The Drugability Of The Active Components Isolated From Yuanhu Zhitong Compound

Objective:Yuanhu Zhitong compound is mainly composed of Rhizoma Corydalis and Angelica dahurica, with the effect of regulating Qi and activating blood analgesia, the modern clinical found that has a good effect on gastric ulcer. Under the guidance of the TCM theory, this text main from the aspects of the pharmacodynamics, molecular biology, pharmaceutics, pharmaceutical dynamics to explore the feasibility of TCM components and the relevance of main compounds pharmacological activity with Yuanhu Zhitong compound, aim to develop a system evaluation for drugability of Yuanhu Zhitong compound. Though this way to provides basis and strategy for the next new drug research and development, and further study on Yuanhu Zhitong compound, in addition, also to provides ideas for the research of other classical prescription compatibility, pharmacodynamic material basis, action mechanism, and the innovation of TCM components.Methods:The study used the orthogonal test method, chose the content of the effective parts and extraction rate as multi index comprehensive evaluation method to determine the optimum extraction process. The properties of total alkaloids easy to soluble in acid water but hard to caustic soda and coumarin can be dissolved in ethyl acetate were successfully applied to purify effective parts, then established a quality standard about them. The active components were divided into different match-pair groups on the basis of the baseline increase and decrease with the same proportion of TCM components theory. The test selected different match-pair groups of total alkaloids with coumarin and TDE with IMP as research object, gastric ulcer rat model was iuduced by anhydrous alcohol as disease model, from the terms of tissue morphology, the index of ulcer, ulcer inhibition rate and pathologic degree to determined which was the best group,illustrated the rationality of compatibility of TCM and the relevance with original formula. The Caco-2 cell was Chosen as the cell model, under different conditions, though inspected the cell uptake amount of effective components to explore the absorption mechanism of the effective components and compatibility. Effective components were made into solid dispersions, though the indexes of solubility and dissolution to selected out the best material and proportion between drug and carrier material. Finally, through the pharmacokinetic experiment in rats to evaluated preparation.Results and conclusion:The best extraction condition for total alkaloids of Rhizoma corydalis was 8 times 60% ethanol extracted 3 times and 2 h per once. The herb liquor was concentrated to 0.3 g/mL, added the mass fraction is 36%～38% of concentrated hydrochloric acid to controlled the pH to 2.0, added 1 time of petroleum ether extract 2 times, recovery the acid water layer, used strong ammonia to adjusted pH to 11.0,1 time amount of petroleum ether extract 3 times, recovery organic layer, the total alkaloids content could reach to 50%, the content of TDE was not less man 55.6mg/g. The best extraction condition for coumarin of Angelica dahurica was 10 times 75% ethanol extracted 3 times,3h per once. Angelica dahurica herb liquor was concentrated to 2g/mL,2 times amounts of petroleum ether extracted one time,abandoned petroleum ether,2 times amounts of ethyl acetate extracted 3 times, combined the ethyl acetate layer, the total coumarin content could reach to 50%, which of them the IMP content was not less than 42.5mg/g. The results of fingerprint picture showed the different batch of samples have a highly similarities, the effective parts were identified by TLC, the result showed that the spots of characteristic components were quite clear and had a good separation,water content less than 5.0%. Among the different match-pair groups, the effect of Rhizoma corydalis total alkaloids:Angelica dahurica total coumarin (9.4:5.3), TDE:IMP (0.46:0.44) on gastric ulcer induced by anhydrous alcohol in rats were the best, and equal to the original compound group which the total alkaloids:coumarin was 2:1, better than the single drug group. This result not only proved that Rhizoma corydalis total alkaloids, Angelica dahurica total coumarin-TDE、IMP were the main active components, but also elucidated that the original compound is reasonable.Caco-2 Cell experiment results showed that absorbed quantity of TDE and IMP by cells were in a time-dependent manner, and affected by the concentration gradient, the absorption of them was an active transportation mediated by transporter, when TDE and IMP worked together, the experience found that TDE could not promote the absorption of IMP; but IMP could promote the cells absorbed quantity of TDE to a certain extent.So the effect of TDE and IMP work together is better than the separated, this probably related to the cells absorbed quantity of TDE. The solid dispersion was prepared by the carrier of PVP K30 can increased the dissolution and solubility of TDE and IMP significantly. DSC and XRD were used to detect the nature of the studied forms, the analysis suggested that TDE and IMP were present in an amorphorous form in the solid dispersion. The solid dispersions whice the drug carrier ratio was1:1, raw medicine, physical mixture were applied to the pharmacokinetic experiment in rats, the experimental results showed that the preparation of solid dispersions with IMP of TDE could increase the concentration of peak blood drug Cmax and AUC, t1/2 z significantly (P<0.05) and reduce Vz/F and CLz/F (P<0.05) in the rats,so, the solid dispersion could decrease the eliminate rate, prolong the acting time of TDE and IMP in the body, so as to improve the absorption of drugs.