The Study On The Compatible Relationship Of Shuang Shen Tong Guan Based On The Pharmacokinetics

Of traditional Chinese medicine composition is complicated, into the body after a number of components.The response of the body to the Chinese native medicine ingredient complex.Compound drug compatibility, in the main effective components in vivo pharmacokinetic process interact. Main ingredients of metabolites in the body will change because of compatibility, which is from the perspective of the pharmacokinetic study of Chinese medicine compound compatibility relations.Pharmacokinetics of Chinese medicineand focus on the body the disposal process of Chinese native medicine ingredient. From Chinese medicine and the interaction process of the organism, respectively from the drug absorption, distribution, metabolism and excretion phase inspection had experienced a series of content and the nature of the change, so as to analysis from the aspects of dynamics and drug metabolism process of drug disposition by the body.The Chinese medicine compound compatibility of different before and after combination.Part I Study on the Compatible Relationship of Shuang Shen Tong Guan Based on the PharmacokineticsChapter 1:Object: To establish the ginsenoside, salvia phenolic acids and corydalis alkaloid in rat plasma main ingredients of LC-MS/MS analysis method.Methods: ginsenosides are divided into two groups, group A:Rg1, F1 and Rh1, group B:Re, Rbi, Rd, Rb2/3, Rc, Rf.Alkaloids can be divided into two groups, group A:Ber. THP、Pal、DHC、Acrp. Gla and Jat, group B:eBer、Cor、Wor、Pro、Cop, THJ and THB. Salvia phenolic acids composition can be divided into two groups, group A: SAA, SAB and LA, group B:SAC and RA. Ginsenosides and alkaloids for chromatographic column chromatography column is used:SymmetryLuna C18(150mm×2.1mm, L×I.D).Phenolic acids used:chromatographic column for Luna C18(50mm×4.6mm, L×I.D). Ion source for the ESI source, scanning mode select multiple reaction monitoring (MRM) mode. Results:were confirmed by methodology, the specificity of this method, the precision and accuracy, the matrix effect, stability and recovery project all comply with the relevant requirements.9 kinds of ginseng saponin, Rg1 ginsenosides, Re, Rb1, Rd,Rb2/3, Re, Rf, F1 and linear range of Rh1:A group of ginsenosides 0.625～80μg·L-1 A group of ginsenosides 1.25～160μg·L-1。14 kinds of yanhusuo alkaloids -- Tetrahydropalmatine, Berberine, Palmatine, Dehydrocorydaline, Corydaline, Worenine, Protopine, Epiberberine, Glaucine, Coptisine, TetrahydroJatrorrhizine,Tetrahydroberberine and Allocryptopine.The linear range is as follows: group A of alkaloids are 0.195～25 μg·L-1, group B of alkaloids are 0.781～100μg·L-10.195-25μg·L-1; Salvianolic acid B, Salvianolic acid A and Lithospermic acid are 0.78～100μg·L-1, Salvianolic acid C and Rosmarinic acid are 0.39～50μg·L-1.Chpater 2:Object. To determine compatibility of different dosage groups, the double parameter through coronal of ginseng saponin, rhizoma corydalis alkaloid and salvia miltiorrhiza phenolic acids blood drug C-t data and the main pharmacokinetic parameters.According to the composition of blood, the pharmacokinetic parameters of comparing single herbs group with all the pharmacokinetic behavior of different components, thereby double parameter interpretation from the perspective of pharmacokinetic coronally compatibility mechanism. Methods:the first part is used to establish the various ingredients in rat plasma of LC-MS/MS analysis method, the group of SSTQ ginseng, salvia, corydalis, ginseng+salvia group, ginseng+corydalis group and salvia + corydalis, components in rat plasma were determined. Using Winnonlin 6.0 pharmacokinetic software to analyze the experimental data, after each pharmacokinetic parameters, through the statistical software SPSS 19.0 software Wilconxon rank and inspection. Results:the experiment of double pass 28 into the coronal investigates the different compatibility of blood components in the current drug doses can only get 9 composition curve when finished medicine, ginseng saponins respectively Rb1,Rd,Rb2/3,Rc, THP, DHC, THJ, SAB and LA.The results show that different components of blood compatibility of these into the AUC value had no obvious effect, there was no statistically significant difference.Part Ⅱ Study on the Compatible Relationship of Shuang Shen Tong Guan Based on liver metabolic enzymesObject: the early stage of the application group established Cocktail probe substrate method of evaluation system, investigation of different compatibility groups participate through coronal, after continuous dosing effects on CYP450 enzyme activity in mice.Preliminary discussion on compound compatibility and the relationship of the drug metabolic enzymes in the body, looking for compound relative to the single herbs potential superiority.From the pharmacokinetic metabolic link to interpret the rationality of the prescription and compatibility mechanism. Methods:to select 5 kinds of FDA suggestion of the hepatic metabolic enzymes CYP1A2, CYP 2 C9, CYP 2C19, CYP 2D6 and CYP 3A4.The corresponding probe substrates mixed into Cocktail probe substrates.All party group, ginseng, salvia miltiorrhiza, yuan hu group and the blank group, continuous dosing for 15 days, the last day to give mixed probe substrates.Using LC-MS/MS analysis method in rat plasma content determination, to probe the substrate and its metabolites by increase in the number of reduce and its metabolites probe substrate reaction corresponding metabolic enzyme activity, for each probe drug and its metabolites in the AUC value is compared. Results: the different compatibility groups of each probe drugs and their metabolites of AUC of the ratio of the difference is not significant, indicating that the drug doses in double parameter through the effective parts and coronal compatibility of formula of 5 kinds of major hepatic metabolism enzyme had no obvious effect.