Medicinal moxa composition for preventing and treating irregular menstruation and coronary heart disease

Abstract

The invention discloses a medicinal moxa composition for preventing and treating irregular menstruation and coronary heart disease. The medicinal moxa composition comprises ligusticum wallichii, angelica sinensis, radix rehmanniae preparata, radix paeoniae rubra, indigo naturalis 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 heat, can synergistically act on a plurality of key targets related to irregular menstruation and coronary heart disease, participates in regulation and control of a plurality of pathways, and provides a scientific basis for co-disease treatment.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of traditional Chinese medicine, and particularly relates to a medicine and moxa composition for preventing and treating irregular menstruation and coronary heart disease. BACKGROUND

[0002] Irregular menstruation and coronary heart disease are common combinations of female diseases, and their pathological mechanisms are related to each other. Irregular menstruation mainly manifests as cycle disorder, abnormal menstrual flow, prolonged or shortened menstrual period, etc. According to traditional Chinese medicine, it is related to liver stagnation and blood stasis, kidney deficiency, deficiency of qi and blood, or blood heat. Modern medical research shows that irregular menstruation is closely related to an increased risk of cardiovascular diseases, especially that fluctuation of estrogen level can affect vascular endothelial function and promote the formation of atherosclerosis. Coronary heart disease is mainly caused by coronary atherosclerosis to cause myocardial ischemia and hypoxia, and the clinical manifestations are angina pectoris, chest tightness, shortness of breath, etc. Western medicine commonly uses hormone drugs (such as contraceptives) to treat irregular menstruation, but can cause liver and gallbladder, cardiovascular side effects and increase the risk of thrombosis. Anti-platelet drugs (such as aspirin) and hormone drugs have a superimposed risk of bleeding in the treatment of coronary heart disease, and beta blockers can inhibit menstrual cycle regulation, resulting in reduced or irregular menstrual flow. These treatment contradictions make the patients with comorbidities face great risks. SUMMARY

[0003] The purpose of the present application is to provide a medicine and moxa composition for preventing and treating irregular menstruation and coronary heart disease.

[0004] In order to achieve the above purpose, the technical scheme adopted by the present application is as follows: A medicine and moxa composition for preventing and treating irregular menstruation and coronary heart disease, the medicine and moxa composition comprises a traditional Chinese medicine composition and moxa, and the traditional Chinese medicine composition is made of raw materials in the following proportions by weight: 4-19 parts of chuanxiong, 3-16 parts of danggui, 3-17 parts of radix rehmanniae preparatae, 5-18 parts of red peony root and 6-21 parts of indigo, and the weight ratio of the traditional Chinese medicine composition to the moxa is 2-5:5-9.

[0005] In order to further realize the present application, the traditional Chinese medicine composition in the above medicine and moxa composition is preferably made of raw materials in the following proportions by weight: 13 parts of chuanxiong, 11 parts of danggui, 12 parts of radix rehmanniae preparatae, 12 parts of red peony root and 14 parts of indigo, and the weight ratio of the traditional Chinese medicine composition to the moxa is 4:7.

[0006] The beneficial effects of the present application compared with the prior art are as follows: I. Pathological relationship of foot lesser yang meridian with irregular menstruation and coronary heart disease The foot Chujueyin liver meridian is closely related to the pathogenesis of irregular menstruation and coronary heart disease. The liver meridian starts at the junction of the big toe, goes up the foot, is one inch away from the medial malleolus, is eight inches above the ankle, is handed over to the Taiyin, goes up the medial malleolus, goes along the femoral vein, enters the hair, circles the clitoris, reaches the lower abdomen, holds the stomach, belongs to the liver, collaterals the gallbladder, goes through the diaphragm, spreads the ribs, goes up the throat, and enters the temple, connects the eye, and goes out of the forehead, and meets the Du Meridian at the vertex. Its branches go from the eye to the inside of the cheek, circle the inside of the lips. Its branches go from the liver, go through the diaphragm, and go up to the lungs. This running path is closely related to menstruation and heart function.

[0007] For irregular menstruation, the liver governs blood storage, regulates excretion, regulates qi movement, governs the blood sea, and directly affects the menstrual cycle, amount, and color. The liver meridian runs in the lower abdomen and the genital organ, and liver depression, qi stagnation or blood deficiency can cause irregular menstruation, less amount or pain. Liver excretion failure, qi movement stagnation, depression in the chest, chest fullness; blood stasis, stasis in the chest, heart and blood vessels are not in harmony, so the chest pain does not subside. Emotional discomfort, liver excretion failure, affects qi and blood, qi stagnation and collateral obstruction, leading to liver blood deficiency, and further affecting menstrual function. The medicinal moxa composition of the present application can directly act on the liver meridian running area by acupoint moxibustion administration, soothe the liver and regulate qi, activate blood and resolve stasis, improve qi and blood circulation, and thus relieve the symptoms of irregular menstruation.

[0008] For coronary heart disease, the liver meridian intersects with the hand shaoyin heart meridian and the hand jueyin pericardium meridian in the chest, and the chest is the place where qi and blood gather. The liver meridian affects the function of heart and lung, liver excretion failure, qi movement stagnation, depression in the chest, can lead to the occurrence of chest pain (coronary heart disease). Liver stagnation can affect the circulation of heart and blood vessels, leading to chest pain symptoms. The liver meridian and the pericardium meridian have the same name, and the obstruction of liver meridian and blood circulation can affect the heart and blood vessels, leading to heart and blood vessels obstruction, and causing chest pain. The medicinal moxa composition of the present application can regulate the circulation of liver meridian and blood, improve the obstruction of heart and blood vessels, and thus relieve the symptoms of coronary heart disease.

[0009] Two, analysis of the prescription of traditional Chinese medicine The medicinal moxa composition of the present application follows the principle of traditional Chinese medicine prescription, and is matched according to the monarch, minister, assistant and messenger. Each medicinal material cooperates to achieve the effect of treating irregular menstruation combined with coronary heart disease.

[0010] Moxa is the monarch, which has the effects of warming the meridians, dispelling cold and pain, promoting blood circulation and removing meridian obstruction. It is warm in nature, pungent in taste, and belongs to liver, spleen and kidney meridians, which can warm and unblock the meridians, promote the circulation of qi and blood, and improve the cold and damp stasis of liver meridian. Moxa dominates in the medicinal moxa composition of the present application, which directly acts on the liver meridian running area by burning, improves the circulation of qi and blood, and relieves the symptoms of irregular menstruation and coronary heart disease.

[0011] Chuanxiong and Danggui are ministerial herbs, which have the effects of activating blood and resolving stasis, and promoting qi and nourishing blood. Chuanxiong is pungent and warm, and belongs to the pericardium and liver meridians, and is a blood qi herb. It has the effects of ascending to the brain, promoting qi, relieving pain, activating blood and resolving stasis, and dispelling wind and dredging collaterals. Danggui is pungent and sweet and warm, and belongs to the heart and liver meridians, and has the effects of activating blood and resolving stasis, and tonifying and harmonizing blood. When they are used together, chuanxiong regulates the dryness of danggui, and danggui prevents the warm and dampness of chuanxiong. They can regulate blood and blood stasis, tonify blood without stagnation, and activate blood without damaging the normal body, and improve the symptoms of qi and blood stasis.

[0012] Chishao and Qingdai are auxiliary herbs, which have the effects of clearing heat and cooling blood, and resolving stasis and detoxifying. Chishao is pungent and bitter, and has a slight cold nature, and belongs to the liver meridian, and has the effects of activating blood and resolving stasis, and cooling blood and resolving abscesses. Qingdai is salty and cold, and belongs to the liver meridian, and has the effects of cooling blood and resolving spots, and clearing heat and detoxifying. When they are used together, chishao is good at activating blood, and qingdai is good at cooling blood, and they can clear the heat of the liver meridian, and activate blood and detoxify, and prevent the excessive warm and dryness from damaging the yin fluid.

[0013] Shudihuang is a ministerial herb, which has the effects of nourishing yin and blood, and benefiting essence and filling marrow. It is sweet and slightly warm, and belongs to the liver and kidney meridians, and can fill essence and marrow, nourish yin and blood, and tonify the liver and kidney. On the one hand, shudihuang can nourish yin and blood, and regulate the whole prescription, and prevent the excessive warm and dryness from damaging the yin fluid. On the other hand, shudihuang can guide the medicinal effect to the liver and kidney meridians, and improve the treatment effect on irregular menstruation and coronary heart disease.

[0014] The medicinal moxa composition of the present application is based on the theory of treating heart and liver together, and starts from the liver meridian of Foot-Jueyin, and improves the symptoms of irregular menstruation and coronary heart disease through the effects of soothing the liver and regulating qi, activating blood and resolving stasis, and clearing heat and cooling blood. Chuanxiong activates blood and regulates qi, danggui tonifies blood and regulates menstruation, shudihuang nourishes yin and blood, chishao activates blood and resolves stasis, and qingdai clears heat and cools blood, and the five herbs form a balanced system of tonifying without stagnation, and activating blood without damaging the normal body. The results of the present research show that the medicinal moxa composition of the present application can significantly improve the regularity of the menstrual cycle, and reduce the frequency of angina pectoris in patients with coronary heart disease, and regulate the blood lipid level.

[0015] III. Mechanism of action of volatile components The volatile components in the medicinal moxa composition of the present application are the key material basis for the treatment effect. Moxa is the main component, and contains rich volatile oil substances, including eucalyptol, camphor, terpinenol, etc., and these components have a significant transdermal penetration effect. The volatile oil of moxa can change the structure of the lipid bilayer of the stratum corneum, increase the intercellular space, and promote drug absorption. Terpinenol in the volatile oil of moxa can directly act on the heart and lung vascular system, improve microcirculation, and the pungent and dispersing properties of the volatile oil of moxa can directly act on the skin, promote local blood circulation through the heat effect, and enhance drug penetration. During the burning process of the medicinal moxa stick prepared in the present application, the volatile components of moxa are released, and after contacting with the skin, a concentration gradient is quickly formed, which promotes the diffusion of drug molecules from the epidermis to the dermis and subcutaneous tissue, and improves the bioavailability of the drug.

[0016] The volatile components of Chuanxiong and Danggui show unique synergistic effects in external treatment. Chuanxiong volatile oil (mainly containing Chuanxiongzine, volatile oil, etc.) has significant transdermal penetration ability, which can promote the in vitro transdermal absorption of drugs such as triptolide and improve the efficiency of drug penetration through the skin barrier. Danggui volatile oil also has excellent skin permeability, which can significantly improve the transdermal absorption effect of various drugs. The synergistic effect of Danggui and Chuanxiong volatile oil not only enhances the drug transdermal absorption capacity, but also promotes skin absorption and improves the circulation of qi and blood throughout the body, regulates local microcirculation, and improves the symptoms of irregular menstruation and coronary heart disease.

[0017] The volatile components of Chishao and Qingdai play a role in clearing heat and cooling blood, removing blood stasis and detoxifying in external treatment. Chishao contains volatile components such as aconitum phenol and peony glycoside, which can promote local blood circulation, dissipate blood stasis, and relieve pain. Lipophilic indigo components in Qingdai can penetrate the stratum corneum of the skin and directly act on the skin lesion, inhibit the overexpression of inflammatory factors (such as IL-17, VEGF), reduce inflammation, and reduce the local and systemic inflammatory burden. The combination of these volatile components and the warm and unobstructed properties of moxa can not only promote drug absorption, but also prevent excessive dryness from causing yin fluid depletion, forming a good dynamic balance.

[0018] After processing, Rehmannia glutinosa is rich in polysaccharides and other components, which can promote the transdermal absorption of drugs and enhance the therapeutic effect of other medicinal materials.

[0019] The volatile components of each drug are absorbed through the skin and enter the systemic circulation, and some drugs are transmitted to the brain edge system through olfactory receptors, producing systemic regulation. This dual mechanism makes the medicinal moxa composition of the present application have unique advantages in the treatment of irregular menstruation combined with coronary heart disease.

[0020] Four, the advantages and characteristics of external treatment The medicinal moxa composition of the present application uses external moxibustion for administration, which can bypass the first-pass effect of the liver and the metabolic process of the gastrointestinal tract, directly act on the skin and subcutaneous tissue, and improve the bioavailability of drugs. External administration can precisely act on the meridian of Foot Lesser Yin, such as the lateral costal region, the lower abdomen, and the genital organs, enhancing the treatment specificity. External administration can promote local blood circulation through thermal effect, increase the concentration of drugs in the target area, and enhance the therapeutic effect.

[0021] External administration also has the advantages of high safety and few side effects. Compared with oral administration, external administration avoids the potential toxicity of drugs to the digestive system and liver. The drugs for external administration mainly act on the local area, and the systemic absorption is limited, greatly reducing the risk of toxicity. External administration can flexibly adjust the dosage and frequency of drug use according to the patient's condition, which is convenient for long-term use and improves treatment compliance. BRIEF DESCRIPTION OF DRAWINGS

[0022] Figure 1 The intersection of active ingredients between different databases in the experimental examples of the present application; Figure 2 The intersection of target points between different databases in the experimental examples of the present application; Figure 3 The Venn diagram of the intersection of target points of the effect of the traditional Chinese medicine Ai on irregular menstruation combined with coronary heart disease in the experimental examples of the present application; Figure 4 The drug-compound-target-disease network diagram in the experimental examples of the present application; Figure 5 The compound connectivity ranking column chart in the experimental examples of the present application; Figure 6 The TOP compound drug source Sanji diagram in the experimental examples of the present application; Figure 7 The STRING interaction diagram in the experimental examples of the present application; Figure 8 The PPI interaction network diagram in the experimental examples of the present application; Figure 9 The core target connectivity ranking column chart in the experimental examples of the present application; Figure 10 The GO enrichment analysis column chart in the experimental examples of the present application; Figure 11 The GO enrichment analysis pie chart in the experimental examples of the present application; Figure 12 The KEGG enrichment analysis scatter plot in the experimental examples of the present application; Figure 13 The KEGG enrichment analysis pie chart in the experimental examples of the present application; Figure 14 The TOP target TOP pathway Sanji diagram in the experimental examples of the present application; Figure 15 The compound-target-pathway-disease network diagram in the experimental examples of the present application; Figure 16 The Top10 active ingredient and Top10 target docking energy heat map in the experimental examples of the present application. DETAILED DESCRIPTION

[0023] The present application will be further described below in conjunction with the drawings and specific embodiments.

[0024] A medicine Ai composition for preventing and treating irregular menstruation combined with coronary heart disease, the medicine Ai composition comprising a traditional Chinese medicine composition and moxa, the traditional Chinese medicine composition being made of raw materials in the following weight proportions: Szechuan lovage root 4-19 parts, Chinese angelica 3-16 parts, prepared rehmannia 3-17 parts, red peony root 5-18 parts, and blue lead 6-21 parts, and the weight ratio of the traditional Chinese medicine composition to the moxa being 2-5:5-9.

[0025] The Chinese medicine composition in the above medicine moxa composition is preferably made of raw materials in the following proportions by weight: 13 parts of Chuanxiong, 11 parts of Danggui, 12 parts of Shudihuang, 12 parts of Chishao and 14 parts of Qingdai, and the weight ratio of the Chinese medicine composition to moxa is 4:7.

[0026] Embodiment: Embodiment 1: Chuanxiong 120g, Danggui 90g, Shudihuang 90g, Chishao 150g, Qingdai 180g and moxa 1575g.

[0027] Embodiment 2: Chuanxiong 260g, Danggui 220g, Shudihuang 240g, Chishao 240g, Qingdai 280g and moxa 2170g.

[0028] Embodiment 3: Chuanxiong 380g, Danggui 320g, Shudihuang 340g, Chishao 360g, Qingdai 420g and moxa 3276g.

[0029] Experimental example, network pharmacology and molecular docking: First, the collection of active ingredients and target points in the medicine moxa composition of the present application: The chemical components of Chuanxiong Rhizoma, Angelica sinensis, Radix Rehmanniae Preparata, Radix Paeoniae Rubra and Qingdai are collected by using TCMSP / BATMAN / HERB / ETCM, and the active ingredients of the medicinal Ai composition of the application are further screened out by taking oral bioavailability (OB) ≥ 30% and druglikeness (DL) ≥ 0.18 as screening conditions. The target points obtained from the database are standardized by using the gene name of the Uniprot database, and the repeated target points are removed. Finally, the active ingredients and the target points of the drug are obtained. The target points related to the disease are retrieved from the GeneCards / CTD / DrugBank database, the target points related to the disease are retrieved by taking “Menstrual Irregularities” as the keyword, the gene name of the standardized disease target points is summarized and the repeated target points are removed; the target points related to the disease are retrieved from the GeneCards / OpenTargets / CTD / DrugBank database, the target points related to the disease are retrieved by taking “Coronary heart disease” as the keyword, the gene name of the standardized disease target points is summarized and the repeated target points are removed, and the intersection genes of menstrual irregularities combined with coronary heart disease are taken as the final genes of the disease. Finally, the potential target points of menstrual irregularities combined with coronary heart disease are obtained. The one-to-one correspondence between the active ingredients of the medicinal Ai composition of the application and the target points is introduced into the Cytoscape3.9.1 software, and a drug-compound-target-disease network diagram is constructed. The medicinal Ai composition of the application is used on the intersection target points related to menstrual irregularities combined with coronary heart disease, and is introduced into the STRING database, the species is selected as “Homosapiens”, the confidence is set as ≥ 0.4, the interaction relationship between the proteins is obtained, and the core target points are screened. The medicinal Ai composition of the application and the target points related to menstrual irregularities combined with coronary heart disease are subjected to GO function enrichment analysis and KEGG pathway enrichment analysis by using the RclusterProfiler4.6.2 package respectively. The core TOP pathway, the key target points and the active ingredients are selected, and a “drug-compound-target-pathway-disease” network is constructed.

[0030] The 3D structure of the main active compound in the medicinal Ai composition of the application is downloaded from the PubChem database, and the 3D structure of the core target protein is downloaded from the Protein Data Bank database. The core target protein is subjected to preliminary treatment such as removing solvent molecules by using Pymol 2.6.0 software, and is further subjected to hydrogenation treatment and charge treatment by using AutoDockTools 1.5.7. The core target protein and the active compound are saved as “pdbqt” format files, and appropriate lattice positions and sizes are set. Finally, the docking of the ingredients and the target points is completed by Autodock Vina.

[0031] II. Results and analysis 1. Collection of active ingredients in the medicinal Ai composition of the present application and prediction of target points By searching the components of the medicinal Ai composition of the present application through a drug database, active ingredients satisfying OB≥30% and DL≥0.18 were screened, and 13 effective components of Chuanxiong Rhizoma, 13 active components of Qingdai, 31 effective components of Chishao and 11 effective components of Danggui were obtained. After deleting the repeated common components, a total of 57 active ingredients were obtained, as shown in Table 1. Figure 1 The potential action targets of the active ingredients of the drugs were obtained through the database, and after deleting the repeated targets, a total of 784 drug targets were obtained, as shown in Table 2. Figure 2

[0032] 2. Collection of related targets of menstrual irregularities combined with coronary heart disease and screening of the treatment target points of the medicinal Ai composition of the present application The disease search of “Menstrual Irregularities” was screened according to the threshold value through the search results of Gene Cards Score>=5 / CTD Score>=20 / Drug Bank database, and the disease search of “Coronary heart disease” was screened according to the threshold value through the search results of Gene Cards Score>=40 / Open Targets Score>=0.3 / CTD Score>=50 / Drug Bank database. The gene names of the standardized disease targets were collected and de-duplicated to obtain 175 disease targets and the effective component targets of the medicinal Ai composition of the present application. After mapping, 82 common action targets were determined as the potential targets of the medicinal Ai composition of the present application acting on menstrual irregularities combined with coronary heart disease, as shown in Table 3. Figure 3

[0033] 3. Construction and analysis of drug-compound-target-disease network The drug-compound-target-disease network is shown in Table 4. Figure 4 The network graph has 138 nodes and 528 edges, and the edges represent the targeting relationship between the compounds and the targets. Among them, 50 active ingredients act on 82 targets (part of the compound targets are not in the intersection and are deleted). The Network Analyzer plug-in is used to analyze the network topology properties. In the network graph, the size of the node represents the size of the degree value of the node. The larger the degree value, the stronger the hub role of the node in the network. The top 20 main component degree values are ranked as shown in Table 5. Figure 5 Based on this analysis, it is found that the main active ingredients in the active ingredients include baicalein, Baicalin, kaempferol, beta-sitosterol, ellagic acid, naringenin, Delta-D, sitosterol, etc. Figure 6 ​​The drug source Sankey diagram of the TOP compound is drawn, in which different shapes represent drugs, compounds and targets, and the color depth represents the degree weight in the network.

[0034] 4. PPI network analysis The 82 intersection targets of drug treatment diseases are introduced into the STRING database to obtain the PPI relationship, and then introduced into the Cytoscape software for analysis, as shown in Figure 7 . The network diagram has 82 nodes and 1400 edges, and the edges represent the association between the targets (delete isolated targets without intersection). The Network Analyzer plug-in is used to analyze the network topology properties, calculate the degree value, set the color depth and the size of the node to reflect the size of the degree value, and select the top 30 core nodes according to the degree value (CC / BC / degree) ranking to draw the network diagram, as shown in Figure 8 . The core targets are ALB, IL6, TNF, AKT1, IL1B, TP53, MAPK3, PPARG, etc., which are the key targets of the medicinal composition of the application for treating menstrual disorder combined with coronary heart disease, as shown in Figure 9 .

[0035] 5. GO function enrichment analysis and KEGG pathway analysis Based on R clusterProfiler, the 82 intersection targets of drug treatment diseases are subjected to GO enrichment analysis, and the top 15 entries of biological process (BP), molecular function (MF) and cellular component (CC) with P<0.05 are selected to draw a diagram, as shown in Figure 10-11 . The vertical coordinate represents each entry of GO, and the horizontal coordinate represents the number of targets enriched in the entry. BP mainly involves gland development cell response to chemical stress, response to exogenous stimulus, response to extracellular stimulus, cellular response to oxidative stress, regulation of smooth muscle cells, response to oxidative stress, response to lipopolysaccharide, smooth muscle cell proliferation, response to nutrient levels, etc.; MF mainly includes ligand-activated transcription factor activity of nuclear receptor activity, steroid binding, cytokine receptor binding, heme binding, tetrapyrrole binding, receptor ligand activity, signal receptor activator activity, cytokine activity, estrogen 16-alpha-hydroxylase activity, growth factor activity, etc. CC mainly involves membrane raft membrane microdomain, caveolae, endoplasmic reticulum lumen, platelet alpha granule, vesicle lumen, platelet alpha granule lumen, plasma membrane raft, Golgi lumen, secretory granule lumen, cytoplasmic vesicle lumen, collagen-containing extracellular matrix, etc. The target is subjected to KEGG pathway enrichment analysis, and a total of 155 signal pathways are enriched, and the top 30 pathways with P<0.05 in the downloaded results are selected to draw a diagram for visual analysis, as shown inFigure 12-13 As shown in the figure, the enrichment results revealed that the pathways involved mainly include those related to blood lipids and atherosclerosis, the AGE-RAGE signaling pathway in diabetes, chemical oncogenesis and receptor activation, proteoglycans in cancer, endocrine resistance, the HIF-1 signaling pathway, EGFR tyrosine kinase inhibitor resistance, bladder cancer, fluid shear stress and atherosclerosis, hepatitis B, pancreatic cancer, colorectal cancer, and human cytomegalovirus infection. These pathways communicate with each other and play an important role 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 .

[0036] 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 168 nodes and 931 edges (50 components, 82 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 comorbid menstrual disorders and coronary heart disease.

[0037] 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 MOL000358, MOL000359, MOL000422, MOL001002, MOL002135, MOL002157, MOL002714, MOL002776, MOL004328, and MOL010861 in the drug composition of this invention and the top 10 core targets in the PPI network: AKT1, ALB, BCL2, CASP3, IL1B, IL6, MAPK3, PPARG, TNF, and TP53. The docking results are shown in [Figure number missing]. Figure 16 .

[0038] Clinical trial example: Clinical trial case 1: Menstrual irregularities Irregular menstruation refers to the abnormal performance of women in the cycle, amount, color, quality, etc. of menstruation, which is one of the common gynecological diseases. Common irregular menstruation in traditional Chinese medicine can be divided into menorrhagia, metrorrhagia, irregular menstruation, menorrhagia, oligomenorrhea, and prolonged menstrual period. If the above symptoms are not treated or treated, it may develop into metrorrhagia or amenorrhea. Ovulation disorders in western medicine can be attributed to this disease category. The main clinical symptoms are the abnormal performance of the cycle, amount, color, quality, etc. of menstruation, which can be accompanied by lower abdominal pain, fatigue, soreness of the waist and knees, cold, irritability, etc.

[0039] 1 Data and methods 1.1 General data Select 50 cases of irregular menstruation patients from August 2024 to September 2024 in the outpatient department of Tujia Community Health Service Center of Shapingba District Maternal and Child Health Hospital in Shaopingba District, aged 19-49 years old, with an average age of (36.220±8.522) years old.

[0040] 1.2 Inclusion and exclusion criteria Inclusion criteria: (1) meet the diagnostic criteria of irregular menstruation; (2) patients voluntarily participate in this study, sign the informed consent form. Exclusion criteria: (1) history of drug allergy; (2) combined with malignant tumor, important organ dysfunction, blood system disease, immune dysfunction, mental illness; (3) cervical and pelvic lesions; (4) patients with poor treatment compliance, difficult to cooperate with moxibustion on time.

[0041] 1.3 Grouping and treatment methods 50 cases of irregular menstruation patients were randomly divided into control group (25 cases) and experimental group (25 cases). The control group was aged 21-48 years old, with an average age of (35.840±8.355) years old. The experimental group was aged 19-49 years old, with an average age of (36.600±8.841) years old. There was no statistically significant difference in the comparison of data between the two groups (P>0.05), which was comparable, as shown in Table 1. P >0.05), with comparable, as shown in Table 1.

[0042] The patients in the control group were treated with oral administration of the Chinese medicine decoction prescribed by the outpatient department and ordinary moxibustion. The patients in the experimental group were treated with oral administration of the Chinese medicine decoction prescribed by the outpatient department and moxibustion with the medicine moxa prepared in Example 2. The treatment started on the 5th day of the menstrual cycle, and the Chinese medicine decoction and moxibustion were administered 3 times a week, with each moxibustion lasting for 20 minutes. The treatment lasted for 3 weeks, and then the moxibustion was stopped until the 5th day of the 2nd menstrual cycle. The moxibustion was then resumed, and the number of times and duration of moxibustion were the same as before. The patients in both groups were treated for 2 menstrual cycles. The specific acupoints for moxibustion were as follows: the 1st moxibustion was performed on the acupoints of Taichong, Xingjian and Quguang; the 2nd moxibustion was performed on the acupoints of Taichong, Xingjian and Yungu; and the 3rd moxibustion was performed on the acupoints of Taichong, Xingjian and Shaofu. The acupoints were selected on both sides.

[0043] 1.4 Evaluation criteria for therapeutic effect 1.4.1 Clinical efficacy Cure: the menstrual cycle, menstrual period, menstrual blood color and amount of bleeding returned to normal, and symptoms such as abdominal pain and fatigue disappeared; Marked effect: the menstrual cycle, menstrual amount, menstrual color, menstrual quality and symptoms were significantly improved, the menstrual cycle returned to the range of (28±7) d, and the menstrual period returned to within 7 d; Effectiveness: the menstrual cycle, menstrual amount, menstrual color, menstrual quality and symptoms were improved; Ineffectiveness: the symptoms did not change, and in some cases, they even worsened.

[0044] Total effective rate = (number of cured cases + number of markedly effective cases + number of effective cases) / total number of cases Total marked effective rate = (number of cured cases + number of markedly effective cases) / total number of cases 1.4.2 Clinical symptom score The clinical symptom score of patients with irregular menstruation was calculated before and after treatment. According to the clinical symptoms of irregular menstruation combined with daily clinical practice, a clinical symptom score table for irregular menstruation was developed. The clinical symptom scores of patients with lower abdominal pain, fatigue, soreness of waist and knees, cold intolerance and irritability were calculated. Each score was assigned 0, 2, 4 or 6 points according to the severity of the symptoms. See Table 2 below.

[0045] 1.5 Statistical analysis The data were analyzed using SPSS 27.0 software. Count data was expressed as a percentage and analyzed using the chi-square test. Measurement data was expressed in the form of x±s and analyzed using the t-test to determine whether there was a statistically significant difference between the data.

[0046] 2 Results 2.1 Comparison of clinical efficacy between the two groups After treatment, the total effective rate of the control group was 80%, and the total effective rate of the experimental group was 96%, indicating that the menstrual cycle, menstrual amount, menstrual color and menstrual quality of patients in both groups were improved, and there was no statistically significant difference (P>0.05). P ​​=0.095>0.05), but compared with the total effective rate of 32% in the control group, the total effective rate of 60% in the experimental group was significantly higher ( P =0.047<0.05), indicating that the experimental group had better clinical efficacy. See Table 3.

[0047] 2.2 Comparison of clinical symptom scores between the two groups Compared with before treatment, the clinical symptom evaluation scores of menstrual disorders in both groups decreased significantly after treatment. P <0.01 indicates that the clinical symptoms of both groups of patients improved after treatment, and the experimental group had lower scores for each clinical symptom compared with the control group. P <0.05), indicating that the experimental group was more effective in improving patients' clinical symptoms. See Table 4.

[0048] Clinical trial case 2: Coronary heart disease Coronary heart disease, also known as coronary atherosclerotic heart disease, is a common cardiovascular disease. Typical clinical symptoms include chest tightness, chest pain, fatigue, and shortness of breath, as well as nausea and vomiting. In severe cases, it can lead to heart failure and sudden death. In traditional Chinese medicine, there is no specific name for coronary heart disease; it is generally categorized under "chest pain" based on clinical symptoms.

[0049] 1. Materials and Methods 1.1 General Information Fifty patients with coronary heart disease 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 September 2024 were selected as the study subjects. There were 22 males and 28 females, aged 52-78 years, with a mean age of (68.000±6.263) years.

[0050] 1.2 Inclusion and Exclusion Criteria Inclusion criteria: (1) Clinical diagnosis of coronary heart disease; (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.

[0051] 1.3 Grouping and Treatment Methods Fifty patients with coronary heart disease were randomly divided into a control group (n=25) and an experimental group (n=25). The control group consisted of 11 males and 14 females, aged 52-78 years, with a mean age of (68.120±6.747) years. The experimental group consisted of 11 males and 14 females, aged 53-78 years, with a mean age of (67.880±5.876) years. There were no statistically significant differences in age between the two groups. P >0.05), which is comparable, see Table 5.

[0052] Patients in the control group continued oral medication for coronary heart disease as previously prescribed, combined with regular moxibustion treatment. Patients in the experimental group continued oral medication for coronary heart disease as previously prescribed, combined with moxibustion treatment using the medicated moxa prepared from the composition in Example 3. Moxibustion was performed 3 times a week, 20 minutes each time, for a total of 4 weeks. Specific acupoints for moxibustion: First treatment: Taichong, Xingjian, Ququan; Second treatment: Taichong, Xingjian, Yingu; Third treatment: Taichong, Xingjian, Shaofu, bilaterally.

[0053] 1.4 Efficacy Evaluation Criteria A symptom evaluation scoring system for coronary heart disease was developed based on the main clinical symptoms and actual clinical conditions. Patients' clinical symptom scores for chest pain, chest tightness, shortness of breath, dizziness, and fatigue were tallied before and after treatment. Each symptom score was assigned a score of 0, 1, 2, or 3 points according to its severity, as shown in Table 6 below.

[0054] 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.

[0055] 2 Results Comparison of clinical symptom scores between the two groups: Compared with before treatment, the clinical symptom scores of coronary heart disease in both groups decreased significantly after treatment. P <0.05 indicates that the clinical symptoms of both groups of patients improved after treatment; compared with the control group, the clinical symptom score of the experimental group was lower after treatment ( P <0.05), the results showed that moxibustion treatment can improve the clinical symptoms of coronary heart disease, and the medicated moxa prepared by the composition in Example 3 was more effective than ordinary moxibustion. P <0.05). See Table 7.

[0056] .

Claims

1. A pharmaceutical composition for the treatment of dysmenorrhea and co-morbid coronary heart disease, characterized in that, The medicine moxa composition comprises a Chinese medicine composition and moxa, the Chinese medicine composition is made of raw materials in the following weight proportions: Szechwan lovage root 4-19 parts, Chinese angelica 3-16 parts, prepared rehmannia 3-17 parts, red peony root 5-18 parts, and blue lead 6-21 parts, and the weight ratio of the Chinese medicine composition and moxa is 2-5:5-9.

2. The pharmaceutical composition for treating and preventing dysmenorrhea and co-morbid coronary heart disease according to claim 1, wherein The medicine moxa composition comprises a Chinese medicine composition and moxa, the Chinese medicine composition is made of raw materials in the following weight proportions: Szechwan lovage root 4-19 parts, Chinese angelica 3-16 parts, prepared rehmannia 3-17 parts, red peony root 5-18 parts, and blue lead 6-21 parts, and the weight ratio of the Chinese medicine composition and moxa is 2-5:5-9.

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