| Object:Oral administration is the most common clinical method of drug application. Because it is convenient,economical and safer. After have the drug that will be absorbed into the blood by the gastrointestinal mucosa, play the role of local or systemic treatment. However, the process of oral absorption will be affected by many factors which led to the slow and irregular absorption and bioavailability, such as drug formulation,drug concentration,the way of transmembrane transport,first pass elimination of the liver. Through the material basis and mechanism of traditional Chinese medicine research that to understand the process of pharmacological active ingredient of Chinese medicine in the body transfer, absorption and interaction, and then to provide evidence for Chinese medicine formulations selection,,prescription filter,process optimization,,quality assessment,,improvement of oral bioavailability.Method:The topic chose Schisandra as the model drug which is widely used in clinical for liver protection and choleretic, Using orthogonal experimental design to optimize the preparation of total lignans of Schisandra, and to establish the in situ intestinal perfusion model and Caco-2 cell transport model to investigated the effect of concentration, pH, absorption enhancers and P-gp inhibitors on to research intestinal absorption of total lignans of Schisandra.Result:â‘ The best extraction of total lignans of Schisandra is to extract 2 times per 60min by 60% EtoH of 10 times.â‘¡The result of in situ intestinal perfusion display that four active ingredients of Schisandrol A,Schisantherin A,Schisandrin A and Schisandrin B, while the concentration doubled, the absorption rate constant (Ka) and apparent permeability coefficient (Papp) was not significantly different Within the concentration range in the study (P>0.05). Add SDS and EDTA which are the two common absorption enhancers, to compare with the normal group, Schisandra four active ingredients of Schisandra on the absorption rate constant (Ka), conversion rate of absorption per unit of time (A%) and the apparent permeability coefficient (Papp) were significantly lower (P<0.05), and absorption half-life (t1/2) was significantly longer (p<0.05). Adding P-gp inhibitors verapamil (VP) compared with normal group, four active ingredients of Schisandra on the absorption rate constant (Ka), absorption half-life (t1/2) is not significant difference. But was able to increase the amount of Schisandrin A and Schisandrin B significantly (P<0.05), while the correlation coefficient of absorption of Tween 80 were significantly decreased (P<0.05).â‘¢results of Caco-2 cell model transport show that:To compared with the medium dose group, in the high and low dose group, Ka and Papp of Schisandrol A and Schisantherin A are significant difference (P<0.05) about the transfer on polycarbonate membrane. After adding absorption enhancers SDS, Ka and Papp of Schisandrol A and Schisantherin A are significantly higher (P<0.05). after adding P-gp inhibitors verapamil (VP), Ka and Papp of Schisandrol A and Schisantherin A are significantly higher in the AP-BL direction of transit (P<0.05), but in the BL-AP direction of transit, Ka and Papp of the two active ingredients are both significantly lower (P<0.05).Conclusion:Four active ingredients of total lignans of Schisandra include Schisandrol A,Schisantherin A,Schisandrin A and Schisandrin B are not only the carrier-mediated transport in intestine, but also all the substrate of P-gp. By adding the P-gp inhibitor verapamil can inhibits efflux function of P-gp to promote intestinal absorption of drugs.The research explore the absorption mechanism of active ingredients by multi-angle method and multi-biopharmaceutical models. There is prepare to provide a theoretical basis for Schisandra relevant preparations and development,process optimization,quality control and to improve its bioavailability. |
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