Study On The Preparation Technology And Pharmacodynamics Of Compound Gankang Tablets

Objective:Compound Gankang Tablet is a self-made preparation for the former First Hospital of the People's Liberation Army.It has been used clinically for more than 30 years.According to the theory of traditional Chinese medicine,the cause of liver disease is mainly caused by infection of external evils,liver main venting,and abnormal blood storage function.Compound Gankang tablets are mainly composed of traditional Chinese medicine extracts such as Astragalus,Angelica,Astragalus,Salvia miltiorrhiza,Bupleurum and so on.They have the functions of soothing liver and relieving stagnation,regulating qi and relieving pain,clearing away heat and detoxifying,diluting water and dampness,promoting blood circulation and removing blood stasis,cooling blood and soothe the nerves.Chronic hepatitis,persistent hepatitis and early cirrhosis have a good therapeutic effect.The clinical efficacy of this drug is positive.In order to better ensure the quality of the drug,the quality standard of Compound Gankang Tablet was studied,the draft quality standard of the drug was drafted,and the extraction preparation process of the drug was also studied by orthogonal test.The pharmacological effects of Compound Gankang Tablet were preliminarily studied,which laid a foundation for the large-scale production,clinical application and follow-up study of Compound Gankang Tablet.Methods:?1?Using orthogonal test,the content of baicalin,ferulic acid and ointment were used as evaluation indexes,and the best extraction process was preferred.?2?The main Chinese herbal medicines Huangqi,Angelica,Astragalus,Salvia,and Bupleurum in the prescription of Compound Gankang Tablets were identified by thin-layer chromatography,and the weight difference?disintegration time limit and so on were carried out according to the provisions of the 2015 Chinese Pharmacopoeia.Time limit and microbial limit test;the contents of baicalin,ferulic acid and astragaloside in the drug were determined by HPLC?high performance liquid chromatography?were determined by high performance liquid chromatography,and the content of three main components of three batches of Compound Gankang tablets were determined.?3?Pharmacodynamic study,70 SPF SD rats were divided into blank group,solvent group,model group,compound Gankang tablets low,medium and high dose groups and biphenyl diester positive control group,on the first and sixth days of the experiment the other groups except the blank group and the solvent group,the model of chemical acute liver injury induced by CCl₄ peanut oil solution was induced by ip?peritoneal injection?,and the solvent group was given ip solvent peanut oil,except for the blank group and the solvent group.The other groups outside the model group were administered ig?gavage?for 7 days,and blood was taken from the carotid artery 12hours after the last administrationof the experiment,and serum alanine aminotransferase?ALT?and aspartate aminotransfer enzyme?AST?levels were measured;Making liver pathology slices,HE staining,pathological changes of liver tissue under light microscope;determination of total superoxidedismutase?T-SOD?levels and the activity of the glutathione peroxide enzyme?GSH-Px?and the content of lipid peroxidation product?MDA?in liver tissue.Results:?1?The optimal extraction process and preparation method were as follows:Weighing eight Chinese herbs according to the prescription amount,and 10 times the amount of water was added to cook twice,each time for 1 h,filtered,and the filtrates were combined and concentrated to relative an extract of density 1.30-1.35?60-70°C?,dried,ground and sieved.The fine powder is granulated with 90%ethanol and dried to a dry state at 50°C or lower.Add appropriate amount of magnesium stearate and talc,mix well,press into 1000 pieces,and wrap the film coat to obtain.?2?The results of quality standard research are as follows:the identification images of Astragalus,Angelica,Astragalus,Salvia miltiorrhiza and Bupleurum are clear,the correspondence is clear,the repeatability and specificity are good,and the operation is simple and easy.In the content determination,the peak of baicalin was 11.8 min,the peak of ferulic acid was 10.1 min,and the peak of astragaloside was 4.5 min.There was a good linear relationship with the peak area in the range of 30.00?g·mL^-1 to 300.00?g·mL^-1?0.64?g·mL^-132.00?g·mL^-1 and 32.88?g·mL^-1328.80?g·mL^-1.?3?Pharmacodynamic experiments showed that during the modeling period,the serum levels of ALT and AST in the model group were significantly increased?P<0.01?,suggesting that the model of liver injury was successful,compared with the blank group,The activity of SOD in liver tissue of model group rats was significantly decreased?P<0.01?,the content of MDA was significantly increased?P<0.01?,and the activity of GSH-Px was significantly decreased?P<0.05?,indicating the antioxidation capacity of liver tissue in model group was significantly lower.Compared with the model group,the levels of SOD and GSH-Px in the different dose groups and the positive control group were significantly increased?P<0.01 or P<0.05?,and the MDA content of the low-dose group had a decreasing trend,but the difference was not statistically significant?P>0.05?.The liver was observed by the naked eye.The liver of the CCl₄ model group was swollen,the appearance was yellow-brown,and there was bleeding on the surface of the liver.The Compound Gankang tablets were low,medium,the liver of the high-dose group and the positive control group had slight swelling,but compared with the model group,the degree of swelling was reduced.In the blank group and the solvent group,the liver was not swollen,and its appearance was reddish brown,soft in texture and good in elasticity.Conclusion:This study identified the TLC?thin layer chromatography?of Astragalus,Angelica,Astragalus,Salvia,and Bupleurum into the draft quality standard.The contents of baicalin,ferulic acid and astragaloside in the drug were determined by HPLC?high performance liquid chromatography?.At the same time,the weight difference of the tablets,the time limit of disintegration and the microbial limit were examined,and these contents were included in the draft quality standard.The draft quality standard can be used as the quality control standard for Compound Gankang tablets,in line with the relevant regulations of the state on hospital preparations.And the pharmacodynamic study of Compound Gankang tablets,the experimental results show that Compound Gankang tablets have a good liver-protecting effect.