UPLC-MS法研究薏苡仁油纳米粒离体肠吸收机制及特性

目的：考察薏苡仁油纳米粒在大鼠小肠的吸收特性，探讨薏苡仁油纳米粒的吸收部位及吸收机制。方法：采用大鼠离体外翻肠囊模型，以莪术醇为内标，薏苡仁油纳米粒药效特征成分甘油三油酸酯为评价指标，超高效液相色谱-质谱联用分析法测定大鼠肠吸收液中甘油三油酸酯的浓度，并比较在相同质量浓度下薏苡仁油原料、薏苡仁油纳米粒在大鼠十二指肠、空肠、回肠和结肠等不同肠段的累积吸收量，以及不同给药剂量下大鼠空肠的吸收情况，探讨薏苡仁油纳米粒的吸收机制。结果：薏苡仁油纳米粒中特征成分甘油三油酸酯在不同肠段中90 min时的累积吸收量按十二指肠、空肠、回肠、结肠依次下降，除回肠与结肠两者之间以外，均存在显著性差异（P<0.05）；在高、中、低3种不同给药剂量条件下，在空肠段的吸收随着时间的增加而增加，以肠囊内甘油三油酸酯浓度的对数值lnC对取样时间t做线性回归，相关系数r大于0.990，表现出一级吸收动力学过程，吸收速率常数（K_a）均随药物剂量的增加而增加；在相同剂量下，薏苡仁油纳米粒特征成分在大鼠空肠90 min的累积吸收量是薏苡仁油原料的1.1倍。结论：大鼠小肠上中段是薏苡仁油纳米粒的最佳吸收部位，为被动吸收，其吸收呈一级动力学过程；与薏苡仁油原料相比，薏苡仁油纳米粒可明显改善薏苡仁油甘油三油酸酯的肠吸收。

Objective: To study the intestinal absorptive characteristics of nanoparticles of coix seed oil in rats and to investigate the absorption sites and absorption mechanism of nanoparticles of coix seed oil. Methods: The isolated everted gut sac model was used,curcumenol was chosen as internal standard,olein was chosen as representative component,and the method of UPLC-MS was established to determine olein concentration of intestinal absorption liquid in rat. The accumulative absorption of the coix seed oil and nanoparticles of coix seed oil in duodenum,jejunum,ileum and colon of rats with the same administration dosage and that in jejunum with different administration dosage were studied,and the absorption mechanisms of oral nanoparticles of coix seed oil were investigated. Results: The cumulative absorption of the characteristic components—olein of nanoparticles of coix seed oil in different intestinal segments after 90 min drop in turn,from duodenum,jejunum,ileum to colon,and there were significant differences except between ileum and colon(P<0.05).In high,medium and low dosage conditions,the absorption of jejunum segment increased with time,and the natural logarithm of concentration of olein was significantly correlated with sampling time in all three different dosages,and the square of correlation coefficient exceeded 0.990,which showed first order rate process,the absorption rate constant(Ka)increased with the increase of the dose,indicating that it might be passive absorption.With the same administration dosage,the accumulative absorption amount of olein at 90 min in the nanoparticles of coix seed oil was 1.1-fold that in the coix seed oil. Conclusion: The upper and middle part in small intestine of nanoparticles of coix seed oil is the best absorption site,and the absorption can be passive absorption,showing the first-order kinetics;the intestinal absorption of olein can be significantly improved by nanoparticles of coix seed oil comparing with coix seed oil.