盐酸小檗碱的溶解度及油水分配系数与大鼠在体肠吸收之间的相关性研究

Correlativity Between Solubility O/W Partition Coefficients of Berbenine Hydrochloride and Intestinal Absorption in Rats in Situ

关键词:  盐酸小檗碱  在体单向肠灌流法  吸收  溶解度  油水分配系数

Key words:  berbenine chloride  in situ single pass perfusion  absorption  solubility  O/W partition coefficients

摘要:

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(50，100，150 μg·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(P_eff)有上升趋势，且高浓度与低浓度相比，P_eff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。

Abstract:

OBJECTIVE To determine the equilibrium solubility and the partition coefficient of Berbenine Hydrochloride (BH) and to evaluate its intestinal absorption characteristic. METHODS The solubility and partition coefficient of BH were measured by shaking flask-UV spectrophotometry．The absorptions of three concentrations(50, 100, 150 μg·mL^-1) of BH in different intestinal segments were studied by phenol red assay and gravimetry. The concentrations of BH and phenol red were determined by HPLC. RESULTS The solubility of BH was increased with the pH increase of the buffer solution，and oil-water partition coefficient was decreased with increasing the pH of the buffer solution. Phenol red assay was better to reduce experimental error than gravimetry. There was positive correlation between the Permeability coefficient(P_eff) of each intestine and concentrations of BH, and it has obvious difference(P<0.05) between the high concentration and low concentration. BH was well absorbed in jejunum at high and middle concentration, however, well absorption was observed in duodenum at low concentration. CONCLUSION In the experimental range, results of partition cofficients was in good accordance with predictive ones. BH was well absorbed at upper intestine than lower intestine over the concentration range. Extension of BH absorption time at upper intestine, could improve bioavailability.