Medicinal folium artemisiae argyi composition for preventing and treating chronic gastroenteritis and esophageal reflux codisease

Abstract

The invention discloses a medicinal moxa composition for preventing and treating chronic gastroenteritis combined with esophageal reflux, which comprises rhizoma atractylodis, wrinkled gianthyssop herb, fortune eupatorium herb and moxa, and can improve the symptoms of chronic gastroenteritis and esophageal reflux through the effects of strengthening spleen and stomach, eliminating dampness and dissolving turbidity, regulating qi and relieving pain and the like. Agastache rugosus is used for resolving dampness and regulating the middle warmer, fortune eupatorium herb is used for enlivening the spleen and promoting appetite, and the four medicines are compatible to form a balanced system for strengthening the spleen and stomach and eliminating dampness and turbidity. A plurality of volatile active ingredients of the medicinal moxa composition act on a plurality of key targets related to chronic gastroenteritis and esophageal reflux co-disease through moxibustion. Volatile components generated by combustion of the medicinal moxa composition directly act on esophageal mucosa and spleen and stomach areas, a'local-whole body 'synergistic effect mode is formed in combination with a warm effect and meridian stimulation, and a new thought and theoretical basis are provided for prevention and treatment of chronic gastroenteritis combined with esophageal reflux.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a medicinal composition for the prevention and treatment of chronic gastroenteritis complicated with esophageal reflux disease. Background Technology

[0002] Chronic gastroenteritis and gastroesophageal reflux disease (GERD) are comorbidities of the digestive system, presenting a conflict between acid suppression and prokinetic therapy in their treatment. Chronic gastroenteritis mainly manifests as abdominal pain, diarrhea, and indigestion, falling under the category of "stomach pain" in Traditional Chinese Medicine (TCM), often related to spleen and stomach weakness and internal damp-heat. GERD, on the other hand, is characterized by acid reflux, heartburn, and retrosternal pain, falling under the category of "upward reversal of stomach qi" in TCM, often caused by disharmony between the liver and stomach, and impaired stomach function. Western medicine commonly treats chronic gastroenteritis with acid-suppressing drugs (such as PPIs) and prokinetic drugs (such as domperidone). However, long-term use of acid-suppressing drugs leads to reduced gastric acid secretion, affecting nutrient absorption and intestinal flora balance; prokinetic drugs, on the other hand, may cause extrapyramidal side effects (tremors, depression) and QT interval prolongation, contradicting the treatment of GERD. Furthermore, the interaction between acid-suppressing and prokinetic drugs may trigger gastrointestinal dysfunction. Summary of the Invention

[0003] The purpose of this invention is to provide a medicinal composition for the prevention and treatment of chronic gastroenteritis complicated with gastroesophageal reflux disease.

[0004] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A medicinal composition for preventing and treating chronic gastroenteritis complicated with gastroesophageal reflux disease. The medicinal composition comprises a traditional Chinese medicine composition and moxa wool. The traditional Chinese medicine composition is made from the following raw materials in the following weight ratio: 4-17 parts of Atractylodes lancea, 6-20 parts of Pogostemon cablin and 5-17 parts of Eupatorium fortunei. The weight ratio of the traditional Chinese medicine composition to the moxa wool is 2.5-6:7.5-11.

[0005] To further realize the present invention, the traditional Chinese medicine composition in the above-mentioned medicated mugwort composition is preferably made from the following raw materials in the following weight ratio: 11 parts of Atractylodes lancea, 13 parts of Pogostemon cablin and 11 parts of Eupatorium fortunei, and the weight ratio of the traditional Chinese medicine composition to mugwort floss is 4:9.

[0006] The advantages of this invention compared to the prior art are as follows: I. Formulation Compatibility and Synergistic Mechanism The formulation of the medicated composition of this invention embodies the traditional Chinese medicine principle of "principal, assistant, adjuvant, and guide" in its formulation. Through synergistic effects, each herb forms a multi-target regulatory treatment mode.

[0007] The medicinal composition of this invention uses mugwort floss as the main ingredient, combined with Atractylodes lancea, Pogostemon cablin, and Eupatorium fortunei. It has the effects of warming and unblocking the meridians, drying dampness and strengthening the spleen, and aromatically resolving turbidity. It can effectively prevent and treat chronic gastroenteritis complicated with esophageal reflux.

[0008] Moxa floss is used as the monarch drug, taking advantage of its effects of warming and dredging the meridians, dispelling cold and relieving pain. Chronic gastroenteritis and esophageal reflux are mostly caused by deficiency-cold in the spleen and stomach and internal obstruction of damp-turbidity. Moxa floss is warm in nature, which can warm and dredge the meridians, disperse cold-dampness, promote local qi and blood circulation, and accelerate mucosal repair.

[0009] Atractylodes lancea is used as the ministerial drug, taking advantage of its functions of drying dampness and strengthening the spleen, dispelling wind and cold. Atractylodes lancea has a pungent smell and a strong flavor, and its nature is dispersing and sweating. It enters the spleen and stomach to eliminate dampness, dry dampness and strengthen the spleen. "Yujue Yaojie" states that: "It dries the soil and promotes diuresis, purges fluid-retention and eliminates phlegm, promotes blood circulation and removes fullness... It dispels mountain and river miasma."

[0010] Agastache rugosa is used as the ministerial drug, taking advantage of its effects of aromatic turbidity-resolving and stopping nausea. Agastache rugosa is pungent and warm. "Leigong Paozhi Yaoxingjie" states that "it enters the lung meridian to regulate qi" and "enters the spleen and stomach to harmonize the middle". "Bencao Zhengyi" says that it "is aromatic without being too pungent, warm without being overly dry, and can dispel gloomy dampness-evil". The combination of Atractylodes lancea and Agastache rugosa targets the pathogenesis of "dampness blocking the middle-jiao" in chronic gastroenteritis and esophageal reflux.

[0011] Eupatorium fortunei is used as the assistant drug, taking advantage of its functions of aromatic pestilence-resolving and spleen-waking and stomach-promoting. Eupatorium fortunei is pungent in flavor and neutral in nature; it belongs to the spleen, stomach and lung meridians; its functions are aromatic dampness-resolving, spleen-waking and stomach-promoting, inducing diaphoresis and relieving summer heat; it is mostly used for damp-turbidity blocking the middle-jiao, stuffiness and fullness in the epigastrium with nausea and vomiting, sweet taste in the mouth, and excessive salivation with bad breath. "Plain Questions·Strange Disease Theory" records: "Therefore, its qi overflows upwards and turns into consumptive thirst. It is treated with orchid to remove the stale qi." It is used in combination with Atractylodes lancea and Agastache rugosa to enhance the dampness-resolving effect, and is used in combination with moxa floss, Atractylodes lancea and Agastache rugosa to prevent excessive warm-dryness from causing consumption of yin-fluid and balance the properties of the whole formula.

[0012] In this formula, moxa floss is used as the monarch drug to warm and dredge the meridians, dispel cold and transform dampness, and invigorate the yang qi of the spleen and stomach; Atractylodes lancea and Agastache rugosa are used as the ministerial drugs to synergistically enhance the effects. Atractylodes lancea dries dampness and strengthens the spleen, removing dampness from the muscle surface, and Agastache rugosa aromatically resolves turbidity, stops nausea and harmonizes the middle, and the two together remove damp-turbidity in the middle-jiao. Eupatorium fortunei is used as the assistant drug to assist the ministerial drugs in enhancing the power of dampness-resolving and spleen-waking. Its nature is mild, and it can also promote the production of body fluid, restrain the warm-dryness of moxa floss and Atractylodes lancea, and prevent damage to yin-fluid, reflecting the subtlety of "eliminating the nature and retaining the use". The combination of the four drugs closely adheres to the core pathogenesis of "failure of the spleen to transport normally and endogenous damp-turbidity". Moxa floss guides the drugs to enter the meridians and runs through the whole process. Atractylodes lancea strengthens the spleen to treat the root cause, and Agastache rugosa and Eupatorium fortunei resolve turbidity to treat the symptoms, taking both the root cause and symptoms into account, and regulating both cold and heat. Through the synergistic effects of warming yang and transforming dampness, aromatic spleen-waking, and dredging collaterals and relieving pain, the functions of the spleen and stomach in receiving and transporting are restored, so that dampness is removed, the spleen is strengthened, and the stomach qi descends, jointly treating the disease.

[0013] II. Volatile Components and Their External Application Mechanisms The volatile components in the medicated moxa composition of this invention are the key material basis for its external therapeutic effect. The volatile components of moxa wool include eucalyptol, thujone, camphor, borneol, and terpinen-4-ol, which have significant antibacterial, anti-inflammatory, and antioxidant effects. The volatile oils of moxa wool have a significant inhibitory effect on common oral pathogens such as Staphylococcus aureus and Streptococcus, effectively reducing the risk of oral infection, while simultaneously accelerating wound healing by promoting local blood circulation. The thermal effect generated by burning moxa wool can activate local TRPV1 channels and heat shock proteins, improve local microcirculation, regulate inflammatory responses, promote mucosal repair, and relieve pain. The volatile oils of moxa wool (such as eucalyptol and camphor) have strong penetrating power and can synergistically deliver other drugs directly to the affected area, forming the unique advantage of "treating with both medicine and heat."

[0014] The volatile components of Atractylodes lancea mainly include atractylone, atractylol, and β-cineole, which have the effects of drying dampness and strengthening the spleen. These volatile components act directly on the gastrointestinal mucosa, inhibiting pathogens such as Helicobacter pylori and reducing inflammatory responses. Simultaneously, they regulate gastrointestinal motility, improve the function of the lower esophageal sphincter, and reduce gastric acid reflux, thus inhibiting gastric acid secretion and improving gastroenteritis. β-cineole in Atractylodes lancea volatile oil can inhibit gastric acid secretion, counteract gastric smooth muscle spasms caused by acetylcholine, and relieve symptoms such as abdominal distension, nausea, and vomiting. Furthermore, when Atractylodes lancea is mixed with Artemisia argyi volatile oil (Atractylodes lancea volatile oil), its antibacterial effect can be significantly enhanced through atomization or fumigation, inhibiting pathogens and reducing inflammatory responses.

[0015] The volatile oil of patchouli contains abundant compounds such as 1,8-cineole, patchouli ketone, and patchouli alcohol, which possess broad-spectrum antibacterial, anti-inflammatory, antiviral, and antioxidant activities. Patchouli volatile oil has a significant inhibitory effect on common gastrointestinal pathogens and can effectively prevent secondary infections of ulcers. The 1,8-cineole and patchouli ketone components in patchouli volatile oil have broad-spectrum antibacterial, anti-inflammatory, and antioxidant activities; their volatile components act directly on the ulcer surface through the smoke of moxa, effectively preventing secondary infections and accelerating wound healing. Simultaneously, the antispasmodic and antiemetic effects of patchouli can relieve esophageal spasms and reflux symptoms. The volatile oil components of Atractylodes lancea and patchouli work synergistically to inhibit pathogens and promote mucosal repair.

[0016] The volatile components of *Eupatorium fortunei* include linalool, *Eupatorium fortunei* ketone, and p-cymene acetate nerol ester, which have a neutral nature and dampness-resolving effect. Volatile components of *Eupatorium fortunei*, such as p-cymene acetate nerol ester, can clear stagnant qi in the spleen and stomach, forming a synergistic effect with *Atractylodes lancea* and *Pogostemon cablin* to jointly regulate the qi mechanism of the spleen and stomach. The anti-inflammatory and immunomodulatory components of *Eupatorium fortunei* can reduce esophageal mucosal inflammation, prevent excessive heat and dryness leading to yin fluid depletion, and balance the overall medicinal properties of the formula.

[0017] III. Synergistic Effect of Volatile Components and Meridians The unique feature of the medicated composition of this invention lies in the synergistic effect of its volatile components and meridian effects. This synergistic effect is mainly reflected in the following aspects: 1. Synergistic Effect of Volatile Components and Meridians / Acupoints: The Foot Taiyin Spleen Meridian runs along the abdomen and around the esophagus, and is closely related to chronic gastroenteritis and esophageal reflux. Volatile components (such as eucalyptol and butyramide) in the smoke produced by burning moxa can diffuse along the meridian lines, enhancing the therapeutic effect of moxibustion. This dual "matter-energy" effect can significantly improve the local microenvironment of the esophageal mucosa and accelerate wound healing. When moxibustion is applied to acupoints on the Spleen Meridian such as Yinlingquan and Sanyinjiao, the volatile components of Atractylodes lancea, Pogostemon cablin, and Eupatorium fortunei can synergistically enhance the spleen-strengthening, dampness-removing, and aromatic-clearing effects, forming the unique advantage of "treating with both medicine and heat."

[0018] 2. Synergistic Regulation of Volatile Components and Meridian Function: Chronic gastroenteritis and esophageal reflux are often related to dysfunction of the Foot Taiyin Spleen Meridian, especially "spleen deficiency and dampness obstruction" leading to upward reversal of stomach qi. The volatile components in the medicated composition of this invention regulate the Qi mechanism of the Triple Burner through meridian conduction, promote the coordinated function of the spleen, stomach, kidneys, and other organs, and improve the overall condition of chronic gastroenteritis and esophageal reflux. At the same time, these volatile components inhibit inflammatory responses and infection risks by directly acting on the esophageal mucosa and gastrointestinal region, forming a "local-systemic" synergistic effect.

[0019] 3. Synergistic effect of volatile components and meridian sensation transmission: The medicated moxa composition of the present invention produces a "moxa sensation transmission" phenomenon during moxibustion, meaning the patient can feel the heat sensation transmitted along the meridians to the affected area. This moxa sensation transmission is closely related to the diffusion path of the volatile components. The volatile components in the moxa smoke can diffuse along the meridian lines, enhancing the intensity and range of the moxa sensation transmission, allowing the therapeutic effect to be more effectively transmitted to the esophagus and gastrointestinal region, improving the therapeutic effect, significantly improving gastrointestinal motility, regulating gastric acid secretion, and reducing inflammatory responses.

[0020] IV. Characteristics and Mechanism of Action of the Artemisia argyi Composition of the Invention The medicinal composition of the present invention, as a topical preparation, has the following main characteristics: 1. Pharmacological Effect: Volatile components act directly on the esophageal mucosa. When the medicated moxa composition of this invention is ignited, the volatile components in the moxa wool, Atractylodes lancea, Pogostemon cablin, and Eupatorium fortunei are released, forming moxa smoke. These volatile components exert a local therapeutic effect through direct contact with the esophageal mucosa or by inhalation into the oral cavity. When the volatile oils in the moxa smoke adhere to the mucosal surface, they can both antibacterially disinfect and protect the wound, promoting the growth of granulation tissue. Atractylodes lancea volatile oil inhibits gastric acid secretion, Pogostemon cablin volatile oil relieves gastric spasms, and Eupatorium fortunei volatile oil reduces inflammation. These three, along with the volatile oils of moxa wool, work synergistically to form a dual effect of "bactericidal + mucosal protection."

[0021] 2. Thermal Effect: Warm stimulation improves local blood circulation. The warm stimulation generated by moxibustion is a crucial aspect of its therapeutic effect. This stimulation activates transient receptor potential family (TRPV1) channels and heat shock protein (HSP) molecular targets, promoting blood circulation in the esophageal mucosa and gastrointestinal region, accelerating wound metabolism and tissue repair. For patients with chronic gastroenteritis and esophageal reflux, microcirculatory disturbances under high humidity and resistance are a significant reason for the difficulty in healing. Moxibustion improves local microcirculation through its warming effect, enhancing tissue repair capabilities. Simultaneously, by regulating systemic microcirculation, it improves the digestive function of the spleen and stomach, creating a synergistic "local-systemic" effect.

[0022] 3. Meridian Effect: Regulating gastrointestinal function through the Foot Taiyin Spleen Meridian. The Foot Taiyin Spleen Meridian runs along the abdomen and around the esophagus, and is closely related to chronic gastroenteritis and esophageal reflux. Moxibustion on acupoints along the Spleen Meridian, such as Yinlingquan and Sanyinjiao, can regulate the Qi mechanism of the middle Jiao, improve symptoms of dampness obstruction, and, synergistically with the dampness-resolving effects of Atractylodes lancea, Pogostemon cablin, and Eupatorium fortunei, enhance the therapeutic effect on gastroenteritis and esophageal reflux. Moxibustion at Yinlingquan can strengthen the spleen, remove dampness, and regulate fluid metabolism; moxibustion at Sanyinjiao can harmonize spleen and stomach function, promote gastrointestinal motility, and regulate the tone of the lower esophageal sphincter through the vagus nerve, reducing gastric acid reflux. Attached Figure Description

[0023] Figure 1 This represents the intersection of active ingredients between different databases in the experimental examples of this invention; Figure 2 This represents the intersection of target points between different databases in the experimental examples of this invention. Figure 3 This is a Venn diagram showing the intersection of the target points of the traditional Chinese medicine Artemisia argyi in the experimental examples of this invention for chronic gastroenteritis complicated with esophageal reflux disease; Figure 4 This is a drug-compound-target-disease network diagram from the experimental examples of this invention; Figure 5 This is a bar chart ranking the connectivity of compounds in the experimental examples of this invention. Figure 6 Sankey diagram of the drug source of the TOP compound in the experimental examples of this invention; Figure 7 This is a STRING interaction diagram from an experimental example of the present invention; Figure 8 This is a PPI interaction network diagram from an experimental example of the present invention; Figure 9 This is a bar chart ranking the connectivity of core target points in the experimental examples of this invention. Figure 10 This is a bar chart of GO enrichment analysis in the experimental examples of this invention; Figure 11 This is a pie chart of GO enrichment analysis in the experimental examples of this invention; Figure 12This is a scatter plot of KEGG enrichment analysis in the experimental examples of this invention; Figure 13 This is a pie chart of KEGG enrichment analysis in the experimental examples of this invention; Figure 14 This is a Sankey diagram of the TOP pathway at the TOP target in the experimental examples of this invention. Figure 15 This is a compound-target-pathway-disease network diagram from the experimental examples of this invention; Figure 16 This is a heat map of the docking energy of the Top 10 active ingredients and Top 10 target sites in the experimental examples of this invention. Detailed Implementation

[0024] The present invention will be further described below with reference to the accompanying drawings and specific embodiments.

[0025] A medicinal composition for preventing and treating chronic gastroenteritis complicated with gastroesophageal reflux disease, comprising a traditional Chinese medicine composition and moxa wool, wherein the traditional Chinese medicine composition is made from the following raw materials in the following weight ratio: Atractylodes lancea 4-17 parts, Pogostemon cablin 6-20 parts and Eupatorium fortunei 5-17 parts, and the weight ratio of the traditional Chinese medicine composition to moxa wool is 2.5-6:7.5-11.

[0026] The traditional Chinese medicine composition in the above-mentioned medicated mugwort composition is preferably made from the following raw materials in the following weight ratio: 11 parts of Atractylodes lancea, 13 parts of Pogostemon cablin and 11 parts of Eupatorium fortunei, with the weight ratio of the traditional Chinese medicine composition to mugwort floss being 4:9.

[0027] Example: Example 1: Atractylodes lancea 80g, Pogostemon cablin 120g, Eupatorium fortunei 100g, and Artemisia argyi 900g.

[0028] Example 2: 220g of Atractylodes lancea, 260g of Pogostemon cablin, 220g of Eupatorium fortunei, and 1575g of Artemisia argyi.

[0029] Example 3: Atractylodes lancea 340g, Pogostemon cablin 400g, Eupatorium fortunei 340g and Artemisia argyi 1980g.

[0030] Experimental examples, network pharmacology, and molecular docking: I. Collection of active ingredients and targets in the medicated composition of the present invention: Using TCMSP / BATMAN / HERB / ETCM, chemical components of Atractylodes lancea, Pogostemon cablin, and Eupatorium fortunei were collected respectively. The active ingredients of the drug composition of this invention were further screened using OB≥30% and DL≥0.18 as screening criteria. For targets obtained from databases, the gene names of drug targets were standardized and deduplicated using the Uniprot database. Finally, the active ingredients and targets of the drug were obtained. Disease-related targets were retrieved from the Gene Cards / Open Targets / CTD databases. Using "gastroenteritis" as the keyword, disease-related targets were retrieved, and the gene names of disease targets were standardized and deduplicated. Similarly, disease-related targets were retrieved from the GeneCards / Open Targets / CTD databases. Using "gastroesophageal reflux" as the keyword, disease-related targets were retrieved, and the gene names of disease targets were standardized and deduplicated. The intersection genes of chronic gastroenteritis with esophageal reflux comorbidity were used as the final disease genes. Finally, potential targets for chronic gastroenteritis with esophageal reflux comorbidity were obtained. A Venn diagram showing the intersection of targets between different databases was also drawn. Common targets were identified as those related to the treatment of chronic gastroenteritis with gastroesophageal reflux disease (GERD) comorbidity of the drug-artemisia composition of this invention. The one-to-one correspondence between the active ingredients and targets of the drug-artemisia composition of this invention was imported into Cytoscape 3.9.1 software to construct a drug-compound-target-disease network diagram. A PPI network diagram was constructed using the STRING database, and the intersection targets related to the drug-artemisia composition of this invention acting on chronic gastroenteritis with GERD comorbidity were imported into the STRING database to screen for core targets. The drug-artemisia composition of this invention and the relevant targets of chronic gastroenteritis with GERD comorbidity were subjected to GO functional enrichment analysis and KEGG pathway enrichment analysis using the RclusterProfiler 4.6.2 package, respectively. Core TOP pathways, along with their key targets and active ingredients, were selected to construct a "drug-compound-target-pathway-disease" network.

[0031] The 3D structures of the main active compounds in the drug composition of this invention were downloaded from the PubChem database, and the 3D structures of the core target proteins were downloaded from the Protein Data Bank database. Autodock Vina was used to perform the docking of the components and targets.

[0032] II. Results and Analysis: 1. Collection of active ingredients and target prediction in the medicated composition of the present invention By searching drug databases, the components of the medicated composition of this invention were retrieved, and active ingredients meeting the requirements of OB≥30% and DL≥0.18 were screened, yielding 10 active ingredients from Atractylodes lancea, 5 from Pogostemon cablin, and 14 from Eupatorium fortunei. Duplicate common ingredients were removed, resulting in a total of 29 active ingredients, as shown below. Figure 1 Potential drug targets for active pharmaceutical ingredients were identified through a database. After removing duplicate targets, a total of 418 drug targets were obtained. (See attached database.) Figure 2 .

[0033] 2. Collection of relevant targets for chronic gastroenteritis complicated with esophageal reflux disease and screening of therapeutic targets for the drug composition of the present invention. The search results for "gastroenteritis" were filtered according to a threshold using the Gene Cards Score>=5 / Open Targets Score>=0.1 / CTD Score>=50 database. The search results for "gastroesophageal reflux" were also filtered according to a threshold using the Gene Cards Score>=5 / Open Targets Score>=0.01 / CTD Score>=5 / Drug Ban database. Gene names of standardized disease targets were summarized, duplicates were removed, and the intersection was taken to obtain 407 disease targets. The intersection of these targets with the active ingredient targets of the drug composition of this invention was then mapped, identifying 119 common targets. These are considered potential targets for the drug composition of this invention to act on chronic gastroenteritis complicated with esophageal reflux disease. (See...) Figure 3 .

[0034] 3. Construction and analysis of drug-compound-target-disease network See the drug-compound-target-disease network. Figure 4 The network graph has 148 nodes and 471 edges, with edges representing the targeting relationships between compounds and targets. 25 active ingredients act on 119 targets (some compounds whose targets were not in the intersection were removed). The network topology was analyzed using the Network Analyzer plugin. In the network graph, the size of a node represents its degree value; a higher degree value indicates a stronger pivotal role in the network. The top 20 principal components are ranked by degree value. Figure 5 Based on this analysis, the main active ingredients found include wogonin, luteolin, beta-sitosterol, acacetin, paeoniflorin, and atropine. Figure 6 This is a Sankey diagram of the top compounds and drug sources. Different shapes in the diagram represent drugs, compounds, and targets, and the shades of color represent the degree weights in the network.

[0035] 4. PPI Network Diagram Analysis 119 intersecting drug targets related to disease treatment were imported into the STRING database to obtain PPI relationships, and then imported into Cytoscape software for analysis. Figure 7 The network graph has 119 nodes and 2271 edges, where edges represent the relationships between target points (isolated target points with no intersection were removed). The Network Analyzer plugin was used to analyze the network topology, calculate degree values, and set the color intensity and node size to reflect the degree values. The top 30 core nodes were selected based on their degree values ​​(CC / BC / degree), and the network graph was drawn. See [link to graph]. Figure 8 The core targets are IL6, TNF, TP53, IL1B, PTGS2, STAT3, and JUN, which are key targets for the treatment of chronic gastroenteritis complicated with esophageal reflux disease using the drug composition of this invention. (See details...) Figure 9 .

[0036] 5. GO functional enrichment analysis and KEGG pathway analysis Based on R clusterProfiler, GO enrichment analysis was performed on 119 intersection targets related to drug treatment diseases. The top 15 items of biological process (BP), molecular function (MF), and cellular component (CC) with P < 0.05 were selected to create maps, as shown below. Figure 10 As shown in Figure 11, the vertical axis represents each entry of GO, and the horizontal axis represents the number of targets enriched with that entry. BP mainly involves responses to exogenous stimuli, responses to oxidative stress, cellular responses to chemical stress, responses to peptides, responses to oxidative stress, responses to lipopolysaccharides, responses to bacterial molecules, responses to reactive oxygen species, and responses to estradiol, etc. MF mainly includes R polymerase II-specific D-binding transcription, D-binding transcription factor binding, heme binding, tetrapyrrole binding, cytokine receptor binding, cytokine activity, nuclear receptor activity, ligand-activated transcription factor activity, transcriptional co-regulatory factor binding, signal receptor activator activity, BH3 domain binding, etc. CC mainly involves membrane rafts, membrane microdomains, pits, protein kinase complexes, transcriptional regulatory complexes, plasma membrane rafts, transferase complexes, transfer phosphorus-containing groups, serine / threonine protein kinase complexes, vesicle cavities, cytoplasmic vesicle cavities, presynaptic membrane components, and secretory granule cavities, etc. KEGG pathway enrichment analysis was performed on the target, resulting in 176 signaling pathways. This study selected the top 30 pathways (P < 0.05) from the downloaded results for visualization analysis. Figure 12As shown in Figure 13, the enrichment results revealed that the main signaling pathways involved were lipid-atherosclerosis, diabetes AGE-RAGE, IL-17, prostate cancer, hepatitis B, human cytomegalovirus infection, measles, hepatitis C, PI3K-Akt, apoptosis, and small cell lung cancer. These pathways communicate with each other and play important roles in the development and progression of diseases. Furthermore, this study also constructed a Sankey diagram of TOP pathways related to TOP targets, as shown in Figure 13. Figure 14 .

[0037] 6. Construction and analysis of drug-compound-target-pathway-disease network The inventors selected core TOP pathways and their key targets and active ingredients, constructing a "compound-target-pathway-disease network." For example... Figure 15 As shown, the network consists of 178 nodes and 1103 edges (25 components, 119 targets, and 30 signaling pathways, drugs, and diseases). Different node shapes represent different active ingredients, key targets, and regulatory pathways in the drug-artemisia composition of this invention, and the color intensity represents the degree weight in the network. Each active ingredient corresponds to multiple targets, and each target connects to multiple components, reflecting the multi-component, multi-target mechanism of action of the drug-artemisia composition of this invention in preventing and treating chronic gastroenteritis complicated with esophageal reflux disease.

[0038] 7. Molecular docking Based on the ranking of active ingredient scores in the active ingredient-target network diagram and a literature review, this study performed molecular docking between the active ingredients MOL000006, MOL000049, MOL000173, MOL000184, MOL000358, MOL000359, MOL000492, MOL001689, MOL001924, and MOL002219 in the drug composition of this invention and the top 10 core targets in the PPI network: BCL2, EGFR, IL1B, IL6, JUN, NFKB1, PTGS2, STAT3, TNF, and TP53. The docking results are shown in [Figure number missing]. Figure 16 .

[0039] Clinical trial example: Clinical Trial Case 1: Chronic Gastroenteritis Chronic gastroenteritis is a common disease of the intestinal system, related to infection and physical and chemical irritants. Clinical manifestations include loss of appetite, upper abdominal discomfort, acid reflux, nausea, and vomiting. It can also present as recurrent indigestion and abdominal distension. Traditional Chinese medicine categorizes it according to clinical manifestations as "stomach pain," "gastric fullness," "heartburn," and "acid reflux."

[0040] 1. Materials and Methods 1.1 General Information Fifty patients with chronic gastroenteritis who visited the outpatient clinics of the Traditional Chinese Medicine Department of Shehong Maternal and Child Health Hospital and Shapingba Tuwan Community Health Service Center from August to October 2024 were selected as the study subjects. There were 18 males and 32 females, aged 40-79 years, with a mean age of (64.680±9.811) years.

[0041] 1.2 Inclusion and Exclusion Criteria Inclusion criteria: (1) Clinical diagnosis of chronic gastroenteritis; (2) Patients who voluntarily participate in this study and sign an informed consent form. Exclusion criteria: (1) History of drug allergy; (2) Patients with malignant tumors, dysfunction of vital organs, hematological diseases, or mental illness; (3) Patients with poor treatment compliance who have difficulty cooperating with moxibustion on time.

[0042] 1.3 Grouping and Treatment Methods Fifty patients with chronic gastroenteritis were randomly divided into a control group (n=25) and an experimental group (n=25). The age of the control group ranged from 40 to 79 years, with a mean age of (65.600±10.432) years. The age of the experimental group ranged from 40 to 77 years, with a mean age of (63.760±9.270) years. There were no statistically significant differences in patient data between the two groups. P >0.05), which is comparable, see Table 1.

[0043] Patients in the control group received oral Chinese herbal decoctions prescribed by outpatients based on syndrome differentiation, combined with regular moxibustion. Patients in the experimental group received oral Chinese herbal decoctions prescribed by outpatients based on syndrome differentiation, combined with moxibustion using the medicated moxa prepared from the composition in Example 2. Moxibustion was performed three times a week for 20 minutes each time, for a total of four weeks. Specific acupoints for moxibustion were: Shangqiu, Dadu, and Jingqu, bilaterally.

[0044] 1.4 Efficacy Evaluation Criteria 1.4.1 Clinical efficacy The clinical symptom scores of patients with chronic gastroenteritis were statistically analyzed before and after treatment. A self-developed clinical symptom scoring scale for chronic gastroenteritis was used, based on the clinical symptoms of chronic gastroenteritis and daily clinical practice. The higher the comprehensive score, the more severe the clinical symptoms of chronic gastroenteritis, as shown in Table 2 below.

[0045] 1.5 Statistical Analysis Data were analyzed using SPSS 27.0 software. Quantitative data were analyzed using... Represented in the form of, using Test whether the differences between the data are statistically significant.

[0046] 2 Results Comparison of clinical symptom scores of chronic gastroenteritis between the two groups: Compared with before treatment, the clinical symptom scores of chronic gastroenteritis in both groups decreased significantly after treatment, indicating that the clinical symptoms of both groups were significantly improved after treatment. P <0.01); compared with the control group after treatment, the clinical symptom score of chronic gastroenteritis in the experimental group was lower after treatment ( P <0.05), the results showed that the moxa prepared by the composition in Example 2 had better therapeutic effect than ordinary moxibustion, as shown in Table 3.

[0047] Clinical Trial Case 2: Gastroesophageal Reflux Disease Gastroesophageal reflux disease (GERD) is a common and frequently occurring internal medicine condition caused by the reflux of stomach or duodenal contents into the esophagus, resulting in uncomfortable symptoms and / or complications. Acid reflux and heartburn are typical symptoms of GERD. The refluxed material can irritate or damage the esophagus and other tissues or organs, leading to chest pain, pharyngitis, chronic cough, asthma, and dental erosion. In Traditional Chinese Medicine, this condition is categorized under "acid reflux," "heartburn," and "stomach pain."

[0048] 1. Materials and Methods 1.1 General Information Fifty patients with gastroesophageal reflux who visited the outpatient clinics of the Traditional Chinese Medicine Department of Shehong Maternal and Child Health Hospital and Shapingba Tuwan Community Health Service Center from August to October 2024 were selected as the study subjects. There were 22 males and 28 females, aged 34-81 years, with a mean age of (63.500±11.937) years.

[0049] 1.2 Inclusion and Exclusion Criteria Inclusion criteria: (1) Clinical diagnosis of gastroesophageal reflux; (2) Patients who voluntarily participate in this study and sign an informed consent form. Exclusion criteria: (1) History of drug allergy; (2) Patients with malignant tumors, dysfunction of vital organs, hematological diseases, abnormal immune function, or mental illness; (3) Patients with poor treatment compliance who have difficulty cooperating with moxibustion on time.

[0050] 1.3 Grouping and Treatment Methods Fifty patients with gastroesophageal reflux disease were randomly divided into a control group (n=25) and an experimental group (n=25). The age of the control group ranged from 37 to 76 years, with a mean age of (63.680 ± 11.183) years. The age of the experimental group ranged from 34 to 81 years, with a mean age of (63.320 ± 12.877) years. There was no statistically significant difference in age between the two groups. P >0.05), which is comparable, see Table 4.

[0051] Patients in the control group received oral Chinese herbal decoctions prescribed by outpatients based on syndrome differentiation, combined with regular moxibustion. Patients in the experimental group received oral Chinese herbal decoctions prescribed by outpatients based on syndrome differentiation, combined with moxibustion using the medicated moxa prepared from the composition in Example 3. Moxibustion was performed three times a week for 20 minutes each time, for a total of four weeks. Specific acupoints for moxibustion were: Shangqiu, Dadu, and Jingqu, bilaterally.

[0052] 1.4 Efficacy Evaluation Criteria The clinical symptom scores of patients with gastroesophageal reflux were statistically analyzed before and after treatment. A clinical symptom scoring scale for gastroesophageal reflux was developed based on clinical symptoms of gastroesophageal reflux and daily clinical practice. The higher the comprehensive score, the more severe the clinical symptoms of gastroesophageal reflux (see Table 5).

[0053] 1.5 Statistical Analysis Data were analyzed using SPSS 27.0 software. Quantitative data were analyzed using... Represented in the form of, using Test whether the differences between the data are statistically significant.

[0054] 2 Results Comparison of clinical symptom scores for gastroesophageal reflux between the two groups: Compared with before treatment, the clinical symptom scores for gastroesophageal reflux in both groups decreased significantly after treatment, indicating that the clinical symptoms of both groups improved significantly after treatment. P <0.01); compared with the control group after treatment, the experimental group had a lower clinical symptom score of gastroesophageal reflux after treatment ( P <0.05), the results showed that the moxa prepared by the composition in Example 3 had better efficacy than ordinary moxibustion, as shown in Table 6.

[0055] .

Claims

1. A pharmaceutical composition for preventing and treating chronic gastroenteritis combined with esophageal reflux comorbidity, characterized in that, The medicine-Ai composition comprises a Chinese medicine composition and Ai, wherein the Chinese medicine composition is made of raw materials in the following proportions by weight: 4-17 parts of Atractylodes lancea, 6-20 parts of Agastache rugosa and 5-17 parts of Pterocephalus tottus, and the weight ratio of the Chinese medicine composition to Ai is 2.5-6:7.5-11.

2. The medicated composition for preventing and treating chronic gastroenteritis complicated with gastroesophageal reflux disease as described in claim 1, characterized in that, The medicine-Ai composition comprises a Chinese medicine composition and Ai, wherein the Chinese medicine composition is made of raw materials in the following proportions by weight: 11 parts of Atractylodes lancea, 13 parts of Agastache rugosa and 11 parts of Pterocephalus tottus, and the weight ratio of the Chinese medicine composition to Ai is 4:9.

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