Medicinal folium artemisiae argyi composition for preventing and treating common diseases of cystic hyperplasia of mammary glands and uterine prolapse

Abstract

The invention discloses a medicinal moxa composition for preventing and treating common diseases of breast cystic hyperplasia and uterine prolapse. The medicinal moxa composition comprises pericarpium citri reticulatae viride, ligusticum wallichii, radix bupleuri and moxa. The medicinal moxa composition disclosed by the invention has the core effects of soothing liver and regulating qi, promoting blood circulation to remove blood stasis, lifting up yang and yang, and warming and activating meridians. By adjusting qi movement of gallbladder channels and liver channels of foot-Shaoyang, liver depression and qi stagnation caused by cystic hyperplasia of mammary glands and sinking of middle qi caused by uterine prolapse are improved, and cooperative prevention and treatment of common diseases are achieved. Through multi-target regulation and control, inflammatory response of cystic hyperplasia of mammary glands and tissue relaxation of uterine prolapse are effectively relieved, and a scientific basis is provided 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 comorbid breast cystic hyperplasia and uterine prolapse. Background Technology

[0002] Fibrocystic breast disease manifests as breast tenderness, nodules, or lumps, often related to endocrine disorders and liver qi stagnation. Traditional Chinese medicine believes it is mainly caused by liver qi stagnation and phlegm-blood stasis. Uterine prolapse manifests as a mass protruding from the vagina and a feeling of heaviness, often caused by childbirth injury, prolonged increased abdominal pressure, or pelvic floor muscle relaxation. Traditional Chinese medicine believes it is mainly caused by sinking of middle qi and kidney qi deficiency.

[0003] Current Western medicine treatments include: (1) Hormone therapy: Tamoxifen and other hormones can regulate endocrine function, but there is a risk of bidirectional regulation; (2) Surgery: Segmental mastectomy or pessary can improve symptoms, but the trauma is significant; (3) Physical therapy: Breast massage can relieve hyperplasia, but the effect is limited; (4) Traditional Chinese medicine treatment: Xiaoyao pills and other traditional Chinese medicines can soothe the liver and regulate qi, but long-term use is required. Although Western medicine treatments can control symptoms, they lack synergistic treatment plans for comorbidities, and long-term medication has significant side effects.

[0004] Current TCM treatment methods include: (1) Soothing the liver and regulating qi: Bupleurum and Citrus reticulata can improve breast hyperplasia; (2) Raising yang qi: Astragalus and Cimicifuga can relieve uterine prolapse; (3) External application of Chinese medicine: such as Glauber's salt external application can relieve breast swelling and pain; (4) Acupuncture: such as Baihui acupoint can raise yang and lift prolapse. TCM treatment is holistic, but it lacks a standardized plan for breast cystic hyperplasia combined with uterine prolapse, and there is insufficient research on the synergistic mechanism of the two diseases. Summary of the Invention

[0005] The purpose of this invention is to provide a medicinal composition for preventing and treating comorbid breast cystic hyperplasia and uterine prolapse.

[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 comorbid breast cystic hyperplasia and uterine prolapse, 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: 3-13 parts of green tangerine peel, 4-15 parts of Sichuan lovage rhizome and 5-18 parts of bupleurum root, and the weight ratio of the traditional Chinese medicine composition to the moxa wool is 2.5-8:5-15.

[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: 6 parts of green tangerine peel, 7 parts of Sichuan lovage rhizome and 8 parts of bupleurum root, and the weight ratio of the traditional Chinese medicine composition to mugwort floss is 4.5:8.5.

[0008] The advantages of this invention compared to the prior art are as follows: The comorbid mechanism of cystic breast hyperplasia and uterine prolapse is mainly reflected in: (1) Both diseases are related to qi imbalance. Breast hyperplasia is mostly due to liver qi stagnation, and uterine prolapse is mostly due to qi sinking. (2) According to traditional Chinese medicine theory, the Foot Shaoyang Gallbladder Meridian runs along the ribs, breasts and the outer side of the lower limbs, which is closely related to liver qi stagnation and qi sinking. (3) Bupleurum can soothe the liver and regulate qi, which can improve breast hyperplasia. Bupleurum can raise yang qi, which can relieve qi sinking in uterine prolapse.

[0009] I. The properties, flavors, meridian tropism, and compatibility of medicinal substances: Green tangerine peel is the principal ingredient, entering the liver, gallbladder, and stomach meridians. It has the effects of soothing the liver and regulating qi, promoting qi circulation and relieving pain, eliminating stagnation and resolving masses, and breaking up qi stagnation and nodules. It directly targets liver qi stagnation in mammary cystic hyperplasia and insufficient middle qi in uterine prolapse. The qi-breaking and nodule-resolving effects of green tangerine peel complement the warming and meridian-unblocking effects of mugwort, forming the unique advantages of external preparations.

[0010] Chuanxiong (Ligusticum striatum) and Chaihu (Bupleurum chinense) are used as assistant herbs. Chuanxiong enters the liver, gallbladder, and pericardium meridians, and has the effects of promoting blood circulation, regulating qi, dispelling wind, and relieving pain. Known as the "qi-regulating herb in the blood," Chuanxiong can promote blood circulation, remove blood stasis, regulate qi, and relieve pain. Together with Qingpi (Citrus reticulata peel), it enhances the effects of soothing the liver, regulating qi, and promoting blood circulation. Chaihu (Bupleurum chinense) enters the liver and gallbladder meridians, and has the effects of soothing the liver, relieving depression, and raising yang. The volatile oil of Chaihu can be absorbed transdermally through the heat of moxibustion. Its liver-soothing and depression-relieving effects can alleviate liver qi stagnation in breast cystic hyperplasia, while its yang-raising and depression-lifting effects can improve qi deficiency in uterine prolapse. Chuanxiong and Chaihu work synergistically to enhance the liver-soothing, blood-activating, and qi-raising effects of the principal herbs.

[0011] Artemisia floss, used as an adjuvant, enters the liver, spleen, and kidney meridians, possessing the effects of warming the meridians and dispelling cold, promoting blood circulation and removing blood stasis, and eliminating dampness and relieving itching. Artemisia floss is warm in nature and has strong penetrating power, allowing the medicine to directly reach the Foot Shaoyang meridian and the uterus, warming and unblocking the meridians, dispelling cold and relieving pain. The combination of the volatile oil and thermal effect of artemisia floss forms a unique external application mechanism, both warming and unblocking the meridians and harmonizing the cold and heat properties of other medicines. Its warm nature can neutralize the slightly cold properties of Citrus reticulata peel and Bupleurum chinense, preventing side effects such as dry mouth and constipation during treatment. The near-infrared rays generated by burning artemisia floss can promote the deep penetration of medicinal components, while its warming and tonifying effect on kidney yang can enhance the kidney qi's ability to consolidate the uterus, further improving the deficiency-cold constitution associated with uterine prolapse.

[0012] The formulation of this invention's mugwort composition forms a balanced system of volatile components with varying degrees of cold and heat: green tangerine peel and chuanxiong rhizome are warm in nature, bupleurum root is slightly cold, and mugwort floss is warm. This balance not only warms and unblocks the meridians, preventing the cold nature of the medicine from damaging yang, but also soothes the liver and relieves stagnation, preventing excessive heat from damaging yin. The slightly cold nature of bupleurum root neutralizes the warming and drying properties of green tangerine peel and mugwort floss, while the warm nature of mugwort floss prevents spleen and stomach discomfort caused by excessive coldness from bupleurum root. This balanced formulation allows the external application of this invention's mugwort composition to exert both a warming and unblocking effect while maintaining the liver-soothing and qi-regulating efficacy, avoiding the side effects that may be caused by a single drug.

[0013] The medicinal moxa composition of this invention uses green tangerine peel to soothe the liver and regulate qi, chuanxiong rhizome to invigorate blood and promote qi circulation, bupleurum root to raise yang qi, and moxa wool to warm the meridians, dispel cold, and invigorate blood and remove blood stasis. The combination of these four herbs conforms to the treatment principle of "soothing the liver and regulating qi, invigorating blood and removing blood stasis, and raising yang qi," simultaneously resolving the pathological contradictions of two diseases. In this medicinal moxa composition, bupleurum root can both soothe the liver and regulate qi to improve breast hyperplasia and raise yang qi to alleviate uterine prolapse; green tangerine peel soothes the liver and improves breast distension and pain, while also regulating pelvic floor muscle function; it avoids the risks of bidirectional hormone regulation and surgical trauma, ensuring high safety; moxibustion warms and unblocks, improving local microcirculation and promoting drug penetration and absorption. This medicinal moxa composition, through the regulation of the Gallbladder Meridian of Foot-Shaoyang, can achieve systemic treatment of two diseases, possessing significant theoretical innovation and clinical application value.

[0014] II. Mechanism of action of topical volatile substances in preventing and treating fibrocystic breast disease Fibrocystic breast disease (known as "breast lumps" in Traditional Chinese Medicine) is mostly caused by liver qi stagnation and phlegm-blood stasis, manifesting as breast swelling and pain, lumps, and symptoms that worsen before menstruation. The medicated composition of this invention prevents and treats this disease through the external application mechanism of the following volatile components: (1) The volatile oils of Citrus reticulata peel and Bupleurum chinense work synergistically to soothe the liver and relieve depression. Limonene (68%) in the volatile oil of Citrus reticulata peel is absorbed transdermally through the heat of moxibustion, directly acting on breast tissue, inhibiting ERα / ERβ activity, and reducing estrogen-dependent hyperplasia of breast cells. Lauraldehyde, anethole, and other components in the volatile oil of Bupleurum chinense are absorbed transdermally through the heat of moxibustion, regulating the HPA axis, reducing estrogen levels in the body, and alleviating inflammatory response and abnormal hyperplasia of breast tissue. In particular, lauraldehyde and other components exert an analgesic effect by inhibiting cyclooxygenase activity and reducing prostaglandin E2 levels. This mechanism synergizes with the anti-inflammatory effect of moxa wool. The synergistic release of the volatile components of the two forms a dual mechanism of action of "soothing the liver and resisting estrogen".

[0015] (2) The volatile oils of Ligusticum chuanxiong and Artemisia argyi work synergistically to promote blood circulation and unblock meridians. The hesperidin and limonene in the volatile oil of Ligusticum chuanxiong work synergistically with the infrared radiation from Artemisia argyi to improve local microcirculation in the breast and promote the excretion of inflammatory factors and toxins. The 1,8-cineole and thujone in the volatile oil of Artemisia argyi have anti-inflammatory and antibacterial effects, which can reduce inflammatory damage to breast tissue. Although ligustrazine is not a volatile component, its anti-fibrotic effect (inhibition of the TGF-β / Smad pathway) can be indirectly achieved through the enhanced local blood supply from moxibustion, promoting tissue repair. This synergistic mechanism of "blood circulation-anti-inflammation" effectively relieves the pain and lump symptoms of cystic hyperplasia of the breast.

[0016] (3) The lauraldehyde and other components in Bupleurum chinense volatile oil inhibit the COX-2 and NF-κB pathways, and together with 1,8-cineole in Artemisia argyi, reduce the levels of IL-6 and TNF-α, forming an "anti-inflammatory network". The synergistic release of the volatile components of the two enhances the therapeutic effect of the medicated Artemisia argyi composition of the present invention.

[0017] (4) The infrared radiation and thermal effect of moxa wool synergistically promote drug penetration. The near-infrared radiation (accounting for 30% of the energy output) generated during moxibustion can penetrate the skin 3-5 cm and reach the breast tissue, promoting the deep penetration of drug components. At the same time, the thermal stimulation of moxibustion can dilate local blood vessels, accelerate blood circulation, and promote the excretion of metabolic waste. This "photothermal synergy" mechanism ensures that the volatile components of the moxa wool composition of the present invention can effectively reach the breast lesion and exert a therapeutic effect.

[0018] (5) The meridian effect of the moxibustion composition of the present invention synergistically regulates the flow of Qi and blood. Moxibustion stimulates acupoints of the Gallbladder Meridian of Foot-Shaoyang (such as Guanyuan and Sanyinjiao), and the therapeutic effect is transmitted to the breast area along the meridian through meridian sensation, regulating the Qi of the liver and gallbladder, and improving emotional fluctuations and endocrine disorders. This "meridian-local" synergistic mechanism regulates the pathogenesis of breast cystic hyperplasia as a whole, achieving the effect of treating both the symptoms and the root cause.

[0019] III. Topical Volatile Mechanisms for Preventing and Treating Uterine Prolapse Uterine prolapse (known as "yin ting" in Traditional Chinese Medicine) is often caused by a deficiency of Qi in the middle Jiao (middle burner) and insufficient kidney Qi. It manifests as the uterus descending from its normal position along the vagina, and in severe cases, protruding outside the vaginal opening. The medicinal composition of this invention prevents and treats this condition through the external application mechanism of the following volatile components: (1) The volatile oils of Bupleurum and Artemisia argyi work synergistically to raise Yang and lift prolapse. Components such as lauraldehyde and anethole in Bupleurum argyi volatile oil are absorbed transdermally through the heat of moxibustion, regulating the HPA axis and stabilizing hormone levels. Components such as 1,8-cineole and thujone in Artemisia argyi volatile oil have a warming and tonifying effect on kidney Yang, enhancing the kidney's ability to consolidate the uterus. The synergistic release of the volatile components of both forms a dual mechanism of "raising Yang and warming the kidney," effectively improving the cold constitution associated with uterine prolapse.

[0020] (2) The volatile oils of Ligusticum chuanxiong and Artemisia argyi synergistically improve pelvic floor blood circulation. The hesperidin and limonene in the volatile oils of Ligusticum chuanxiong synergistically improve pelvic floor microcirculation with the infrared radiation from Artemisia argyi, promoting local blood supply, excretion of inflammatory factors and toxins, and enhancing tissue elasticity. The heat stimulation of moxibustion can activate the transient receptor potential family (TRPV1 channel), increasing blood flow to the uterine ligament area and providing sufficient nutrition for tissue repair. The anti-fibrotic effect of ligustrazine (inhibition of the TGF-β / Smad pathway) can be indirectly achieved through the enhanced local blood supply from moxibustion, promoting pelvic floor tissue repair. This synergistic mechanism of "blood activation and warming" effectively alleviates local blood circulation disorders in uterine prolapse.

[0021] (3) The infrared radiation and thermal effect of moxa wool synergistically promote drug penetration. The near-infrared radiation generated during moxibustion can penetrate the skin 3-5 cm, reaching the pelvic region and promoting the deep penetration of drug components. At the same time, the thermal stimulation of moxibustion can dilate local blood vessels, accelerate blood circulation, and promote the excretion of metabolic waste. This "photothermal synergy" mechanism ensures that the volatile components of the moxa wool composition of this invention can effectively reach the pelvic lesions and exert a therapeutic effect.

[0022] (4) The meridian effect of the moxibustion composition of the present invention synergistically regulates the flow of Qi and blood. Moxibustion stimulates acupoints of the Gallbladder Meridian of Foot-Shaoyang (such as Guanyuan and Sanyinjiao), and transmits the therapeutic effect along the meridian to the uterine area through meridian sensation, regulating the Qi of the liver and gallbladder and improving the sinking of Qi in the middle Jiao. The lifting and tonifying effect of Bupleurum chinense combined with the warming and tonifying effect of moxa wool activates the PI3K / AKT pathway, enhances the contraction function of the pelvic floor smooth muscle, and improves the supporting force of the pelvic floor muscles. This synergistic mechanism of "meridian-whole" regulates the pathogenesis of uterine prolapse as a whole, achieving the effect of treating both the symptoms and the root cause.

[0023] V. Overall Volatile Mechanisms of Synergistic Prevention and Control of Comorbidities Breast cystic hyperplasia and uterine prolapse appear to be two different diseases, but their occurrence and development are intrinsically linked. Traditional Chinese medicine believes that both are related to the imbalance of Qi in the Gallbladder and Liver meridians of the Foot Shaoyang: Liver Qi stagnation leads to breast hyperplasia, while Qi deficiency and sinking lead to uterine prolapse. The medicinal composition of this invention achieves synergistic prevention and treatment of comorbidities through the following external application mechanism of volatile components: (1) The volatile components of the moxibustion composition of this invention form a complex pharmacochemical effect. The limonene in the volatile oil of Citrus reticulata peel, lauraldehyde in the volatile oil of Bupleurum chinense, hesperidin in the volatile oil of Ligusticum chuanxiong, and 1,8-cineole in the volatile oil of Artemisia argyi, etc., are absorbed transdermally through the heat of moxibustion, forming a complex pharmacochemical system. These volatile components, through different pathways of action, synergistically regulate the Qi of the liver and gallbladder, improving emotional fluctuations and endocrine disorders, which are common pathogenesis of both diseases. The liver-soothing and Qi-regulating effects of Citrus reticulata peel and the Yang-raising and prolapse-lifting effects of Bupleurum chinense form a dual effect of "liver-soothing and lifting," which not only improves the Qi stagnation in mammary hyperplasia but also enhances the Qi in uterine prolapse.

[0024] (2) The thermal and photoradiation effects of the moxibustion composition of this invention form a synergistic promoting mechanism. The stable heat of 40-60℃ generated by moxibustion dilates blood vessels, promotes blood circulation, and accelerates the excretion of metabolic waste. At the same time, the near-infrared and far-infrared spectra generated during moxibustion combustion produce a warming effect in deep tissues, promote local blood circulation, and play a role in regulating the immune, endocrine, and nervous systems. This synergistic mechanism of "thermal-photoradiation" ensures that the volatile components of the moxibustion composition can effectively reach the breast and pelvic lesions to exert a therapeutic effect.

[0025] (3) The meridian effect of the medicated moxibustion combination forms a holistic regulatory system. Moxibustion, through the action of acupoints, transmits its therapeutic effects along the meridians to all parts of the body, ultimately playing a role in regulating the yin and yang of the internal organs and tonifying deficiency and purging excess. When acupoints are stimulated by moxibustion, they can release more energy and regulate cell metabolism. The meridian effect of the medicated moxibustion combination guides the medicine directly to the breast and pelvic regions by stimulating acupoints of the Gallbladder Meridian of Foot-Shaoyang, while simultaneously regulating the Qi of the liver and gallbladder, improving emotional fluctuations and endocrine disorders, which are common pathogenesis of the two diseases. This "meridian-local" synergistic mechanism regulates the pathogenesis of the co-disease as a whole, achieving the effect of treating both the symptoms and the root cause.

[0026] (4) The balanced combination of cold and warm properties in the medicated moxa composition forms a safe and effective treatment system. Green tangerine peel and Sichuan lovage rhizome are warm in nature, while Bupleurum root is slightly cold, and moxa wool is warm, forming a balanced combination. This balance can both warm and unblock the meridians, avoiding the cold nature of the medicine from damaging Yang, and soothe the liver and relieve stagnation, preventing the medicine from being too hot and damaging Yin. The slightly cold nature of Bupleurum root can neutralize the warm and drying nature of green tangerine peel and moxa wool, preventing side effects such as dry mouth and constipation during treatment. Green tangerine peel and Bupleurum root work together to relieve liver stagnation, improving the Qi stagnation in breast hyperplasia and the Qi stagnation in uterine prolapse; Sichuan lovage rhizome invigorates blood and unblocks the meridians, improving blood circulation in the breast and pelvic floor tissues, promoting inflammation resolution and tissue repair; Bupleurum root raises the middle Qi, and moxa wool warms and tonifies kidney Yang, enhancing intra-abdominal pressure and uterine support, improving uterine prolapse. This balanced combination ensures the safety and effectiveness of the medicated moxa composition for external use.

[0027] In summary, the medicated mugwort composition achieves synergistic prevention and treatment of breast cystic hyperplasia and uterine prolapse through the synergistic effects of the pharmacochemical, thermal, photoradiation, and meridian effects of its volatile components. The liver-soothing and qi-regulating properties of green tangerine peel, the yang-raising and prolapse-lifting properties of bupleurum, the blood-activating and qi-regulating properties of chuanxiong, and the warming and cold-dispersing properties of mugwort form a complete therapeutic system that can improve local symptoms and regulate the overall qi mechanism, achieving a holistic treatment effect. The unique advantages of this external preparation make it an ideal choice for treating these two diseases. Attached Figure Description

[0028] 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 herb Artemisia argyi in the experimental examples of this invention for the comorbidities of mammary cystic hyperplasia and uterine prolapse. 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 6Sankey 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 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

[0029] The present invention will be further described below with reference to the accompanying drawings and specific embodiments.

[0030] A medicinal moxa composition for preventing and treating comorbid breast cystic hyperplasia and uterine prolapse, 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: 3-13 parts of green tangerine peel, 4-15 parts of Sichuan lovage rhizome and 5-18 parts of bupleurum root, and the weight ratio of the traditional Chinese medicine composition to the moxa wool is 2.5-8:5-15.

[0031] 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: 6 parts of green tangerine peel, 7 parts of Sichuan lovage rhizome and 8 parts of bupleurum root, and the weight ratio of the traditional Chinese medicine composition to mugwort floss is 4.5:8.5.

[0032] Example: Example 1: 90g of green tangerine peel, 120g of Sichuan lovage rhizome, 150g of bupleurum root, and 720g of mugwort floss.

[0033] Example 2: 180g of green tangerine peel, 210g of Sichuan lovage rhizome, 240g of bupleurum root, and 1190g of mugwort floss.

[0034] Example 3: 260g of green tangerine peel, 300g of Sichuan lovage rhizome, 360g of bupleurum root, and 1725g of mugwort floss.

[0035] 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 Citrus reticulata peel, Ligusticum chuanxiong rhizome, and Bupleurum chinense were collected respectively. The active ingredients of the drug-artemisia composition of this invention were further screened using OB≥30% and DL≥0.18 as screening criteria. For the targets obtained from the database, the gene names of the drug targets were standardized using the Uniprot database and duplicates were removed. Finally, the active ingredients and targets of the drug were obtained.

[0036] Targets related to the disease were retrieved from the GeneCards / OpenTargets / CTD / DrugBank databases. Using "Breast fibrocystic" as the keyword, the gene names of the disease-related targets were compiled, standardized, and deduplicated. Similarly, targets related to the disease were retrieved from the GeneCards / OpenTargets database using "Uterine prolapse" as the keyword. The intersection genes of comorbid breast fibrocystic disease and uterine prolapse were used as the final disease genes. Potential targets for comorbid breast fibrocystic disease and uterine prolapse were obtained. A drug-compound-target-disease network diagram was constructed. A PPI network diagram was constructed using the STRING database to screen core targets. The drug composition of this invention and the relevant targets of comorbid breast fibrocystic disease and uterine prolapse were subjected to GO functional enrichment analysis and KEGG pathway enrichment analysis, respectively, using the RclusterProfiler 4.6.2 package. By selecting core TOP pathways and their key targets and active ingredients, a "drug-compound-target-pathway-disease" network was constructed.

[0037] 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.

[0038] 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. Nine active ingredients from Citrus reticulata peel, 13 active ingredients from Ligusticum chuanxiong rhizome, and 24 active ingredients from Bupleurum chinense root were obtained. Duplicate common ingredients were removed, resulting in a total of 41 active ingredients. (See...) Figure 1 Potential drug targets for active pharmaceutical ingredients were identified from a database. After removing duplicate targets, a total of 909 drug targets were obtained. (See attached database.) Figure 2 .

[0039] 2. Collection of relevant target points for comorbid breast cystic hyperplasia and uterine prolapse, and screening of therapeutic target points for the drug composition of the present invention. The search results for "Breast fibrocystic" were filtered according to thresholds using GeneCards Score>=20 / OpenTargets Score>=0.01 / CTD Score>=10 / DrugBank databases. The search results for "Uterine prolapse" were also filtered according to thresholds using GeneCards Score>=10 / OpenTargets Score>=0.01 databases. Gene names of standardized disease targets were summarized, duplicates were removed, and the intersection was taken to obtain 69 disease targets. The intersection of these targets with the active ingredient targets of the medicated composition of this invention was then mapped, identifying 41 common targets. These are considered potential targets for the medicated composition of this invention to act on comorbid breast fibrocystic disease and uterine prolapse. (See...) Figure 3 .

[0040] 3. Construction and analysis of drug-compound-target-disease network See the drug-compound-target-disease network. Figure 4 The network graph has 83 nodes and 280 edges, with edges representing the targeting relationships between compounds and targets. 38 active ingredients act on 41 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, baicalin, nobiletin, kaempferol, delphinidin, Delta-D, and naringenin. 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.

[0041] 4. PPI Network Diagram Analysis Forty-one 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 89 nodes and 1714 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 CTNNB1, AKT1, TP53, TNF, EGF, EGFR, and IL6, which are key targets for the treatment of fibrocystic breast disease complicated with uterine prolapse using the drug composition of this invention. (See below) Figure 9 .

[0042] 5. GO functional enrichment analysis and KEGG pathway analysis Based on R clusterProfiler, GO enrichment analysis was performed on 41 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 Figure 11 shows the KEGG pathway enrichment analysis. The vertical axis represents each GO entry, and the horizontal axis represents the number of targets enriched for that entry. BP mainly involves glandular development regulation, epithelial cell proliferation, smooth muscle cell proliferation, response to radiation, myocyte proliferation, epithelial cell proliferation regulation, positive regulation of smooth muscle, and cellular response to abiotic stimuli. MF mainly includes cytokine receptor binding, cytokine activity, growth factor activity, receptor ligand activity, signal receptor activator activity, protease binding, ubiquitin-protein ligase binding, nitric oxide synthase regulator activity, ubiquitin-like protein ligase binding, and growth factor receptor binding. CC mainly involves platelet α-granules, luminal platelet α-granules, vesicle lumen, organelle outer membrane, heteropolymer SMAD protein complex, outer membrane, raft protein complex, SMAD protein complex, and collagen-containing extracellular matrix. KEGG pathway enrichment analysis was performed on the targets, resulting in 153 signaling pathways. In this study, the top 30 pathways with P < 0.05 were selected for visualization analysis, as shown in the figure. Figure 12As shown in Figure 13, the enrichment results revealed that the main signaling pathways involved included the AGE-RAGE signaling pathway in diabetes, tumor proteoglycans, endocrine resistance, colorectal cancer, breast cancer, prostate cancer, pancreatic cancer, EGFR tyrosine kinase inhibitor resistance, bladder cancer, gastric cancer, melanoma, and glioma. 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, as shown in Figure 13. Figure 14 .

[0043] 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 113 nodes and 635 edges (38 components, 41 targets, and 30 signaling pathways, drugs, and diseases). Different node shapes represent different active ingredients, key targets, and regulatory pathways in the medicated 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 medicated composition of this invention in preventing and treating comorbid breast cystic hyperplasia and uterine prolapse.

[0044] 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, MOL000358, MOL000422, MOL000546, MOL002157, MOL002776, MOL004328, MOL004798, MOL005828, and MOL010861 in the drug-artemisia composition of this invention and the top 10 core targets AKT1, CDH1, EGF, EGFR, ESR2, IL1B, MMP2, SMAD3, TGFB1, and TP53 in the PPI network. The docking results are shown in […]. Figure 16 .

[0045] Clinical trial example: Clinical trial case 1: fibrocystic breast disease Fibrocystic breast disease is a type of breast hyperplasia, a benign condition caused by the combined effects of physiological hyperplasia and disordered healthy breast structure. The main clinical symptoms include lumps, breast pain, and nipple discharge. This condition is most common in middle-aged women, but can also occur in adolescents and postmenopausal women. In Traditional Chinese Medicine, it falls under the category of "breast lumps."

[0046] 1. Materials and Methods 1.1 General Information Fifty patients with cystic breast hyperplasia who visited the outpatient clinics of the Traditional Chinese Medicine Department of Shehong Maternal and Child Health Hospital and Tuwan Community Health Service Center in Shapingba District from August to October 2024 were selected as the study subjects. Their ages ranged from 21 to 61 years, with a mean age of (43.220±9.730) years.

[0047] 1.2 Inclusion and Exclusion Criteria Inclusion criteria: (1) Clinical diagnosis of cystic breast hyperplasia; (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.

[0048] 1.3 Grouping and Treatment Methods Fifty patients with fibrocystic breast disease were randomly divided into a control group (n=25) and an experimental group (n=25). The control group ranged in age from 24 to 61 years, with a mean age of (44.560 ± 9.996) years. The experimental group ranged in age from 21 to 56 years, with a mean age of (41.880 ± 9.466) years. There were no statistically significant differences in patient data between the two groups. P >0.05), which is comparable, see Table 1.

[0049] The control group received oral administration of a modified Guizhi Fuling Wan decoction combined with regular moxibustion. The experimental group received oral administration of a modified Guizhi Fuling Wan decoction combined with moxibustion using the medicated moxa prepared according to the composition in Example 2. Moxibustion was performed 3 times a week for 20 minutes each time, for a total of 4 weeks. Specific acupoints for moxibustion were: Zulinqi and Xiaxi for the first treatment; Zulinqi and Yanggu for the second treatment; and Zulinqi and Yangfu for the third treatment, all bilaterally.

[0050] 1.4 Efficacy Evaluation Criteria Cured: The patient's breast lump disappears and there is no recurrence within 3 months; breast pain disappears, and no further medication is needed. Significantly Effective: After treatment, the patient's symptoms such as breast lump and pain are significantly relieved, but medication is still required. Effective: The patient's breast lump shrinks, and breast pain is relieved; continued medication is necessary. Ineffective: The patient's breast lump does not disappear or improve, breast pain does not improve and may even worsen; medication is ineffective.

[0051] Overall effective rate = (Number of cured cases + Number of cases with significant improvement + Number of cases with improvement) / Total number of cases Overall efficacy rate = (Number of cured cases + Number of cases with significant improvement) / Total number of cases 1.5 Statistical Analysis Data were analyzed using SPSS 27.0 software. Count data were expressed as percentages. test.

[0052] 2 Results After treatment, the total effective rate in the control group was 52%, and the total effective rate in the experimental group was 80%, indicating that the clinical symptoms of cystic breast hyperplasia improved in both groups after treatment, with no significant statistical difference. P =0.072>0.05), but compared with the total effective rate of 24% in the control group, the total effective rate of 56% in the experimental group was significantly higher ( P =0.042<0.05), the results show that the moxibustion prepared with the composition in Example 2 has better therapeutic effect. Table 2.

[0053] Clinical trial case 2: Uterine prolapse Uterine prolapse refers to the descent of the uterus from its normal position along the vagina due to factors such as pelvic floor tissue degeneration or trauma, resulting in weakened pelvic floor support. The uterus may descend below the level of the ischial spines at the external os of the cervix, or even the entire uterus may protrude outside the vaginal opening. Clinical manifestations include lumbosacral pain, a feeling of heaviness or pressure, and the protrusion of a mass from the vulva.

[0054] 1. Materials and Methods 1.1 General Information Twenty-six patients with uterine 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. Their ages ranged from 42 to 82 years, with a mean age of (62.656±9.800) years.

[0055] 1.2 Inclusion and Exclusion Criteria Inclusion criteria: (1) Clinical diagnosis of uterine prolapse; (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.

[0056] 1.3 Grouping and Treatment Methods Twenty-six patients with uterine prolapse were randomly divided into a control group (n=13) and an experimental group (n=13). The control group ranged in age from 42 to 77 years, with a mean age of (61.539 ± 9.413) years. The experimental group ranged in age from 48 to 82 years, with a mean age of (63.231 ± 8.843) years. There was no statistically significant difference in age between the two groups. P (>0.05), indicating comparability. See Table 3.

[0057] Patients in the control group received oral administration of a modified Buzhong Yiqi Decoction combined with regular moxibustion. Patients in the experimental group received oral administration of the modified Buzhong Yiqi Decoction combined with moxibustion using medicated moxa prepared from the composition described in Example 3. Moxibustion was performed three times a week for 20 minutes each time, for a total of six weeks. Specific acupoints for moxibustion were: Zulinqi and Xiaxi for the first treatment; Zulinqi and Yanggu for the second treatment; and Zulinqi and Yangfu for the third treatment, all bilaterally.

[0058] 1.4 Efficacy Evaluation Criteria Cured: Symptoms such as lumbosacral pain and a feeling of heaviness disappear and there is no recurrence within 3 months; no further medication is needed. Significantly Effective: Symptoms such as lumbosacral pain and a feeling of heaviness are significantly improved, but medication is still required. Effective: Symptoms such as lumbosacral pain and a feeling of heaviness have improved to some extent; continued medication is necessary. Ineffective: The above criteria are not met.

[0059] Overall effective rate = (Number of cured cases + Number of cases with significant improvement + Number of cases with improvement) / Total number of cases Overall efficacy rate = (Number of cured cases + Number of cases with significant improvement) / Total number of cases 1.5 Statistical Analysis Data were analyzed using SPSS 27.0 software. Count data were expressed as percentages. test.

[0060] 2 Results Comparison of total effective rates between the two groups: After treatment, the total effective rate in the control group was 46.2%, and the total effective rate in the experimental group was 76.9%, indicating that the clinical symptoms of uterine prolapse improved in both groups after treatment, with no significant statistical difference. P =0.226>0.05), but compared with the total effective rate of 23.1% in the control group, the total effective rate of 69.2% in the experimental group was significantly higher (=0.226>0.05), P =0.047<0.05), the results show that the moxibustion prepared with the composition in Example 3 has better therapeutic effect. See Table 4.

[0061] .

Claims

1. A pharmaceutical composition for preventing and treating co-morbidity of breast cystic hyperplasia and uterine prolapse, characterized in that, The medicine moxa composition comprises a traditional Chinese medicine composition and moxa, the traditional Chinese medicine composition is made of raw materials in the following weight ratio: green skin 3-13 parts, Sichuan lovage 4-15 parts and bupleurum 5-18 parts, and the weight ratio of the traditional Chinese medicine composition and moxa is 2.5-8:5-15.

2. The pharmaceutical composition for preventing and treating co-morbidity of cystic hyperplasia of mammary glands and uterine prolapse according to claim 1, wherein The traditional Chinese medicine composition is made of raw materials in the following weight ratio: green skin 6 parts, Sichuan lovage 7 parts and bupleurum 8 parts, and the weight ratio of the traditional Chinese medicine composition and moxa is 4.5:8.5.

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