Preparation Of Zhiling Compound Granules And Study On Sedative Good Sleep

Objective:This study intends to develop Zhiling compound granules by studying the preparation process,pharmacodynamics,pharmacokinetics,quality standard and preliminary stability of the granules to improve the dosage form of clinical decoction Zhiling compound with sedative good sleep.It provides the reference for the development and research of drugs.Methods:Firstly,according to the clinical extraction method of traditional Chinese medicine and the chemical properties of active components,the extraction process of granules is studied by L₉（3⁴）orthogonal test and the contents of geniposide and hesperidin are used as indexes.After that,the diluent,wetting agent and the ratio of extractum to diluent are investigated by single factor test.The orthogonal test is used to select the best molding process by investigating molding rate,angle of repose,bulk density,moisture absorption rate and dissolution rate.The quality standard research and preliminary stability test of granules are conducted.In terms of pharmacodynamics,the effect of sedative good sleep in Zhiling compound decoction and granules is affirmed by spontaneous activity experiments,and the maximum tolerance test is carried out.In terms of pharmacokinetics,a method for the determination of geniposide in rats is established by HPLC.Pharmacokinetic studies of one blood collection in one animal and multiple blood collection in same animal is then conducted.Results:The optimum extraction process was extracting for thrice with 1.0 h,0.5 h,0.5 h successively by 10 times water.According to the study,the optimum molding process of granules was as follows:the ratio of 1 to 0.75 between extractum and soluble starch.The 70%ethanol was wetting agent with an amount of 24%extractum dosage to make soft material.Final preparation was obtained by drying and sorting granules.The methods for the identification of gastrodia elata and corydalis tuber in granules,the determination of geniposide and hesperidin by HPLC and total polysaccharide in granules by UV were established respectively in quality control.The quality standard of granules was established initially and the result of the preliminary stability test showed that the indexes met the requirements.Efficacy test confirmed that Zhiling compound decoction and granules had sedative good sleep effect.The maximum tolerance test showed that the maximum tolerance multiple was 135.44.It showed that the granules were safe,and the daily dose of adults should not be more than 15 times.Two pharmacokinetic studies showed that the atrioventricular model of geniposide in granules after oral administration was one-compartment model.The geniposide first reached a peak of absorption concentration quickly in vivo,and then could appear the second peak due to the hepatic and intestinal circulation.Finally,the absorption concentration of the geniposide tended to zero.In two pharmacokinetic studies of geniposide in rats,t_1/2（13.70 h,8.07 h）and T_max（0.25 h,0.50 h）indicated that geniposide was absorbed quickly in rats after oral administration.Conclusion:This study shows that Zhiling compound granules are effective and non-toxic,the preparation process is reasonable,and the method is stable and feasible,which provides a theoretical guidance for the development of drugs with sedative good sleep.