Study On The Classic Prescription Guizhi Jia Gegen Decoction

As the carrier of the theory of traditional Chinese medicine,classic famous prescriptions are the crystallization of clinical experience of previous dynasties,the outstanding representatives of traditional Chinese medicine prescriptions,and the most quintessential treasure in the great treasure house of traditional Chinese medicine.The state had encouraged the development of traditional Chinese medicine,and increased the development of classic and famous prescriptions.The research and development of classic and famous prescription compound preparations must adhere to inheritance and innovation,and respect the past instead of following the past in any way.This topic carried out the research on the classical famous formula Guizhi jia Gegen Decoction,mainly including the research on the prescription of Guizhi jia Gegen Decoction,the research on the substance reference and the efficacy.One The research on the prescription of Guizhi jia Gegen DecoctionThe research on the prescription of Guizhi jia Gegen Decoction includes the prescription source,prescription composition,prescription dose,efficacy indications,evolution of prescription meaning,the origin of medicinal materials,decocting method,use attention,processing of medicinal materials,etc.The results showed that Guizhi jia Gegen Decoction was written by Zhang Zhongjing in the Eastern Han Dynasty.Prescription composition: Puerariae Lobatae Radix,Cinnamomi Ramulus,Paeoniae Radix Alba,Glycyrrhizae Radix et Rhizoma(roasted),Rhizoma Zingiberis Recens,Jujubae Fructus.Prescription dose: Guizhi jia Gegen Decoction was first published in Treatise on Cold Sickness in the Eastern Han Dynasty.After changes in different dynasties,the dosage of Guizhi jia Gegen Decoction also underwent great changes.This research will discuss the dose conversion in different dynasties,and then synthesize the final dose conversion in combination with modern clinical drug safety.It is finally determined that 1 liang is about 3 g.The dosage of each medicine should be: 12 g of Puerariae Lobatae Radix,6 g of Cinnamomi Ramulus,6 g of Paeoniae Radix Alba,6 g of Glycyrrhizae Radix et Rhizoma(roasted),9 g of Rhizoma Zingiberis Recens,12 pieces of Jujubae Fructus.Functions and Indications:Jieji Fabiao,Shengjin Shujing.Indications: exogenous wind-cold type of common cold;Preparation method: 2000 m L water,add Puerariae Lobatae Radix first,boil,evaporate 400 m L,remove the foam,then add other five herbs,boil 600 m L,filter.The research results of prescription medicinal materials: Puerariae Lobatae Radix,a leguminous plant,is the dried root of Pueraria lobata(Wild.)Ohwi,Cinnamomi Ramulus,a Lauraceae plant,is the dried tender Cinnamomum cassia Pres,and Paeoniae Radix Alba,a Ranunculaceae plant,is the dried root of Paeonia lactiflora Pall.Glycyrrhizae Radix et Rhizoma belongs to a legume plant.Rhizoma Zingiberis Recens belongs to a plant of Zingiberaceae,and the medicinal site is its fresh rhizome.Jujubae Fructus is a plant of Rhamnaceae.Two The research on the substance reference of Guizhi jia Gegen DecoctionThe research on the substance reference of Guizhi jia Gegen Decoction is divided into two parts: preparation process and quality standard.The results of the preparation process research are as follows: using the electromagnetic oven to boil the casserole,boiling it in a gentle fire,and the power of the fire is 220 ℃,and the gentle fire is 100 ℃.The specific process: weigh 12 g of Puerariae Lobatae Radix,6 g of Cinnamomi Ramulus,6 g of Paeoniae Radix Alba,6 g of Glycyrrhizae Radix et Rhizoma(roasted),9 g of Rhizoma Zingiberis Recens,and 12 pieces of Jujubae Fructus.Add 2000 m L of water,add Puerariae Lobatae Radix,boil it with fire,remove the foam,adjust the fire to continue to boil for 60 min,add the remaining medicinal materials,continue to boil it with fire for 130 min,filter it while it is hot,cool the filtrate,and then add water to adjust the volume to 600 m L.Concentrate under reduced pressure(70 ℃)to 300 m L,freeze dry(T<-40 ℃,Vac< 20 Pa)for 24 h.Research content of quality standard: the characteristic map method and content determination method of the substance reference of Guizhi jia Gegen Decoction were formulated,and the characteristic map analysis and quality value transmitting analysis were carried out.In addition,the HPLC fingerprint of 15 batches of substance references of Guizhi jia Gegen Decoction,a classic famous recipe,was established to analyze and evaluate their quality in combination with the chemical pattern recognition method,providing a reference for their quality control.The detection method of the characteristic map of the reference sample was established,and the similarity range and peak attribution of the characteristic map spectrum were clarified,combined with the content range The range of transfer rate and extract rate were used to analyze the quantity value transfer between the prepared slices and the corresponding objects of the material standard,and the key quality attributes of the material standard of Guizhi Jiagegen Decoction were clarified.In the characteristic atlas,29 common peaks were identified,and the corresponding peaks were classified.Peaks 3～14,16～19 and 21～25 were from Puerariae Lobatae Radix.Peak 26 to Cinnamomi Ramulus;Peaks 1,15 came from Paeoniae Radix Alba,peaks 20,27～29came from Glycyrrhizae Radix et Rhizoma,peak 2 came from Jujubae Fructus Fructus.Eleven components were identified by comparison with the reference substance,namely,peak 1: gallic acid,peak 8: 3’-hydroxypuerarin,peak 11: puerarin,peak 12: puerarin apigenin,peak 13: 3’-methoxy puerarin,peak 15: paeoniflorin,peak16: daidzin,peak 20: glycyrrhizin,peak 22: genistein,peak 26: cinnamic acid,peak28: ammonium glycyrrhizinate.The similarity between the HPLC fingerprints of 15 batches of Guizhi jia Gegen Decoction and the control fingerprints was more than0.94.The three chemical pattern recognition methods can divide the samples into two types;Eleven main differential components were screened out,among which puerarin,3’-methoxy puerarin,puerarin apigenin,daidzein,3’-hydroxypuerarin and gallic acid were identified.The average content of puerarin,paeoniflorin,glycyrrhizin and ammonium glycyrrhizinate in the four index components of 15 batches of substance references was 14.92 mg/g,9.35 mg/g,3.97 mg/g and 4.69 mg/g,respectively.All batches met the standard(± 30% mean).Because the cooking time is too long,the indicator component cinnamaldehyde contained in Cinnamomi Ramulus is unstable due to heating,and the content of cinnamaldehyde is found to be low and almost non-existent in the detection,so no indicator component was selected for the detection of Cinnamomi Ramulus.The extraction rate of 15 batches of substance references of Guizhi jia Gegen Decoction is 16.85% ～ 21.78%,with an average extraction rate of19.56%.The extraction rate of each batch is 70% ～ 130% of the average value.On the whole,the transfer rate of the corresponding material object from the decoction pieces to the material standard is relatively stable.Three The pharmacodynamic study of Guizhi jia Gegen DecoctionThe pharmacodynamic study of Guizhi jia Gegen Decoction was divided into three parts: UHPLC-Q-TOF-MS analysis,molecular docking analysis and pharmacodynamic analysis.Qualitative analysis of the components of Guizhi Jiagegen Decoction was carried out through UHPLC-Q-TOF-MS,and then the qualitative components were molecular docking with the disease target.Finally,the animal pharmacodynamic experiments were conducted.The results of UHPLC-Q-TOF-MS analysis were as follows: 61 components were identified in the Guizhi jia Gegen Decoction,and 11 components were found in the blood of rats after oral administration.The results of molecular docking were as follows: the binding energy of 8 components in the blood of rats after oral administration with disease target molecules were all less than-4,indicating that the molecular docking experiment was successfully completed.8 components in the blood of rats after administration were closely related to disease targets,so these 8 components were identified as potential pharmacodynamic substances.The results of pharmacodynamic analysis were as follows: Body temperature and body weight analysis: within 14 days of modeling and administration,the weight gain of rats in model group,positive group,high,medium and low dose groups was significantly reduced,and body temperature was significantly increased(P < 0.05).The growth rate was slow in the first week,indicating the successful construction of the wind-cold type of common cold model.The decrease rate of body weight and temperature in the treatment group of Guizhi jia Gegen Decoction was higher than that in the model group,which indicated that Guizhi jia Gegen Decoction had a significant effect on wind cold.Analysis of blood indexes: Compared with model group,the white blood cell count and lymphocyte ratio in Guizhi jia Gegen Decoction treatment group and positive group were significantly increased(P < 0.05),while the monocyte ratio and neutrophil ratio were significantly decreased(P < 0.05).Compared with the blank group,the lymphocyte ratio and neutrophil ratio of the high dose group and the positive group were close to the blank group(P < 0.05).Analysis of immune organ index: The thymus index and spleen index of the model group were significantly lower than the blank group.The organ indexes of Guizhi jia Gegen Decoction treatment group were higher than model group(P < 0.05).But there was no significant difference between the low-dose groups(P > 0.05).Histopathological analysis: No pathological phenomenon was found in the blank group by microscope examination,and there were obvious neutrophil infiltration,bleeding,compensatory vacuoles and interstitial hyperplasia in the lung tissues of the model group.However,the appearance of lung tissue in the groups treated with different doses of Guizhi jia Gegen Decoction was nearly normal except for some areas with slight thickening,interstitial hyperplasia and compensatory vacuoles.Analysis of the contents of inflammatory factors and immunoglobulin A: The levels of Ig A,IL-1β,TNF-α and IL-6 in the model group were significantly higher than the blank group(P < 0.01),indicating abnormal immune and inflammatory responses in rats.After a week of treatment with different doses of Guizhi jia Gegen Decoction,the inflammation level was significantly reduced,and showed a certain amount of effect relationship.Compared with the model group,the levels of Ig A,IL-1β,TNF-α and IL-6 in high-dose,medium-dose and positive groups were significantly decreased(P < 0.01).These results indicate that Guizhi jia Gegen Decoction can effectively improve the immune system of rats,so as to achieve the effect of treating wind-cold type of common cold.Four Study on the Preparation Technology of Guizhi jia Gegen Decoction GranulesOrthogonal experimental design was used to screen the extraction process of Guizhi jia Gegen Decoction granules,and single factor experiments were used to optimize the forming process.Taking the extraction rate and the total peak area of the indicator components as indicators,the final extraction process was determined as follows: taking each decoction piece from Guizhi jia Gegen Decoction,adding 10 times the amount of water,extracting twice,soaking for 30 minutes,and extracting for 30 minutes.The drying process did not choose freeze-drying,which had been previously investigated,but chose pulse drying with higher drying efficiency and more suitable for industrial production,which had relatively less impact on the effective components in the prescription,Ensure the stability of chemical composition.Based on the indicators of bulk density,angle of repose,and molding rate,the optimal molding process is to add soluble starch to the raw material powder at a ratio of 1: 1.2,and use 95% ethanol as the wetting agent to granulation.