| It is worthy of studying that combination(component type and quantity)prescription(including demolition party group)compatibility of Chinese herbal can be generated on the chemical composition of traditional Chinese medicine in vivo pharmacokinetics significant role,and is closely related to the efficacy and side effects.The most important several data including the prescription(including demolition party group)composition(component type and quantity),the main pharmacokinetic pharmacodynamic characteristics between the amount of volume exist the complex relationship of a lot of nonlinear,high noise,multi-factor.This paper based on"prediction of complex systems can be studied through model simulations" principles and using the method of system simulation established the dynamic mathematical model of the ratio of mutual compatibility of the four primary components which are berberine,baicalin,geniposide,palmatine.Thus,in a certain range,that can be thinked as the simulation model of the whole party.By comparing the differences of different PK-PD in model system and analyzing the role of the characteristics of the main component compatibility portfolio,it could clarify the mechanisms in which substances play in the role of anti-cerebral ischemia and guide to use clinical medicine in more rational way.Purposes:A comparative study of pharmacokinetics in rats of cerebral ischemia and exploration the interacted law between each component,combined the data of anti-oxidative free radical,then curves of concentration-time-effect were built,which can verify result of pharmacodynamic preliminary.Contents:1.Comparative study of simulation portfolio group of geniposide themed:Compared the pharmacokinetic characteristics of main ingredients in berberine+baicalin+geniposide group,berberine+geniposide group,baicalin+ geniposide group,berberine+baicalin+geniposide+palmatine group,baicalin+geniposide+ palmatine group in vivo using rats with cerebral ischemia.Meanwhile,figured out the different pharmacokinetic characteristic between rats-MCAO and rats-normal after being administered;2.Comparative study of simulation portfolio group of baicalin themed:Compared the pharmacokinetic characteristics of main ingredients in berberine+baicalin+geniposide group,berberine+baicalin group,baicalin+ geniposide group,berberine+baicalin+geniposide+palmatine group,berberine+baicalin+palmatine group,berberine+baicalin+palmatine group,baicalin+geniposide+ palmatine group,berberin + palmatine group in vivo using rats with cerebral ischemia.Meanwhile,figured out the different pharmacokinetic characteristic between rats-MCAO and rats-normal after being administered;3.Comparative study of simulation portfolio group of palmatine themed:Compared the pharmacokinetic characteristics of main ingredients in berberine+baicalin+geniposide+palmatine group,berberine+baicalin+palmatine group,berberine+baicalin+palmatine group,baicalin+geniposide+ palmatine group,berberin + palmatine group in vivo using rats with cerebral ischemia.Meanwhile,figured out the different pharmacokinetic characteristic between rats-MCAO and rats-normal after being administered;4.Comparative study of simulation portfolio group of berberine themed;Compared the pharmacokinetic characteristics of main ingredients in berberine+baicalin+geniposide group,berberi ne+gen i posi de group,berberine+ palmatine group,berberine+ baicalin group,berberine+ palmatine+geniposide group,berberine+baicalin+geniposide+palmatine group,baicalin+geniposide+ palmatine group in vivo using rats with cerebral ischemia.Meanwhile,figured out the different pharmacokinetic characteristic between rats-MCAO and rats-normal after being administered;5.Classified integration of indicative constituents in each analog combinationsin group;6.Collected anti-free radical oxidation data in each analog combinationsin pharmacodynamic n rats of cerebral ischemia,the drug combination in vivo drug integrate all indicators of cerebral ischemia in rats pharmacokinetic establish the plasma concentration-time-effect curves.Methods:1.The formulated into prepare various analog combinations using berberine,baicalin,geniposide,palmatine extract substance.After administration,draw blood at a predetermined different time points.2.Established content detection methods of berberine,baicalin,geniposide,palmatine in the plasma;examined pharmacodynamic influence law of the main component of the different groups of drugs at pathological state and normal state;3.Make comprehensive integration in each analog combinations using user-defined weight coefficient based on AUC,studying the function of each herb in prescription,and the interaction between them;4.Conducted the pharmacodynamic study of the anti-free radical oxidation and measured SOD and MDA contents of plasma at different time points;combined total integration of indicative constituents in each analog combination,which can verify result of pharmacodynamic preliminary.Results and Conclusions:Pharmacokinetic studies:1)after oral administration,compared with the normal group,cerebral ischemia in rats for the absorption of the main ingredients are relatively good performance in peak time is short,high peak concentration pharmacokinetic the parameters;berberine+baicalin+geniposide+ palmatine;2)for geniposide model group,the all-party group Huanglianjiedu soup combination group compared with the simulation,geniposide palmatine+berberine group is not rather than the whole in the side of the absorption,AUC(0-?)was respectively 218.277±38.916 mg/L·h and 208.272±72.411 mg/L·h;next is geniposide+berberine group and geniposide+berberine+palmatine group,AUC(0-?)was respectively 130.812±48.276 mg/L·h and 116.686±7.483 mg/L·h,next is geniposide +baicalin+ palmatine + berberine group and geniposide +baicalin+berberine group and geniposide +baicalin group,AUC(0-?)was respectively 92.18±12.078,78.739±7.503,72.009±8.601 mg/L·h;for baicalin model group,comparing the all-party group HLJDT with the simulation group,the whole group has the same absorption with geniposide +baicalin group,AUC(0-?)was respectively 66.732±10.169 and 63.798±11.642 mg/L·h,next is baicalin+geniposide+palmatine+berberine group and baicalin+geniposide + palmatine group and baicalin+geniposide +berberine group and baicalin+berberine group,AUC(0-?)was between 20 mg/L·h and 30 mg/L·h,next is baicalin+palmatin+palmatine group;For palmatine model group,comparing the all-party group HLJDT with the simulation group,palmatine+berberine group and palmatine+berberine group have the best absorption,AUC(0-?)was respectively 46.47±9.542 mg/L·h and 48.398±26.521 mg/L·h,have the more longer average dwell time,MRT(0-±)was respectively 151.546±106.088 h,151.546±106.088 h.All-party group and the rest of the group to absorb considerable,were relatively poor absorption.For berberine model group,comparing the HLJDT group with the simulation group,the HLJDT group has the best absorption,AUC(0-?)is 161.92±44.503 mg/L·h,followed by berberine+geniposide+baicalin+palmatine group and berberine+geniposide group and berberine+geniposide+palmatine group,AUC(0-?)are 62.301±37.328 mg/L·h and 49.635±7.149 mg/L·h and 45.888±7.18 mg/L·h.Surplusthe has the worst absorption,AUC(0-?)were nearly 20 mg/L·h.3)After HLJDT and various analog combination group are integrated,we found that palmatine+berberine+geniposide group and berberine+geniposide group are most closesd to the HLJDT group,AUC(0-?)are 175.356±30.948,104.961±35.376,134.64±38.35 mg/L·h,MRT(0-?)are 42.528±11.715,27.749±15.01,51.19±17.02 h;Tmax are 0.5±0,0.75±0,0.542±0.102 h;Cmax are 10.118±0.627,9.15±0.527,8.05±1.43 mg/L,the worst absorption is berberine+ baicalin group,AUC(0-?)is 16.362±2.523 mg/L·h,the absorption of the remaining combinations simulation group were substantially the same and between the two.Results of anti-free radical oxidation showed that cerebral ischemia cause to hypoxic injury occurred on rats,after being administered,the contents of SOD had an ascending trend in 72h and the levels of MDA decreased significantly.It resulted from HLJDT simulation groups can improve the hypoxic injury caused by cerebral ischemia.HLJDT in the rebound effect of reducing the level of MDA and SOD is close to palmatine + berberine+geniposide group;curves of SOD and the curves of MDA showed no significant dose-effect relationship from the PK/PD model. |
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