Traditional Chinese medicine composition for treating hyperplasia of mammary glands as well as preparation and application of traditional Chinese medicine composition

Abstract

The invention relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition for treating hyperplasia of mammary glands as well as preparation and application thereof. According to the traditional Chinese medicine composition disclosed by the invention, the prescription is formed through repeated knock verification in a clinical application process by adopting various prescriptions and accurate dialectical analysis, and the traditional Chinese medicine composition consists of cowherb seed, semen brassicae, fructus perillae, semen raphani and fructus evodiae. The traditional Chinese medicine composition disclosed by the invention is prepared into an external hot-compress emplastrum, the hyperplasia of mammary glands is treated in a thermal therapy manner when the external hot-compress emplastrum is used, skin pores are expanded under the action of hot compress, various traditional Chinese medicine components are promoted to enter a body and act on diseased regions, and the external hot-compress emplastrum is relatively convenient to use due to an external use manner. The traditional Chinese medicine composition can well relieve breast pain and reduce breast lumps, has a remarkable effect in the aspect of improving breast symptoms, is high in safety and free of obvious adverse effects, and can be widely applied to breast diseases such as hyperplasia of mammary glands and pure breast pain.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a traditional Chinese medicine composition for treating breast hyperplasia and its preparation and application. Background Technology

[0002] Breast hyperplasia is a non-inflammatory, non-neoplastic condition caused by excessive proliferation and incomplete involution of breast tissue before and after the menstrual cycle, leading to structural disorders of the breast. Clinically, it mainly manifests as varying degrees of breast pain, palpable nodules, or diffuse glandular thickening that occurs with the menstrual cycle or emotional changes. Its incidence rate is approximately the highest among breast diseases, reaching 75%, and it shows a slow but increasing trend year by year, affecting younger women. Studies show that about 70% of women have experienced breast pain. Most patients with breast hyperplasia are more prone to irritability, restlessness, chest tightness, insomnia, and sadness due to recurrent pain, which can severely impact their daily work and life. Some even associate breast pain caused by breast hyperplasia with breast cancer, leading to anxiety and depression.

[0003] Currently, Western medicine treatments for breast hyperplasia are relatively limited and generally have limited efficacy. Surgical treatments are highly invasive and have many complications, while other treatments such as ice or heat compresses, wearing sports bras, placebo interventions, and oral medications have drawbacks including long treatment cycles, poor patient compliance, numerous adverse reactions, and low clinical efficacy.

[0004] Traditional Chinese medicine (TCM) has a long history of treating breast hyperplasia with proven clinical efficacy. Treatment is generally divided into internal and external therapies. Internal therapies include oral administration of herbal decoctions and prepared Chinese medicines. These treatments require continuous adherence, and the high cost and potential liver and kidney toxicity with long-term use often prevent patients from persisting. External therapies such as acupuncture, massage, and scraping all require professional medical personnel and are not very convenient. Topical application of Chinese herbal plasters is safer and more convenient than other routes of administration, resulting in higher patient compliance. Summary of the Invention

[0005] The purpose of this invention is to provide a traditional Chinese medicine composition for treating breast hyperplasia, its preparation and application. This traditional Chinese medicine composition for treating breast hyperplasia has a significant effect on improving breast symptoms, and is highly safe with no obvious adverse effects, making it more suitable for market application.

[0006] In a first aspect, the present invention provides a traditional Chinese medicine composition for treating breast hyperplasia, comprising the following raw materials: Vaccaria segetalis, Sinapis alba, Perilla frutescens, Raphanus sativus, and Evodia rutaecarpa, in a weight ratio of 6:6:5:5:2.

[0007] In a second aspect, the present invention provides a traditional Chinese medicine compound preparation with the above-mentioned traditional Chinese medicine composition as the active ingredient, wherein the traditional Chinese medicine compound preparation is an external hot compress plaster (Wuzi Hot Compress Plaster).

[0008] Furthermore, the aforementioned traditional Chinese medicine compound preparation is a water extract obtained by mixing and pulverizing the raw materials according to the formula amount; extracting with water, concentrating and drying; or an alcohol extract obtained by extracting with 30-90% ethanol, concentrating and drying; or a drug component obtained by further purification of the above extracts.

[0009] It is made by mixing with plaster base and then applying a heat pack.

[0010] Furthermore, the traditional Chinese medicine compound preparation comprises: 1-30% (preferably 30%) of traditional Chinese medicine ingredients, 10-70% (preferably 30%) of thermoplastic rubber, 5-30% (preferably 20%) of tackifier, 5-20% (preferably 10%) of softener, 1-15% (preferably 9%) of transdermal penetration enhancer, 0.1-5% (preferably 1%) of heating agent, and a heating pack.

[0011] Furthermore, the medicinal components of the Chinese medicine are obtained by pulverizing the above five Chinese medicines into fine powder; extracting with water, concentrating and drying to obtain an aqueous extract; or extracting with 30-90% ethanol, concentrating and drying to obtain an alcoholic extract; or further purifying the above extracts to obtain medicinal components.

[0012] Furthermore, the water extract is prepared by pulverizing the raw materials in the specified weight proportions into a fine powder; extracting twice with water, the first time with 8 times the amount of water for 1 hour, and the second time with 6 times the amount of water for 0.5 hours, combining the extracts, concentrating to a relative density of 1.20-1.30 (25°C), and drying to obtain the water extract.

[0013] Furthermore, the alcohol extract is prepared by pulverizing the raw materials in the specified weight proportions into a fine powder; extracting twice with 70% ethanol, the first time with 8 times the amount of raw material for 1 hour, and the second time with 6 times the amount of raw material for 0.5 hours; combining the extracts; concentrating to a relative density of 1.20-1.30 (25°C); and drying to obtain the alcohol extract.

[0014] Furthermore, the thermoplastic rubber is selected from styrene-butadiene-styrene block copolymer (SBS) or styrene-isoprene-styrene block copolymer (SIS); preferably styrene-isoprene-styrene block copolymer (SIS).

[0015] The tackifier is selected from rosin, modified rosin, rosin ester, or terpene resin; preferably terpene resin.

[0016] The softener is selected from naphthenic oil, liquid paraffin, phthalate, citrate, castor oil, hydrogenated palm oil, or silicone oil; preferably liquid paraffin.

[0017] The transdermal penetration enhancer is selected from azone, propylene glycol, oleic acid, menthol, borneol, or eucalyptus oil; menthol is preferred.

[0018] The heating agent is selected from chili extract or plant essential oil; chili extract is preferred.

[0019] The heating pack described is a self-heating iron-based oxidation reaction system.

[0020] In a preferred embodiment of the present invention, the traditional Chinese medicine compound preparation comprises: 30% traditional Chinese medicine ingredients, 30% thermoplastic rubber, 20% tackifier, 10% softener, 9% transdermal penetration enhancer, 1% heating agent, and heating pack.

[0021] Furthermore, the preparation method of the traditional Chinese medicine compound preparation includes the following steps: heating 30% of thermoplastic rubber to 80-180℃, and after complete melting, adding 20% ​​tackifier and 10% softener, stirring evenly, then adding 9% transdermal penetration enhancer, 1% exothermic agent, and 30% traditional Chinese medicine ingredients, mixing and stirring evenly, then coating, cutting, and packaging.

[0022] In a third aspect, the present invention provides the use of the traditional Chinese medicine composition as described above in the preparation of a medicament for treating breast hyperplasia.

[0023] In a fourth aspect, the present invention provides the use of the traditional Chinese medicine compound preparation described above in the preparation of a medicament for treating breast hyperplasia.

[0024] Furthermore, the aforementioned breast hyperplasia is a syndrome of breast hyperplasia caused by liver stagnation and phlegm accumulation.

[0025] Furthermore, the treatment of breast hyperplasia is specifically manifested in at least one of the following B1)-B6):

[0026] B1) Relieves breast pain;

[0027] B2) Reduce the hardness of the mass;

[0028] B3) Reduce the size and extent of the lump;

[0029] B4) Improves patients' mood changes such as anxiety and depression;

[0030] B5) Reduce shear wave elastography (SWE) measurements;

[0031] B6) Reduce the level of patients' blood rheological parameters.

[0032] The pharmacological effects of each raw material in the traditional Chinese medicine composition of the present invention are as follows:

[0033] Perilla seed: The dried, ripe fruit of the perilla plant (Perilla frutescens), belonging to the Lamiaceae family. It has the effects of lowering qi and resolving phlegm, relieving asthma, and moistening the intestines. It is mainly used for phlegm accumulation and shortness of breath, cough and asthma, and constipation due to intestinal dryness. Modern pharmacological studies have shown that perilla seed and its active ingredients have lipid-lowering, cough-relieving, asthma-relieving, memory-enhancing, blood sugar-lowering, liver-protecting, antibacterial, anti-allergic, and anti-tumor effects.

[0034] White mustard seed: The seed of the white mustard plant (Sinapis alba), a member of the Brassicaceae family. It has the effects of regulating qi and resolving phlegm, warming the middle jiao and dispelling cold, and unblocking meridians and relieving pain. It is mainly used for cough and asthma due to phlegm retention, chest and rib distension and pain, nausea and vomiting, aphasia due to stroke, numbness and pain in the limbs, beriberi, carbuncles, boils, and traumatic swelling and pain. Modern pharmacological research shows that white mustard seed has antitussive, expectorant, antiasthmatic, anti-inflammatory, analgesic, and antitumor effects.

[0035] Radish seed: The dried, mature seed of the radish plant (Radish), a member of the Brassicaceae family. It has the effects of relieving indigestion and bloating, and resolving phlegm and bloating. It is mainly used for food stagnation, abdominal distension and pain, constipation, diarrhea due to food stagnation, and cough with phlegm. Modern pharmacological research shows that the main components of radish seed have anti-tumor, lipid-lowering and liver-protecting, hypoglycemic, antioxidant, anti-inflammatory, antibacterial, anti-anxiety, cardiovascular protective, and central nervous system protective effects.

[0036] Evodia rutaecarpa: The dried, nearly mature fruit of Evodia rutaecarpa, Evodia rutaecarpa var. sparsely hairy, or Evodia rutaecarpa var. sparsely hairy, belonging to the Rutaceae family. It has the effects of dispelling cold and relieving pain, suppressing nausea and vomiting, and tonifying yang and stopping diarrhea. It is mainly used for Jueyin headache, cold hernia abdominal pain, cold-damp beriberi, menstrual cramps, abdominal distension and pain, vomiting and acid regurgitation, early morning diarrhea, and externally for oral ulcers; hypertension. Modern pharmacological studies have shown that Evodia rutaecarpa and its active ingredients have analgesic, anti-inflammatory, gastrointestinal protective, anti-tumor, central nervous system protective, and glucose and lipid metabolism regulating effects.

[0037] Wang Bu Liu Xing (Semen Vaccariae): The dried, mature seeds of *Vaccaria segetalis*, a plant in the Caryophyllaceae family. It has the effects of promoting blood circulation, regulating menstruation, promoting lactation, and reducing swelling. It is mainly used for insufficient lactation, amenorrhea, dysmenorrhea, and mastitis. Modern pharmacological research shows that the chemical components contained in Wang Bu Liu Xing have anti-tumor, lactation-promoting, antibacterial, anti-inflammatory, antioxidant, and anticoagulant effects.

[0038] The advantages of this invention are:

[0039] 1. The traditional Chinese medicine composition of the present invention was developed by the inventor through extensive research, precise diagnosis, and repeated verification in clinical application. It consists of Wang Bu Liu Xing (Semen Vaccariae), Bai Jie Zi (Semen Sinapis Albae), Zi Su Zi (Semen Perillae), Lai Fu Zi (Semen Radix Radix Radix), and Wu Zhu Yu (Fructus Evodiae). Wang Bu Liu Xing is the principal ingredient, Bai Jie Zi, Zi Su Zi, and Lai Fu Zi are the assistant ingredients, and Wu Zhu Yu is the adjuvant ingredient. The whole formula works together to resolve phlegm and dissipate nodules, promote blood circulation and unblock collaterals, regulate qi and dispel cold.

[0040] 2. This invention relates to a topical thermotherapy patch made from a traditional Chinese medicine composition. It combines traditional acupoint application with modern manufacturing techniques. The formulation uses a novel thermoplastic rubber as the patch's framework material, increasing the drug loading capacity of traditional rubber plasters from below 5% to 30%. This avoids the drawbacks of traditional rubber plasters using hazardous materials like gasoline for solvents, and traditional black plasters using toxic excipients such as red lead (primarily lead tetroxide). This invention uses novel thermoplastic rubber, tackifiers, and softeners as main materials. After melting and dispersing them uniformly at a specific temperature, the drug components are added, increasing the drug loading capacity to 30%. This increased drug loading enhances the therapeutic effect. The formulation also includes a transdermal penetration enhancer to improve the transdermal effect of the drug components. Therefore, the dosage form of this invention is advanced, the process is simple, the production process is environmentally friendly, and the formulation is stable. When used, it treats breast hyperplasia through thermotherapy. Under the effect of heat, skin pores dilate, promoting the entry of the various Chinese medicine components into the body and acting on the lesion site. Furthermore, it is a convenient topical application.

[0041] 3. The herbal composition of this invention can effectively relieve breast pain and shrink breast lumps. It has a significant effect on improving breast symptoms and is highly safe with no obvious adverse effects. It can be widely used for breast diseases such as breast hyperplasia and simple mastalgia. Attached Figure Description

[0042] Figure 1 The outer packaging of the Five-Ingredient Hot Compress Plaster of this invention.

[0043] Figure 2 Example 2: Schematic diagram of the clinical trial research process.

[0044] Figure 3 Comparison of total pain scores among the three groups of patients after treatment; Note: A: Five-Herb Hot Compress Plaster Group, B: Placebo Hot Compress Plaster Group, C: Placebo Plaster Group; Inter-group comparison. This indicates that P < 0.05. This indicates that P < 0.01.

[0045] Figure 4 Comparison of total hyperplasia scores among the three groups of patients after treatment; Note: A: Five-Seed Hot Compress Plaster Group, B: Placebo Hot Compress Plaster Group, C: Placebo Plaster Group; Inter-group comparison. This indicates that P < 0.05. This indicates that P < 0.01.

[0046] Figure 5Comparison of hyperplasia scores among the three groups of patients after treatment: (a) mass extent score, (b) mass hardness score, (c) mass size score; Note: A: Five-Herb Hot Compress Plaster Group, B: Placebo Hot Compress Plaster Group, C: Placebo Plaster Group; Inter-group comparison. This indicates that P < 0.05. This indicates that P < 0.01.

[0047] Figure 6 Comparison of total breast pain and hyperplasia scores among the three groups of patients after treatment; Note: A: Five-Seed Hot Compress Plaster Group, B: Placebo Hot Compress Plaster Group, C: Placebo Plaster Group; Inter-group comparison. This indicates that P < 0.01.

[0048] Figure 7 Comparison of anxiety and depression scores among the three groups of patients after treatment; Note: A: Five-Seed Hot Compress Plaster Group, B: Placebo Hot Compress Plaster Group, C: Placebo Plaster Group; Inter-group comparison. This indicates that P < 0.01.

[0049] Figure 8 Comparison of breast hardness AVE values ​​and regional AVE values ​​among the three groups of patients after treatment: (a) Hardness AVE value, (b) Regional AVE value; A: Five-Herb Hot Compress Plaster Group, B: Placebo Hot Compress Plaster Group, C: Placebo Plaster Group; Inter-group comparison. This indicates that P < 0.05. This indicates that P < 0.01. Detailed Implementation

[0050] The specific implementation methods provided by the present invention will be described in detail below with reference to the embodiments.

[0051] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, performed according to the techniques or conditions described in the literature in this field or according to the product instructions. Unless otherwise specified, the materials and reagents used in the following examples are commercially available.

[0052] Example 1: The traditional Chinese medicine composition of the present invention

[0053] A traditional Chinese medicine composition for treating breast hyperplasia, comprising the following raw materials: Vaccaria segetalis, Sinapis alba, Perilla frutescens, Raphanus sativus, and Evodia rutaecarpa; wherein the Vaccaria segetalis, Sinapis alba, Perilla frutescens, Raphanus sativus, and Evodia rutaecarpa are combined in a weight ratio of 6:6:5:5:2.

[0054] Example 2: The external hot compress plaster of the present invention

[0055] (1) Vaccaria segetalis, Sinapis alba, Perilla frutescens, Raphanus sativus and Evodia rutaecarpa were pulverized into fine powder in a weight ratio of 6:6:5:5:2; water was extracted twice, the first time with 8 times the amount of water for 1 hour, and the second time with 6 times the amount of water for 0.5 hours. The extracts were combined and concentrated to a relative density of 1.20-1.30 (25℃). The water extract was obtained after drying.

[0056] (2) Novel rubber plaster formulation: 30% drug components, 30% thermoplastic rubber, 20% tackifier, 10% softener, 9% transdermal penetration enhancer, 1% heating agent, and heating pack. Excipients: Heating pack (iron-based oxidation reaction system).

[0057] (3) The preparation process of the new rubber plaster is as follows: 30% of thermoplastic rubber (styrene-butadiene-styrene block copolymer SBS) is heated to 80°C and completely melted. Then, 20% of tackifier (rosin) and 10% of softener (naphthenic oil) are added and stirred evenly. Then, 9% of transdermal penetration enhancer (menthol), 1% of exothermic agent (capsicum extract) and 30% of drug components are added. After mixing and stirring evenly, the plaster is applied, cut and packaged.

[0058] The patch consists of a patch and a heating pack, measuring 12×7cm. When using it, the skin-friendly side of the patch is applied directly to the lesion on the breast, and the heating pack is applied to the back of the patch. The application time is approximately 30 minutes.

[0059] Example 3: The external hot compress plaster of the present invention

[0060] (1) Vaccaria segetalis, Sinapis alba, Perilla frutescens, Raphanus sativus and Evodia rutaecarpa were pulverized into fine powder in a weight ratio of 6:6:5:5:2; extracted twice with 70% ethanol, the first time with 8 times the amount of ethanol for 1 hour, and the second time with 6 times the amount of ethanol for 0.5 hours. The extracts were combined and concentrated to a relative density of 1.20-1.30 (25℃). After drying, the ethanol extract was obtained.

[0061] (2) Novel rubber plaster formulation: 30% drug components, 30% thermoplastic rubber, 20% tackifier, 10% softener, 9% transdermal penetration enhancer, 1% heating agent, and heating pack. Excipients: Heating pack (iron-based oxidation reaction system).

[0062] (3) The preparation process of the new rubber plaster is as follows: 30% of thermoplastic rubber (styrene-butadiene-styrene block copolymer SBS) is heated to 180°C and completely melted. Then, 20% of tackifier (rosin) and 10% of softener (naphthenic oil) are added and stirred evenly. Then, 9% of transdermal penetration enhancer (menthol), 1% of exothermic agent (capsicum extract) and 30% of drug components are added and mixed evenly. The mixture is then coated, cut and packaged.

[0063] The patch consists of a patch and a heating pack, measuring 12×7cm. When using it, the skin-friendly side of the patch is applied directly to the lesion on the breast, and the heating pack is applied to the back of the patch. The application time is approximately 30 minutes.

[0064] Example 4: Clinical efficacy study of a traditional Chinese medicine composition for treating mammary hyperplasia

[0065] 1. Materials and Methods

[0066] 1.1 Source of Cases

[0067] Patients who visited the Department of Breast Disease at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, affiliated with Shanghai University of Traditional Chinese Medicine, between June and August 2024 (outpatient / inpatient) were selected.

[0068] 1.2 Diagnostic criteria

[0069] 1.2.1 Western Medicine Diagnostic Criteria

[0070] The Western medicine diagnostic criteria are based on the 2023 standards issued by the Breast Disease Professional Committee of the World Federation of Chinese Medicine Societies.

[0071] The 2018 edition of the "Expert Consensus on the Clinical Diagnosis and Treatment of Breast Hyperplasia with Integrated Traditional Chinese and Western Medicine" states: (1) Clinical manifestations: The breast has varying degrees of swelling, stinging or dull pain, and the pain is related to menstruation and emotional changes; or there is localized non-menstrual cycle pain. (2) Physical examination: Single or several granular nodules, cord-like nodules and localized or diffuse glandular thickening can be felt in one or both breasts. The shapes are different and can increase, decrease or harden or soften with changes in menstrual cycle or emotional changes. Some patients may have nipple discharge or itching. The discharge is usually pale yellow, colorless or milky white serous fluid. Bloody discharge is rare. (3) Auxiliary examination: Breast ultrasound or mammography or breast MRI can diagnose breast hyperplasia. Among them, breast ultrasound is the preferred imaging examination method. (4) Pathological examination: It suggests lobular hyperplasia, fibroadenosis, sclerosing adenosis or cyst, ductal epithelial hyperplasia, blunt ductal adenosis, adenosis with apocrine metaplasia. (5) Exclude other breast lesions such as benign breast tumors, mastitis during or outside of lactation, and malignant breast tumors.

[0072] Diagnostic criteria: Premenopausal women who exhibit at least one of the following clinical manifestations or physical examination findings, along with any one of the auxiliary imaging or pathological examinations, and who have excluded other breast lesions, can be diagnosed with breast hyperplasia.

[0073] 1.2.2 Traditional Chinese Medicine Diagnostic Criteria

[0074] The TCM diagnostic criteria are based on the 2023 edition of the "Expert Consensus on the Clinical Diagnosis and Treatment of Breast Hyperplasia with Integrated Traditional Chinese and Western Medicine" issued by the Breast Disease Professional Committee of the World Federation of Chinese Medicine Societies, and the TCM syndrome differentiation diagnostic criteria for Liver Qi Stagnation and Phlegm Stagnation established in "Traditional Chinese Medicine Surgery": Primary symptom: Breast lump, firm but not firm; distending or stabbing pain, which fluctuates with mood, often worsening before menstruation and relieved after menstruation. Secondary symptoms: With or without chest tightness and hypochondriac distension, prone to depression and irritability, insomnia and dreaminess, irritability and bitter taste in the mouth; irregular menstruation or dysmenorrhea, even with blood clots. Primary tongue: Thin white or yellow coating. Primary pulse: Wiry, thready or slippery pulse. Secondary tongue: Pale red, dark red, or bluish-purple tongue, or ecchymosis on the tongue edges and tip, or thick, swollen, bluish-purple sublingual veins, yellow and greasy coating. Secondary pulse: Choppy pulse.

[0076] Diagnostic criteria: At least one primary symptom plus two secondary symptoms, combined with tongue and pulse examination, can lead to a diagnosis of breast hyperplasia with liver stagnation and phlegm accumulation.

[0077] 1.2.3 Inclusion Criteria

[0078] (1) Premenopausal women aged 20-50;

[0079] (2) Meets the Western medical diagnostic criteria for breast hyperplasia;

[0080] (3) Meets the TCM diagnostic criteria for breast hyperplasia with liver stagnation and phlegm accumulation;

[0081] (4) Those who voluntarily participate in this study, provide informed consent, and sign an informed consent form.

[0082] 1.2.4 Exclusion Criteria

[0083] (1) Patients with concurrent mastitis, malignant breast tumors, or other breast diseases that warrant surgery;

[0084] (2) Having serious primary diseases of the cardiovascular, cerebrovascular, liver, kidney and hematopoietic systems;

[0085] (3) Those who have undergone relevant treatments for breast hyperplasia within 3 months prior to this treatment (including oral and topical medications, acupuncture, etc.), or those who have used hormone preparations, oral contraceptives, or hormone replacement therapy drugs within the past 6 months;

[0086] (4) Individuals with skin trauma, ulcers, skin infections, or keloid scarring at the application site, or those allergic to the patch;

[0087] (5) Patients who have had part or total oophorectomy or uterine removal;

[0088] (6) Those with cognitive impairment who have difficulty understanding the content of the scale and completing the self-assessment of the scale;

[0089] (7) Pregnant or breastfeeding women or those who plan to become pregnant within the next three months;

[0090] (8) Participants in other clinical trials concurrently.

[0091] 1.2.5 Rejection and shedding criteria

[0092] (1) Those who do not meet the inclusion criteria and were mistakenly included;

[0093] (2) Patients who, after signing the informed consent form, were unable to receive the plaster treatment for other reasons;

[0094] (3) Those who use drugs that may affect the experimental results during the experiment (painkillers, hormone drugs, etc.);

[0095] (4) Patients who choose to withdraw from the clinical trial for their own reasons

[0096] (5) If a serious adverse event occurs, the intervention will be stopped and the patient will be withdrawn from the trial after evaluation by the researchers.

[0097] Patients already enrolled but meeting any of the above criteria should be excluded; the reasons for exclusion of all excluded patients should be accurately recorded. For dropout cases, the reasons for dropout should be recorded in detail, and their case reports should be retained for future reference.

[0098] 1.2.6 Ethical Requirements

[0099] This invention strictly adheres to the Declaration of Helsinki and relevant regulations for clinical research. Each participant must carefully read and sign the informed consent form. Our hospital's ethics review committee approval number is 2024-150; registered with the Chinese Clinical Trial Center, registration number: ChiCTR2400086580.

[0100] 2. Test Plan

[0101] 2.1 Grouping Method

[0102] According to the research protocol, the 139 selected research subjects were numbered, and 139 random numbers were generated using a random number table method. The random numbers were then sorted according to their size, and designated personnel used SPSS 22.0 to randomly divide the 139 research subjects into the Wuzi Hot Compress Plaster Group, the Placebo Hot Compress Plaster Group, and the Placebo Plaster Group.

[0103] 2.2 Treatment methods

[0104] Five-Seed Hot Compress Patch Set: This external hot compress patch, prepared using the method described in Example 2, is made from a mixture of five herbs: Vaccaria segetalis, Sinapis alba, Perilla frutescens, Raphanus sativus, and Evodia rutaecarpa, extracted in a specific ratio. Patients are instructed to begin use 7 days before menstruation, applying 1-2 patches 1-2 times daily for 20-40 minutes each time, discontinuing use at the onset of menstruation, for a total of 3 menstrual cycles.

[0105] Placebo hot compress patch group: Patients were given a topical hot compress patch prepared using the method described in Example 2, derived from the herbal composition of Example 1. This patch was made by mixing and extracting five herbs—Vaccaria segetalis, Sinapis alba, Perilla frutescens, Raphanus sativus, and Evodia rutaecarpa—in a specific ratio, representing 5% of the original herbal content of the Five-Seed Hot Compress Patch. Patients were instructed to begin use 7 days before menstruation, applying 1-2 patches 1-2 times daily for 20-40 minutes each time, discontinuing use at the onset of menstruation, for a total of 3 menstrual cycles.

[0106] Placebo patch group: Patients were given a topical patch prepared using the method described in Example 2, which consisted of five herbs: Vaccaria segetalis, Sinapis alba, Perilla frutescens, Raphanus sativus, and Evodia rutaecarpa, extracted in a specific ratio. The patch contained 5% of the original herbal ingredients in the Five-Seed Hot Compress Patch. Patients were instructed to begin use 7 days before menstruation, applying 1-2 patches 1-2 times daily for 20-40 minutes each time, and discontinuing use at the onset of menstruation. This treatment was continued for 3 menstrual cycles.

[0107] 3. Observation Indicators

[0108] 3.1 Breast pain score

[0109] Before and after treatment, patients self-evaluate their breast pain using the Principal Indication (PRI), Visual Acuity Scale (VAS), and Producer Pain Scale (PPI), assigning scores to each. The total score is then calculated as the final pain score.

[0110] 3.2 Breast hyperplasia score

[0111] Before and after treatment, two senior physicians specializing in breast diseases scored breast hyperplasia according to the "Evaluation Standards for the Efficacy of Traditional Chinese Medicine Diagnosis and Treatment of 104 Diseases in 24 Specialties" issued by the State Administration of Traditional Chinese Medicine in 2002. The average score was then calculated. The scoring criteria are as follows:

[0112] (1) Grading and scoring of mass texture

[0113] Grade 0: No mass - 0 points

[0114] Grade 1: Soft texture like normal glandular tissue — 3 points

[0115] Level 2: Texture as firm as the tip of a nose - 6 points

[0116] Level 3: Texture as hard as the forehead - 9 points

[0117] (2) Grading and scoring of the distribution range of the mass

[0118] Grade 0: No mass - 0 points

[0119] Grade 1: The lump is localized to one breast quadrant — 3 points

[0120] Grade 2: Lumps are located in two breast quadrants – 6 points

[0121] Grade 3: Lumps are located in all three breast quadrants – 9 points

[0122] Grade 4: Lumps are located in four breast quadrants – 12 points

[0123] (3) Mass size grading and scoring (based on the largest mass diameter)

[0124] Grade 0: No mass - 0 points

[0125] Grade 1: Mass with a maximum diameter ≤ 2cm – 3 points

[0126] Grade 2: Mass with a maximum diameter of 2.1cm-5cm—6 points

[0127] Grade 3: Maximum diameter of the mass > 5cm - 9 points

[0128] 3.3 Anxiety and Depression Score

[0129] Before and after treatment, patients self-evaluated their anxiety and depression levels and assigned scores, as detailed in Table 1 below:

[0130] Table 1 Hospital Anxiety and Depression Scale

[0131]

[0132] 3.4 Shear Wave Elastic Imaging Indicators

[0133] Before and after treatment, the same ultrasound physician with more than 5 years of ultrasound examination experience used shear wave elastography to explore the breast hyperplasia area and hardness of both breasts of the patient and took the breast with the higher Young's modulus (AVE) value for recording and calculation.

[0134] 3.5 Blood rheological parameters

[0135] Changes in blood rheological parameters, including whole blood viscosity, plasma viscosity, whole blood low-shear reduced viscosity, and whole blood high-shear reduced viscosity, were observed before and after treatment. All parameters were measured by the Department of Laboratory Medicine at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, affiliated with Shanghai University of Traditional Chinese Medicine.

[0136] 3.6 Overall Effectiveness Criteria

[0137] The main efficacy indicators of this invention refer to the "Expert Consensus on the Clinical Diagnosis and Treatment of Breast Hyperplasia with Integrated Traditional Chinese and Western Medicine" formulated by the Breast Disease Professional Committee of the World Federation of Chinese Medicine Societies in 2023. The total effective rate at the end of the treatment period = (Number of patients with effective treatment / Total number of patients) × 100%, where the number of patients with effective treatment includes the number of cured patients, the number of patients with significant improvement, and the number of patients with effective treatment. The specific efficacy index is calculated as follows: Efficacy Index = (Pre-treatment score - Post-treatment score) / Pre-treatment score × 100%. Note: The pre-treatment and post-treatment scores = pain score + hyperplasia score.

[0138] (1) Cured: Breast pain is significantly relieved and breast signs are significantly improved, with an efficacy index ≥90%;

[0139] (2) Significant effect: breast pain is relieved, breast signs improve, and the efficacy index is 60%-89%;

[0140] (3) Effective: Mild relief of breast pain, mild improvement of breast signs, efficacy index of 31%-59%;

[0141] (4) Ineffective: There is no change in breast pain, no change in breast signs, or imaging suggests a change in the nature of the mass, and the efficacy index is ≤30%.

[0142] 3.7 Safety Indicators

[0143] Blood routine tests and liver and kidney function tests were performed on all subjects before and after the trial (measured by the Department of Laboratory Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, affiliated to Shanghai University of Traditional Chinese Medicine). Adverse reactions (local skin itching, pain, redness and swelling, rash, blisters, local skin damage, burns, gastrointestinal reactions, etc.) that occurred during the two groups of medication were observed and recorded.

[0144] 4. Statistical methods

[0145] All data were analyzed using SPSS 22.0 software. Quantitative data are expressed as mean ± standard deviation. Data conforming to a normal distribution were analyzed using ANOVA; those not conforming to a normal distribution were analyzed using nonparametric tests. Two-way ANOVA was used to determine statistical significance, with P < 0.05 considered statistically significant.

[0146] 5. Results

[0147] 5.1 General Information

[0148] 5.1.1 One-way ANOVA showed no statistically significant difference in age among the patients (P>0.05), indicating comparability. Table 2 shows a comparison of the ages of the three groups of patients.

[0149] Table 2 Comparison of age among the three groups of patients ( ±S)

[0150]

[0151] 5.1.2 According to the Kruskal-Wallis H test in Nonparametric Tests, there were no statistically significant differences in height, weight, and BMI among the patients (P>0.05), indicating comparability. Table 3 shows a comparison of height, weight, and BMI among the three groups of patients.

[0152] Table 3 Comparison of height, weight and BMI among the three groups of patients ( ±S)

[0153]

[0154] 5.1.3 According to the Kruskal-Wallis H test in Nonparametric Tests, there were no statistically significant differences among the patients in terms of menarche, menstrual period, and menstrual cycle (P>0.05), indicating comparability. Table 4 shows a comparison of menarche, menstrual period, and menstrual cycle among the three groups of patients.

[0155] Table 4 Comparison of menarche, menstrual period and menstrual cycle among the three groups of patients ( ±S)

[0156]

[0157] 5.1.4 According to the Kruskal-Wallis H test in Nonparametric Tests, there was no statistically significant difference in the total score (pain score + hyperplasia score) among the three groups of patients before treatment (P>0.05), indicating comparability. The comparison of the total score (pain score + hyperplasia score) of the three groups of patients before treatment is shown in Table 5.

[0158] Table 5. Comparison of total pain hyperplasia scores among the three groups of patients before treatment [M (P25, P75)]

[0159]

[0160] 5.1.5 According to the Kruskal-Wallis H test in Nonparametric Tests, there was no statistically significant difference in pain scores among the three groups before treatment (P>0.05), indicating they were comparable. The comparison of pain scores among the three groups before treatment is shown in Table 6.

[0161] Table 6 Comparison of pain scores before treatment among the three groups of patients [M (P25, P75)]

[0162]

[0163] 5.1.6 According to the Kruskal-Wallis H test in Nonparametric Tests, there was no statistically significant difference in hyperplasia scores among the three groups before treatment (P>0.05), indicating they were comparable. The comparison of hyperplasia scores among the three groups before treatment is shown in Table 7.

[0164] Table 7 Comparison of pre-treatment hyperplasia scores among the three groups of patients [M (P25, P75)]

[0165]

[0166] 5.1.7 According to the Kruskal-Wallis H test in Nonparametric Tests, there was no statistically significant difference in anxiety and depression scores among the three groups before treatment (P>0.05), indicating they were comparable. Table 8 shows the comparison of anxiety and depression scores among the three groups before treatment.

[0167] Table 8 Comparison of anxiety and depression scores among the three groups of patients before treatment [M (P25, P75)]

[0168]

[0169] 5.1.8 One-way ANOVA showed no statistically significant difference in rigidity AVE values ​​and regional AVE values ​​among the three groups before treatment (P>0.05), indicating comparability. Table 9 shows the comparison of rigidity AVE values ​​and regional AVE values ​​among the three groups before treatment.

[0170] Table 9 Comparison of pre-treatment rigidity AVE values ​​and regional AVE values ​​among the three groups of patients ( ±S)

[0171]

[0172] 5.2 Clinical efficacy

[0173] 5.2.1 Comparison of total pain scores (see Table 10) Figure 3 )

[0174] Nonparametric tests showed that within-group comparisons before and after treatment were statistically significant (P < 0.001, see Table 10); between-group comparisons after treatment were statistically significant (P < 0.05 or P < 0.01). In terms of efficacy, the Five-Seed Hot Compress Plaster Group > Placebo Hot Compress Plaster Group > Placebo Plaster Group (see Table 10). Figure 3 .

[0175] Table 10 Comparison of total pain scores before and after treatment in the three groups of patients [M (P25, P75)]

[0176]

[0177] 5.2.2 Comparison of total hyperplasia scores (see Table 11) Figure 4 )

[0178] Nonparametric tests showed that within-group comparisons before and after treatment were statistically significant (P < 0.001, see Table 11); between-group comparisons after treatment were statistically significant (P < 0.05 or P < 0.01). In terms of efficacy, the Five-Seed Hot Compress Plaster Group > Placebo Hot Compress Plaster Group > Placebo Plaster Group (see Table 11). Figure 4 .

[0179] Table 11 Comparison of total hyperplasia scores before and after treatment in the three groups of patients [M (P25, P75)]

[0180]

[0181] 5.3.3 Comparison of various scores for hyperplasia (see Table 4) Figure 5 )

[0182] According to nonparametric tests, the scores for breast hardness, size, and extent of lumps in the Wuzi Hot Compress Patch group were significantly lower after treatment than before treatment (P < 0.001), indicating statistical significance (see Table 12). Intergroup comparisons after treatment were also statistically significant (P < 0.05 or P < 0.01). In terms of efficacy, the Wuzi Hot Compress Patch group > the placebo hot compress patch group > the placebo patch group, with the Wuzi Hot Compress Patch showing a more significant effect in improving breast hardness and lump extent (see Table 12). Figure 5 .

[0183] Table 12 Comparison of hyperplasia scores before and after treatment in the three groups of patients [M (P25, P75)]

[0184]

[0185] 5.3.4 Comparison of total pain hyperplasia scores (Table 13) Figure 6 )

[0186] Nonparametric tests showed that within-group comparisons before and after treatment were statistically significant (P < 0.001, see Table 13); between-group comparisons after treatment were also statistically significant (P < 0.001). In terms of efficacy, the Five-Seed Hot Compress Plaster Group > Placebo Hot Compress Plaster Group > Placebo Plaster Group (see Table 13). Figure 6 .

[0187] Table 13 Comparison of total pain hyperplasia scores before and after treatment in the three groups of patients [M (P25, P75)]

[0188]

[0189] 5.3.5 Comparison of overall treatment effectiveness (see Table 14)

[0190] The overall efficacy scores after treatment in the three groups of patients showed the following results: In the Wuzi Hot Compress Plaster group (44 patients), 1 patient showed significant improvement, 40 patients showed improvement, and 3 patients showed no improvement, with a total effective rate of 93.18%; in the placebo hot compress plaster group (42 patients), 18 patients showed improvement, and 24 patients showed no improvement, with a total effective rate of 42.86%; and in the placebo plaster group (43 patients), 1 patient showed improvement, and 42 patients showed no improvement, with a total effective rate of 2.38%. The comparison of the total effective rates among the three groups showed a statistically significant difference (P < 0.001). The efficacy comparison was as follows: Five-Herb Hot Compress Plaster Group > Placebo Hot Compress Plaster Group > Placebo Plaster Group.

[0191] Table 14 Comparison of total effective rates among the three groups after treatment

[0192]

[0193] 5.3.6 Comparison of Anxiety and Depression Scores (see Table 15) Figure 7 )

[0194] Nonparametric tests showed that within-group comparisons before and after treatment were statistically significant (P < 0.001). Anxiety and depression improved in all three groups compared to before treatment (Table 15). Between-group comparisons after treatment were statistically significant (P = 0.025 < 0.05). The Wuzi Hot Compress Plaster group showed better improvement in anxiety and depression than the placebo hot compress plaster group (see Table 15). Figure 7 .

[0195] Table 15 Comparison of anxiety depression scores before and after treatment in the three groups of patients [M (P25, P75)]

[0196]

[0197] 5.3.7 Comparison of AVE values ​​for hypertrophic hardness and regional AVE values ​​(see Table 16) Figure 8 )

[0198] Paired-samples t-test showed that after treatment, the breast hyperplasia hardness AVE values ​​and regional AVE values ​​measured by SWE in all three groups decreased compared with before treatment (P < 0.001), indicating statistical significance. One-way ANOVA showed that the differences between groups after treatment were statistically significant (P < 0.01). In terms of improving breast hyperplasia hardness AVE values ​​and regional AVE values, the Wuzi hot compress plaster group was superior to the placebo plaster group, and the placebo hot compress plaster group was superior to the placebo plaster group (see [reference needed]). Figure 8 .

[0199] Table 16 Comparison of breast hyperplasia hardness AVE value and regional AVE value before and after treatment in three groups of patients ( ±S)

[0200]

[0201] 5.3.8 Changes in blood rheology (see Table 17)

[0202] According to the Wilcoxon test in Nonparametric Tests, the whole blood viscosity and plasma viscosity of patients in the Wuzi Hot Compress Plaster group were lower after treatment than before treatment, and the difference was statistically significant (P<0.05), as shown in Table 17.

[0203] Table 17 Changes in hemorheological parameters before and after treatment in the three groups of patients [M (P25, P75)]

[0204]

[0205] 6. Conclusion

[0206] Clinical research results indicate that the Five-Seed Hot Compress Plaster of this invention has a positive therapeutic effect on breast hyperplasia. It can effectively relieve breast pain in patients with breast hyperplasia, reduce the size, extent, and hardness of lumps, improve anxiety and depression, and enhance patients' quality of life. During treatment, no significant abnormalities were observed in the blood routine tests and liver and kidney functions of any patient. No adverse events such as local skin itching, pain, redness, swelling, rash, blisters, local skin damage, burns, or gastrointestinal reactions occurred in any patient. This demonstrates that the herbal composition of this invention has high safety and no significant adverse effects.

[0207] The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the embodiments described. Those skilled in the art can make various equivalent modifications or substitutions without departing from the spirit of the present invention, and these equivalent modifications or substitutions are all included within the scope defined by the claims of this application.

Claims

1. A traditional Chinese medicine composition for treating breast hyperplasia, characterized in that, It is composed of the following raw materials: Vaccaria segetalis, Sinapis alba, Perilla frutescens, Raphanus sativus, and Evodia rutaecarpa, in a weight ratio of 6:6:5:5:

2.

2. A traditional Chinese medicine compound preparation with the traditional Chinese medicine composition as described in claim 1 as the active ingredient, characterized in that, The aforementioned traditional Chinese medicine compound preparation is a topical hot compress plaster.

3. The traditional Chinese medicine compound preparation according to claim 2, characterized in that, The aforementioned traditional Chinese medicine compound preparation is made by mixing and pulverizing the raw materials according to the formula; extracting with water, concentrating and drying to obtain an aqueous extract; or extracting with 30-90% ethanol, concentrating and drying to obtain an alcoholic extract; or further purifying the above extracts to obtain the drug components, mixing them with the plaster matrix, and then applying a heat pack.

4. The traditional Chinese medicine compound preparation according to claim 2, characterized in that, The traditional Chinese medicine compound preparation includes: 1-30% traditional Chinese medicine ingredients, 10-70% thermoplastic rubber, 5-30% tackifier, 5-20% softener, 1-15% transdermal penetration enhancer, 0.1-5% heating agent, and heating pack.

5. The traditional Chinese medicine compound preparation according to claim 4, characterized in that, The medicinal components mentioned are obtained by pulverizing five Chinese herbs—Vaccaria segetalis, Sinapis alba, Perilla frutescens, Raphanus sativus, and Evodia rutaecarpa—into fine powder; extracting with water, concentrating, and drying to obtain an aqueous extract; or extracting with 30-90% ethanol, concentrating, and drying to obtain an alcoholic extract; or further purifying the above extracts to obtain the medicinal components. The thermoplastic rubber is selected from styrene-butadiene-styrene block copolymer (SBS) or styrene-isoprene-styrene block copolymer (SIS). The tackifier is selected from rosin, modified rosin, rosin ester, or terpene resin; The softener is selected from naphthenic oil, liquid paraffin, phthalate, citrate, castor oil, hydrogenated palm oil, or silicone oil; The transdermal penetration enhancer is selected from azone, propylene glycol, oleic acid, menthol, borneol, or eucalyptus oil; The heating agent is selected from chili extract or plant essential oil; The heating pack described is a self-heating iron-based oxidation reaction system.

6. The traditional Chinese medicine compound preparation according to claim 5, characterized in that, The preparation method of the traditional Chinese medicine compound preparation includes the following steps: heating 30% of thermoplastic rubber to 80-180℃, and after it is completely melted, adding 20% ​​tackifier and 10% softener, stirring evenly, then adding 9% transdermal penetration enhancer, 1% exothermic agent and 30% drug components, mixing and stirring evenly, then coating, cutting and packaging.

7. The use of the traditional Chinese medicine composition as described in claim 1 in the preparation of a medicament for treating breast hyperplasia.

8. The use of a traditional Chinese medicine compound preparation as described in claim 2 in the preparation of a medicament for treating breast hyperplasia.

9. The application according to claim 7 or 8, characterized in that, The breast hyperplasia described is a syndrome of liver stagnation and phlegm accumulation.

Images