鸦胆子油油水分配系数及其乳剂大鼠在体肠吸收特性研究

O/W partition coefficient of brucea javanica oil and absorption characteristics of its emulsion in rat intestine in situ

目的:测定鸦胆子油的油水分配系数,并考察鸦胆子油乳在大鼠的肠吸收性质及机制。方法:采用经典摇瓶法测定鸦胆子油的油水分配系数(P);采用在体单向肠灌流法模型研究不同浓度鸦胆子油乳在大鼠的十二指肠、空肠、回肠及结肠的吸收情况,并测定其吸收速率常数(Ka)、吸收率(Fa)和表观渗透系数(Papp)。结果:鸦胆子油疏水常数logP的平均值为1.193。鸦胆子油乳在小肠(十二指肠、空肠、回肠)吸收较好,在结肠吸收较少且不规则。其Ka、Fa和Papp按十二指肠、空肠、回肠依次下降且差异显著(P<0.05),不同浓度在同一肠段随着浓度增加,吸收也随之增加,高浓度与低浓度相比,Fa和Papp差异显著(P<0.05),Ka没有显著性差异。结论:鸦胆子油透过生物膜的能力较强。鸦胆子油乳在十二指肠吸收最佳,在小肠内的吸收为一级动力学过程,并无自身浓度抑制作用,可能主要为被动转运机制。

Objective： To determine the O/W partition coefficient of brucea javanica oil and investigate the absorption characteristics and mechanism of its emulsion in rat intestine. Methods： The shake-flask method was employed to determine the O/W partition coefficient （ P ） of brucea javanica oil. The absorptions of six concentrations of brucea javanica oil emulsion in different intestinal segments were studied by in situ rats single pass perfusion model, and the absorption rate constant （Ka）, absorption rate （Fa） and apparent permeability coefficients （Papp） were determined. Results： The logP of brucea javanica oil was 1.193. Brucea javanica oil emulsion was absorbed at all intestinal segments. However, the absorption of small intestine was better than that of colon. The Ka, Fa and Papp of various intestinal segments decreased in turns in duodenum, jejunum and ileum （P〈 0.05）. Drug concentration had little significant effect on the Ka in the same intestinal segment. The uptake of the drug increased when the concentration rose, and the Fa and Papp at the high concentration were significantly improved compared with those at the low concentration （P〈 0.05）. Conclusion： According to the logP, it was conjectured that brucea javanica oil could easily permeate the membrane. The absorption of the duodenum was the best at various segments of rat intestine. The absorption of small intestine was first-order kinetics without highest saturated concentration and passive transport mechanism might be the major factor.