脂质制剂体外动态肠吸收模型的建立及评价

Establishment and evaluation of a dynamic in vitro intestinal absorption model of lipid formulations

根据脂质制剂肠消化吸收的特性,本文在体外脂解模型基础上,引入肠吸收评价方法,建立了一种用于筛选评价脂质制剂的新型体外动态肠吸收模型,包括肠消化和肠组织培养两大体系。探究模型重要参数(Ca2+、葡萄糖、K+)的影响,发现Ca2+浓度的增加能显著增强脂质制剂的肠消化;葡萄糖浓度的递增能显著减慢肠组织活性衰减;K+虽能维持肠组织的活性,但其浓度变化对肠组织活性衰减并无显著性影响;最终选择Ca2+10 mmol.L-1、葡萄糖15 mmol.L?1和K+5.5 mmol.L-1为模型参数。利用该模型评价TypeⅠ脂质制剂得到的体外吸收曲线与大鼠体内吸收曲线呈现极显著的点对点相关性(r=0.995 6,P<0.01)。本模型可望应用于脂质制剂的筛选、评价及预测。

A new dynamic in vitro intestinal absorption model for screening and evaluating lipid formulations was established by means of the characteristics of the intestinal digestion and absorption of the lipid formulations.This model was composed of two systems,including intestinal digestion and the intestinal tissue culture,which drew the evaluation method of intestinal absorption into the in vitro lipolysis model.The influence of several important model parameters such as Ca2＋,D-glucose,K＋ on the two systems of this model has been investigated.The results showed that increasing of Ca2＋ concentration could be significantly conductive to intestinal digestion.The increasing of D-glucose concentration could stepped significantly down the decay of the intestinal activity.K＋ was able to maintain intestinal activity,but the influence of different concentration levels on the decay of the intestinal activity was of no significant difference.Thus the model parameters were set up as follows： Ca2＋ for 10 mmol-L-1,D-glucose for 15 mmol-L-1 and K＋ for 5.5 mmol-L-1.Type Ⅰ lipid formulation was evaluated with this model,and there was a significant correlation between the absorption curve in vitro and absorption curve in vivo of rats（r = 0.995 6,P 0.01）.These results demonstrated that this model can be an attractive and great potential method for the screening,evaluating and predicting of the lipid formulations.