The Absorption Kinetics Of Main Constituents From Complex Prescription Yanghuosanqi Tablets

Dosage form is the carrier of drug and the terminal style of clinical medication. Reasonability of dosage form design has an effect on therapeutic effects directly. Compound prescriptions is one of Chinese medicine characteristics.Most of compound prescriptions were delivered by oral path.Mainly dosage form design based on purpose of clinic,compliance of patients,physico-chemical property of drug。However few drugs were designed based on Gastrointestinal absorptive character which is also important.In this study,Yanghuosanqi was selected as a model medicine.Characters of its absorption and metabolism were studied with a four-site perfused rat intestinal model and a human Caco-2 cell culture model.Purpose of this study was to offer a basement for new dosage forms and high quality Chinese medicine.1 Firstly model drugs were prepared and quality control was established,compound prescriptions Yanhuosanqi was made up of epimedium and notoginseng.In order to ensure the stability of tested drugs,five flavonoids and 3 saponins were selected as the detection index.All the compounds were detected with HPLC-DAD-ELSD.3.38mg Icarrin was contained in 101.3mg Epimedii extract and also in 112.0mg Yanghuosanqi. Notoginseng saponins contained in 112.0mg Yanghuosanqi were equivalent as in 16.9mg Notoginseng extract.So the ratio of icariin,Notoginseng extract,Epimedii extract and Compound prescriptions Yanghuosanqi should be 3.38:16.90:101.29:112.03.2 A four-site perfused rat intestinal model was established.Intestinal absorption kinetics of main components in compound prescriptions Yanhuosanqi were studied with this model for the first time.(1)Study on the stability of model drugs was necessarily.Firstly chemical stability of compounds in model drugs was investigated in order to ensure the reliability of results in perfused rat intestinal model and Caco-2 cell model.Stability of tested drugs in hank's balanced salt solution during temperature 37℃±0.5℃and pH differ from5.5to 8.0 was investigated.Degradation constant was calculated.The results showed that compounds such as icariin,Sanchinoside R1,Ginsenoside Rg1,Ginsenoside Rb1 were stable in different pH solutions.So all tested drugs were suitable for the vitro perfusion test.(2)Methodology of perfusion sample analysis was established.The HPLC detection method of icariin,Sanchinoside R1,Ginsenoside Rg1,Ginsenoside Rb1 contained in perfused rat intestinal model sample was established.Results indicated that linearity,precision,repeatability,stability,recovery of these compounds fit the bill in this method.(3)Intestinal absorption kinetics of icarrin in purified compound,Epimedii extract and Yanghuosanqi and 3 saponin analogs in notoginseng in perfused rat intestinal model were studied.The results indicated that permeability of icariin in duodenum and jejunum was far more than propranolol which was generally acknowledged as a medicine with good absorption.It was cuased by that icariin was metabolized into two metabolites. Apparent coefficients of permeability and eliminate percentage of icariin in pure compound was significantly higher than it in Epimedii extract and Yanghuosanqi. however apparent coefficients of permeability and eliminate percentage of icariin in Epimedii extract and Yanghuosanqi have hardly significant difference.It showed that Notoginseng in Yanghuosanqi have no effect on the Intestinal Absorption dynamics of icariin.Hydrolysis of icariin in intestina was inhibited in compound prescriptions Yanghuosanqi for the competition by the flavones analogs.Apparent coefficients of permeability and eliminate percentage of icariin were caused by LPH hydrolysis.3 A Caco-2 cell model was established.Absorption and transport kinetics of main components in Yanhuosanqi were studied with this model for the first time.The apparent coefficients of permeability of 20μM icariin was(0.62±0.032)×10^-6 cm·s^-1.The coefficients was low and the absorption was not well.P_B-Aof icariin was 4.83 times higher than P_A-B,which showed that there might be protein excreted it Caco-2 cell model.The mechanism of icariin absorption showed that there may be P-gp excretion. P_B-Aand P_A-B,excretion and membrane through of Epimedii extract and Yanghuosanqi was lower than icariin.In all,LPH hydrolysis and P-gp excretion were effected on icariin in intestine.The coefficients of permeability of icariin was low which showed the absorption was hard. Besides that the saponins in compound prescriptions also have poor absoption.So reduction of the flavones metabolism in gastro intestine and improvement of flavones and saponins transmembrane transport should be applied in modern dosage form design in order to improve the therapeutic effect.