，（97．44-1．1）％。大鼠尾静脉注射给予热毒宁注射液和栀子苷单体后栀子苷在大鼠体内的药动学过程均符合二室模型，t1/2分别为（0．58±0．11），（0．55±0．20）h，MRT0-t分别为（0．414-0．05），（0．334-0．05）h，二者的主要药动学参数均无显著性差异。结论：建立的方法灵敏、快速、准确，适用于栀子苷在大鼠体内的药动学研究。热毒宁注射液中其他成分对栀子苷在大鼠体内药动学行为无显著性影响。Objective： To establish a RP-HPLC method to determine plasma concentration of geniposide in rats, and compare pharmacokinetic characteristics of geniposide in Reduning injection and geniposide monomer in rats. Method： Twelve male SD rats were divided into two groups randomly, which were injected Reduning injection and geniposide by tail vein, respectively. Orbital blood at different time points, with syringoside as internal standard, plasma was precipitated proteins with acetonitrile and centrifuged at 13 000 r· min-1 for 10 min. RP-HPLC analysis was performed on an Agela Cls column （4.6 mm x 150 mm, 5 μm） with acetonitrile- water （14： 86） as mobile phase, main pharmacokinetics parameters were calculated with PhoenixTM WinNonlin 6. 1 software. Result： Geniposide showed good linearity in 0. 100-120 mg .L-1 with r =0. 998 7, the lowest limit of quantization of geniposide was 0. 100 mg .L-1, the mean extraction recoveries of plasma samples with low, medium and high concentration were （ 85.9 ± 1.7 ） %, （96.6 ± 2.3 ） % and （97.4 ± 1.1 ） %, respectively. Concentration-time profiles of geniposide were fitted with the two-compartment model both for Reduning injection and geniposide monomer, t1/2 were （0.58 ±0. 11） and （0.55 ±0.20） h, MRT0-t, were （0.41 ±0.05） and （0.33 ±0. 05 ） h, respectively, main pharmacokinetic parameters had no significant differences between Reduning injection and geniposide monomer. Conclusion： This developed method was sensitive, rapid and accurate for investigating pharmacokinetics of geniposide in rats. Experimental results showed that the other constituents in Reduning injection have no significant impact on pharmacokinetics of geniposide in rats.

关 键 词：热毒宁注射液 栀子苷 反相高效液相色谱 药代动力学 药-时曲线 紫丁香苷 

分 类 号：R283.6[医药卫生—中药学] R945[医药卫生—中医学]