Studies On Preparation Of Yangxue Injection And Its Pharmacokinetics In Animals

Yangxue injection is multi-component Chinese Medicine and composed of sodium ferulate,tetramethylpyrazine hydrochloride,tanshinol sodium and sodium tanshinone IIA sulfonate,which are effective substances of Ligusticum chuanxiong Hort.And Salvia miltiorrhiza.In this study,preformulation research,optimization of preparation technology,research of quality control method,pharmacodynamic experiments,pharmacokinetics in rats and Beagles have been performed.An RP-HPLC method was estbalished based on both the physical and chemical properties of sodium ferulate,tetramethylpyrazine hydrochloride,tanshinol sodium and sodium tanshinone IIA sulfonate.Methodological study results indicated that the method was simple,accurate,reproducible,and can be used to quantitative detection of Yangxue injection.Single factor test and orthogonal design test was used to screen the dosage of ethanol,sodium thiosulfate and ethylenediamine tetraacetic acid disodium,with the content of sodium ferulate,tetramethylpyrazine hydrochloride,tanshinol sodium and sodium tanshinone IIA sulfonate and the osmotic pressure molar concentration of injection as index.The ratio of ethanol,sodium thiosulfate and ethylenediamine tetraacetic acid disodium were 2.0%,0.10%and 0.03%respectively,which was proved efficaciously by validation test.Determination of the content of drug substances,research of quality control method and preliminary stability tests have been completed.The labeled amounts of sodium ferulate,tetramethylpyrazine hydrochloride,tanshinol sodium and sodium tanshinone IIA sulfonate were initially determined to be 100 mg,30 mg,25 mg and 11 mg respectively.Content of each component should be within the range of between 95%to 105%of the labeled amount.Rats were given high fat diet for 4 weeks to establish model of hyperlipidemia.Before and after the drug administration,the whole blood viscosity at high-middle-low shear rate,and the levels of triglycerides,total cholesterol,high-density lipoprotein cholesterol were measured.The results showed that Yangxue injection could reduce HGB,HCT,the whole blood viscosity at low shear rate,the levels of total cholesterol and triglycerides obviously.A simple and sensitive HPLC method was developed to study the pharmacokinetics of sodium ferulate,tetramethylpyrazine hydrochloride,tanshinol sodium and sodium tanshinone IIA sulfonate in rats and Beagle dogs.Meanwhile,a new method of area under the absorbance-wavelength curve was developed to get total concentration of multicomponents in plasma.Yangxue injection was injected into the rats through tail veins and Beagle dogs were administrated by intravenous infusion.The blood was collected at the concerned time.Concentrations of single component and multicomponent in plasma were determined by HPLC and AUAWC method respectively.The pharmacokinetics parameters were calculated with the software 3P97 on basis of the analysis results.The concentration-time profiles of sodium ferulate and tetramethylpyrazine hydrochloride after iv administration were found to fit with one-compartment while that of tanshinol sodium and sodium tanshinone IIA sulfonate fitted with two-compartment in both rats and Beagle dogs by HPLC.The data from AUAWC showed Yangxue injection with multicomponents had one-compartment model in both rats and Beagle dogs.