Preparation Of Microemulison Of Tanshinone IIA And Its Pharmacokinetics In Rabits

Objective:Tanshinone IIA(Tan-IIA,TS) 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 TS 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 prepare the Microemulsion of Tan-IIA. 2.To establish the methods for the quality evaluation of the microemulsion. 3.To study the pharmacokinetics of the microemulsion in rabbits.Methods:1.Preparation of microemulsion of Tan-IIA: Prepare the microemulsion of Tan- IIA by the methods of high pressure emulsion, investigate the best proportion to obtain emulsion among PC, glycerin, Pluronic(F68) of prescription. The effect on the microemulsion structure and drug loading caused by the proportion was also studied. 2.The study of quality evaluation: HPLC method is adopted to test the encapsulation efficiency and drug loading of Tan- IIA; observing the conformation of microemulsion under transmission electron microscope(TEM); measuringthe particle diameter and the distribution via measuring equipment of particle diameter;Stability: the microemulsion of Tan- IIA is observed to study its aspect,pH,conformation and leakage ration, which is deposited under different temperature for 1 months. 3.The study on pharmacokinetics of Tan- IIA microenmulsion: 5 rabbits were given Tan- IIA microemulsion, iv 2mg·kg-1.The concentrations of Tan- IIA were determined by HPLC method.Results:1.The concentration of Tan- IIA is 0.1%; the best proportion is PC 2%, glycerin 2.25%, Pluronic 2%, respectively.2.Through high pressure emulsion the mean diameter of microemulsion is 151nm , encapsulation efficiency of Tan- IIA is 73.29%,drug loading of Tan- IIA is 0.073%.3.No obvious difference in conformation,pH is found after the microemulsion preparation was deposited under 4℃,25℃respectively for 1 month. In addition, there is a bit decrease of drug loading with the increase of temperature. 4. Plasma drug concentration–time course of Tan- IIA after iv administration of Tan- IIA was found to be fitted to a two compartment open model and its pharmacokinetic parameters were as follows: AUC0-∞,AUC0-t,T1/2α,T1/2βare 230.16.53μg·mL-1·min,190.57μg·mL-1·min,12.97min,226.45min, respectively.Conclusion:1. The method of high -pressure emulsion used in preparation of Tan- IIA microemulsion is in accordance to the requirement.2. The emulsion should be deposited under low temperature,away from sunshine.The characterization of our study1. No report available on microemulsion of Tan- IIA is found at home and abroad.2. This is the first study on pharmacokinetics of microemulsion injection of Tan- IIA in rabbits, which lay foundation for further study.