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目的测定盐酸小檗碱(BH)的平衡溶解度和油水分配系数,并研究BH的大鼠肠吸收机制。方法采用摇瓶-紫外分光光度法测定平衡溶解度及油水分配系数;分别采用酚红法和重量法校正灌流液体积,研究BH 3个剂量组(50,100,150μg.mL 1)在大鼠不同肠段的吸收情况。采用HPLC对灌流前后BH、酚红含量进行测定。结果 BH溶解度随pH值的增加而增加,油水分配系数则相反;酚红法较重量法能更好的减少实验误差,BH在低、中、高3个浓度下,各肠段的有效渗透系数(Peff)有上升趋势,且高浓度与低浓度相比,Peff均有统计学差异(P<0.05);高、中浓度时,BH在空肠吸收较好;低浓度时,BH在十二指肠吸收较好。结论在实验浓度范围内,油水分配系数的预测结果与实际肠吸收结果基本一致;BH在肠道上端比下端吸收更好,延长药物在肠道上段的吸收时间,可达到提高生物利用度的目的。
OBJECTIVE To determine the equilibrium solubility and oil-water partition coefficient of berberine hydrochloride (BH) and to study the intestinal absorption mechanism of BH in rats. Methods The equilibrium solubility and oil-water partition coefficient were determined by shake flask-UV spectrophotometry. The volume of perfusate was corrected by phenol red method and gravimetric method, respectively. The effects of BH 3 dose group (50, 100, 150 μg.mL 1) Absorption. The contents of BH and phenol red before and after perfusion were determined by HPLC. Results The solubility of BH increased with the increase of pH value, but the oil-water partition coefficient was opposite. Compared with the gravimetric method of phenol red method, the experimental error could be reduced better. Under the low, middle and high concentrations of BH, the effective permeability coefficient (Peff) showed an upward trend, and Peff had a significant difference between high and low concentrations (P <0.05). In high and medium concentrations, BH absorbed in the jejunum. At low concentrations, Intestinal absorption better. Conclusions In the experimental concentration range, the prediction results of the oil-water partition coefficients are basically the same as the actual intestinal absorption results; BH absorbs better at the upper end of the intestine than the lower end, prolongs the absorption time of the drug in the upper intestine, and achieves the purpose of improving the bioavailability .