The Initial Impact Study Of Achyranthes On Tongsaimai Pellets Main Active Ingredients In Vivo Pharmacokinetics And Distribution

This study was composed of the literature and experimental studies of two parts.In the literature study, the reviews were processed from "studies on the Meridian tropism of literature and experimental research methods" and "The chemical constituents’research progress of each crude drugs of Tongsaimai prescription" two aspects. The studies on the Meridian tropism of literature and experimental research methods point out that the meridian tropism research should be conducted with the study of mechanism of Chinese medicine, and taking the advantage of the modern technology to conduct the meridian tropism further and more systematically investigated. In the chemical constituents research progress of each crude drugs of Tongsaimai prescription study, each crude drugs chemical composition and the related pharmacological actions were summarized to lay the foundation of the qualitative analysis and quantitative research, as well as the pharmacokinetic and tissue distribution study of the chemical composition of Tongsaimai, providing material basis for the rational use and clinical research of TSM after subtracting Achyranthes bidentata simultaneously.In the experimental study, it was processed mainly from "The influence of chemical composition of Tongsaimai after subtracting Achyranthes bidentata in vitro studies"、"The influence of chemical composition in plasma in vivo of Tongsaimai after subtracting Achyranthes bidentata"、"Studies on the effects of Achyranthes bidentata on Tongsaimai pellets main active ingredients chlorogenic acid、isoliquiritin、 harpagoside and glycyrrhizin in vivo pharmacokinetics" and "Studies on the effects of Achyranthes bidentata on Tongsaimai pellets main active ingredients tissue distribution in vivo" four aspects.In the research of "The influence of chemical composition of Tongsaimai after subtracting Achyranthes bidentata in vitro studies", according to the mass spectrometry for the precise molecular weight information and cracking multistage mass spectrometry to identify the chemical composition in Tongsaimai pellets. The determination of ten kinds of effective composition content of Tongsaimai pellets was established employing super high performance liquid chromatography-tandem mass spectrometry analysis method at the same time. The content influence of the ten chemical components of Tongsaimai was compared after subtracting Achyranthes bidentata. The established method was specific, rapid and accurate for the determination of ten effective components in Tongsaimai pellets. The results showed that, there were no significant impacts on Tongsaimai active compounds content after subtracting Achyranthes bidentata.In the research of "The influence of chemical composition in plasma in vivo of Tongsaimai after subtracting Achyranthes bidentata". Accord ing to the mass spectrometry for the precise molecular weight information and cracking multistage mass spectrometry to identify the chemical composition in plasma after oral adminimistration TSM and its optimized formula39compounds were analyzed in plasma of optimized formula and30compounds were analyzed in plasma of Tongsaimai pellets through Xcalibur2.2SP1data processing system. These different compounds between the two groups were not reported for ischemic stroke disease to have certain pharmacodynamics effects. Therefore, preliminary analysis showed that there were no significant impacts on Tongsaimai active compounds in plasma after subtracting Achyranthes bidentata.In"studies on the effects of Achyranthes bidentata on Tongsaimai pellets main active ingredients chlorogenic acid、isoliquiritin、harpagoside and glycyrrhizin in vivo pharmacokinetics", a method for the simultaneous determination of chlorogenic acid、 isoliquiritin、harpagoside and liquiritigenin in rat plasma was established by UPLC-MS/MS. It turned out that the analytes of Tongsaimai pellets groups Cmax and AUC(o-∞) values were higher than that with Achyranthes bidentata group, and the Cmax values of chlorogenic acid had significantly difference (p<0.05), the AUC(o-∞) values of chlorogenic acid and glycyrrhizin had significantly difference (p<0.05); The Tmax and CL values of two groups had no significantly difference (p>0.05). Results showed that the established method was specific, rapid, accurate and sensitive for the studies of Tongsaimai pellets four main active ingredients in rat in vivo pharmacokinetic, and Achyranthes bidentata have varying degrees of effects on Tongsaimai pellets four main active ingredients in rat in vivo pharmacokinetic behaviors.In"studies on the effects of Achyranthes bidentata on Tongsaimai pellets main active ingredients tissue distribution in vivo", a method for the simultaneous determination of chlorogenic acid、isoliquiritin、harpagoside and other six compounds in rat tissue was established by UPLC-MS/MS.To compare the impacts on the distribution of each component in the organization of subtracting Achyranthis bidentata, eight compounds was quantitative analyzed in the organization by UPLC-MS/MS, From the overall time of different components distribution, the component distribution of drug concentrations in the organization of subtracting Achyranthes bidentata group was higher than Tongsaimai pellets group.Through the contrast experiment of tissue distribution results,it turned out that, adding or subtracting radix achyranthis bidentatae have different degree of influence of each component in each organization. We can reveal scientific rationality of subtracting radix Achyranthis bidentatae of Tongsaimai from one aspect.This study was processed the medicinal properties of radix achyranthis bidentatae "virtue" downward "characteristics" through the literature research and experimental research two aspects, completed the comparative analysis of chemical components in vivo and in vitro, by means of chemical composition in vitro and in vivo pharmacokinetics and tissue distribution of impact analysis. Preliminary reveals the radix achyranthis bidentatae "virtue downside" of the medicinal nature characteristics and the correlation between endogenous and exogenous substances in specific distribution of scientific connotation. Simultaneously reveals the famous proprietary Chinese medicine Tongsaimai to subtracting radix Achyranthis bidentatae science and rationality for the treatment of ischemic cerebral apoplexy.