Study On The Preparation Technology And The Quality Control Method Of Kaixinjieyu Granule

KaiXinJieYu granule is the clinic experience formula of Guang’anmen hospital of China Academy of Chinese Medical Science,all formula is com-posedby five medicinal materials,ginseng,bupleurum,radix rubra,morinda and licorice.This formula have effect on enriching the kidney and strengthen-ing Yang-qi,tonifying spleen and calming the heart,soothing liver-qi stagna-tion,alleviating fever and eliminating rheum.Clinical use at treating vascular depression and have sgnificant effect.This subject develop KaiXinJieYu granulebased on experience formula,and expect to provide research gist for developmentof proprietary Chinese medicines.Objective:1.Research and lay down preparation technology of KaiXinJieYu gran-ule,define the key technological parameter.2.Research the quality control method of KaiXinJieYu granule.Methods:1.Define each link parameters of KaiXinJieYu granule:extracting,con-centration,drying,molding.（1）Extract technological route screening:Screen extracting technological route with index of ginseng total saponins,paeoni-florin content and pharmacological evaluation.（2）Extract technological route:For alcohol extraction,adopt single factor test and orthogonal test with index of ginseng,saponins Rg₁,Re,Rb₁ content to optimize technological parameter.For aqueous extraction,adopt orthogonal test with index of paeoniflorin con-tent to optimize technological parameter.（3）Concentration technology:For al-cohol extraction,adopt single factor test with index of ginseng,saponins Rg₁,Re,Rb₁ content;for aqueous extraction,adopt single factor test with index of paeoniflorin content to investigate concentration temperature and concentration density,then define technological parameter of alcohol extraction and aqueous extraction.（4）Drying technology:Adopt single factor test with index of ginseng saponins Rg₁,Re,Rb₁ content and paeoni-florin content to investigate and comparevacuum drying,microwave drying,spray drying with drying temperature,thendefine drying technological param-eter.（5）Molding technology:Adopt single factor test with index of softwood condition and ratio of molding to investigate wet granulating excipient match/ethanol concentration.Adopt single factortestwith reference of taste evaluation to investigate the kind and dosage of corrigent.Investigate the drying time of granule with index of ginseng saponins Rg₁,Re,Rb₁ content and paeoniflorin content.Investigate the character of complete gran-ule,include angle of repose,critical relative humidity,dissolubility,granule size.2.Refering to the relevant literature and method,investigate ginseng,bupleurum,licorce,radix rubra of KaiXinJieYu granule by TLC.Adopt sin-gle factor test and methodology to investigate and establish the HPLC of con-tent determination of ginseng saponins Rg₁,Re,Rb₁ and paeoniflorin.Results:1.KaiXinJieYu granule preparation procedure:mix 8 times 70%lcohol than ginseng and radix bupleurum,extract 3 times,every time 1.5 h,filtra-tion.mix herb residue and the other 3 medicinal materials,add 10 times wa-ter（more1.3 times for the first time）,extract 2 times,Every time 1.5 h,filtra-tion.Concentrate alcohol extract under reduced pressure in 60℃⁷0℃to ex-tractum whose relative density keep 1.08¹.12（40℃⁵0℃）,standby applica-tion.Concentrate under reduced pressure in 70℃⁸0℃to extractum whose relative density keep 1.22¹.26（40℃⁵0℃）,standby application.Mix the two extractums,vacuum drying the mixture in 60℃to produce drying extrac-tum,smash the drying extractum into fine powder,standby application.Mix extractum,dextrin,starch on mix design of 1:0.4:0.6,add 1%stevioside,then proceed wet granulation with wetting agent（85%lcohol）,dry for 1h in70℃and process granule.The granule’s traits producted under this prepara-tion technology can conform to Pharmacopoeia rules all round.2.Quality control method of KaiXinJieYu granule:（1）The TLC estab-lished for ginseng,radix bupleurum,glycyrrhizae,radix paeoniae rubra is ex-clusive without any disturbing.（2）The content determination of ginseng sapo-nins’s paeoniflorin:Under the environment of detection wave 203nm,col-umn temperature 30℃,flow rate 1.0 mL.min^-1,sample size 10uL,use acetoni-trile and water as mobile phase to proceed gradient elution.between 0³0min,19%acetonitrile;between 30⁷0 min,19%²9%acetonitrile;between70¹00 min,29%³8%acetonitrile.（3）the content determination of paeoni-florin paeoniflorin:Under the environment of detection wave 230nm,Col-umn temperature 30℃Flow rate 1.0 mL.min^-1,sample size 10uL,use mixture（acetonitrile:water,14:86）as mobile phase to proceed gradient elution.Conclusion:The preparation procedure defined for KaiXinJieYu granule is stability,scientific,and can be used for industrial production;the quality control meth-od research on TLC and content determination can provide basis for produc-tionquality control of KaiXinJieYu granule.