川芎油自微乳化软胶囊大鼠在体肠吸收研究

In situ absorption of self-microemulsifying soft capsule of volatile oil from rhizome of Ligusticum chuanxiong in rats' intestine

为了考察川芎油剂型选择的合理性,进行了原料、包合物和自微乳化软胶囊的比较吸收实验;并进一步明确自乳化软胶囊的小肠吸收特点,进行了不同浓度、不同肠段、有无胆汁分泌的在体肠吸收实验。通过药液在肠腔内循环,以藁本内酯为川芎油的指标性成分测定不同时间回流液中蒿本内酯浓度变化,得到药物的吸收情况。结果表明,自微乳化软胶囊显著提高藁本内酯的吸收(P<0.001),效果最好。400μg·mL-1藁本内酯的吸收显著高于200和100μg·mL-1(P<0.001),而后两个浓度的吸收无差异。胆管结扎与否不影响药物吸收。自乳化软胶囊可被大鼠全肠段吸收,其中十二指肠吸收最好,各肠段Ka、Papp是十二指肠>空肠>回肠=结肠。

In order to investigate the rationality of formulation, the absorption behavior of volatile oil from rhizome of ligusticum chuanxiong （VOC） was compared with that of β-cyclodextrin inclusion complex and self-microemulsifying soft capsule （SMESC）. To study the properties of intestinal absorption in situ of SMESC, a series of studies were carried out including the absorption at different concentrations, at different intestinal regions and under different bile secretion conditions. The samples of the perfusion solution were collected at certain intervals. Ligustilide （LD） was chosen as marker component of VOC and the concentrations of which in the perfusion samples were determined by HPLC method. The results demonstrated that the absorption of LD in SMESC was the best and the absorption of VOC increased apparently （P 〈 0.001）. The absorption of LD at concentration of 400 μg·mL^-1 was better than that at 200 μg·mL^-1 and 100 μg·mL^-1 （P 〈 0.001）, while there was no significant difference between the absorption at concentrations of 200 μg·mL^-1 and 100 μg·mL^-1. The absorption of SMESC was not apparently influenced by bile secretion. SMESC could be absorbed in whole intestinal segments. The absorption rate constants （Ka） or apparent permeability coefficients （Papp） of SMESC showed duodenum 〉 jejunum 〉 colon = ileum. Ka and Papp of SMESC at duodenum were significantly higher than that at the other regions of intestine （P 〈 0.001）.