Study On Formulated Granules Of Tussilago Farfara L. And Aster Tataricus L. F.

Tussilago farfara L.and Aster tataricus L.f.are a classic medicine pair.From the Qin and Han Dynasties to the contemporary,it is an important part of Chinese medicine preparation for relieving cough and phlegm.With the accelerating pace of life,the traditional soup decoction is no longer suitable for the current pace of life.Chinese medicine formula granules are granules made from traditional Chinese medicine decoction pieces,which are made by decoction,concentration and drying,which meet the needs of convenient life.The combined decoction of Chinese medicinal materials is not only the accumulation of single medicines,but also a series of chemical changes such as complexation,co-dissolution and so on.Therefore,it is of great significance to study the difference between the combined use of formula granules of Tussilago farfara L.and Aster tataricus L.f.and the couplet medicines granule.The content of this study is divided into three parts.The first part elaborates the study of formula granules of Tussilago farfara L.,which provides a feasible reference for the preparation of formula granules of Tussilago farfara L.and the replacement of water decoction by formula granules.The second part optimizes the preparation technology of Aster tataricus L.f.,and studies the quality of self-made formula granules of Aster tataricus L.f.,which provides the preparation of formula granules of Aster tataricus L.f.and the replacement of water decoction by formula granules.the chemical constituents of the formula granules of Tussilago farfara L.and Aster tataricus L.f.and couplet medicines granule were studied,and the differences of their chemical constituents were compared.1.Study on the Tussilago farfara L.formula granules1.1 Study on the quality of Tussilago farfara L.According to the requirements of the first edition of the Chinese Pharmacopoeia of the 2015 edition,the thin layer identification,alcohol soluble extract and tussilagone content of the Tussilago farfara L.were determined.The 3 batches medicinal herbs all met the requirements of the pharmacopoeia.The HPLC method was established to determine the chlorogenic acid and rutin.methanol-acetonitrile-0.1%formic acid was used as mobile phase gradient elution.After methodological investigation,it was found that the method was stable and feasible.1.2 Study on preparation technologyThe chlorogenic acid and rutin transfer rate were used as indicators to determine by single factor experiment.The factors of water addition,extraction time and extraction times were taken as the influencing factors of water extraction process.Using L₉?3⁴?orthogonal test design method,the chlorogenic acid,rutin transfer rate and dry paste yield were comprehensive evaluation indicators.The best water extraction process is based on comprehensive scoring:For the first time,14-fold water was added to extract 1.5 hours,and for the second and third times,12-fold water was added to extract 1.5 hours each time.Comparing chlorogenic acid,rutin content and concentration effect,comparing atmospheric concentration and different temperature Concentrated under reduced pressure,finally selected at 50?under reduced pressure,pressure control at 0.095-0.097 kPa.With the content of chlorogenic acid,rutin and dry extract rate as comprehensive evaluation indexes,the filtration and impurity removal processes with different rotating speeds and time were investigated,and the results showed that 4000r/min had the best effect.1.3 Study on the quality of formula granulesThe molding process was based on the particle formation rate,moisture absorption rate and angle of repose as the comprehensive evaluation index,and the molding process was determined by comprehensive score.According to the requirements of the granules in the fourth edition of the Chinese Pharmacopoeia of2015,The moisture,particle size and solubility of the granules are in line with the Chinese Pharmacopoeia standards.HPLC method is used to determine the content of chlorogenic acid and rutin in the granules and the thin layer identification method.It provides a theoretical basis for the quality control of the colza flower formula.The average content of chlorogenic acid and rutin was 4.10 mg/g and 1.10 mg/g,respectively.1.4 Similarity evaluationBy using the similarity evaluation system of chromatographic fingerprint of traditional Chinese medicine?TCM?,the similarity of three batches of Tussilago farfara L.,Decoction and formula granules was evaluated by HPLC.It was found that the similarity was above 0.9,and their chemical constituents were consistent.2.Study on Aster tataricus L.f.formula granules2.1 Study on the quality of Aster tataricus L.f.According to the requirements of the first edition of the Chinese Pharmacopoeia of the 2015 edition,the identification of the thin layer,water,total ash,acid-insoluble ash,water-soluble extract,and shionone content,all three batches of medicinal herbs meet the requirements of the pharmacopoeia.A UV method was established for the determination of total flavonoids with the absorbance was determined with sodium nitrite-aluminium nitrate-sodium hydroxide.The total flavonoids in three batches of Aster tataricus L.f.were 9.34,8.26 and 8.34 mg/g,respectively.2.2 Preparation process researchThe total flavonoids were used as indicators to pass the single factor.The influencing factors were determined by the experiment,the amount of water added,the extraction time and the number of extractions.the total flavonoid transfer rate and the dry paste yield were comprehensively scored,and the L₉?3⁴?orthogonal test design method was used to optimize the best water according to the comprehensive score.The extraction process is that the first time added 12 times the amount of water for 1.5h,the second and third times plus 10 times the amount of water,each extraction for 1.5h.Use total flavonoids content and concentration effect as indicators,evaluate the atmospheric pressure concentration and concentration method at different temperatures,finally determine the drying under reduced pressure at 50?,the pressure is controlled at 0.095-0.097kpa.Comprehensive evaluation index of total flavonoids content and dry paste rate,inspect different impurity removal processes,select 3000r/min centrifugation according to comprehensive score.In the preferred molding process,the molding process was based on the particle formation rate,moisture absorption rate and angle of repose as the comprehensive evaluation index,and the molding process was determined by comprehensive score.2.3 Study on the quality of formula granulesAccording to the requirements of the granules in the fourth edition of the Chinese Pharmacopoeia of 2015,the moisture,particle size and melting properties of the granules are all in accordance with Chinese Pharmacopoeia standards.A method for the determination of total flavonoids in granules by UV method and a thin layer identification method for granules were established.The average content of total flavonoids in the granules was 6.86 mg/g.2.4 Similarity evaluationBy using the similarity evaluation system of chromatographic fingerprint of traditional Chinese medicine?TCM?,the similarity of three batches of Aster tataricus L.f.,Decoction and formula granules was evaluated by HPLC.It was found that the similarity was above 0.9,and their chemical constituents were consistent.3.Comparisons of Chemical Compositions between the formula granules in combination and couplet medicines granuleUPLC-Q-TOF-MS method was established for the determination of the chemical constituents of the formula granulesin combination with couplet medicines granule.Compared with the difference of chemical composition between them,30common compounds were found,while 3,5-di-tert-Butyl-4-hydroxybenzaldehyde was unique compound in couplet medicines granule,and 2'-Deoxyadenosi-ne and DL-Malic acid were the unique compounds in formula granules in combination.There are obvious differences in chemical composition between them.Among them,DL-arginine,cryptochlorogenic acid,neochlorogenic acid,chlorogenic acid,7-hydroxycoumarin,rutin,quercetin,isochlorogenic acid C,isochlorogenic acid B,isochlorogenic acid A,kaempfero,ferulic acid and other compounds in the couplet medicines granule were higher than in formula granules in combination;Guanine,L-phenylalanine,salicylic acid,4-hydroxybenzoic acid,4-methylumiferyl-a-D-glucyranoside,caffeine,etc.Phenylpharylic acid,vanvanillin,vanillin,galanin,senosinine,renrenifform kkcrichchnine,sencristine,ferulic acid,hypericin,kaempol-3-O-rubenoside,kaempferol-3-O-rutinosioside,kaempferol-3-O-glucosglucoside,isoniate,2,2-dimethyl-6-acetylchromanone?Beta-amyrine?7?-?3'-Ethyl-cis-crotonoyloxy?-1?--?2'-methylbutyryloxy?-3?14?-de--hyro-E-notonipetranone in the formula granules in combination were higher than couplet medicines granule.The contents of rutin,chlorogenic acid,kaempferol and quercetin,which are the basis of antitussive,phlegm-resolving and asthma-relieving drugs in couplet medicines granule,are obviously higher than those in formula granules when they are used together;the contents of nephrotoxic compounds such as senecionine and senkirkine in the formula granules in combination are higher than the couplet medicines.It is in agreement with the result that the two drugs can both enhance cough relieving and asthma when they are decocted together,and can also reduce toxicity.