| Objective:Tongtong recipe,composed of panax pseudo-ginseng,pueraria, ginkgo leaf,etc,is an empirical prescription of senile disease department in our hospital.With the effect of blood-activating and stasis-eliminating, circulation-promoting and collaterals-activating,the recipe was widely applied in the treatment of ischemia encephalopathy such as blockage of brain vessels, hemiparalysis secondary to apoplexy,insufficient blood supply of brain and cerebral arteriosclerosis,etc.The original prescription was decoction.It had been applied clinically for many years and got a significant effect.In order to serve the patients better during application,to get a well-controlled quality and to promote the paitients'compliance,we changed the recipe into granule and did a systematic research on aspects of extraction process,preparation process,quality standard and preparation preliminary stability.Methods:The extraction process Contents of TPNS,puerarin and total flavonol glycosides in the main medicines were determined by HPLC and methodologically inspected.Proper solvent was extracted by pharmacodynamics screening experiment. Orthogonal experiment design was applied to optimize extraction process parameters which affected results of extraction seriously such as ethanol concentration,ethanol volume,extraction time and extraction frequency,while active component and extraction rate were selected as evaluation parameters.The preparation process Hydroscopicity was selected as evaluation parameter to optimize the type and matching of adjuvant during molding process.Orthogonal experiment was used to optimize molding process parameters such as matching ratio between extractive and adjuvant and concentration and dosage of wetting agent, meanwhile molding rate and moisture absorption percentage were selected as evaluation parameters.Quality standard of Tongtong Granule was carried out through pilot scale productionPreparation preliminary stability experiment According to the requirement for granule defined in TCM new drug stability test,stability acceleration test of Tongtong granule was carried out.Results:The extraction process①Reproducibility and stability of HPLC determination of TPNS,puerarin and total flavonol glycosides contents showed good through methodologically inspection.And such a method could exactly refect the active component in the recipe.②Ethanol-extraction and water-extraction of Tongtong recipe demonstrated significant anti-thrombosis effect which was more powerful in ethanol-extraction.③The optimal extract process was as follows:reflux extraction with 8-folds of 70%ethanol for 3 times,1 hour per time.The preparation process①Minimal influence on hydroscopicity of extract in adjuvant could be gained when the ratio between lactose and dextrin was 3 to 2.②The best molding conditions were as follows:2 times of adjuvant,70%ethanol as wetting agent with the concentration of 12%(mL/g) and wet granulation.③Pilot scale production:normal character,reasonable particle size distribution,excellent solubility, bulk density of 0.5951 g·mL-1,angle of repose of 31.04°,critical relative humidity (CRH) of 70%.Inspection,identification and assaying all met the requirements.Quality standard formulation Including prescription,preparation method, character,identification,inspection,assaying,function and indication,usage and dosage,specification,storage,etc.Preparation preliminary stability inspection Samples' character was stable during experiment period and each item of inspection data was within the normal range.Conclusion:The extraction and preparation process was reasonable and feasible. The established quality standard was objective and practical of controlling the finished product quality and complied with standards of Chinese pharmacopoeia. Tongtong granule has a favourable application prospect.
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