黄连-吴茱萸配伍中盐酸小檗碱在大鼠体内的药动学研究  

Pharmacokinetics study on berberine hydrochloride in rats administered with Coptidis rhizoma-Evodiae fructus

作　　者：解海[1,2] 郑艳超[1] 张振秋[1] 李旭[2] 李素华[2] 

机构地区：[1]辽宁中医药大学药学院,辽宁大连116600 [2]大连大学附属中山医院,辽宁大连116600

出　　处：《华西药学杂志》2013年第4期388-391,共4页West China Journal of Pharmaceutical Sciences

摘　　要：目的比较黄连-吴茱萸提取液中盐酸小檗碱在腹泻、急性胃溃疡动物模型与正常大鼠体内的药动学差异,探讨病理状态对盐酸小檗碱在体内过程的影响。方法 ig番泻叶制备腹泻模型,ig乙醇制备急性胃溃疡模型。ig 10 g.kg-1黄连-吴茱萸(1∶1)提取液给正常大鼠和腹泻大鼠模型,ig 6 g.kg-1黄连-吴茱萸(6∶1)提取液给正常大鼠和急性胃溃疡大鼠模型。采用HPLC法分别测定盐酸小檗碱的药动学参数,色谱柱为Diamonsil C18(150 mm×4.6 mm,5μm),流动相为乙腈-甲醇-0.05 mol.L-1磷酸二氢钾溶液(23∶12∶65),流速1.0 mL.min-1,检测波长345 nm,柱温30℃。结果胃溃疡模型组和正常组药动学参数比较,Tmax延后,AUC0-t、AUC0-∞增大,MRT0-T延长;腹泻模型组与其正常组药动学参数相比较,t1/2延长,MRT0-∞延长。黄连-吴茱萸(1∶1)组较黄连-吴茱萸(6∶1)组达峰时间明显滞后,AUC0-t、AUC0-∞增大。结论黄连-吴茱萸(6∶1)提取液在胃溃疡模型大鼠中吸收速度减慢,但吸收量多,体内滞留时间稍延长。黄连-吴茱萸(1∶1)提取液在腹泻模型大鼠中消除稍慢,MRT0-∞延长。随吴茱萸的增加,盐酸小檗碱的Cmax和AUC增加。OBJECTIVE To compare the pharmacokinetics of berberine hydrochloride between diarrhea,acute gastric ulcer animal model and normal rats after administered with the extract if Coptidis rhizoma and Evodiae fructus couple and investigate the influence of the pathological state on the process of berberine hydrochloride in vivo.METHODS Models of diarrhea and acute gastric ulcer were induced by ig administration of Folium sennae and ethanol,respectively.10 g·kg-1 Coptidis rhizoma and Evodiae fructus（1：1） and 6 g·kg-1 Coptidis rhizoma and Evodiae fructus（6：1） were ig administered to diarrhea mouse model and acute gastric ulcer mouse model,respectively.While both of them were also administered to normal mouse as control.Pharmacokinetics parameters was determined by HPLC with a Diamonsil C18（150 mm×4.6 mm,5 μm） and the mobile phase was acetonitrile-methanol-0.05 mol·L-1 potassium dihydrogen phosphate solution（23：12：65） with a flow rate of 1.0 mL·min-1.The detection wavelength was 345 nm and column temperature was 30 ℃.RESULTS Compared with normal group,Tmax was delayed,AUC0-t、AUC0-∞ was increased and MRT0-T was prolonged in gastric ulcer model group.While t1/2 and MRT0-∞ were prolonged in diarrhea model group.In addition,AUC0-t,AUC0-∞ of Coptidis rhizoma and Evodiae fructus（1：1）was obviously higher than that of Coptidis rhizoma and Evodiae fructus（6：1）.CONCLUSION The absorbed velocity of Coptidis rhizoma and Evodiae fructus（6：1） in the mouse model of acute gastric ulcer was slower,but the absorbed dose increased and the residence time in vivo prolonged slightly.The elimination rate of Coptidis rhizoma and Evodiae fructus（1：1） was slower in the mouse model of diarrhea and the MRT0-∞was prolonged relatively.As the ratio of Coptidis rhizoma to Evodiae fructus increased,the Cmax and AUC of berberine hydrochloride were improved.

关 键 词：黄连 吴茱萸 HPLC 盐酸小檗碱 药代动力学 

分 类 号：R917[医药卫生—药物分析学]