Studies On Pharmaceutics And Pharmacokinetics Of Tanshinone Ⅱ_A Microemulsion For Injection

Objective: TanshinoneⅡ_A(Tan-Ⅱ_A) is the oil-soluble effective component of Chinese traditional medicine, Tanshin, and the chief pharmacological effects are anti-oxidation, activities in heart vessels system, anti-bacteria and diminishing inflammation, anti-tumor etc. Especially, the effects of anti-tumor attract wide concern in academic circle. Due to the low degree of solubility in water, the weakness of absorption to solid medicine and the difficulties in being made into vein preparation, the clinical application of Tan-Ⅱ_A is limited.Because of its tiny particle of mean diameters, high degree of bioavailability , comparatively stronger appetency to lymph system and target affinity, microemulsion as a carrier of medicines is suitable for injection. Nevertheless, none of the microemulsion in the form of injection is on sale at home and abroad.The purpose of the study are as follows:1.To carry out the performulation study of Tan-IIA Microemulsion.2.To optimized the Tan-Ⅱ_A microemulsion formulation with a simplex lattice design and evaluation the technology of progress for Tan-Ⅱ_A microemulsion.3.To study the pharmacokinetics of the microemulsion in mice.Methods: 1.Performulation study of Tan-Ⅱ_A microemulsion: Prepare the analysis methods for Tan-Ⅱ_A microemulsion; determined the physico-chemical property of Tan-Ⅱ_A ;through drawing the pseudoternary phase diagram of microemulsion with compound surfactant ,the microemulsion area had been found .2.Optimizing the microemulsion formulation by the method of simplex lattice design ,selecting the solubility of Tan-Ⅱ_A and average particle as the response wariables ,the final formulation had been found,and processing factors were studied based on the optimized formulation;the encapsulation efficiency of Tan-ⅡA were tested by the HPLC method;obserying the conformation of microemulsion under transmission electron microscope(TEM);measuiring the particle diameter and the distribution via measuring equipment of particle diameter. 3.The study on pharmacokinetics of Tan-Ⅱ_A microenmulsion: 20 mice were given Tan-Ⅱ_A microemulsion iv 9.5mg·kg^-1.The concentrations of Tan-Ⅱ_A were determined by HPLC method,using the DAS software analysis parameters.Results: 1.The Tan- IIA is liposolubility drug ,we can learn from the result of pseudoternary phase diagram the O/W microemulsion region of compound serfactants system was larger.2.The mean diameter of Tan-Ⅱ_A microemulsion formula I and formulaⅡare 107.4nm and 151.4nm respectively ,encapsulation efficiency of fomula I and formulaⅡare 92.28% and 90.13%, respectively. 3. Plasma drug concentration–time course of Tan-Ⅱ_A after iv administration of formulaⅡTan-Ⅱ_A microemulsion was found to be fitted to a two compartment open model and its pharmacokinetic parameters were as follows: AUC_0-∞,AUC_0-t,T_1/2α,T_1/2β are 65.433 mg·l^-1·h,81.721 mg·l^-1·h,2.365h,14.956h, respectively.Conclusion: 1.The Tan-Ⅱ_A is liposolubility drug, the O/W microemulsion region of compound surfactants system was larger than using single surfactant.2. The basic character parameters of fomulaⅠand formulaⅡare well with the simplex lattice design and processing factor study .3. Plasma drug concentration–time course of Tan-Ⅱ_A after iv administration was fitted to a two compartment open model,the T_1/2α and T^1/2β are longer than earlier reports which are fit for the characters of the microemulsion. The characterization of our study : 1. No report available on microemulsion of Tan-Ⅱ_A is found at home and abroad. 2. The pseudoternary phase diagram of microemulsion were drawn to determine the microemulsion area,the simlex lattice design were used to optimize the formulation.The method is scientific and advanced. 3. This is the first study on pharmacokinetics of microemulsion injection of Tan-Ⅱ_A in mice, which lay foundation for further study.