| The modern research for compatibility regularity of Formulas of tradional chinese medicine(TCM) is a key point and difficult point for research of TCM modernization. With the progess of science and the acceleration of the course of TCM modernization, the active component or composition compatibility has become the new model of research for compatibility regularity of formulas of TCM. The research project is a part of the national"973"Project:Investigation in compatibility regularity of Formulas of TCM. In this paper, the recipe of GuanxinⅡwas selected to as a tool. To obtain a scientific illustration to the compatibility principle,and to acquaire an evaluation for the reasonable existance of decoction from the deep research of effectt on the pharmacokinetics of Danshensu(DSS) and Ferulic acid(FA) exerted by GuanxinⅡin different compatibility formulas and in Different Formulations.In brief,the experiment aimed to provide a new example illustration for the perfection of composition compatibility modal.Aim:To obtain a reasonable illustration to compatibility regularity of GuanxinⅡand it's scientific meaning from the research for pharmacokinetic course of DSS and FA in vivo in different compatibility formulas and in Different formulations of GuanxinⅡ.Methods:1.A ZORBAX Eclipse plus C18(2.1×10mm,1.8μm) column was used as the stationary phase.The mobile phase was composed water and acetonitrile with the volum ratio of 83/17. Taking ESI(-) as ionization source,multiple reaction monitoring.Meanwhile, selecting a reasonable sample pretreatment with the aim of establishing a method to analyze DSS and FA in beagle dog plasma.2.To dismember GuanxinⅡby efficacy,that was, group of GuanxinⅡwhole composition extracts(group A), GuanxinⅡHUOXUE composition extracts(group B), GuanxinⅡLIQI composition extracts(group C), GuanxinⅡDANSHEN extracts(group D) and GuanxinⅡCHUANXIONG extracts(group E).Besides, the group of GuanxinⅡdecoction(group F) was added. Beagle dogs were administrated different GuanxinⅡ compatibility formula and GuanxinⅡdecoction as above. The experiment was performanced according to Latin square design,with 6 cycles to repeat. LC-MS/MS was application to detect the concentration of DSS and FA in plasma. Pharmacokinetic parameters were calculated by related softwares: AUC,MRT,T1/2,Vz/F,CLz/F,Cmax,Tmax and inter-group differences were compared.Results:1.A method which is sensitive, peculiar, precise and reliable to determine the quantities of DSS and FA in Beagle plasma is established.2.In the research of pharmacokinetics of DSS and FA in different GuanxinⅡcompatibility formulas in Beagle dogs,compared with group B and group D, the Cmax and AUC(0→t) of DSS in group A are all on the rise;compared with group C and group E, the CLz/F of FA in group A is decreased,however, the V of FA in group A is increased. On the wholel, the pharmacokinetic parameters of DSS and FA in different GuanxinⅡcompatibility formulas are all the similar,but no significance.3.In the research of pharmacokinetics of DSS and FA in different GuanxinⅡformulations in Beagle dogs, compared with group A, the AUC(0→t),Cmax and CLz/F of DSS in group F are all on the increase(P<0.01 or 0.05), nevertheless, V and MRT(0→t) of DSS in group A are decreased(P<0.01 or 0.05); compared with group A, the Tmax and MRT(0→t) of FA in group F are all on the increase(P<0.01 or 0.05), however, Cmax,CLz/F and V of FA in group A are decreased(P<0.01).That is, the Cmax and bioavailability of DSS in GuanxinⅡdecoction are much higher, the elimination of FA is much slower and the mean residence time of FA is much longer than in GuanxinⅡwhole composition extracts.Conclusions:1. Pharmacokinetics of DSS and FA from different GuanxinⅡcompatibility formulas,dismembered by efficacy, in Beagle dogs are all the same,having no significant difference.2. The maximum concentration and bioavailability of DSS in GuanxinⅡdecoction are much higher, the elimination of FA is much slower and the mean residence time of FA is much longer than in GuanxinⅡwhole composition extracts.3.Comprehensively analysis,combining pharmacokinetics with pharmacodynatics of GuanxinⅡ,shows that the efficacy of GuanxinⅡexerted by activating blood and dissolving stasis,with the help of promoting the circulation of Qi and regulating vital energy.4.The reasonability of decoction's existence is proved. This study illustrates the principle of compatibility dismembered by efficacy in the light of pharmacokinetics,exploring tentatively the methods by using effective composition to researchIn this article we undertook a preliminary explore in the formulas regularity of TCM by dividing formulas into different components based on their activating blood and regulating vital energy differences; the rationality of existence of chinese traditional decoction is observed by comparing the in vivo process of traditional decoctions and effective components recombination formulation; blood sample treatment procedure containing DSS and FA simultaneously is established which provides a methodology model for biological sample pretreatment and pharmacokinetics research of TCM. |
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