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目的测定白头翁皂苷B3的表观溶解度及油水分配系数,并研究其大鼠在体肠吸收机制。方法 HPLC-ELSD法测定B3的表观溶解度和油水分配系数,重量法计算大鼠在体单向肠灌流实验中吸收速率常数(Ka)和表观吸收系数(Papp)。结果白头翁皂苷B3在37℃有机溶剂中的表观溶解度较低,在碱性磷酸盐缓冲液中的表观溶解度较高;白头翁皂苷B3在不同磷酸盐缓冲液中的油水分配系数相差不大;白头翁皂苷B3在大鼠十二指肠、空肠、回肠和结肠的Ka和Papp没有显著性差异(P>0.05);白头翁皂苷B3在0.05~2.5 mg/m L随着浓度提高出现过饱和现象;加入P-糖蛋白抑制剂维拉帕米和P-糖蛋白底物地高辛后,都能显著提高白头翁皂苷B3的Ka值。结论在实验浓度范围内,溶解度和油水分配系数能够较好地预测肠吸收情况;白头翁皂苷B3不完全依赖浓度梯度转运,细胞膜上的载体蛋白参与了药物的转运过程,其小肠吸收机制并不完全为被动转运;受吸收部位影响较小,无特殊的吸收窗;P-糖蛋白介导了白头翁皂苷B3的小肠吸收。
Objective To determine the apparent solubility of Pulsatilla saponin B3 and the partition coefficients of oil and water, and to study its mechanism of intestinal absorption in vivo. Methods HPLC-ELSD was used to determine the apparent solubility and oil-water partition coefficient of B3. The gravimetric method was used to calculate the absorption rate constant (Ka) and apparent absorption coefficient (Papp) of rat in the one-way intestinal perfusion experiment. Results The apparent solubility of Pulsatilla saponin B3 in organic solvent at 37 ℃ was low, and its apparent solubility in alkaline phosphate buffer was high. The oil-water partition coefficients of Pulsatilla saponin B3 in different phosphate buffers were similar. There was no significant difference between Pulsatilla saponin B3 and Ka and Papp in rat duodenum, jejunum, ileum and colon (P> 0.05); Pulsanne B3 in 0.05-2.5 mg / m L supersaturated with increasing concentration; Adding P-glycoprotein inhibitor verapamil and P-glycoprotein substrate digoxin, can significantly improve the Pulsatilla saponin B3 Ka value. Conclusion In the experimental concentration range, solubility and oil-water partition coefficient can predict intestinal absorption well; Pulsigena glycosides B3 do not completely depend on the concentration gradient transport, the carrier protein on the cell membrane involved in drug transport process, and its intestinal absorption mechanism is not complete Passive transport; less affected by the absorption site, no special absorption window; P-glycoprotein mediated Pulsatilla saponin B3 intestinal absorption.