The Study On PK-PD Sustained Release Evaluation Of Ganershu Pellets

Ganershu pellets,consisting of the sarmentosum,bupleurum and other Chinese medicine,The effective parts include total saponin,totalflavonoids,total alkaloid,total organic acid.In the research,we studied the efficacy of the different effective parts and their mixture on protecting liver and reducing enzyme in liver injury mice,so as to make the validation for the the different effective parts of Ganershu compound.Then we take main active ingredients as the representative,though the studies of pharmacokinetic and pharmacodynamic(PK-PD)on Ganershu sustained-release pellets and normal pellets,providing the basis for the the vivo sustained release evaluation of Ganershu pellets.The main contents of this essay are as follows:1.Screening of effective fraction from Ganershu pelletsThe research establish mice liver injury model by administration with 0.2%CCl4.Given the total flavonoids,total saponins,total alkaloids,total organic acid 4 parts and the mixture,Determining the AST,ALT,TBIL and liver tissue SOD activity,and MDA level in mouse serum,after taking observation of of the liver tissue biopsy of the effective parts.The result is that 4 effective parts of Ershu compound have different levels of function on protecting liver and reducing enzyme,the mixed group of four fractions,flavonoids and saponins can significantly inhibit the acute liver injury in mouse serum ALT,AST activity relative to the total alkaloids and total organic acid group.Provide the basis for the late selection of the pharmacokinetic and pharmacodynamic indicators of sustained-release formulations.2.Pharmacokinetic and pharmacodynamic research of the intermediatesIn this research,taking naringin and naringenin as index components,which are two of effective parts.After taking Ganershu compount intermediates,adopt high performance liquid chromatography to determinate the blood concentration in rats at different time points.And the AST is taken as pharmacodynamic indicator,determination of the variation of the pharmacodynamic indicators with the concentration in the pathological state rats.To establish concentration-time-effect relationship,based on relational examination to pharmacokinetic and pharmacodynamic.Establish the vivo analysis methods for Ganershu compound.The aim is to provide the basis for the evaluation to later part of the Ganershu sustained-release pellets in vivo.3.The establishing of PK-PD combined model and study of Ganershu sustained-release evaluation on sustained-release pellets and normal pellets.The research determine the blood concentration of naringenin by high performance liquid chromatography in dogs at different time points(PK),and take AST as pharmacodynamic indicator,determination of the variation of the pharmacodynamic indicators with the concentration in the pathological state dogs by adopting plasma concentration method and pharmacological effect method.By comprising the pharmacokinamic and pharmacodynamic parameters between Ganershu sustained-release pellets and Ganershu common pellets,including the halt-time,the peak concentration,the residence time in vivo and the apparent volum of distribution and so on,it proved that the halt-time is extend and the peak concentration is reduced of the sustained-release pellets.At the same time,we established the PK-PD model of two indicators to calculate the kinetic parameters of combined model effect(E),in order to evaluate the susutained release characteristics of Ganershu pellets.It avoids the limitations of pharmacokinamic method that traditional Chinese medicine alone selects some indicators ingredients in vivo evaluation,and provids the basis for its clinical application.