Study On The Druggability Of Resibufo-genin That The Active Ingredient In Chansu

Systematical research of the Druggability of RBG. The contents of the study include:1. The study of Physical and chemical properties:Using the balance method to research the Solubility of RBG in Phosphate buffer pH2.0, pH5.0,pH5.8, pH6.8, pH7.4, pH8.0, temperature of25℃and37℃. Using Shake-flask method to research the oil-water partition coefficient(LogP), Using the Distribution system composed by N-octanol—Phosphate buffer pH2.0、pH5.0、pH5.8、pH6.8、pH7.4. pH8.0to research the oil-water partition coefficient. Study on the Stability of RBG in different pH conditions and different temperature conditions. The result of study shows that the RBG has a low solubility in strong acidic environment and Similar LogP in different pH. RBG within five hours of the strong acid and strong alkaline conditions decreased, stability is poor; Content changed little in pH3～11and it has a good stability; Temperature on the RBG stability has little effect.2. Determination of plasma protein binding rate:Using the equilibrium dialysis method to determinate the plasma protein binding rate of RBG. The result of study shows that equilibration time is48h; The plasma protein binding rate in three concentrations are98.76%、98.88%、98.72%.3. The study of absorption kinetics in Gastrointestinal:Using the intestinal perfusion method to research. The result of study show that the Absorption rate of Stomach is89%;The Cumulative uptake of three concentrations RBG in the entire small intestine are79.7%、85.5%、88.3%; Colon is not the main absorption site; Small intestine is the main absorption site.4. Stability studies of the gastrointestinal tract:Using the balance method to research the content changes at different time points, so come to the concentration-time curve to determine the stability; The result of study shows that RBG is unstable in the Gastric juice acidic environment, The content decreased to less than10%in4hours, Pepsin has little effect on RBG and accelerated it decomposition before2hours.But RBG has a good stability in artificial intestinal fluid relatively, within24h the content can reach more than70%, Trypsin has significant effect on it’s decomposition, RBG in the decomposition rate of without trypsin intestinal is higher than the added trypsin intestinal.5. Pharmacokinetic studiesUsing the plasma concentrations of Determination method to research the pharmacokinetic of RBG. The result of study show that RBG is elimination of nonlinear dynamics.