玳玳果黄酮降脂滴丸的肠吸收动力学特性

Absorption dynamics of Citrus Aurantium flavonoid lipid-lowering dropping pills by valgus intestinal capsule model

目的:考察玳玳果黄酮降脂滴丸的肠吸收特性并探讨其作用机制。方法:采用大鼠外翻肠囊模型,建立同时测定大鼠肠吸收液中玳玳果黄酮降脂滴丸特征药效成分新橙皮苷和柚皮苷含量的液-质联用(UPLC-MS)分析法,比较玳玳果黄酮降脂滴丸与原料玳玳果黄酮降脂提取物在大鼠不同肠段的累积吸收量,分析不同质量浓度大鼠空肠段的吸收过程,探讨其肠吸收部位及机制。结果:玳玳果黄酮降脂滴丸特征药效成分新橙皮苷和柚皮苷90 min时的累积吸收量由多到少依次是空肠、十二指肠、回肠和结肠;玳玳果黄酮降脂滴丸在高、中、低剂量下空肠的累积吸收量随时间的增加而增加,相关系数r>0.95,且随着药液质量浓度的增加新橙皮苷和柚皮苷的Ka均增加,符合一级药动学过程;在等剂量给药下,玳玳果黄酮降脂滴丸中新橙皮苷和柚皮苷的累积吸收量约是玳玳果黄酮降脂提取物的1.6倍。结论:玳玳果黄酮降脂滴丸在全肠道均有吸收,小肠的上中段为最佳吸收部位,新橙皮苷和柚皮苷吸收可能为被动吸收循环入体,制成的玳玳果黄酮降脂滴丸可显著改善提取物在肠道的吸收,提高其口服生物利用度。

OBJECTIVE To explore intestinal absorption characteristics and underlying mechanism of Citrus Aurantium flavonoid lipid-lowering dropping pills.METHODS Effective components of Citrus Aurantium flavonoid lipid-lowering dropping pills were chosen as analysis object with rat gut sac model in vitro to establish the UPLC-MS method of simultaneous determination of neohesperidin and naringin in intestinal fluid.Uptake accumulation of Citrus Aurantium flavonoid lipid-lowering dropping pills and extract of Citrus Aurantium flavonoid lipid-lowering dropping pills in different rat intestinal segments were compared and the absorption process of different concentrations in rat jejunum segment were analyzed to discuss the intestinal absorption and mechanism of Citrus Aurantium flavonoid lipid-lowering dropping pills.RESULTS The results of rat intestinal absorption in vitro showed that,90 min accumulation absorption of neohesperidin and naringin,the characteristic pharmaceutical ingredients of Citrus Aurantium flavonoid lipid-lowering dropping pills,decreased sequentially in the order：jejunum,duodenum,ileum and colon.The cumulative absorption of Citrus Aurantium flavonoid lipid-lowering dropping pills at high,medium and low doses in jejunum increased over time,the correlation coefficient r was over 0.95,and Ka values of neohesperidin and naringin increased as solution concentration increased,which satisfied the first order pharmacokinetics.At equal doses,the accumulation uptake of neohesperidin and naringin were 1.6 times of the extract of Citrus Aurantium flavonoid lipid-lowering dropping pills.CONCLUSION Citrus Aurantium flavonoid lipid-lowering dropping pills can be absorbed in the whole intestine,but the best absorption site is middle and upper intestinal segment.It is possible that neohespiridin and naringin can be passively absorbed into circulation,so Citrus Aurantium flavonoid lipid-lowering dropping pills can significantly improve absorption of extract in intestine,and oral bioavailability.