Medicinal folium artemisiae argyi composition for preventing and treating rectocele and dyspepsia codiseases

Abstract

The invention discloses a medicinal moxa composition for preventing and treating rectocele and dyspepsia. The medicinal moxa composition comprises radix bupleuri, fructus aurantii, pericarpium citri reticulatae viride and moxa. The medicinal moxa composition disclosed by the invention directly acts on body surface acupuncture points through a synergistic effect of volatile components released by combustion and heating power, and particularly aims at related acupuncture points of hand-Shaoyang meridians, so that multi-target treatment of a co-disease of rectocele and dyspepsia is realized. According to the treatment principle of soothing liver and regulating qi and lifting up yang and yang, the traditional Chinese medicine composition is externally used for regulating qi movement, improving liver and gall dredging functions and promoting transportation and transformation of spleen and stomach, so that the treatment purpose is achieved. Volatile components in the medicinal folium artemisiae argyi composition have remarkable antibacterial, anti-inflammatory, anti-oxidation and intestinal flora regulating effects, can synergistically act on multiple key targets related to rectocele and dyspepsia, participate in regulation and control of multiple pathways, and provide a scientific basis for co-disease treatment.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a medicinal composition for preventing and treating rectal prolapse combined with indigestion. Background Technology

[0002] Rectal prolapse manifests as a mass protruding from the anus, accompanied by a feeling of heaviness or pressure. Causes include chronic constipation, childbirth injury, and pelvic floor muscle relaxation. Traditional Chinese medicine believes it is often due to a sinking of Qi in the middle Jiao (middle burner) and impaired lung Qi circulation. Indigestion manifests as loss of appetite, abdominal distension, and belching. Causes include insufficient gastric motility, abnormal gastric acid secretion, and improper diet. Traditional Chinese medicine believes it is often due to liver Qi stagnation and spleen and stomach weakness.

[0003] Current Western medical treatments include: Drug therapy: Alpha-receptor agonists can improve rectal prolapse, but pose cardiovascular risks; Surgery: such as rectal fixation, can improve symptoms, but is highly invasive; Dietary adjustments: High-fiber diets can improve constipation, but adherence is poor; Prokinetic drugs: such as domperidone, can relieve indigestion, but may cause gastrointestinal discomfort. While Western medical treatments can control symptoms, they lack synergistic treatment options for comorbidities, and long-term medication has significant side effects.

[0004] Current TCM treatment methods include: raising Yang Qi (Astragalus membranaceus and Cimicifuga foetida can improve rectal prolapse); soothing the liver and regulating Qi (Bupleurum chinense and Citrus reticulata can relieve indigestion); external application of Chinese herbal medicine (such as Glauber's salt) to relieve rectal prolapse; and acupuncture (such as Baihui acupoint to raise Yang Qi and lift prolapse). While TCM treatment is holistic, it lacks standardized protocols for rectal prolapse combined with indigestion, and research on the synergistic mechanism of these two conditions is insufficient. Summary of the Invention

[0005] The purpose of this invention is to provide a medicated composition for preventing and treating rectal prolapse combined with indigestion.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A medicinal moxa composition for preventing and treating rectal prolapse combined with indigestion, 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: Bupleurum chinense 2-10 parts, Citrus aurantium 4-15 parts and Citrus reticulata 1-7 parts, and the weight ratio of the traditional Chinese medicine composition to moxa wool is 3.5-8:6-12.

[0007] 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: 4 parts Bupleurum, 7 parts Citrus aurantium and 3 parts Citrus reticulata peel, and the weight ratio of the traditional Chinese medicine composition to mugwort floss is 5:9.

[0008] The advantages of this invention compared to the prior art are as follows: The comorbidity mechanism of rectal prolapse and dyspepsia is mainly reflected in: both diseases are related to qi movement disorder. Rectal prolapse is mostly due to the sinking of middle qi, while dyspepsia is mostly due to stagnation of liver qi. According to traditional Chinese medicine theory, the Hand-Shaoyang Gallbladder Meridian circulates through the hypochondrium and abdomen, and is closely related to stagnation of liver qi and sinking of middle qi. Bupleurum can soothe the liver and regulate qi, improving dyspepsia; it can also lift yang qi and relieve the sinking of middle qi in rectal prolapse.

[0009] I. The properties, tastes, meridian tropism and compatibility relationship of drugs The characteristics of the medicated moxa composition of the present invention can be summarized as "soothing the liver and regulating qi, lifting yang and raising prolapse, warming and dredging the meridians, and regulating the spleen and stomach".

[0010] Bupleurum is the monarch drug in the formula, with the effects of soothing the liver and relieving depression, reconciling the exterior and interior, and lifting yang and raising prolapse. The effect of soothing the liver and relieving depression of Bupleurum can regulate the qi movement of the liver and gallbladder, improve the state of stagnation of liver qi, and thus indirectly regulate the function of the spleen and stomach; the effect of lifting yang and raising prolapse of Bupleurum can lift the sinking qi and improve the symptoms of rectal prolapse caused by qi deficiency and sinking, which is of great significance for the treatment of dyspepsia and rectal prolapse. During the moxibustion process, the slightly cold property of the volatile oil of Bupleurum becomes mild in the smoke released after combustion, making it more suitable to act on the body surface acupoints through external application, directly acting on the acupoints related to the Hand-Shaoyang Meridian, such as Zhigou acupoint and Waiguan acupoint, etc. By stimulating the nerves and blood vessels around the acupoints, it can regulate the rise and fall of qi movement and improve the symptoms of rectal prolapse and dyspepsia.

[0011] Fructus Aurantii is the ministerial drug, with the effects of breaking qi and relieving distension, regulating qi and resolving phlegm. The effect of breaking qi and relieving distension of Fructus Aurantii can promote gastrointestinal peristalsis and improve the symptoms of dyspepsia; the effect of regulating qi and relieving distension can also promote gastrointestinal peristalsis and improve the symptoms of dyspepsia; the effect of regulating qi and resolving phlegm can regulate qi movement and improve the state of stagnation of liver qi. In the combustion state, the volatile oil of Fructus Aurantii can be released with the smoke, enhancing the regulatory effect on the spleen and stomach. During the moxibustion process, the volatile oil components of Fructus Aurantii can be released with the smoke, acting synergistically with the volatile oil of Bupleurum to enhance the antibacterial and anti-inflammatory effects, improve the balance of intestinal flora, and thus synergistically treat dyspepsia and rectal prolapse.

[0012] Pericarpium Citri Reticulatae Viride is the adjuvant drug, with the effects of regulating qi and relieving stagnation, promoting digestion and removing stagnation. The effect of regulating qi and relieving stagnation of Pericarpium Citri Reticulatae Viride can regulate qi movement and improve the state of stagnation of liver qi; its effect of promoting digestion and removing stagnation can promote digestion and improve the symptoms of dyspepsia. During the moxibustion process, the volatile oil components of Pericarpium Citri Reticulatae Viride can be released with the smoke. The pungent-warm property of Pericarpium Citri Reticulatae Viride complements the warm nature of moxa wool, jointly enhancing the effect of lifting yang and raising prolapse, which has a significant effect on the treatment of rectal prolapse, and can also enhance the antibacterial and anti-inflammatory effects, improve the balance of intestinal flora, and thus synergistically treat dyspepsia and rectal prolapse.

[0013] Artemisia floss, used as a guiding herb, possesses the effects of warming the meridians and dispelling cold, promoting blood circulation and unblocking collaterals, eliminating dampness and relieving itching, and killing parasites and stopping bleeding. The warming nature of artemisia floss can neutralize the cold nature of Bupleurum chinense, Citrus aurantium, and Citrus reticulata peel, preventing the bitter and cold herbs from harming the spleen and stomach. Its ability to guide fire back to its source can draw upward-floating deficiency fire back to the kidney meridian, regulating the balance of Yin and Yang. Its ability to promote blood circulation and unblock collaterals can accelerate the absorption and efficacy of the medicine. During moxibustion, the volatile oil components of artemisia floss are released with the smoke, directly acting on relevant acupoints of the Hand Shaoyang Meridian, such as Zhigou and Waiguan, stimulating the nerves and blood vessels around the acupoints, regulating the ascending and descending of Qi, and improving symptoms of rectal prolapse and indigestion. Simultaneously, the antibacterial effect of artemisia floss can enhance the antibacterial effects of Bupleurum chinense and Citrus aurantium, making it an indispensable guiding herb in the formula.

[0014] The medicinal moxibustion composition of this invention uses Bupleurum to soothe the liver and regulate Qi, Citrus aurantium to promote Qi circulation and relieve abdominal distension, Citrus reticulata peel to break up Qi stagnation and eliminate accumulation, and Artemisia argyi to warm the meridians, dispel cold, and invigorate blood circulation. The combination of these four herbs conforms to the treatment principle of "soothing the liver and regulating Qi, raising Yang Qi, and eliminating stagnation," simultaneously resolving the pathological contradictions of two diseases. In this medicinal moxibustion composition, Bupleurum can both soothe the liver and regulate Qi to improve indigestion and raise Yang Qi to alleviate rectal prolapse; Citrus aurantium can improve abdominal distension caused by indigestion and promote the recovery of pelvic floor muscle function; it avoids hormone dependence and surgical trauma, ensuring high safety; and moxibustion can improve local microcirculation and promote drug penetration and absorption. This medicinal moxibustion composition, through the regulation of the Hand Shaoyang Gallbladder Meridian, can achieve systemic treatment of two diseases, possessing significant theoretical innovation and clinical application value.

[0015] II. Synergistic Mechanism of Volatile Components The medicated composition of the present invention releases multiple volatile components through external application. These components synergistically act on multiple key targets related to rectal prolapse and indigestion, forming a multi-layered therapeutic mechanism: Antibacterial and anti-inflammatory effects: The volatile oil components in Artemisia argyi (such as thujone, eucalyptol, and δ-elemene) and those in Bupleurum chinense (such as myrcene and eugenol) work together to form a broad-spectrum antibacterial network. The volatile oil in Artemisia argyi can inhibit Trichophyton rubrum by up to 67%, and its mechanism of action is related to disrupting the fungal cell membrane and inhibiting cell wall synthesis. The volatile oils in Bupleurum chinense (such as α-spinasterol, myrcene, and eugenol) have significant antibacterial, anti-inflammatory, antioxidant, and intestinal flora regulating effects, especially against dermatophytes such as Staphylococcus aureus. The limonene and β-mosine in Citrus aurantium and Citrus reticulata peel have significant antibacterial and anti-inflammatory effects, significantly inhibiting the growth of bacteria such as Escherichia coli and Staphylococcus aureus. These components work together to inhibit the growth of intestinal pathogens, improve the balance of intestinal flora, and reduce inflammatory responses, thereby synergistically treating indigestion and rectal prolapse.

[0016] Regulating Gut Microbiota: The volatile components of the medicated moxibustion composition of this invention act on the intestines through external application, regulating the gut microbiota structure. Moxibustion at the Shenque acupoint can reduce the growth of pathogenic bacteria, increase the proliferation of beneficial bacteria, improve the structure of the gut microbiota in mice with ulcerative colitis, and enhance its diversity and richness. The volatile oil components in Bupleurum chinense and Citrus reticulata also have antibacterial effects, which can diffuse into the intestines through smoke, inhibiting the growth of pathogenic bacteria and promoting the reproduction of beneficial bacteria, thus forming a healthier gut microbiota environment. This mechanism of regulating gut microbiota is of great significance for treating indigestion and preventing the recurrence of rectal prolapse.

[0017] Anti-inflammatory effects: The volatile components in the Artemisia composition of this invention can inhibit inflammatory responses through multiple pathways. Thujone and eucalyptol in the Artemisia argyi volatile oil can reduce the body's inflammatory response by inhibiting JAK / STAT1 / 3 phosphorylation and the release of pro-inflammatory mediators (NO, PGE2, and ROS) from macrophages. α-spinasterol and other components in Bupleurum chinense volatile oil can improve the inflammatory state by regulating the estrogen receptor (ESR1) and Rap-1 signaling pathways. Limonene and β-mosine in Citrus aurantium and Citrus reticulata peel have significant anti-inflammatory effects and can inhibit the production of various pro-inflammatory factors. These components work together to reduce intestinal inflammation and mucosal damage, and improve indigestion symptoms by inhibiting the expression of pro-inflammatory factors such as TNF-α and IL-6.

[0018] Improving Microcirculation: The heat from moxibustion promotes local blood and lymphatic circulation, relieves smooth muscle spasms, and improves tissue metabolism. The far-infrared radiation (40-60℃) generated by burning moxa wool penetrates the skin 3-5 cm, directly acting on blood vessel walls, dilating local capillaries, and accelerating blood circulation. The volatile oils from Bupleurum, Citrus aurantium, and Citrus reticulata are released under heat, allowing for absorption through the skin and direct action on the tissues and nerve endings surrounding acupoints, improving local microcirculation and promoting drug absorption and efficacy.

[0019] Regulation of the neuroendocrine system: The volatile components of the moxibustion composition of this invention can improve gastrointestinal dysfunction caused by liver qi stagnation by regulating the neuroendocrine system. Studies have shown that moxibustion can affect immune and endocrine functions by transmitting signals to the body through regulation of transient receptor potential family (TRP) and heat shock proteins. Components such as α-spinasterol in Bupleurum chinense volatile oil can act on the neuroendocrine system and regulate the hypothalamic-pituitary-adrenal axis. Components such as β-mosine in Citrus reticulata volatile oil have sedative and neurotransmitter-regulating effects, which can alleviate the inhibition of gastrointestinal function by liver qi stagnation. These components work together to improve gastrointestinal dysfunction caused by liver qi stagnation by regulating neurotransmitter and hormone levels, thereby synergistically treating indigestion and rectal prolapse.

[0020] III. Mechanisms for the Synergistic Prevention and Treatment of Rectal Prolapse and Indigestion Rectal prolapse and indigestion appear to be two different diseases, but their occurrence and development are intrinsically linked. Traditional Chinese medicine believes that both are related to liver qi stagnation, spleen and stomach weakness, and abnormal qi circulation. The medicated moxa sticks prepared from the medicated moxa composition of this invention, administered externally, allow the volatile components of each herb to work synergistically, achieving comprehensive prevention and treatment of both diseases. This invention addresses liver stagnation and promotes the regulation of Qi, improving liver qi stagnation: Liver qi stagnation can lead to gastrointestinal dysfunction, resulting in indigestion and rectal prolapse. Bupleurum, Citrus aurantium, and Citrus reticulata all have liver-soothing and qi-regulating effects, regulating liver and gallbladder Qi and improving liver qi stagnation. The volatile components of this invention's herbal composition can be absorbed through the skin, directly acting on relevant acupoints along the liver and gallbladder meridians to regulate liver and gallbladder Qi, improve liver qi stagnation, and thus indirectly improve spleen and stomach function, alleviating indigestion symptoms.

[0021] Raising Yang and Lifting Prolapse: Qi deficiency and prolapse can lead to rectal mucosal relaxation, which in turn can cause rectal prolapse. Both Bupleurum and Citrus reticulata have the effect of raising Yang and lifting prolapse, which can lift the sunken Qi and improve the symptoms of rectal prolapse caused by Qi deficiency and prolapse. Furthermore, the heat generated by burning moxa wool stimulates specific acupoints, such as Baihui and Changqiang, to lift the sunken Qi and improve the state of Qi deficiency and prolapse, thereby treating rectal prolapse.

[0022] Warming and unblocking meridians, improving microcirculation: The warming and unblocking effect of moxa wool can promote local blood circulation and improve tissue metabolism. The infrared radiation generated by burning moxa wool can promote vasodilation, improve microcirculation, and accelerate drug absorption and efficacy. This warming and unblocking effect is of great significance for improving local symptoms such as rectal prolapse and indigestion.

[0023] Regulating gut microbiota and improving digestive function: Gut microbiota imbalance can lead to digestive disorders, resulting in indigestion and rectal prolapse. The volatile components in the medicated moxa composition of this invention can regulate the balance of gut microbiota through antibacterial effects. These components also diffuse into the intestines through the smoke produced by burning moxa, inhibiting the growth of pathogenic bacteria and promoting the reproduction of beneficial bacteria, thus creating a healthier gut microbiota environment, improving digestive function, and alleviating indigestion symptoms.

[0024] Anti-inflammatory and antibacterial properties, improving the local environment: Inflammation is an important pathogenesis of rectal prolapse and indigestion. The volatile components in the medicated composition of this invention have significant anti-inflammatory and antibacterial effects, which can improve the local environment of the intestine and rectum. Furthermore, the combustion of the medicated composition of this invention produces anti-inflammatory factors (such as TNF-α, IL-6, etc.), which reduce the inflammatory response and improve the local environment of the intestine and rectum, thereby treating rectal prolapse and indigestion. Attached Figure Description

[0025] Figure 1 This represents the intersection of active ingredients between different databases in the experimental examples of this invention; Figure 2This 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 effects of the traditional Chinese medicine Artemisia argyi on the comorbidities of rectal prolapse and indigestion in the experimental examples of this invention. 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 diagram of the PPI interaction network in the experimental examples of this 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 12 This 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

[0026] The present invention will be further described below with reference to the accompanying drawings and specific embodiments.

[0027] A medicated moxa composition for preventing and treating rectal prolapse combined with indigestion, 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: Bupleurum chinense 2-10 parts, Citrus aurantium 4-15 parts and Citrus reticulata 1-7 parts, and the weight ratio of the traditional Chinese medicine composition to the moxa wool is 3.5-8:6-12.

[0028] The traditional Chinese medicine composition in the medicated mugwort composition is preferably made from the following raw materials in the following weight ratio: 4 parts Bupleurum, 7 parts Citrus aurantium and 3 parts Citrus reticulata peel, with the weight ratio of the traditional Chinese medicine composition to mugwort floss being 5:9.

[0029] Example: Example 1: Bupleurum 100g, Citrus aurantium 200g, Citrus reticulata peel 50g, and Artemisia argyi 600g.

[0030] Example 2: Bupleurum 160g, Citrus aurantium 280g, Citrus reticulata peel 120g, and Artemisia argyi 1008g.

[0031] Example 3: Bupleurum 250g, Citrus aurantium 375g, Citrus reticulata peel 175g, and Artemisia argyi 1200g.

[0032] 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 Bupleurum chinense, Citrus aurantium, and Citrus reticulata 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 the database, 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 GeneCards / OpenTargets database. Using "Rectalprolapse" as the keyword, disease-related targets were retrieved and their gene names were standardized and deduplicated. Similarly, disease-related targets were retrieved from the GeneCards / OpenTargets / CTD / DrugBank databases. Using "dyspepsia" as the keyword, disease-related targets were retrieved and their gene names were standardized and deduplicated. The intersection genes of rectal prolapse combined with dyspepsia were then used as the final disease genes. 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 to screen core targets. The drug-artemisia composition of this invention and related targets of rectal prolapse combined with dyspepsia were subjected to GO functional enrichment analysis and KEGG pathway enrichment analysis using the R clusterProfiler 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.

[0033] 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.

[0034] 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. This yielded 24 active ingredients from Bupleurum chinense, 7 from Citrus aurantium, and 9 from Citrus reticulata. Duplicate common components were removed, resulting in a total of 32 active ingredients. (See attached...) Figure 1 Potential drug targets for active pharmaceutical ingredients were identified through a database. After removing duplicate targets, a total of 654 drug targets were obtained. (See attached database.) Figure 2 .

[0035] 2. Collection of relevant targets for rectal prolapse combined with dyspepsia and screening of therapeutic targets for the drug composition of the present invention. The search results for "Rectal prolapse" were filtered according to a threshold using the Gene Cards Score>=2 / Open Targets Score>=0.01 database. The search results for "dyspepsia" were filtered according to a threshold using the Gene Cards Score>=2 / Open Targets Score>=0.01 / CTD Score>=20 / Drug Bank database. Gene names of standardized disease targets were summarized, duplicates were removed, and the intersection was taken to obtain 89 disease targets. The intersection of these targets with the effective ingredient targets of the present invention's drug composition was then determined. After mapping, 60 common targets were identified as potential targets for the present invention's drug composition to act on rectal prolapse combined with dyspepsia. (See...) Figure 3 .

[0036] 3. Construction and analysis of drug-compound-target-disease network See the drug-compound-target-disease network. Figure 4 The network graph has 89 nodes and 332 edges, with edges representing the targeting relationships between compounds and targets. 25 active ingredients act on 60 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 quercetin, nobiletin, baicalin, kaempferol, delphinidin, Delta-D, and naringenin. Figure 6This 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.

[0037] 4. PPI Network Diagram Analysis Eighty-three 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 60 nodes and 1098 edges, where edges represent the relationships between target points (isolated target points with no intersection are removed). The Network Analyzer plugin is 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 are selected based on their degree values ​​(CC / BC / degree), and the network graph is then drawn. See [link to diagram]. Figure 8 The core targets are AKT1, IL6, TP5, TNF, NFKB1, BCL2, IL1B, MAPK3, PTGS2, etc., which are key targets for the treatment of rectal prolapse complicated with indigestion by the drug composition of this invention. (See below) Figure 9 .

[0038] 5. GO functional enrichment analysis and KEGG pathway analysis Based on R clusterProfiler, GO enrichment analysis was performed on 60 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 10-11 As shown. The vertical axis represents each entry of GO, and the horizontal axis represents the number of targets enriched with that entry. BP mainly involves cellular responses to chemical stress, oxidative stress, lipopolysaccharide, bacterial molecules, smooth muscle cell regulation, smooth muscle cell proliferation, myocyte proliferation, responses to reactive oxygen species, and regulation of apoptosis signaling pathways. MF mainly includes cytokine activity, cytokine receptor binding, receptor ligand activity, signal receptor activator activity, phosphatase binding, heme binding, growth factor receptor binding, protein phosphatase binding, tetrapyrrole binding, growth factor activity, and insulin receptor substrate binding. CC mainly involves membrane rafts, membrane microdomains, indentations, plasma membrane rafts, vesicle cavities, secretory granule cavities, cytoplasmic vesicle cavities, the outer plasma membrane, platelet α-granule cavities, the nuclear membrane, phosphatidylinositol 3-kinase complexes, and class IA. KEGG pathway enrichment analysis was performed on the target, resulting in 171 signaling pathways. This study selected the top 30 pathways (P < 0.05) from the downloaded results for visualization analysis. Figure 12-13 As shown in the figure, the enrichment results revealed that the AGE-RAGE signaling pathway is mainly involved in diabetes, lipids and atherosclerosis, Chagas disease, fluid shear stress and atherosclerosis, HIF-1 signaling pathway, IL-17 signaling pathway, human cytomegalovirus infection, TNF signaling pathway, colorectal cancer, hepatitis B, and proteoglycan signaling pathways in 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, see [link to diagram]. Figure 14 .

[0039] 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 119 nodes and 821 edges (25 components, 60 targets, 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 rectal prolapse combined with indigestion.

[0040] 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 MOL000098, MOL000354, MOL000358, MOL000422, MOL000546, MOL002776, MOL004328, MOL004798, MOL005828, and MOL010861 in the drug composition of this invention and the top 10 core targets in the PPI network: AKT1, BCL2, IL1B, IL6, MAPK3, NFKB1, PTGS2, TGFB1, TNF, and TP53. The docking results are shown in [Figure number missing]. Figure 16 .

[0041] Clinical trial example: Clinical trial case 1: Rectal prolapse Rectal prolapse, also known as rectal prolapse, is a common anorectal disease in clinical practice. It refers to the displacement or prolapse of the rectal mucosa, the entire rectal wall, the anal canal, or part of the sigmoid colon outside the anus. Clinically, it manifests as a mass protruding from the anus after prolonged squatting, coughing, or straining. It may or may not be able to be reduced spontaneously.

[0042] 1. Materials and Methods 1.1 General Information Thirty-two patients with rectal prolapse who visited the outpatient clinics 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 15 males and 17 females, aged 42-83 years, with a mean age of (62.656±9.800) years.

[0043] 1.2 Inclusion and Exclusion Criteria Inclusion criteria: (1) Clinical diagnosis of rectal prolapse; (2) Patients voluntarily participate in this study and sign 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 and difficulty in cooperating with moxibustion on time.

[0044] 1.3 Grouping and Treatment Methods Thirty-two patients with rectal prolapse were randomly divided into a control group (n=16) and an experimental group (n=16). The control group ranged in age from 42 to 83 years, with a mean age of (62.375 ± 10.525) years. The experimental group ranged in age from 48 to 77 years, with a mean age of (62.938 ± 9.356) years. There was no statistically significant difference in age between the two groups. P >0.05), which is comparable, see Table 1.

[0045] The control group received oral administration of a modified Buzhong Yiqi Decoction combined with regular moxibustion. The experimental group received oral administration of the modified Buzhong Yiqi Decoction combined with moxibustion using 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 two weeks. Specific acupoints for moxibustion were: Yangchi (GB4), Zulinqi (GB41), and Zusanli (ST36) for the first treatment; Yangchi (GB4), Zulinqi (GB41), and Tianjing (ST20) for the second treatment; and Yangchi (GB41), Zulinqi (GB41), and Zusanli (ST36) for the third treatment, bilaterally.

[0046] 1.4 Efficacy Evaluation Criteria 1.4.1 Overall Effectiveness Cured: Bowel movements are smooth, with no mucosal prolapse or anal pressure during defecation; Effective: Symptoms of difficulty in defecation, incomplete evacuation, and anal pressure are reduced, and defecation is relatively smooth; Ineffective: Related symptoms show no significant improvement or worsen.

[0047] Overall effective rate = (Number of cured cases + Number of effective cases) / Total number of cases 1.4.2 Clinical Symptom Score The clinical symptom scores of patients with rectal prolapse were statistically analyzed before and after treatment. These scores mainly included three symptoms: difficulty in defecation, a feeling of rectal tenesmus, and a feeling of incomplete defecation. Each symptom was scored from 1 to 4 points, with higher scores indicating more severe symptoms. See Table 2.

[0048] 1.5 Statistical Analysis Data were analyzed using SPSS 27.0 software. Count data were expressed as percentages. Inspection; for measurement data Represented in the form of, using Test whether the differences between the data are statistically significant.

[0049] 2 Results 2.1 Comparison of overall effectiveness between the two groups After treatment, the total effective rate in the control group was 31.25%, while the total effective rate in the experimental group was 75%. Compared with the control group, the total effective rate in the experimental group was significantly higher. P =0.32<0.05), indicating that the experimental group had better clinical efficacy. See Table 3.

[0050] 2.2 Comparison of clinical symptom scores between the two groups of rectal prolapse Compared with before treatment, the clinical symptom scores of rectal prolapse decreased in both groups after treatment. P <0.05), indicating that the modified Buzhong Yiqi Decoction combined with moxibustion can improve the clinical symptoms of patients with rectal prolapse; compared with the control group, the experimental group had a lower clinical symptom score of rectal prolapse after treatment, and the results showed that the medicated moxa prepared by the composition in Example 2 had a better therapeutic effect than ordinary moxibustion. P <0.05). See Table 4.

[0051] Clinical trial case 2: Functional dyspepsia Functional dyspepsia is a very common functional disorder of the digestive system in clinical practice, and its dyspeptic symptoms cannot be explained by organic, metabolic, or systemic diseases. It can be divided into two subtypes: postprandial discomfort syndrome and epigastric pain syndrome. Traditional Chinese medicine classifies it under the categories of "stomach distension," "stomach pain," and "abdominal fullness."

[0052] 1. Materials and Methods 1.1 General Information Fifty patients with functional dyspepsia 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 34-74 years, with a mean age of (60.920±10.158) years.

[0053] 1.2 Inclusion and Exclusion Criteria Inclusion criteria: (1) Clinical diagnosis of functional dyspepsia; (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.

[0054] 1.3 Grouping and Treatment Methods Fifty patients with functional dyspepsia were randomly divided into a control group (n=25) and an experimental group (n=25). The control group ranged in age from 34 to 70 years, with a mean age of (60.640 ± 11.172) years. The experimental group ranged in age from 39 to 74 years, with a mean age of (61.200 ± 9.256) years. There was no statistically significant difference in age between the two groups. P (>0.05), indicating comparability. See Table 5.

[0055] The control group received oral administration of a modified Xiangsha Liujunzi Decoction combined with regular moxibustion. The experimental group received oral administration of the modified Xiangsha Liujunzi Decoction 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: Yangchi (GB4), Zulinqi (GB41), and Zusanli (ST36) for the first treatment; Yangchi (GB4), Zulinqi (GB41), and Tianjing (ST20) for the second treatment; and Yangchi (GB41), Zulinqi (GB41), and Zusanli (ST36) for the third treatment. Acupoints were selected bilaterally.

[0056] 1.4 Efficacy Evaluation Criteria The functional dyspepsia scores of patients were statistically analyzed before and after treatment. A functional dyspepsia scoring scale was developed based on the "Expert Consensus on the Diagnosis and Treatment of Functional Dyspepsia with Traditional Chinese Medicine (2017)" and daily clinical practice, as shown in Table 6.

[0057] 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.

[0058] 2 Results Comparison of functional dyspepsia scores between the two groups: Compared with before treatment, the functional dyspepsia scores of both groups decreased significantly after treatment, indicating that the clinical symptoms of both groups improved significantly after treatment. P <0.001; compared with the control group after treatment, the experimental group had a lower functional dyspepsia score after treatment ( P <0.05), the results show that the moxa prepared by the composition in Example 3 has better therapeutic effect than ordinary moxibustion. See Table 7.

[0059] 。

Claims

1. A pharmaceutical composition for preventing and treating co-morbidity of fecal incontinence and dyspepsia, characterized in that, The medicine-Ai composition comprises a Chinese medicine composition and Ai, wherein the Chinese medicine composition is made of the following raw materials in the following proportions by weight: 2-10 parts of Radix Bupleuri, 4-15 parts of Fructus Aurantii and 1-7 parts of Pericarpium Citri Reticulatae Viride, and the weight ratio of the Chinese medicine composition to Ai is 3.5-8:6-12.

2. The pharmaceutical composition for preventing and treating the co-morbidity of prolapse of the rectum and dyspepsia according to claim 1, wherein The medicine-Ai composition comprises a Chinese medicine composition and Ai, wherein the Chinese medicine composition is made of the following raw materials in the following proportions by weight: 4 parts of Radix Bupleuri, 7 parts of Fructus Aurantii and 3 parts of Pericarpium Citri Reticulatae Viride, and the weight ratio of the Chinese medicine composition to Ai is 5:9.

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