小檗碱的油水分配系数及其在体肠循环灌流模型中的肠吸收特性  

Investigation of Apparent Oil /Water Partition Coefficients of Berberine and Its Absorption Characteristics in in situ Intestinal Perfusion Model

作　　者：张玉玲[1,2] 陈健龙[2] 王虑虎 孙丽玲[2] 张诗航[2] 李超英[2] 崔翰明[1] 

机构地区：[1]中国中医科学院广安门医院,北京100053 [2]长春中医药大学,长春130117 [3]广州中一药业有限公司,广州510140

出　　处：《中国实验方剂学杂志》2013年第16期1-4,共4页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家重大新药创制专项(2011ZX09102-011-08)

摘　　要：目的:测定小檗碱和黄连总生物碱中小檗碱的油水分配系数,并研究小檗碱、黄连总生物碱和清热通腑片中小檗碱在大鼠空肠和回肠的吸收特性,同时比较两者的相关性。方法:采用摇瓶法测定小檗碱在正辛醇-水中的表观油水分配系数,采用大鼠在体肠循环灌流模型研究小檗碱的吸收特性,UPLC测定小檗碱质量浓度,计算小檗碱的油水分配系数、肠吸收速度常数(Ka)表观渗透系数(Papp)。结果:小檗碱和黄连总生物碱在肠液/正辛醇中油水分配系数分别为0.213 5,0.175 7。小檗碱在空肠中Ka=0.046 6,Papp=4.88×10-6cm.s-1,回肠中Ka=0.034 9,Papp=4.13×10-6cm.s-1;黄连总生物碱在空肠中Ka=0.035 1,Papp=3.92×10-6cm.s-1,回肠中Ka=0.026 6,Papp=3.21×10-6cm.s-1;清热通腑片在空肠中Ka=0.028 3,Papp=3.11×10-6cm.s-1,回肠中Ka=0.018 1,Papp=2.23×10-6cm.s-1。结论:小檗碱在空肠和回肠中均有吸收,且吸收速率较慢,但空肠吸收速率大于回肠,具有显著性差异;小檗碱的吸收快慢为小檗碱对照品>黄连生物碱物>清热通腑片,小檗碱油水分配系数的预测结果与肠吸收结果基本一致。Objective： To determine apparent oil-water partition coefficient of berberine monomer and berberine in coptis total alkaloids, investigate absorption kinetics of berberine at jejunum and ileum of rats from berberine monomer and coptis total alkaloids and Qingre Tongfu tablets, then compare correlation between apparent oil-water partition coefficient and absorption kinetics. Method： Apparent octanol-water partition coefficient of berberine was determined by shake-flask method, in situ intestinal recirculating perfusion model of berberine was performed to study its absorption at different intestinal regions. The concentrations of berberine were analyzed by UPLC. Calculated berberine intestinal absorption rate constant （Ka） and apparent permeability coefficient （Papp）in different intestinal regions of rats. Result： Oil-water partition coefficient of berberine and coptis total alkaloids were O. 213 5 and 0. 175 7, respectively. Ka of berberine were 0. 046 6 and 0. 034 9 in jejunum and ileum, respectively; While P pp were 4. 88 ×10^-6, 4. 13 ×10^-6cm·s^-1 , respectively. Ka of berberine in coptis total alkaloids were 0. 035 1 and 0. 026 6 in jejunum and ileum, respectively; While Papp were 3.92 ×10^-6, 3.21 ×10^-6cm·s^-1, respectively. Ka of berberine in Qingre Tongfu tablets were 0. 028 3 and 0. 018 1 in jejunum and ileum, respectively; While P pp were 3. 11 ×10^-6and 2.23 ×10^-6cm·s^-1, respectively （n =6）. Conclusion： Berberine had absorption in jejunum and ileum with slow absorption rate, but the former was greated than the latter with a significant difference ; Absorption rate of berberine was in order of berberine reference standard 〉 coptis total alkaloids 〉 Qingre Tongfu tablets, the predicted results of oil-water partition coefficient of berberine were basically the same with intestinal absorption results.

关 键 词：小檗碱 油水分配系数 在体肠循环灌流模型 UPLC 肠吸收 

分 类 号：R945[医药卫生—微生物与生化药学] R283.6[医药卫生—药剂学]