Application of radix clematidis in development of medicine for treating gastroesophageal reflux disease

Abstract

The invention discloses application of radix clematidis in development of a medicine for treating gastroesophageal reflux disease. The radix clematidis is used for repairing an esophageal mucosal barrier function, enhancing an esophageal clearing effect and relieving heartburn and acid regurgitation effects; the generation of proinflammatory factors in colon tissues is inhibited, inflammatory cells are reduced, and the expression of related protease is reduced; the traditional Chinese medicine composition is prepared into corresponding forms of capsules, pills, powder, tablets, granules, oral liquid and injection, can replace surgical operation treatment, is not easy to grasp in symptoms, does not cause wounds, is not ideal in operation effect on part of patients, does not cause postoperative complications such as stenosis and obstruction, is good in curative effect, can inhibit PI3K / AKT expression, and can be used for treating various diseases. Therefore, the effect of relieving gastroesophageal reflux is achieved.

Description

Technical Field

[0001] The invention belongs to the technical field of drug application, and particularly relates to the application of Yunweiling in the development of drugs for treating gastroesophageal reflux disease. Background Art

[0002] Gastroesophageal reflux disease (GERD) is a digestive tract motility disorder in which the contents of the stomach and duodenum flow back into the esophagus, oropharynx, and upper respiratory tract, causing corresponding discomfort. Gastroesophageal reflux has typical symptoms such as heartburn and acid reflux, or atypical symptoms such as chest and abdominal pain, cough, asthma, and eating obstruction.

[0003] At present, the treatment of GERD mainly involves adjusting lifestyle, drug therapy, and endoscopic or surgical treatment. However, due to the slow effect of adjusting lifestyle in the short term, drug therapy is limited by various side effects, the indications of endoscopic and surgical operations are difficult to grasp, and the trauma is large. Some patients have unsatisfactory surgical results, and postoperative complications such as stenosis and obstruction occur, and the efficacy is not satisfactory. What's more, the complex symptoms of GERD lead to misdiagnosis, prompting patients to visit doctors repeatedly, which not only increases the consumption of medical resources, but also leads to tension, anxiety, depression and other emotions, affecting the quality of life of patients, making the treatment of GERD a long-term problem for gastroenterologists.

[0004] The Yi medicine Yunweiling is the root and rhizome of the plant Inula japonica of the Asteraceae family. It is warm in nature, pungent and bitter in taste, and enters the liver and stomach meridians. It is rich in resources in Yunnan and has a long history of medicinal use. The "Southern Yunnan Materia Medica" records that Yunweiling "can cure choking". In southwestern Yunnan, it is used as a food ingredient to treat esophagitis, plum pit qi and other similar diseases. However, there is no specific report on whether this medicine can treat gastroesophageal reflux disease.

[0005] Therefore, the present invention aims to provide use of the drug as a therapeutic drug for gastroesophageal reflux disease. Summary of the invention

[0006] In order to solve the above technical problems, the present invention is achieved through the following technical solutions:

[0007] Application of Yunweiling in the development of drugs for the treatment of gastroesophageal reflux disease;

[0008] The content of Yunweiling in the drug being developed for the treatment of gastroesophageal reflux disease is 8.2 mg / kg, and the administration method is oral administration;

[0009] Further, the gastroesophageal reflux disease is selected from inflammatory gastroesophageal reflux;

[0010] Further, the drug for treating gastroesophageal reflux disease is used for at least one of the following: repairing the barrier function of the esophageal mucosa, enhancing the esophageal clearance function, relieving heartburn and acid reflux; inhibiting the generation of pro-inflammatory factors in colon tissue, reducing inflammatory cells, and reducing the expression of related proteases;

[0011] The proteases are phosphatidylinositol 3-kinase and protein kinase;

[0012] Further, the medicine includes capsules, pills, powders, tablets, granules, oral liquids and injections;

[0013] Furthermore, the main ingredient of the drug for treating gastroesophageal reflux disease is Yunweiling, and one or more pharmaceutically acceptable excipients or additives may be added to improve drug absorption or facilitate administration; the excipients or additives include fillers, diluents, adhesives, absorption enhancers, stabilizers, flavoring agents, and sweeteners.

[0014] The beneficial effects of the present invention are:

[0015] The present invention reduces the excessive response of the esophagus to acid reflux stimulation by regulating the functions of neurotransmitters and receptors, thereby alleviating discomfort such as heartburn and chest pain. At the same time, reducing inflammatory cell infiltration is also an important part of treatment. By inhibiting the release of proinflammatory factors and the aggregation of inflammatory cells, we can effectively reduce the inflammatory response of the esophageal mucosa and promote tissue repair and regeneration. In addition, repairing the barrier function of the esophageal mucosa is also the key to treatment. The use of specific drugs or nutrients can enhance the defense ability of the esophageal mucosa, prevent further damage to the mucosa by acid reflux, and thus accelerate the recovery process. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the technical solution of the embodiment of the present invention, the drawings required for describing the embodiment are briefly introduced below.

[0017] Figure 1 This is an experimental diagram when constructing a mouse model;

[0018] Figure 2 This is a comparison of the actual anatomy of the gastroesophageal tract of mice under different group treatments;

[0019] Figure 3 This is a comparison curve of the body weight of mice under different group treatments;

[0020] Figure 4 This is the visceral sensitivity score diagram of mice under different group treatments;

[0021] Figure 5 HE staining was used to observe tissue morphology under different grouping treatments;

[0022] Figure 6These are actual micrographs of 5-HT detected by immunohistochemistry under different grouping treatments;

[0023] Figure 7 This is the immunohistochemical detection of 5-HT under different group treatments;

[0024] Figure 8 This is a graph showing the expression of PI3K, AKT, TRPV1, CGRP, p-PI3K, and p-AKT detected by WB under different group treatments;

[0025] Fig. 9 It is a Venn diagram of Yunweiling drug targets and gastroesophageal reflux disease therapeutic targets;

[0026] Fig.10 It is the network diagram of active ingredients of Yunweiling effective drugs-predicted targets;

[0027] Fig.11 It is the protein interaction (PPI) network of Yunweiling in the treatment of gastroesophageal reflux disease;

[0028] Fig.12 This is the TOP10 key target map of Yunweiling for the treatment of gastroesophageal reflux disease;

[0029] Fig.13 This is a bar graph of the GO analysis results of Yunweiling in the treatment of gastroesophageal reflux disease. DETAILED DESCRIPTION

[0030] Example 1

[0031] In this embodiment, the present invention discloses the use of Yunweiling in the development of drugs for treating gastroesophageal reflux disease, which is further verified by constructing an animal model experiment;

[0032] Construction of rat gastroesophageal reflux model:

[0033] SPF grade SD male mice were purchased from Sifu Biotechnology Co., Ltd. with a body weight of 200-220 g. The experimental animal use license number is SYXK(Yunnan)K2020-000. The research animals were adaptively raised in the same cage, the room temperature was maintained at 22±2℃, the humidity was controlled at 35%-60%, and they were free to eat and drink.

[0034] One week later, the animals were anesthetized and shaved at the same time. The animals were fixed on the operating table in the supine position with their limbs, and the skin was prepared and disinfected. A longitudinal incision of about 2 cm was made in the midline from the xiphoid process away from the head end. After opening the abdomen, the connective tissue between the liver and stomach was separated and cut. After the cardia was removed, the dorsal esophagus was separated from the blood vessels behind the esophagus and ligated or clamped to prevent bleeding. The esophagus was cut off 0.5 cm above the cardia, and the duodenum was 1 cm below the pylorus, avoiding the blood vessel opening by 5 mm. The lower edge of the esophagus was anastomosed with the duodenal incision using interrupted sutures. After the organs were returned to their positions, the abdomen was closed, the abdominal cavity was flushed with saline, and the abdominal wall and skin were closed and sutured, and the model was constructed.

[0035] The mouse models constructed above were randomly divided into 6 groups, with 3 mice in each group; specifically:

[0036] Control group: no treatment, normal feeding;

[0037] Sham group: only the duodenum was opened, the abdomen was closed after exposing the abdominal organs for 15 minutes, and the animals were fed normally;

[0038] GERD group: After esophageal and duodenal suture, no drug intervention was given and the animals were fed normally;

[0039] GERD+Yunweiling group: Yunweiling was administered orally once a day, with the amount of Yunweiling used being 8.2 mg / Kg / day for 4 weeks;

[0040] GERD+Yunweiling+LY294002 (PI3K-Akt signaling axis inhibitor) group: LY294002 was prepared by adding 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline in sequence, and LY294002 (10ul, 10mmol / L) was injected intraperitoneally twice a week for 4 weeks. LY294002 and Yunweiling were administered at the same time;

[0041] GERD+NC group: To avoid the influence of solvents required for the preparation of LY294002 on the experimental results, this group was specially set up for comparison with GERD+Yunweiling+LY294002 group. The administration method was to give only 10% DMSO: dimethyl sulfoxide, 40% PEG300: polyethylene glycol 300, 5% Tween-80, 45% normal saline) intraperitoneal injection twice a week for 4 weeks.

[0042] The mice in each group were tested for body weight, visceral hypersensitivity, and immunohistochemistry. HE staining was used to observe tissue morphology, and WB was used to detect the expression of PI3K, AKT, TRPV1, CGRP, p-PI3K, p-AKT, and p-TRPV1 in gastroesophageal tissues.

[0043] The weight test results are as follows Figure 3 As shown: The weight of the Control group and the Sham group did not change much, while the weight of the other groups gradually decreased from 0 to 7 days and then stabilized;

[0044] Esophageal visceral hypersensitivity results such as Figure 4 As shown: Compared with the Control group and the Sham group, the esophageal visceral sensitivity scores of GERD rats in the other groups were increased, which means that the esophageal visceral sensitivity of rats was significantly increased under the GERD state. Many studies have confirmed that esophageal visceral hypersensitivity can cause heartburn and chest pain symptoms, and is one of the main mechanisms of GERD. Compared with the GERD group, the esophageal visceral sensitivity scores of the GERD+NC group were increased under all air pressure conditions, which means that the LY294002 solvent can cause an increase in the degree of esophageal hypersensitivity of GERD rats; while the esophageal visceral sensitivity scores of the GERD+Yunweiling group (15mmHg, 30mmHg, 60mmHg) and the GERD+Yunweiling+LY294002 group (30mmHg, 45mmHg, 60mmHg) were lower than those of the GERD group under the three air pressure conditions. , which proved that Yunweiling can alleviate the esophageal visceral hypersensitivity of GERD rats; the esophageal visceral sensitivity score of the GERD+Yunweiling+LY294002 group was lower than that of the GERD+Yunweiling group under the 3 groups of air pressure conditions (15mmHg, 45mmHg, and 60mmHg), and the esophageal visceral sensitivity under the air pressure condition of group 1 (30mmHg) was the same, which proved that Yunweiling can reduce esophageal visceral hypersensitivity, improve heartburn and chest pain symptoms, and treat GERD by affecting the PI3K-Akt signaling axis.

[0045] HE staining results Figure 5As shown in the figure: Control and Sham groups showed no obvious pathological changes. The pathological changes in the GERD group were mainly mucosal congestion and edema, focal mucosal cell shedding, interstitial neutrophils, eosinophils, monocytes and lymphocytes infiltration to varying degrees, and vascular dilation, congestion and edema in the submucosal layer; in the GERD+NC group, interstitial neutrophils, eosinophils, monocytes and lymphocytes infiltration to varying degrees, and vascular dilation, congestion and edema in the submucosal layer; in the GERD+Yunweiling group, a small amount of inflammatory cell infiltration, vascular dilation, congestion and edema in the submucosal layer; in the GERD+Yunweiling+LY294002 group, vascular congestion in the submucosal layer. Compared with the Control group and the Sham group, the gastroesophageal tissue mucosa of GERD rats in the other groups showed pathological changes of inflammatory cell infiltration, vascular dilation, congestion and edema, indicating that GERD rats had esophageal mucosal inflammation. Esophageal mucosal inflammation plays an important role in promoting esophageal mucosal barrier function damage (one of the main pathogenesis of GERD) and the occurrence and development of GERD. Conversely, improving esophageal mucosal inflammation is beneficial to the treatment of GERD. Compared with the GERD group, the GERD+NC group had the same pathological manifestations of esophageal mucosa, which means that the LY294002 solvent did not cause changes in the pathological manifestations of the esophageal mucosa of GERD rats; compared with the GERD group with multiple inflammatory cell infiltrations, the experimental results showed that the GERD+Yunweiling group had only a small amount of inflammatory cell infiltration, proving that Yunweiling can reduce inflammatory cell infiltration and repair esophageal mucosal barrier function damage, thereby playing a role in treating GERD.

[0046] Immunohistochemistry was used to detect the expression of 5-HT. Figure 6 , Figure 7As shown: There was no significant change in expression between the Sham group and the Control group; the expression in the GERD group was increased and statistically significant compared with the Sham group, indicating that the 5-HT level in the esophageal mucosal tissue of GERD rats was increased. There was no significant change in expression between the GERD group and the GERD+NC group, indicating that the LY294002 solvent did not affect the expression level of 5-HT in GERD rats; compared with the GERD group, the GERD+Yunweiling group had a decreased expression of 5-HT and statistically significant, indicating that Yunweiling could downregulate the expression level of 5-HT in GERD rats; compared with the GERD group, the GERD+Yunweiling+LY294002 group had an increased expression but no statistical significance, indicating that inhibiting the PI3K-Akt signaling axis could increase the expression level of 5-HT in GERD rats. 5-HT is an important neurotransmitter in the enteric nervous system and plays an important role in regulating gastrointestinal sensation, movement and sensitivity. Its reduced secretion can lead to relaxation of esophageal smooth muscle and increased sensitivity of esophageal mucosa, both of which are the main mechanisms of GERD. The former can cause esophageal motility to slow down, weaken clearance ability, and more easily cause acid reflux, presenting symptoms of acid reflux; the latter has been mentioned above and is closely related to heartburn and chest pain symptoms. In addition, 5-HT is related to mood regulation, especially anxiety and depression, as shown by the fact that the 5-HT level in the blood of patients with anxiety and depression is often significantly reduced. Conversely, its increased concentration in serum can relieve anxiety and depression. Combined with the experimental results of this study that inhibiting the PI3K-Akt signaling axis can increase the expression level of 5-HT in GERD rats, it can be seen that inhibiting the expression level of the PI3K-Akt signaling axis is beneficial to reducing esophageal mucosal sensitivity, enhancing esophageal clearance, improving acid reflux, heartburn, chest pain symptoms, and relieving anxiety and depression, and can achieve the effect of multi-channel treatment of GERD.

[0047] The results of WB detection of PI3K, AKT, TRPV1, CGRP, p-PI3K, and p-AKT are as follows Figure 8As shown: There was no significant difference in the expression of p-TRPV1 / TRPV1, CGRP, p-PI3K / PI3K, and p-AKT / AKT between the Control group and the Sham group, indicating that sham surgery had no significant effect on the expression levels of the above targets. Compared with the Sham group, the expression of CGRP in the GERD group was significantly reduced, the expression of p-PI3K / PI3K and p-AKT / AKT was significantly increased, and there was no significant difference in the expression of p-TRPV1 / TRPV1, indicating that GERD can significantly reduce the expression level of CGRP and significantly increase the expression levels of p-PI3K / PI3K and p-AKT / AKT. There was no significant difference in the expression of p-TRPV1 / TRPV1, CGRP, p-PI3K / PI3K, and p-AKT / AKT between the GERD group and the GERD+NC group, indicating that the LY294002 solvent had no significant effect on the expression levels of the above targets. Compared with the GERD group, the expression of CGRP in the GERD+Yunweiling group was significantly increased, the expression of p-PI3K / PI3K and p-AKT / AKT (not significant) was decreased, and the expression of p-TRPV1 / TRPV1 was not significantly different, indicating that Yunweiling can significantly increase the expression level of CGRP and downregulate the expression levels of p-PI3K / PI3K and p-AKT / AKT. Compared with the GERD+Yunweiling group, the expression of p-PI3K / PI3K and p-AKT / AKT in the GERD+Yunweiling+LY294002 group was significantly decreased, the expression of CGRP was also decreased, and the expression of p-TRPV1 / TRPV1 was not significantly different, indicating that Yunweiling's relief of GERD is indeed related to the PI3K / AKT signaling axis, and can reduce the expression of PI3K / AKT and inhibit the PI3K / AKT signaling pathway to reduce the expression level of CGRP. Studies by many other scholars have also confirmed that this signaling pathway is related to GERD. Inhibiting this pathway can reduce the release of multiple inflammatory factors, reduce the cell's stress response to acidity, and thus treat GERD, which is similar to the results of this study. GCRP is closely related to the occurrence and development of GERD: First, GCRP can inhibit the degradation of the pain central transmitter SP related endopeptidase, prolong the sensitization time of SP, make it produce more sustained noxious stimulation and reduce the perception and pain threshold, thereby inducing the occurrence and development of GERD; second, CGRP can also directly promote the transmission of nerve stimulation impulse signals to produce perceptual hypersensitivity, which is one of the mechanisms for the formation of GERD visceral hypersensitivity. Previous studies have found that the severity of GERD patients is related to CGRP. Combining the above two mechanisms, it can be seen that reducing the expression level of CGRP is beneficial to reduce pain perception and relieve visceral hypersensitivity, and treat GERD, which once again verifies the effectiveness of Yunweiling in treating GERD.

[0048] In summary, Yunweiling has the effects of relieving visceral hypersensitivity, reducing inflammatory cell infiltration, repairing esophageal mucosal barrier function, alleviating pain perception, and treating GERD. Its mechanism of action may be related to the inhibition of the PI3K / AKT signaling pathway. Inhibiting the expression level of the PI3K-Akt signaling axis is beneficial to reducing esophageal mucosal sensitivity, enhancing esophageal clearance, improving acid reflux, heartburn, chest pain symptoms, and relieving anxiety and depression, and can achieve the effect of multi-channel treatment of GERD.

[0049] Example 2

[0050] In this embodiment, a specific application process of Yunweiling in treating esophageal reflux with corresponding functional targets is provided; the specific steps are as follows;

[0051] S1: Screening of active ingredients of Yunweiling and prediction of its action targets; Obtain the active ingredients of Yunweiling, and obtain the SMILES numbers corresponding to its active ingredients through the PubChem database; Then obtain the action targets and gene names corresponding to the Yunweiling flexible ingredients through the SwissTargetPrediction database;

[0052] S2: Search the database with "gastroesophageal reflux disease" as the keyword, summarize the therapeutic targets of gastroesophageal reflux disease retrieved from the two databases, remove duplicates using EXCEL 2019 software, and obtain the disease therapeutic targets of gastroesophageal reflux disease;

[0053] S3: Using the Venny2.1.0 platform, the intersection of Yunwei flexible ingredient targets and GERD disease targets was determined by constructing a Venn diagram. These intersection targets were considered to be potential targets for Yunweiling in the treatment of GERD. Cytoscape 3.8.2 software was then used to process the data, construct a "drug active ingredient-predicted target" network diagram, and visualize it.

[0054] S4: The intersection targets obtained from the Venn diagram were uploaded to the STRING database (https: / / string-db.org), the species was selected as “homosapiens”, and the confidence score (combinedscore) was ≥ 0.4. The PPI network was constructed, and the obtained PPI network was imported into Cytoscape 3.8.2 software for visualization analysis, and key targets were screened out according to the degree values ​​of the nodes.

[0055] S5: Metascape database was used to perform GO analysis and KEGG pathway enrichment analysis on the potential targets of Yunweiling for gastroesophageal reflux disease. GO analysis mainly includes three aspects: biological process (BP), cellular component (CC) and molecular function (MF). KEGG enrichment analysis was used to analyze the relevant biological pathways of potential target enrichment. Then, the results of GO functional enrichment analysis and KEGG pathway enrichment analysis were visualized using the Microbiological Information Platform (http: / / www.bioinformatics.com.cn) to make bar charts and bubble charts respectively. Among them, the GO functional enrichment analysis selected the annotations of the top 10 protein groups in BP, CC and MF, and the results of KEGG pathway enrichment analysis selected the top 20 pathways in terms of credibility.

[0056] S6: Screening of active ingredients of Yunweiling and prediction of their targets. Through literature and PubChem database retrieval, a total of 17 Yunwei flexible components and their corresponding SMILES numbers were obtained (see Table 1). The SwissTargetPrediction database (Probability*≥0.1) was used to predict the targets corresponding to the Yunwei flexible components. After sorting and removing duplicates, a total of 308 targets and their gene names were screened.

[0057] Table 1 | Effective active ingredients of Yunweiling

[0058]

[0059] S7: Prediction of therapeutic targets for gastroesophageal reflux disease (GERD) and screening of potential targets of Yunweiling for the treatment of GERD. GeneCards database and OMIM database were used to predict potential therapeutic targets for gastroesophageal reflux disease. After sorting and removing duplicates, 1195 predicted therapeutic targets were obtained. The potential targets of Yunweiling's active ingredients and potential therapeutic targets of gastroesophageal reflux disease were intersected using the Venny2.1.0 platform to draw a Venn diagram. See the details for details. Figure 8 As shown, 36 potential targets of Yunweiling for the treatment of gastroesophageal reflux disease were finally obtained.

[0060] S8: Construction of drug active ingredient-prediction target network diagram. The potential targets of Yunweiling for the treatment of GERD and the effective active ingredients of Yunweiling were imported into Cytoscape3.8.2 software to construct the "drug active ingredient-prediction target" network, such as Fig. 9As shown in the figure, the pink quadrilateral represents the effective active pharmaceutical ingredients of Yunweiling, and the shape and size represent the number of potential targets connected to it. The more the number, the larger the quadrilateral. The lavender circle represents the potential target of Yunweiling for gastroesophageal reflux disease. As can be seen from the figure, the number of targets of the six ingredients, Spinacetin, Acacetin, Ursolic acid, Shionone, 1,3,5-trimethoxybenzene, and Vanillic acid, is significantly greater than that of other ingredients, indicating that these three ingredients may be the key pharmacodynamic ingredients. The more potential targets the effective drug ingredient node is set to connect, the larger the node is. It can be observed that six ingredients, including Spinacetin, Acacetin, Ursolic acid, Shionone, 1,3,5-trimethoxybenzene, and Vanillic acid, are significantly larger than other nodes, indicating that these six nodes are the key nodes of the drug ingredients, and the corresponding monomers can be regarded as the key effective drug ingredients of Yunweiling for the treatment of gastroesophageal reflux disease.

[0061] S9: Construction of protein interaction network and selection of key targets for Yunweiling in the treatment of gastroesophageal reflux disease. The intersection targets obtained from the Venn diagram were uploaded to the STRING database (https: / / string-db.org), the species was selected as “homosapiens”, and the confidence score (combinedscore) was ≥ 0.4. The PPI network was constructed and the obtained PPI network was imported into Cytoscape 3.8. software for visualization analysis, such as Fig.10 As shown in the figure, the dots represent the targets. The darker the color and the larger the shape, the more connections the node has with other nodes, and the closer the relationship. The lighter the color and the smaller the shape, the fewer connections the node has with other nodes, and the more distant the relationship. The TOP10 key targets are selected based on the node degree values, such as Fig.11 As shown in the figure, TRPV1 ranks high, ranking 8th, while TPRA1 ranks relatively low. It can be considered as the key target of Yunweiling for gastroesophageal reflux disease and plays an important role in the entire network.

[0062] S10: GO functional enrichment analysis. Metascape database online platform was used to conduct GO functional enrichment analysis on the potential targets of Yunweiling for gastroesophageal reflux disease. P<0.01 was the screening parameter. The results showed that a total of 2209 GO enrichment entries were obtained, including 1816 biological processes (BP), 108 cell composition (CC), and 285 molecular functions (MF). Then, using the microbial information platform, according to the size of the P value, the top 10 entries were selected to produce the GO enrichment analysis diagram as shown in the figure. Fig.12 As shown in the figure, BP: biological process, CC: cell composition, MF: molecular function, the horizontal axis is the number of genes analyzed by GO, and the vertical axis represents the ID and name of the GO analysis. The longer the bar in the figure, the more targets are enriched in this item; the redder the color, the lower the P value of the enrichment result of this item, and the higher the credibility.

[0063] S11: KEGG pathway enrichment analysis. A total of 186 pathways were obtained through KEGG pathway enrichment analysis (P<0.01 was the screening parameter). The top 20 pathways with the highest P value were selected, and the KEGG pathway enrichment analysis bubble chart was drawn using the Microbiological Information Platform.

[0064] The preferred embodiments of the present invention disclosed above are only used to help explain the present invention. The preferred embodiments do not describe all the details in detail, nor do they limit the invention to only the specific implementation methods described.

Claims

1. The application of Yunweiling in the development of drugs for the treatment of gastroesophageal reflux disease.

2. The use of Yunweiling in the development of a drug for treating gastroesophageal reflux disease according to claim 1, characterized in that: The content of Yunweiling in the drug being developed for the treatment of gastroesophageal reflux disease is 8.2 mg / kg, and the administration method is oral administration.

3. The use according to claim 1, characterized in that: The gastroesophageal reflux disease is selected from inflammatory gastroesophageal reflux.

4. The use of Yunweiling in the development of a drug for treating gastroesophageal reflux disease according to claim 1, characterized in that: The drug for treating gastroesophageal reflux disease is used for at least one of the following: repairing the barrier function of the esophageal mucosa, enhancing the esophageal clearance function, relieving heartburn and acid reflux; inhibiting the generation of pro-inflammatory factors in colon tissue, reducing inflammatory cells, and lowering the expression of related proteases; The proteases are phosphatidylinositol 3-kinase and protein kinase.

5. The use of Yunweiling in the development of a drug for treating gastroesophageal reflux disease according to claim 1, characterized in that: The medicine includes capsules, pills, powders, tablets, granules, oral liquids and injections.

6. The use of Yunweiling in the development of a drug for treating gastroesophageal reflux disease according to claim 4, characterized in that: The main ingredient of the drug for treating gastroesophageal reflux disease is Yunweiling, and one or more pharmaceutically acceptable excipients or additives can be added to improve the drug absorption effect or facilitate administration; the excipients or additives include fillers, diluents, adhesives, absorption enhancers, stabilizers, flavoring agents, and sweeteners.

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