Study On Pharmaceutical Preparation Technique And Quality Control Method Of Chaijinfang Based On The Drug System

This thesis is divided into four parts.The first part:literatures and summarizations;The second part:study on Chaijinfang pharmaceutical preparation technology based on the antidepressants system;The third part:quality control study of the series of medication of Chaij infang;The four part:summarize and discuss.Part one:Literatures and summarizationsThis part summarizes the research situation of material foundation of efficacy of Chinese herbs and compound prescription of Chinese medicine.It also reviewed from the chemical components,pharmacological fiunction and metabolism to summarize the current research status of Bupleurum chinense,Curcuma aromatica Salisb,Eupatorium fortunei Turcz,Fallopia multiflora(Thunb.)Harald.and Cinnamomum cassia Presl.116 pieces of references are cited,to guide the study of this subject.Part two:Study on Chaijinfang pharmaceutical preparation technology based on the drug system(1)With the drug system oriented,it determines the sort of Chaijinfang drugs preparation is terpenoids and phenols.Based on the drug system,this study oriented to design preparation process and quality control for drug innovation.Study on Chaijinfang drug extraction process based on the drug system.Using the steam distillation method,it studied on Chaijinfang(except of radix polygoni multiflori)of volatile oil(monoterpene and sesquiterpene location)to the extraction process,the oil content as a index,investigated the soaking time(E),the amount of water(F),and extraction time(G).Combined with the actual production,to determine the optimum extraction conditions of the volatile oil were there:Chai Jin Fang(except of radix polygoni multiflori)plus F2 times with the amount of water for E3 hours and extraction of G4 hours.By orthogonal design L9(34)test method,orthogonal extracts of terpenoids content and phenols content as indexs,four factors of extraction solvent(A),solvent volume(B),extraction time(C),extraction times(D)were investigated.Integrated the p terpenoids content and phenols content of orthogonal extracts,and combined with actual production,the best Chaijinfang extraction technology conditions were determined as:A3B2C3D2,namely solvent extraction A3 with volume of B2 for D2 times,each time C3 hours.(2)Based on the drug system,Chaijinfang drug concentration process was studied,with adsorption and adsorption-desorption rate of terpenoids and phenolsas indexs.After investigated the adsorptive property of 6 kinds of macroporous adsorptive resins,H2 resin was selected due to its best adsorption and separative property of phenols and terpenoids.Then it optimized H2 resin to do concentration technology of phenols and terpenoids.Then with adsorption and transfer rate of terpenoids and phenolsas indexs,it investigated the loading capacity,the ratio of diameter and height,concentration of absorptive solution,absorptive rate,purified solvent,velocity of flow,eluting solvent and et al.The optimized concentration technology of H2 resin is the extraction of Chaijinfang with aqueous dispersion of I3 g/mL was adsorbed to resin coloumn(diameter/height L2)with velocity of flow of M2 BV/h,the retio of loading capacity and resin volume was K3 g:1mL,P2 times volume of resins of water to wipe off impurity with Q2 BV/h velocity of flow,then U1 BV volume of resins of R3%ethanol to elute with the flow of S2 BV/h,collect R3%ethanol elution,vacuum drying for Chaijinfang phenols concentration.Again with R7%ethanol elution V4 BV,elution velocity for S2 BV/h,collect R7%ethanol elution,vacuum drying for Chaijinfang terpenoids concentration.(3)The Chaijinfang drug preparation process of drugs described above was tested and verified through 3 batches of samples of the preparation.The rate of volatile oil of an average was 0.32%(ml/g).The preparation and determination results showed that this extraction and concentration technology was steady and repeatitive.The content of terpenoids and phenols can be almost fully extract(terpenoids the average extraction rate was 86.53%,phenolic extraction yield of 91.05%on average),the average content of 0.50%and 6.09%,respectively.The average extraction yield rate of Saikosaponin B2 and stilbene glucoside was 81.42%and 92.21%,average content of 0.2384%and 1.2456%,respectively.Terpenoids concentration had average extract rate of 1.00%,terpenoids content to an average of 7.60%,the average transfer rate is 81.17%;Phenols concentration had average extract rate of 3.85%,content of phenols in phenols concentration was 16.04%on average,the transfer rate of phenols concentration part was 57.75%on average;an average of 12.28%in the concentration of terpenoids content,the transfer rate of terpenoids concentration part was average 11.64%.In terms of their index component,the average Content of Saikosaponin B2 in terpenoids concentration was 3.68%,the average transfer rate was 77.31%;the content of stilbene glucoside in phenols concentration was 3.47%on average,transfer rate was 60.44%on average.It was suitable for Chaijinfang preparation technology based on drug system.(4)Using reserpine copy depression model building,fluoxetine hydrochloride as the positive control drug,mouse swimming test,tail suspension test and reserpine in mice antagonism experiments has shown that Chaijinfang concentration,alcohol extract and water extract has antidepressant effects,especially Chaijinfang concentration have the most significant antidepressant effect(P<0.01).Combination of neurotransmitter index results,it can draw Chaijinfang concentration antidepressant effect is better than that of alcohol extract is,more better than that of water extract.Give equal raw medicinal materials,the dosage of Chaijinfang concentration(Terpenoids concentration had average extract rate of 1.00%,phenols concentration had average extract rate of 3.85%)is less than that of alcohol extract(extract rate of 18.24%)and water extract(extract rate of 27.10%),it can avoid the excessive dosage of side effects.(5)Study on Chaijinfang concentration quality characterizationChaijinfang concentration from extracts have obvious efficacy and less doses,it found represented by saikosaponin B2 of terpenoids in a more prominent role of antidepressant efficacy.In the drug preparation technology and quality control,it should be particularly concern terpenoids composition and its index component of saikosaponin B2 or related factors.Thus the drug system and correlation analysis of Chaijinfang concentration quality characterization as the direction,it guide and evaluate drug preparation technology and quality control,it also has a guiding significance for drug application and provide a new method for drug innovation.Part three:Study on quality control system of Chaijinfang medication(1)The quantitative method of terpenoids and its index component of saikosaponin B2 by HPLC was established.Using saikosaponin B2 as index component,that the content of the linear regression of saikosaponin B2 was y=1742644x-20112,r=0.9999(n=8).The content of saikosaponin B2 and peak area had a favourable linear relationship in the range of 0.072?g?3.60?g,the average recovery was 100.89%,RSD=2.22%(n=6).It measured that saikosaponin B2 content of Chaijinfang extract was between 0.2367%?0.2395%,saikosaponin B2 content of Chaijinfang terpenoids concentration was between 3.4091%?3.8758%.The saikosaponin B2 as reference standard,calculation on saikosaponin B2 with one component peak area of the same spectrum,as the peak area of terpenoids,and obtains its content,this method makes up the single content of saikosaponin B2 is not enough to reflect a large class of(terpenoids)situation.It measured that terpenoids content of Chaijinfang extract was between 0.47%?0.53%,terpenoids content of Chaijinfang terpenoids concentration was between 6.91%?8.09%.The determination results of the contents of terpenoids in three batches of samples showed that the method was steady and reliable and can be used as the quality control method of terpenoids and saikosaponin B2 in Chaijinfang drugs.(2)The quantitative method of phenols by spectrophotometry which was carried out Trichloride-Ferricyanatum Kalium Colorimetric reaction was established.The linear regression was y=623.62x+0.1442,r=0.9987(n=9),using stilbene glucoside as index component,that the content of stilbene glucoside and absorptance had a favourable linear relationship in the range of 0.2410ug/ml?1.2048ug/ml,the average recovery was 99.98%,RSD=2.28%(n=6).It measured that phenols content of Chaijinfang extract was between 6.00%?6.18%,phenols content of Chaijinfang phenols concentration was between 15.12%?16.69%,phenols content of Chaijinfang terpenoids concentration was between 11.22%?13.31%.The determination results of the contents of phenols in three batches of samples showed that the method was steady and reliable and can be used as the quality control method of phenols in Chaijinfang drugs.(3)The quantitative method of index component of stilbene glucoside by HPLC was established.The linear regression of stilbene glucoside was y=2735220x-249318,r=0.9996(n=6).The content of stilbene glucoside and peak area had a favourable linear relationship in the range of 0.20?g?4.00?g,the average recovery was 99.25%,RSD=2.92%(n=6).It measured that stilbene glucoside content of Chaijinfang extract was between 1.2243%?1.2622%,stilbene glucoside content of Chaijinfang phenolic concentration was between 3.1578%?3.6419%.The determination results of the contents of stilbene glucoside in three batches of samples showed that the method was steady and reliable and can be used as the quality control method of stilbene glucoside in Chaijinfang drugs.Part four:Summarize and Discuss(1)Based on the drug system,Chaijinfang extraction and concentration of the preparation method was established.According to the drug system,it designed Chaijinfang drug prqjaration technology combined with each single herb nature and verified the pharmacodynamics of the concentrations.The result explain Chaijinfang concentration have obvious efficacy and less doses.Concentration quality characterization found represented by saikosaponin B2 of terpenoids in a more prominent role of antidepressant efficacy.Therefore in the concentration process should ensure the terpenoids composition.(2)Chaijinfang drug quality control system was established.The quantitative methods of terpenoids and phenolswith their index components were established by spectrophotometry and HPLC method as quality control methods of Chaijinfang drugs.The chemical type and index component associated with drug system for innovative drug research and development,it also provide a new thinking way to establish scientific,reasonable and strict quality control evaluation system.