离体外翻肠囊法研究白及提取物中6种成分的肠吸收特性

为研究白及提取物中4-(葡萄糖氧基)-肉桂酸葡萄糖氧基苄酯(B12)、2-异丁基苹果酸(B6)、1-4-(葡萄糖氧)苄基]-2-异丁基苹果酸酯(B17)、1,4-二4-(葡萄糖氧)苄基]-2-异丁基苹果酸酯(B14)、二氢菲1(B19)和1,4-二4-(葡萄糖氧)苄基]-2-异丁基苹果酸酯-2-4-O-肉桂酰基-6-O-乙酰基]葡萄糖苷(B23)6个成分在大鼠小肠中的吸收动力学特性。实验采用大鼠离体外翻肠囊模型考察各成分在不同浓度、不同肠段的吸收特性,建立超高效液相色谱-三重四极杆串联质谱联用仪(UPLC-MS/MS)法测定各成分含量,计算累计吸收量和吸收速率常数。结果表明,除B6成分的低浓度外,各成分在不同浓度、不同肠段下均表现为线性吸收,其回归相关系数(R)均达到0.9以上,符合一级吸收速率,且吸收速率常数随着浓度的增加而增加,提示各成分吸收机制为被动吸收;在同一浓度下不同肠段的总体吸收趋势为十二指肠的吸收要大于回肠、结肠和空肠。综上,白及提取物中6种成分在小肠中均有吸收,但小肠对各成分的吸收具有选择性。本研究可为白及提取物的药物临床开发,确定药物剂型方面提供了一定的实验参考。

Study on absorption characteristics of six components from Bletilla striata extract by isolated everted intestine model

The absorption characteristics of the Bletilla striata extract,including blestroside (B12),α-Isobutylmalic acid (B6),gymnosides V (B17),militarine (B14),dihydrophenanthrenes1 (B19) and gymnosides IX (B23) in rats small intestine were investigated.Study on absorption characteristics of different components in different concentrations and different intestinal segments by isolated everted intestine model.A UPLC-MS/MS method was established to determine the contents of each component and to calculate the accumulative absorption and absorption rate constants.The results showed that except for the low concentration of B6,all the components showed linear absorption at different concentrations and different intestinal segments.The regression correlation coefficient ( R ) was above 0.9,which was consistent with the first order absorption rate,and the absorption rate constant increased with the increase of concentration.It is suggested that the absorption mechanism of each component is passive absorption.At the same concentration,the total absorption of different intestinal segments was greater than that of ileum,colon and jejunum.In conclusion,the six components of Bletilla striata extract were absorbed in the small intestine,but the absorption of each component was selective in the small intestine.This study can provide some experimental references for the clinical development of Bletilla striata extract and the determination of drug dosage form.