| This paper includes four chapters.The first chapter:summary of the related literatures;The second chapter:studies on the preparation technology of the drug of Baizhifang based on anti-migraine drug systems;The third chapter:establishment of the quality control methods of the drug of Baizhifang based on anti-migraine drug systems;The fourth chapter:summary and discussion.The first chapter:Summary of the related literaturesSummaring the current situation of research progresses in the chemical constituents and pharmacological research of Baizhi(Angelica Summaring the current situation of research progresses in the chemical constituents and pharmacological activities of Gaoben(Rhizoma Ligustici)and Tianma(Gastrodia elata B1).109 pieces of references are cited.The second chapter:Research on the preparation Technology of the Baizhifang drugs based on anti-migraine drug systemsThis paper based on the thought that natural pharmacy concept drug system is naturalness,collaborative,and affinity,then use the method that our group established,which is the method that is a link between the pharmacokinetic and pharmacodynamics(PK-PD-DI)to study Baizhifang,found that phenolic acids,phthalide and coumarins components in Baizhifang is the components of drug system of Baizhifang anti-migraine effective,based on drug system.therefore this chapter is to study the preparation technology of enriching the phenolic acids,the phthalides and the coumarins.in BaizhifangFirstly,we aim at studying the extraction technology of the Baizhifang drugs based on drug systems(the Baizhifang drugs).Using L9(43)orthogonal test,study the extraction solvent(A),solvent-fold(B),extraction time(C)and extraction times(D),evalued by the extraction ratio of total phenols,ferulic acid,senkyunolide I and imperatorin.To analyse all the experiments results synthetically,the best extraction technology is A3B2C2D2,Namely,the extraction solvent is a%ethanol-water solvent;solvent-fold is b times of the medical material;extraction time is c hour;extraction times is d times.The extraction technology described above was tested.the results show that:the average cream rate is 16.09%,the average content of total phenols was 14.76%,the average extraction ratio was 86.45%;the average content of ferulic acid was 0.59%,the average extraction ratio was 91.97%;the average content of senkyunolide I was 0.25%,the average extraction ratio was 94.23%;the average content of imperatorin was 0.22%,the average extraction ratio was 82.42%.Secondly,using the maximum adsorption volume of chlorogenic acid(the easiest outflow phenolic acids)and the content and the transferring ratio of ferulic acid,senkyunolide I and imperatorin as indexs,we select A resin as the resin of purify the Baizhifang drugs,then using the content and the transferring ratio of ferulic acid,senkyunolide I and imperatorin as indexs,study the the purification technology of A resin,Ultimately,the optimum resin purification process is:Baizhi,Gaoben,Tianma directly mixed in the formula proportion.add c times of a%ethanol-water solvent of the medical material,heat to reflux for b times,each time is dh,then combined the filtrate solvent,less pressure recovery to no alcohol taste(one-eight of solvent volume),add B imes volume of water of the mass of medical material(the sample concentration is C g/ml)to get the sample liquid.the sample liquid is go through the A resin coloumn,the retio of loading capacity and resin volume was 1g:DmL,The diameter/height of the coloumn is 1:E,with velocity of flow of FBV/h,G times volume of resins of water to wipe off impurity,the velocity of flow is HBV/h,then I times volume of resins of J%ethanol to elute with the flow rate ofKBV/h,reclaim the solvent of J%ethanol,vocuum drying,weighting,the phenols acids and the phthalides materials(Baizhifang preparations I)was obtained.then L times volume of resins of M%ethanol to elute with the flow rate of NBV/h,reclaim the solvent of M%ethanol,vocuum drying,weighting,the coumarins materials(Baizhifang preparations II)was obtained.The purification technology described above was tested and verified through 3 batches of samples,the average cream rate of Baizhifang preparations I is 2.29%,the average content of the ferulic acid is 4.41%,the average transferring ratio is 86.00%,the average content of the total phenols is 37.26%,the average transferring ratio is 30.95%;the average content of the senkyunolideⅠ is 1.68%,the transferring ratio is 91.17%;the average cream rate of Baizhifang preparations Ⅱ is 1.46%,the average content of the total phenols is 23.32%,the average transferring ratio is 12.38%;the average content of the imperatorin is 2.10%,the transferring ratio is 70.31%.Finally,the therapeutic effect of preparations of Baizhifang is carried out to verify.the result show that the aqueous extract,the alcohol extract and the enrichment materials of Baizhifang all have the anti-migraine effect,these group have no difference on elevating the content of NO,reducing the content of CGRP,ET-1 in rat brain.and the alcohol extract and the enrichment materials of Baizhifang is higher than the aqueous extract on elevating the content of 5-HT in rat plasma,and the cream rate of the enrichment materials(3.78%)is much less than the alcohol extract(16.04%)and the aqueous extract(36.99%),namely,the content of the phenolic acids,the phthalides and the coumarins is higher,but the therapeutic effect is equal even higer,it shows that the phenolic acids,the phthalides and the coumarins is the main effective material basis of anti-migraine therapeutic effect,it verify the accuracy of the design and optimization of preparation technology and the validity of its enrichment materials.The third chapter:Research on the quality control method of the Baizhifang drug based on anti-migraine drug systemsWe establish methods for the determination of the content of the total phenols,the index component of phenols acids:ferulic acid,the index component of the phthalides:senkyunolide I,the index component of the coumarins:imperatorin.Using the UV-Vis method and ferulic acid as the standard,we establish the method for determination of the content of the total phenols,by which was carried out Trichloride-Ferricyanatum Kalium Colorimetric reaction.The linear regression of ferulic acid was Y=23907X-0.0173,r=0.9990(n=7),the linear range is 0.00612mg～0.04284mg,the average recovery was 101.9%,the RSD is 1.80%.The content of total Phenols in the decoction pieces of Baizhifang is 2.75%,using HPLC method to establish the method for determination of the content of ferulic acid,The linear regression of ferulic acid was Y=5097476.47X-41689.30,r=0.9999(n=8),the linear range is 0.0277μg～2.216μg,the average recovery was 102.0%,the RSD isl.83%.The content of ferulic acid in the decoction pieces of Baizhifang is 0.1170%;using HPLC method to establish the method for determination of the content of senkyunolide I,The linear regression of senkyunolide I was Y=1823649.60X+4061.33,r=0.9999(n=8),the linear range is 0.0129μg～1.032μg,the average recovery was 100.69%,the RSD is 1.55%.The content of senkyunolide I in the decoction pieces of Baizhifang is 0.0421%,using HPLC method to establish the method for determination of the content of imperatorin,The linear regression of imperatorin was Y=4529882.83X-2265.01,r=0.9999(n=8),the linear range is 0.0256μg～2.048μg,the average recovery was 99.31%,the RSD is 2.54%.The content of imperatorin in the decoction pieces of Baizhifang is 0.0436%.The fourth chapter:Summary and Discussionsummarized the work of this paper and discussed the main significance of the enrichment drugs of Bhizhifang into two parts is to make compatibility studies.The innovation of this paper:the preparation technology methods of the Baizhifang drugs were established;the quality control methods of the Baizhifang drugs were established. |
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