Study On Mechanism Of Study On The Preparation Process,quality Standard,stability And Network Pharmacology Of Xiaoyisanjie Granule

Objective:The preparation process of Xiaoyisanjie granules was optimized,the quality standard was established,and stability was investigated.We investigated the treatment of lung cancer using liquid combination,network pharmacology,and molecular docking.We established the preparation process of Xiaoyisanjie granules,determined the corresponding quality standards,tested the stability of three batches of granules.We investigated the treatment of lung cancer using liquid combination,network pharmacology,and molecular docking.Methods:Preparation process:The water absorption rate of the herbs in the formula was used to determine the amount of water to be added to the first decoction,and the L₉（3⁴）orthogonal factor level table was used to design an orthogonal experiment.The dry extract rate and peoniflorin content were used as assessment indexes for comprehensive scoring.After experimental verification,the most suitable extraction method was screened,its modern extraction process was determined,and three batches of process verification were conducted.Based on the orthogonal results,we conducted small pilot tests to determine the content of auxiliary materials to be added to the pellets and investigated the particle size and angle of repose to determine the forming process.Based on the above process research,we completed three batches of pilot tests of“Xiaoyisanjie granules”to clarify the production process parameters.Quality standard:Using thin-layer chromatography qualitative identification method,nine herbs from formula were identified qualitatively.The high performance liquid-phase method was adopted to determine the content of peoniflorin in Xiaoyisanjie granules,and the methodological investigation and durability of the three batches of pilot pellets were studied,thereby determining the maturity and stability of the method for the determination of peoniflorin content.Stability investigation:Accelerated stability test and long-term stability test were conducted on the granules to determine the storage temperature,humidity,and use period of the abbreviated granules.Partial chemical composition present in the granules was detected by liquid mass spectrometry.Network pharmacology study:TCMSP and Swiss Target Prediction database were used to collect the active ingredients and their corresponding targets of the 15 Chinese herbs in the Xiaoyisanjie formula,and the Gene Cards database was used to obtain the target genes related to lung tumor diseases,to obtain the intersection genes between the active ingredient targets and the disease targets,and to draw The“active ingredient-disease-target”network diagram,PPI network diagram and"active ingredient-target-pathway”network diagram were drawn.We also analyzed the main biological processes,molecular functions,cellular components and action pathways of this formula for lung tumor diseases by GO and KEGG enrichment analysis functions,and finally used the final core component to molecularly dock with the core target to verify the affinity and stability of the core component binding to the target protein receptor in the formula.Results:Preparation process:The best extraction process is to decoct 3 times,60 min each time,and the water added was 5.5,4 and 4 times of the total grams of herbs;The loss of active ingredients can be affected by water sedimentation during the preparation of oral liquids,and the advantages of granules being stable and convenient for patients to carry and take,we made the formula of elimination of dissimilarity into granules,and dextrin was used as an excipient for granulation;Quality standard:In the thin layer chromatography identification,the color of the spots corresponding between the single herb and the sample is clear,and there is no negative interference;After the linearity,precision,methodology and durability examination of Xiaoyisanjie granules,the content limit of this product was determined as not less than 8.50mg/bag with peoniflorin in White Paeony Root as the index ingredient.The storage conditions for the elimination of Xiaoyisanjie granules are polyester,polyester aluminized,polyethylene material composite film sealed storage;Stability examination:It will be valid for a provisional period of 18 months.Using liquid mass spectrometry,60 chemical components were detected in the formula.Network pharmacology:140 active ingredients of the drug of Dissemination Formula were obtained by using the database,and the target genes of 218 lung tumors so as to play a therapeutic effect,the core active ingredients are quercetin,lignan,kaempferol,methyl ferulate,β-sitosterol,ellagic acid,diincarvilone A,4-hydroxy-3-methoxy cinnamaldehyde,etc.The key target proteins are AKT1,MAPK1,RELA,PIK3CA,PIK3R1,TNF etc;the main biological processes involved are hormone response,cell migration,transferase activity,junctional kinase activity,lipopolysaccharide response,oxygen content response,smooth muscle cell proliferation,apoptotic signaling pathway regulating cellular stress response,etc;the main pathways of action involved are cancer pathway,lipid and atherosclerosis,PI3K-Akt signaling pathway,Kaposi’s sarcoma-associated herpesvirus infection,AGE-RAGE signaling pathway,etc;finally,the binding stability between core components and core targets was verified by molecular docking.Conclusion:In this study,we have established an excellent and suitable preparation method for the production of Xiaoyisanjie granules,and the results of the thin-layer qualitative identification of the granules and the content determination of the index ingredient paeoniflorin are stable and suitable as a standard for quality control.This study also identifies several chemical components in the granules by UPLC-Q-TOF-MS/MS.Nework pharmacology:The pharmacological basis,pathways of action and mechanisms of elimination of dissimilarity formula in the treatment of lung tumors were investigated from different perspectives,which laid the theoretical foundation for the subsequent research as well as clinical application.