Soy Aglycone Succinate Sodium Salt - Biopharmaceutics And Pharmacokinetics Study

D2 was the derivative of Daidzein (DZ) which was one of the active principles of Pueraria pseudohiruta. Carboxyl group was introduced to D2 by etherification ,so the solubility of D2 was greatly improved .In the studies of D2 physicochemical properties ,it was found that the solubility in water of D2 and D2Na were respectively 0.2mg/ml and 11.69mg/mi , which were 36 times and 2000 times greater than that of DZ .The 01W partition coefficients of D2 at varied pH value 4.68,2.33,0.850. D2 solutions of three doses, 150mg/kg ,75mg/kg and 37.5mg/kg were administrated to mice to study the pharmacology activity of the drug .The results showed D2 can prolong the survival time of mice in the experiments .In the toxicity study ,all the animals of oral administration were survival and no serious toxicity reactions were found .The LD50 value of mice via iv was 0.43mg/kg. A method was developed for the determination of D2Na concentration in animal plasma and other biological samples .Vanillin was used as the internal standard .Analyticai column was HYPERSIL ODS2 ,the mobile phase consisted of methanol-water-10%phosphoric acid(50-50-0.08) .The detection was performed at uv 250 nm. The calibration curve in plasma was linear in the range from 1 to 150 i-t g/ml ,with r=0.9992,and the detection limit of plasma was 0.1 i-i glml .The extraction recoveries of all samples were over 80%, the 3 relative standard deviations for within-day and between-day were below 5.0% .This method was simple ,sensitive and good enough to be used in pharmacokinetic study of the drug. In this report improved intestinal absorption experiments of rat in situ were used to study the absorption of D2. It was found that there was no significant difference in absorptive rate constant and the last percent of absorption in rats between without and with bile duct- ligated , and the last percent of absorption was 38.1% and 42. 1%.The results proved that the transport mechanism of D2 was passive diffusion. The paper reports the phannacokinetics and bioavailobility of D2Na in rats. The experimental results showed that the concentration-time curves of D2Na after iv of 10,20,30mg/kg fit a two-compartment open model, and the concentration-time curves of D2Na fit one-compartment open model with first-order absorption after oral administration The rats were administrated the drug via ig and iv crossly,the absolute availability was 33.8% After iv D2Na in mice, the concentration in tissues was determined by HPLC. The statistical moment analysis results showed that concentration of D2Na was the highest in kidney, followed by liver, heart , brain, spleen , plasma, lung and stomach .The Cm8,, and AUC value at kidney and 昹iver were greater comparatively. It was suggested that AUC combined with Cm8,, were better to evaluate drug distribution.