| JianPi YiQi formula was the clinical experience prescription of Jiangsu integrated traditional Chinese and Western medicine hospital.It was mainly composed of nine kinds of traditional Chinese medicine,such as Codonopsis pilosula,Rhizoma Pinelliae,micalex,Atractylodes macrocephala and Poria cocos.It was mainly used in the treatment of gastric ulcer and chronic atrophic gastritis.The traditional decoction was used as the administration method,which was cumbersome in preparation,difficult to carry and inconvenient to store.In order to make it serve more patients,we planned to use modern preparation technology and quality control methods to prepare modern Chinese medicine preparation with stable process,controllable quality,safety and effective.The specific research content includes the following five parts.1.Preparation process of JianPi YiQi granulesExtraction process research:The whole prescription adopted the method of water extraction,and the weighted comprehensive score value of the ointment extraction rate and the main ingredient hesperidin content in the prescription was used as the evaluation index.The L9(34)orthogonal test method was used to optimize the extraction process,The best extraction process of JianPi YiQi granules was to decoct mica stone for 0.5 h first,then combine with other decoction pieces,add 10 times the amount of water,decoct 3 times,1 h each time.Concentration process research:A single factor experiment was used to compare the vacuum concentration effects at three different temperatures of 65℃,75℃,and 85℃.The determined concentration process:the extract was concentrated under reduced pressure at 75～80℃,and the vacuum degree was-0.08～-0.09 MPa.Research on molding process:The molding process adopted single-factor experiment to optimize the molding process parameters,and the best molding process was determined as follows:the ratio of clear paste to dextrin was 1:1.4,sprayed with 95%ethanol for wet granulation.Under certain technological conditions,three batches of pilot scale-up experiments were carried out on JianPi YiQi granules,and the results showed that the determined preparation process was stable and has high operability.2.Study on quality evaluation of JianPi YiQi granulesIn order to ensure the stable and reliable quality of JianPi YiQi granules,this experiment used TLC qualitative method and HPLC quantitative method to carry out quality evaluation research on JianPi YiQi granules,and established quality standards on this bais.In the qualitative research,the thin-layer chromatography of five medicinal materials including Codonopsis pilosula,Citrus reticulata,Hedyotis diffusa,Rhizoma Pinelliae and Poria cocos with clear spots,strong specificity and good reproducibility was established.In quantitative research,The HPLC method for the determination of the main component hesperidin in JianPi YiQi granules was developed and the methodology was validated.The content of hesperidin in the tentative granules shall not be less than 1.24 mg/g,and the content of each bag was 12 g,and the hesperidin content in each bag of granules shall not be less than 14.88 mg.Refer to the 2020 edition of the Pharmacopoeia of the People’s Republic of China The relevant regulations under the four-part granule item inspected the pilot products,and the results all met the requirements.3.Study on the preliminary stability of JianPi YiQi granulesIn order to ensure the stability of JianPi YiQi granules,this experiment carried out long-term stability and accelerated stability studies.The long-term stability test was to put JianPi YiQi granules at room temperature,and investigated 0,3,6,9 month granules stability,the accelerated stability test was to put JianPi YiQi granules at a constant temperature and humidity box,the temperature was controlled at 40℃ ± 2℃,and the humidity was 75%± 5%,The stability of the preparation was investigated in 0,1,2,3 and 6 months,and the results showed that the quality of JianPi YiQi granules was basically stable under the above conditions.4.The protective effect of JianPi YiQi granules on mice with acute gastric ulcerIn this experiment,the protective effect of JianPi YiQi granules on acute gastric ulcer mice was studied.The results showed that compared with the model control group,mice in the lowdose and high-dose groups of JianPi YiQi granules were in good condition,the gastric ulcer index was reduced,the gastric mucosal injury range was reduced,and the degree of disease was reduced.The content of IL-6 and TNF-α was significantly reduced(p<0.05),the content of MDA and MPO in the gastric tissue homogenate was reduced(p<0.05),and the activity of CAT and SOD content were significantly increased(p<0.05).The results showed that JianPi YiQi granules had a certain protective effect on acute gastric ulcer in mice.5.Pharmacokinetics study of JianPi YiQi RecipeIn this study,high performance liquid chromatography-triple quadrupole tandem mass spectrometry(HPLC-TQ-MS)method was used to analyze the effects of macromolecule and small molecule components in JianPi YiQi prescription on the absorption and metabolism of hesperidin in rats from the perspective of pharmacokinetics,and to provide experimental basis for the impurity removal process of this prescription.The results showed that the removal of macromolecular components in the compound after alcohol precipitation promoted the absorption of hesperidin in the body,and at the same time accelerated the elimination and metabolism of hesperidin in the body.The other ingredients in the compound may promote the absorption of hesperidin in the body,and at the same time delay the elimination and metabolism of hesperidin in the body.In summary,this project optimized the extraction,concentration and molding process of JianPi YiQi granules,formulated quality standards,investigated the stability of the granules,and carried out the protective effect of JianPi YiQi granules on acute gastric ulcers in mice,the research on the pharmacokinetics of the main ingredient hesperidin before and after alcohol precipitation were studied,The research have laid the foundation for the development of JianPi YiQi granules into modern Chinese medicine preparations with feasible technology,controllable quality,safe and effective. |
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