Study On The Preparation Technology And Quality Standard Of Yiqi Fumai Granules

Purpose and significance According to the World Health Organization statistics,the world will have about 23.6 million people died of cardiovascular disease[1]by 2030.Arrhythmia is one of the most common cardiovascular diseases,which is the main cause of sudden cardiac death.Arrhythmia are mainly divided into four categories on the basis of different mechanisms and manifestations,including conduction abnormalities,abnormal formation of excitement,formation and conduction abnormalities and pacemaker caused by arrhythmia.Ventricular Premature Beat(VPB)belongs to the abnormal formation of excitability,refers to the sinus irritation before the arrival of premature contraction,resulting in abnormal autonomy and controling of cardiac activity,which induced coronary heart disease,sudden cardiac death,etc.[3],and this illness seriously affecting people's lives and health.Yiqi Fumai is the prescription of the Beijing University of Traditional Chinese Medicine of Dongfang Hospital,and it composed of Codonopsis pilosula Nannf.,Salvia miltiorrhiza Bge.,Coptis chinensis Franch.,Paeonia lactiflora Pall.,Polygala tenuifolia wild.,Glycyrrhiza uralensis Fisch.,and the other 11 constituents,which is used for the treatment of arrhythmia of Ventricular Premature Beat,the decoction has proven to be effective after years' clinical practice.As the decoction with inconvenience,easy moldy deterioration,poor taste,etc.,and it only suitable for small production.Besides,the quality is difficult to control.In order to solve these problems,we will develope it into granules and the establish a quality standard for granules.Pharmacological studies have shown that the prescription has anti-aconitine,calcium chloride,isoproterenon-induced arrhythmia,the mechanism of action and inhibition of plateau calcium ion current and repolarization of potassium ion currents[2].In this paper,we treat the traditional Chinese medicine theory as a guide and combine with modern pharmaceutical technology to study the preparation of Qi Fumai process and quality standards.MethodsIn this paper,the preparation process and quality standard of Qiqi Fumai Granules were studied.The details are as follows:1.Preparation of Yiqi Fumai GranulesFirst,a method for the simultaneous determination of paeoniflorin,glycyrrhizin and glycyrrhizic acid and the determination of berberine were established by high performance liquid chromatography(HPLC).The rats were subjected to myocardial ischemia reperfusion and ouabain induced guinea pig arrhythmia pharmacological experiments.The four process routes including the whole water extract,the whole water extract alcohol precipitation,some of the water taste of alcohol and some of the taste of alcohol,some medicinal water and some of the three flavors of alcohol were compared by determination of the contents of indicators.The effects of solvent,extraction time and extraction times on the content of the index components were investigated by orthogonal test.The drying process conditions were determined by single factor investigation.And the process of making Yiqi Fumai granules was determined through the study of the molding process.2.Study on Quality Standard of Yiqi Fumai GranulesThe method of qualitative identification and quantitative determination of the compound Yiqi Fumai granules was established.Codonopsis pilosula Nannf.,Coptis chinensis Franch.,Pinellia ternata(Thunb.)Breit.,Polygala tenuifolia wild.,Ziziphus jujube Mill.var.spinosa(Bunge)Hu ex H.F.Chou,Glycyrrhiza uralensis Fisch.,Ligusticum chuanxiong Hort.were identified by thin—layer chromatography(TLC).The content determination conditions of the index components of paeoniflorin,salvianolic acid B,tanshinone ?A were established by high performance liquid chromatography.Results1.Preparation of Yiqi Fumai GranulesThe route selection results show that Codonopsis pilosula Nannf.and other 6 herbs water extract,Salvia miltiorrhiza Bge.other 5 herbs alcohol extract is the relatively superior route according to the pharmacological indicators,and the content of the indicator components.We finally determine the preparation process of Qiqi Fumai granules by process parameters optimization and molding process:Codonopsis pilosula Nannf.,Paeonia lactiflora Pall.and other six herbs boiling water three times,the first time add 10 times the amount of water,extraction 1.5 h,filtration,the second add 8 times the amount of water,extraction 1.5 h,filtration,the third time add 8 times the amount of water,extraction 1.5 h,filtration.Combined three times decoction,concentrated to a relative density of 1.18(55 ?),80 ?.Salvia miltiorrhiza Bge.,Coptis chinensis Franch.and other five herbs with 60%ethanol heating reflux extraction three times,the first time to add 10 times the amount of extraction 2.0 h,filtration;the second time add 9 times,extraction 2.0 h,filtration,then concentrated to a relative density of 1.18(50?)and dried at 70 ?.Combined with water extract and alcohol extract,crushed,over 80 mesh sieve,in accordance with the drug and dextrin at the ratio of 1:1,90%ethanol as a wetting agent made of granules,packaging.2.Study on Quality Standard of Qiqi Fumai GranuleCodonopsis pilosula Nannf.,Coptis chinensis Franch.,Pinellia ternata(Thunb.)Breit.,Polygala tenuifolia wild.,Ziziphus jujube Mill.var.spinosa(Bunge)Hu ex H.F.Chou,Glycyrrhiza uralensis Fisch.,Ligusticum chuanxiong Hort.were identified by thin—layer chromatography(TLC).The conditions of the determination of the content of the paeoniflorin,salvianolic acid B,tanshinone ?A was that acetonitrile for the mobile phase A,the 0.05%phosphoric acid for the mobile phase B,and for gradient elution.The elution conditions are as follows:0?36 min 92%B,36?38 min 92 ? 86%,38?44 min 86%B,44?46 min 86%? 81%B,46?70 min 81%B,70?72 min 81%?66%B,72?94 min 66%B,94?97 min 66?35%B,97?110 min 35%B,110?115 min 35?92%B,115?120 min 92%B.Flow rate 1.3 mL·min-1.The detection wavelength of paeoniflorin was 230 nm,the detection wavelength of salvianolic acid B was 286 nm,and the detection wavelength of tanshinone ?A was 270 nm.The column temperature was 30 ?,and the injection volume was 10_?l.ConclusionsIn this study,the extraction and molding process of Qiqi Fumai Granules were studied,and a stable and feasible granules preparation process was established.Check the project of granules to meet the relevant requirements and qualitative identification of Yiqi Fumai Granules and quantitative determination of the content of the component,which can be controlled the quality of finished products.