Traditional Chinese medicine composition for treating ulcerated wounds of granulomatous lobular mastitis as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention relates to a traditional Chinese medicine composition for treating ulcerative wounds of granulometric lobular mastitis. The traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 5-15 parts of Chinese yam, 5-15 parts of raw sanguisorba officinalis, 5-15 parts of dandelion, 3-10 parts of salvia miltiorrhiza and 3-6 parts of gallnut. In addition, the invention further discloses a preparation method and application of the traditional Chinese medicine composition. Clinical verifications prove that the traditional Chinese medicine composition has the effects of astringing wounds, relieving pain, promoting tissue regeneration and closing up, can remarkably promote healing of wound surfaces after ulceration of granulomatous lobular mastitis and reduce the area of the wound surfaces, is safe and effective, has no obvious adverse reaction, and is suitable for clinical popularization and application.

Description

Technical Field

[0001] This invention relates to a traditional Chinese medicine composition for treating ulcerated wounds of granulomatous lobular mastitis. Furthermore, this invention relates to the preparation method and uses of the traditional Chinese medicine composition. Background Technology

[0002] Granulomatous lobular mastitis (GLM) is a chronic inflammatory disease of the breast, characterized by a sudden appearance of a breast lump, redness, swelling, and pain, which may suppurate and rupture, forming wounds and sinus tracts. Its course generally ranges from 6 months to 2 years, and it is prone to recurrence, significantly impacting patients' quality of life and mental and physical health. Currently, there is no unified treatment plan. Western medicine typically uses hormones, antibiotics, or anti-tuberculosis drugs for conservative treatment, while Traditional Chinese Medicine (TCM) uses oral herbal medicine combined with topical ointments. Patients with local suppuration require incision and drainage, and surgical removal of the lesion may be performed at an appropriate time. GLM currently presents with clinical problems such as long treatment time, numerous adverse reactions, breast disfigurement, painful wound dressing changes, and a high recurrence rate. Among these, the formation and difficulty in healing of wounds caused by suppuration and rupture are the main reasons for prolonged course, painful treatment, and disfigurement. Currently, the main topical medications used in clinical practice to assist in the treatment of GLM ulceration are compound berberine liquid ointment and Kangfuxin liquid, but their efficacy needs improvement. Compound Phellodendron bark liquid ointment is usually used for post-ulceration wounds and wound infections, especially for those with Yang syndrome, such as diabetic foot ulcers and herpes zoster. Kangfuxin liquid is mostly used for digestive system ulcers, oral ulcers, and skin ulcers. There is currently no Chinese medicine composition specifically for post-ulceration wounds of GLM that has been formulated to benefit patients. Summary of the Invention

[0003] In view of the above-mentioned shortcomings of the prior art, according to the embodiments of the present invention, it is desirable to provide a traditional Chinese medicine composition for treating post-ulceration wounds of GLM, and to propose its preparation method and uses.

[0004] In a first aspect, the present invention provides a traditional Chinese medicine composition for treating post-ulceration wounds of GLM, which is made from the following raw materials in parts by weight: 5-15 parts of Dioscorea opposita, 5-15 parts of Sanguisorba officinalis, 5-15 parts of Taraxacum mongolicum, 3-10 parts of Salvia miltiorrhiza, and 3-6 parts of Galla chinensis.

[0005] Preferably, the traditional Chinese medicine composition for treating post-ulceration wounds of GLM is made from the following raw materials in parts by weight: 10 parts of yam, 10 parts of raw Sanguisorba officinalis, 10 parts of dandelion, 10 parts of Salvia miltiorrhiza, and 5 parts of Galla chinensis.

[0006] The pharmacological analysis of the aforementioned traditional Chinese medicine composition for treating post-ulceration lesions of GLM is as follows:

[0007] Yam is the rhizome of the Dioscorea opposita plant, belonging to the Dioscoreaceae family. It is neutral in nature, sweet in taste, and enters the spleen, lung, and kidney meridians. It has the effects of invigorating qi and nourishing yin, tonifying the spleen, lung, and kidneys, and strengthening essence and stopping leukorrhea. Modern pharmacology shows that allantoin, one of the important active ingredients in yam, has anti-irritant, analgesic, anesthetic, and tissue-regenerating effects, promoting the repair of epithelial tissues, healing skin ulcers, and wounds. Furthermore, yam polysaccharides possess significant antioxidant activity, effectively scavenging reactive oxygen free radicals, reducing oxidative damage, and prolonging cell lifespan.

[0008] Sanguisorba officinalis root, the root of the plant Sanguisorba officinalis (family Rosaceae), is slightly cold in nature and has a bitter, sour, and astringent taste. It enters the liver and large intestine meridians and has the effects of cooling the blood, stopping bleeding, detoxifying, and astringing wounds. It is rich in vitamin A-like active substances, which can accelerate the proliferation and migration of epithelial cells, achieving wound re-epithelialization. Modern research shows that Sanguisorba officinalis promotes granulation tissue formation by upregulating EGF; Sanguisorba officinalis root saponin I has a dual effect of scavenging free radicals and inhibiting elastase and MMP-1 activity, significantly increasing type I collagen synthesis in fibroblasts and preventing collagen degradation; in addition, the active ingredient 3,3′-dimethoxy-r-gallic acid-4-xyloside (DEAX) promotes the proliferation, migration, and collagen secretion of NIH3T3 fibroblasts by upregulating TGF-β1, thereby accelerating wound remodeling.

[0009] Dandelion is the whole herb, including the roots, of the dandelion plant (Taraxacum officinale), belonging to the Asteraceae family. It is cold in nature, bitter and sweet in taste, and enters the liver and stomach meridians. It has the effects of clearing heat and detoxifying, reducing swelling and dissipating nodules, and promoting diuresis. Dandelion can exert antibacterial, bacteriostatic, heat-clearing, swelling-reducing, and analgesic effects. Modern research has shown that dandelion polyphenols have antibacterial effects against six pathogenic bacteria, including Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa. Dandelion sterols can dose-dependently reduce the histopathological damage of breast inflammation, inhibit myeloperoxidase (MPO) activity, downregulate pro-inflammatory factors such as TNF-α and IL-1β, and exert anti-inflammatory effects by blocking the TLR4 / NF-κB signaling axis.

[0010] Salvia miltiorrhiza is the dried root and rhizome of the plant Salvia miltiorrhiza in the Lamiaceae family. It is slightly cold in nature and bitter in taste, and enters the heart, pericardium, and liver meridians. It has the effects of promoting blood circulation and regulating menstruation, removing blood stasis and relieving pain, cooling blood and reducing swelling, and relieving irritability and calming the mind. It can take into account both "removing blood stasis" and "regenerating new tissue". Pharmacological studies have confirmed that it increases blood flow and oxygen supply to the wound, accelerates the removal of metabolic waste, stabilizes cell membranes and improves microcirculation; reduces capillary permeability, reduces exudation and edema; inhibits common wound pathogens and reduces the risk of infection; and can also stimulate the proliferation and migration of new capillaries, fibroblasts and epithelial cells by upregulating the expression of growth factors such as VEGF and FGF, thus shortening the healing time.

[0011] Gallnut is the gall on the leaves of the sumac plant (Rhus chinensis), which is parasitized by gall aphids. It is cold in nature, sour and astringent in taste, and enters the lung, kidney and large intestine meridians. It has the effects of astringing the lungs and reducing fire, stopping cough and sweating, astringing the intestines and stopping diarrhea, astringing and stopping bleeding, and astringing and healing wounds. Modern research has confirmed that the active core of gallnut, tannin, plays multiple roles in hemostasis, anti-inflammation, and wound repair: Tannin rapidly forms insoluble complexes to achieve hemostasis by non-specifically precipitating plasma proteins, heavy metal ions, and alkaloids; tannin can downregulate serum and wound IL-1 and IL-6 levels while upregulating basic fibroblast growth factor (bFGF) and ERK1 / 2 phosphorylation levels, inhibiting inflammation and accelerating embryonic fibroblast proliferation through the ERK1 / 2 pathway; furthermore, tannin enhances re-epithelialization and hair follicle regeneration via the ERK1 / 2 signaling axis, improves fibroblast vitality and migration, inhibits lactate dehydrogenase release, and upregulates type I and type III collagen mRNA expression, increasing total collagen soluble content. Simultaneously, it activates the endogenous antioxidant system, synergistically accelerating wound healing and reducing scar formation. Gallnut contains abundant gallic acid, which, upon contact with skin and mucous membrane wounds, immediately coagulates and precipitates proteins secreted by the wound, forming a protective film. The inhibition of secretion caused by coagulated proteins leads to dry mucous membranes; the deposition of proteins in the nerve endings of the skin and mucous membranes can present a mild local anesthetic and analgesic effect.

[0012] Secondly, the present invention provides a method for preparing a traditional Chinese medicine composition for treating post-ulceration wounds of GLM, comprising the following steps: weighing the raw materials by weight: yam, sanguisorba officinalis, dandelion, salvia miltiorrhiza and gallnut, adding 10 times the amount of water and decocting twice, the first time for 60 minutes and the second time for 40 minutes, filtering the decoction, combining the filtrates, letting stand for no less than 12 hours, and taking the supernatant and concentrating it to a relative density of 1.02-1.06 (60℃).

[0013] Preferably, after the concentration and extraction step of the traditional Chinese medicine composition, the method further includes adding an appropriate amount of pharmaceutically acceptable excipients.

[0014] Thirdly, the present invention provides the application of the aforementioned traditional Chinese medicine composition in the preparation of wounds for treating GLM ulceration.

[0015] When using, take 50ml of the medication, soak a sterile gauze pad, wring it out until it is no longer dripping wet, apply it to the ulcerated area after GLM treatment, and cover it with a medical waterproof membrane to prevent the medication from evaporating too quickly. Apply for 0.5 hours each time, once a day. Before removing the gauze, moisten the dried gauze with saline solution, and then slowly peel it off. Remember not to forcefully remove it to prevent secondary damage to the wound.

[0016] Compared with the prior art, the present invention has the following advantages and technical effects: This invention's traditional Chinese medicine composition contains: yam, which invigorates qi and nourishes yin, tonifies the spleen, lungs, and kidneys; salvia miltiorrhiza, which invigorates blood, regulates menstruation, removes blood stasis, relieves pain, cools the blood, and eliminates carbuncles; dandelion, which clears heat and detoxifies, reduces swelling and dissipates nodules, clearing heat and detoxifying, clearing away fire and toxins, while also relieving stagnation of qi and promoting lactation; sanguisorba officinalis, which cools the blood, stops bleeding, detoxifies, and astringes wounds; and gallnut, which astringes the lungs, reduces fire, stops bleeding, and astringes moisture to heal wounds. When used together, during the stage of wound healing (when necrotic tissue has sloughed off and new tissue has grown), the combined effects of these herbs, absorbed through the skin and mucous membranes, promote local blood circulation, maintain wound moisture, effectively promote the healing of skin ulcers in granulomatous lobular mastitis, improve wound exudation, reduce wound pain, and improve the patient's quality of life.

[0017] Subsequent experimental cases and clinical studies have demonstrated that the herbal composition of this invention has significant advantages in treating post-ulceration wounds of GLM, significantly promoting the growth of GLM wounds, improving the healing rate, and alleviating patients' clinical symptoms. Attached Figure Description

[0018] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the following description of the embodiments will be briefly introduced. Obviously, the accompanying drawings described below are only some embodiments of the present invention.

[0019] Figure 1 Comparison of treatment efficacy between two groups of GLM patients [Note: Overall effectiveness = number of cured patients + number of patients with significant improvement + number of patients with improvement].

[0020] Figure 2 Trends in wound area changes in two groups of GLM patients.

[0021] Figure 3 Comparison of wound area between two groups of GLM patients [Note: ns] P >0.05, P <0.05, P <0.01, P <0.01].

[0022] Figure 4 Trends in wound healing rates during treatment in two groups of GLM patients.

[0023] Figure 5 Comparison of wound healing rates between two groups of GLM patients during treatment [Note: ns] P >0.05, P <0.05, P <0.01, P <0.01].

[0024] Figure 6 Comparison of main symptom scores before and after treatment in two groups of GLM patients [Note: ns] P >0.05, P <0.05, P <0.01, P <0.01].

[0025] Figure 7 Comparison of secondary symptom scores before and after GLM treatment in two groups [Note: ns] P >0.05, P <0.05, P <0.01, P <0.01].

[0026] Figure 8 Comparison of total symptom scores before and after treatment in two groups of GLM patients [Note: ns] P >0.05, P <0.05, P <0.01, P <0.01].

[0027] Figure 9 Comparison of symptom score reduction rates between the two groups of GLM patients [Note: ns] P >0.05, P <0.05, P <0.01, P <0.01].

[0028] Figure 10 Wound exudation in two groups of GLM patients at different time points.

[0029] Figure 11 Granulation tissue status of wounds in two groups of GLM patients at different time points.

[0030] Figure 12 Wound pain at different time points in two groups of GLM patients. Detailed Implementation

[0031] The present invention will be further described below with reference to the accompanying drawings and specific embodiments. These embodiments should be understood as illustrative only and not as limiting the scope of protection of the present invention. After reading the description of the present invention, those skilled in the art can make various alterations or modifications to the present invention, and these equivalent changes and modifications also fall within the scope defined by the claims of the present invention.

[0032] Example 1 Weigh out 30g of Chinese yam, 30g of raw Sanguisorba officinalis, 30g of dandelion, 30g of Salvia miltiorrhiza, and 15g of Galla chinensis. Add 10 times the amount of water and decoct twice, the first time for 60 minutes and the second time for 40 minutes. Filter the decoction, combine the filtrates, let stand for no less than 12 hours, and take the supernatant and concentrate it to a relative density of 1.02-1.06 (60℃).

[0033] Example 2 Weigh out 30g of yam, 30g of raw Sanguisorba officinalis, 30g of dandelion, 15g of Salvia miltiorrhiza, and 9g of Galla chinensis. Add 10 times the amount of water and decoct twice, the first time for 60 minutes and the second time for 40 minutes. Filter the decoction, combine the filtrates, let stand for at least 12 hours, and take the supernatant and concentrate it to a relative density of 1.02-1.06 (60℃).

[0034] Example 3 Weigh out 30g of yam, 30g of raw Sanguisorba officinalis, 30g of dandelion, 45g of Salvia miltiorrhiza, and 15g of Galla chinensis. Add 10 times the amount of water and decoct twice, the first time for 60 minutes and the second time for 40 minutes. Filter the decoction, combine the filtrates, let stand for at least 12 hours, and take the supernatant and concentrate it to a relative density of 1.02-1.06 (60℃).

[0035] Example 4 Weigh out 45g of yam, 30g of raw Sanguisorba officinalis, 45g of dandelion, 45g of Salvia miltiorrhiza, and 30g of Galla chinensis. Add 10 times the amount of water and decoct twice, the first time for 60 minutes and the second time for 40 minutes. Filter the decoction, combine the filtrates, let stand for at least 12 hours, and take the supernatant and concentrate it to a relative density of 1.02-1.06 (60℃).

[0036] Example 5 Weigh out 45g of Chinese yam, 45g of raw Sanguisorba officinalis, 45g of dandelion, 45g of Salvia miltiorrhiza, and 30g of Galla chinensis. Add 10 times the amount of water and decoct twice, the first time for 60 minutes and the second time for 40 minutes. Filter the decoction, combine the filtrates, let stand for no less than 12 hours, and take the supernatant and concentrate it to a relative density of 1.02-1.06 (60℃).

[0037] Example 6 Weigh out 15g of yam, 30g of raw Sanguisorba officinalis, 30g of dandelion, 9g of Salvia miltiorrhiza, and 9g of Galla chinensis. Add 10 times the amount of water and decoct twice, the first time for 60 minutes and the second time for 40 minutes. Filter the decoction, combine the filtrates, let stand for no less than 12 hours, and take the supernatant and concentrate it to a relative density of 1.02-1.06 (60℃).

[0038] Experimental Example 1 - A comparative study on the clinical efficacy of the herbal composition of the present invention in treating ulcerated wounds of granulomatous lobular mastitis (using compound Phellodendron amurense liquid as a control). 1. Investigational drug The traditional Chinese medicine composition described in Example 1 was concentrated and extracted, and then an appropriate amount of excipients sodium benzoate and ethylparaben were added. The resulting product was then used in clinical research.

[0039] 2. Case selection Patients who were pathologically diagnosed with granulomatous lobular mastitis and developed ulcers at the Department of Integrated Traditional Chinese and Western Medicine Breast Surgery, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, between December 2023 and December 2025 were included.

[0040] (1) Inclusion criteria: ① Female patients aged 19-50; ②A localized mass in the breast was confirmed by core needle biopsy to be granulomatous lobular mastitis; ③ The skin at the site of the local swelling breaks down, forming a wound; ④ Those who voluntarily join this trial and continue to apply the medication externally for ≥2 months.

[0041] (2) Exclusion criteria: ①Pregnant or breastfeeding women; ② Pathological examination suggests concurrent breast cancer or dysplasia; ③ Patients with severe skin diseases; ④ Individuals with severe allergies, allergic to or contraindicated to any known interventions studied in this study; ⑤ Individuals with combined cognitive or communication impairments; ⑥ Currently participating in other clinical trials; ⑦ Those with concurrent liver, kidney, heart, or lung dysfunction, or coagulation dysfunction.

[0042] (3) Criteria for shedding and rejection: ① Patients who were lost to follow-up after enrollment or had poor compliance, which affected the evaluation of efficacy; ②Those who experience complications or special physiological changes during the experiment and are therefore unsuitable to continue the experiment; ③ Incomplete data prevents the evaluation of effectiveness and safety.

[0043] 3. Research Methods Patients meeting the inclusion criteria were randomly divided into an experimental group and a control group. Both groups received an oral Chai Kui Qing Xiao formula: Bupleurum 6g, Atractylodes macrocephala 15g, Poria cocos 15g, Hedyotis diffusa 30g, Crataegus pinnatifida 15g, Salvia miltiorrhiza 30g, Pyrola rotundifolia 30g, Curcuma longa 12g, Cyperus rotundus 12g, Camellia sinensis root 30g, Scutellaria baicalensis 30g, Taraxacum mongolicum 30g, Semiaquilegia adoxoides 15g, Artemisia capillaris 15g. One dose per day, decocted in water, taken twice daily, half an hour after meals.

[0044] Based on this, the experimental group received external application of the traditional Chinese medicine composition described in Example 1, provided by the Pharmacy Department of Longhua Hospital affiliated with Shanghai University of Traditional Chinese Medicine. When using the composition, 50ml of the medicine was soaked in sterile gauze, wrung out until it was no longer dripping, and applied to the ulcerated GLM wound. A medical waterproof membrane was then used to prevent rapid evaporation of the medicine. Each application lasted 0.5 hours, once daily. The control group received external application of Compound Phellodendron Amurense Liquid from Shandong Hanfang Pharmaceutical Co., Ltd., using the same method as the experimental group. Both groups received treatment for 8 consecutive weeks (4 courses), with each course lasting 2 weeks.

[0045] 4. Observation Indicators (1) Wound area: The wound area was measured using the film tracing method. A plastic film was placed over the breast wound, and the outline was traced with a black marker. The outline of the film was copied onto transparent area measurement paper, and the area was recorded. Follow-up was conducted every 2 weeks for a total of 4 times.

[0046] (2) Wound healing rate: Wound healing rate for each group = (wound area at enrollment - wound area at follow-up) / wound area at enrollment × 100%. Follow-up was conducted every 2 weeks for a total of 4 times.

[0047] (3) TCM symptom score: Total TCM symptom score = Main symptom score + Secondary symptom score Based on the "Standards for Diagnosis and Efficacy Evaluation of Diseases and Syndromes in Traditional Chinese Medicine" and combined with clinical practice, the following efficacy standards were formulated (ZY / T001~001.9-94, Standards for Diagnosis and Efficacy Evaluation of Diseases and Syndromes in Traditional Chinese Medicine [S]): ①Main symptom score 0: Wound healing, no granulation tissue growth, no pus, no perianal redness or swelling; ②Main symptom (2 points): The wound is not completely healed, the granulation tissue is fresh, there is no purulent exudate, and the redness and swelling around the wound are <0.5 cm from the wound edge; ③Main symptom (4 points): The wound is not completely healed, the granulation tissue is relatively fresh, there is a small amount of pus and necrosis, and the redness and swelling around the wound is 0.5-1 cm from the edge of the wound; ④ Main symptoms (6 points): Large wound, granulation tissue hyperplasia and edema, large amount of pus, dirty, redness and swelling around the wound >1 cm from the wound edge.

[0048] ⑤ Secondary symptom score 0: No pain, thirst, dry stool, yellow urine; ⑥ Secondary symptom 1 point: Mild pain, not affecting work and daily life, accompanied by thirst, dry stools, and yellow urine; ⑦ Secondary symptom score 2: Moderate pain, affecting work and daily life; ⑧ Symptom score of 3: Significant pain affecting work and daily life, requiring bed rest. Symptom scores were assessed before treatment and again 8 weeks after treatment.

[0049] (4) Reduction rate of TCM symptom scores: Reduction rate of TCM symptom scores = [(Score before treatment - Score after treatment) / Score before treatment] × 100% 5. Efficacy evaluation criteria Referring to the 2002 edition of the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs," the efficacy of TCM symptom treatment was categorized into clinical cure, significant effect, effective, and ineffective. Using the nimodipine method, the total effective rate was calculated as: (Number of clinically cured cases + Number of cases with significant effect + Number of effective cases) / Total number of cases × 100%. Efficacy was evaluated after 8 weeks of treatment.

[0050] ① Clinically cured: Symptom score reduction rate ≥ 95%; ② Significantly effective: 70% ≤ Symptom score reduction rate < 95%; ③ Effective: 30% ≤ Symptom score reduction rate < 70%; ④ Ineffective: Symptom score reduction rate < 30%.

[0051] 6. Safety assessment: vital signs such as heart rate, blood pressure, respiration, and pulse; condition of the skin at the topical application site; complete blood count and liver and kidney function tests, to be performed before treatment and 8 weeks after treatment.

[0052] 7. Statistical Methods This study used SPSS 26.0 statistical software for data analysis. First, the normality of all continuous variables was assessed using the Shapiro-Wilk test. Normally distributed continuous data were expressed as mean ± standard deviation, and independent samples t-tests were used for inter-group comparisons. Non-normally distributed continuous data were expressed as median (lower quartile, upper quartile) [M(Q1, Q3)], and Mann-Whitney U tests were used for inter-group comparisons. Count data were expressed as frequency (percentage) [n(%)], and chi-square tests or Fisher's exact tests were used for inter-group comparisons. The Mann-Whitney U test was used for comparing ordinal data. For repeated measures data, the generalized estimating equation (GEE) model was used to assess the overall impact of treatment methods, time, and their interaction effects; Friedman's test was used for intra-group comparisons at multiple time points, and the Mann-Whitney U test was used for inter-group comparisons at each time point. The Wilcoxon signed-rank test was used for paired comparisons of symptom scores before and after treatment. Because the data were not normally distributed, the Mann-Whitney U test was also used to compare the reduction rates of symptom scores between groups. All tests were two-tailed. P A value <0.05 is the criterion for determining whether a difference is statistically significant.

[0053] 8. Comparative analysis of clinical efficacy data General information: A total of 84 GLM patients meeting the criteria were included in the trial. Five patients dropped out during the trial, and 79 patients ultimately completed the effective trial, including 39 in the experimental group and 40 in the control group. There were no statistically significant differences in baseline characteristics between the two groups in terms of age, height, weight, and BMI. P >0.05).

[0054] (1) The combination of traditional Chinese medicine significantly improves the therapeutic effect of treating ulceration wounds in fibrous lobular mastitis.

[0055] After 8 weeks of treatment, the overall effective rate in the experimental group was 92.31%, while the overall effective rate in the control group was 67.50%. The overall effective rate in the experimental group was significantly higher than that in the control group. P <0.001)(Table 1, Figure 1 ).

[0056] Table 1. Comparison of treatment efficacy between the two groups of GLM patients [n(%)]

[0057] (2) The traditional Chinese medicine composition significantly reduced the ulceration area of ​​granulomatous lobular mastitis. The wound area of ​​the two groups of GLM patients at each measurement point was assessed using a generalized estimation equation. The overall analysis is shown in Table 2 below: Different treatment methods have different effects on the overall wound area. P <0.001). Different measurement times have varying effects on the overall wound area. P <0.001). Group and time have an interaction effect ( P = 0.012).

[0058] Table 2. Results of generalized estimation equation analysis of wound area changes in two groups of GLM patients

[0059] In both groups, the wound area at 2, 4, 6, and 8 weeks after treatment was significantly smaller than that at initial diagnosis. P <0.05, and with the extension of treatment time, the wound area continued to shrink, and the difference compared with the previous measurement point was also statistically significant. P <0.05 indicates that the therapeutic effect continues to increase over time. Figure 2 (See Appendix 1 and 2).

[0060] The results of the intergroup comparisons are shown in Table 3. Figure 3 At the initial diagnosis, there was no statistically significant difference in wound area between the experimental group and the control group. P =0.118), indicating that the baseline levels of the two groups of patients were comparable. However, starting from the second week of treatment, the median wound area in the experimental group was significantly smaller than that in the control group, and the difference between the groups was statistically significant. P =0.001). This difference persisted and became more significant at 4, 6, and 8 weeks. P <0.001).

[0061] Table 3. Comparison of wound area before and after treatment in the two groups of GLM patients [cm] 2 [M (Q1, Q3)]

[0062] Note: 'a' represents the correction when comparing multiple comparisons with the initial diagnosis. P <0.05; b represents the correction after multiple comparisons compared with week 2. P <0.05; c represents the correction after multiple comparisons compared with week 4. P <0.05; d represents the correction after multiple comparisons compared with week 6. P <0.05; P Friedman's Value represents Friedman's test p-value.

[0063] In summary, both treatments effectively reduced the wound area and promoted healing. The experimental group showed better wound healing results than the control group at 2, 4, 6, and 8 weeks.

[0064] (3) The traditional Chinese medicine composition significantly improved the wound healing rate after ulceration in granulomatous lobular mastitis. A generalized estimation equation was used to assess the overall wound healing rate at each measurement point in the two groups of GLM patients. Different treatment methods and different measurement times had different effects on the overall wound healing rate. P <0.001, no interaction effect between group and time ( P = 0.117). See Table 4.

[0065] Table 4. Results of generalized estimation equation analysis of wound healing rate changes in the two groups of GLM patients

[0066] Both groups showed a significant increase in wound healing rate after treatment, indicating that both treatment methods effectively promoted wound healing (see Table 5). Intra-group comparisons showed that the wound healing rate in the experimental group continued to increase over time, and the differences between each time point and the previous time point were statistically significant. P <0.05. The wound healing rate in the control group also significantly increased during the period from 2 to 6 weeks ( P <0.05, but the change during the 6- to 8-week period did not reach statistical significance ( Figure 4 (See Appendix Tables 3 and 4).

[0067] Table 5. Comparison of wound healing rates between the two groups of GLM patients during treatment [%, M (Q1, Q3)]

[0068] Note: b represents the correction after multiple comparisons compared with week 2. P <0.05; c represents the correction after multiple comparisons compared with week 4. P <0.05; d represents the correction after multiple comparisons compared with week 6. P <0.05; P Friedman's Value represents Friedman's test P value.

[0069] The results of the intergroup comparisons are shown in Table 5. Figure 5 From the second week of treatment, the median wound healing rate in the experimental group was significantly higher than that in the control group. P <0.001). This advantage was maintained at the subsequent 4, 6, and 8 week time points, with all differences being highly statistically significant. P<0.001).

[0070] In summary, both treatment methods can effectively promote wound healing, but the wound healing rate of the experimental group was significantly better than that of the control group at all stages of treatment, suggesting that the experimental group is more effective and faster in accelerating wound healing in GLM patients.

[0071] (4) The traditional Chinese medicine composition significantly improved the symptoms of patients with granulomatous lobular mastitis after ulceration. To compare the effects of the two treatment methods on improving symptoms in GLM patients, this study compared and analyzed the primary symptom scores, secondary symptom scores, and total symptom scores of the two groups of patients before and after treatment.

[0072] Before treatment, there were no statistically significant differences between the two groups in terms of primary symptom scores, secondary symptom scores, and total symptom scores. P >0.05), indicating that the baseline levels of the two groups are comparable (see Table 6-8). Figure 6-8 Intragroup comparisons showed that the scores for primary symptoms, secondary symptoms, and total symptoms were significantly lower in both groups after treatment compared to before treatment. P The value <0.001 indicates that both treatment methods effectively improved the patient's clinical symptoms. Intergroup comparisons showed that after treatment, the experimental group had significantly lower scores for primary symptom, secondary symptom, and total symptom score than the control group, with highly statistically significant differences. P <0.001).

[0073] Table 6. Comparison of main symptom scores before and after treatment in the two groups of GLM patients [M (Q1, Q3)]

[0074] Table 7. Comparison of secondary symptom scores before and after treatment in the two groups of GLM patients [M (Q1, Q3)]

[0075] Table 8. Comparison of total symptom scores before and after treatment in the two groups of GLM patients [M (Q1, Q3)]

[0076] To further quantify the degree of improvement, the reduction rate of symptom scores in the two groups of GLM patients was compared. The results showed that the median reduction rate of symptom scores in the experimental group (75.00%) was significantly higher than that in the control group (57.14%), and the difference was highly statistically significant. P <0.001), indicating that the experimental group had a better overall effect in alleviating patients' symptoms (see Table 9, Figure 9 ).

[0077] Table 9. Comparison of symptom score reduction rates between the two groups of GLM patients [%, M(P)]25 , P 75 )]

[0078] (5) The traditional Chinese medicine composition has good safety in treating ulcers of granulomatous lobular mastitis. During the treatment period of this study, no abnormalities were observed in vital signs such as heart rate, blood pressure, respiration, and pulse in either the experimental or control groups. No adverse reactions such as burning sensation, stinging, itching, or rash occurred during the external application period. Blood routine tests, liver and kidney function, and other relevant indicators were all within the normal range after medication.

[0079] Appendix Table 1 – Changes in wound area in GLM patients in the experimental group; Results of multiple comparisons within the group using Friedman's test.

[0080] Appendix Table 2 – Changes in wound area in GLM patients in the control group: Results of multiple comparisons within groups using Friedman's test

[0081] Appendix Table 3 - Changes in wound healing rate in GLM patients in the experimental group. Results of multiple comparisons within the group using Friedman's test.

[0082] Appendix Table 4 - Changes in wound healing rate in GLM patients in the control group. Results of multiple comparisons within groups using Friedman's test.

[0083] Experimental Example 2 - Clinical observation and comparative study on the efficacy of the traditional Chinese medicine composition of the present invention in treating post-ulceration wounds of granulomatous lobular mastitis (using Kangfuxin liquid as a control). 1. Investigational drug The traditional Chinese medicine composition described in Example 6 was used for clinical research. After decocting the traditional Chinese medicine and combining the filtrates, 150 ml of the juice was collected.

[0084] 2. Case Selection This study included patients with ulcerated granulomatous lobular mastitis who visited the Department of Breast Surgery, Affiliated to Longhua Hospital of Shanghai University of Traditional Chinese Medicine, between October 2019 and October 2021.

[0085] (1) Inclusion criteria: ① Patients who meet the pathological diagnosis of granulomatous lobular mastitis and have had skin ulceration in the breast area for about 1.5 months; ②2cm²≤wound area≤14cm²; ③ Previously, heart, liver, and kidney functions were normal; ④ No other topical medications were used during the treatment period; ⑤ Voluntarily participate in this clinical study, and have not joined other clinical trials and signed informed consent forms.

[0086] (2) Exclusion criteria: ①Pregnant or breastfeeding women; ② Cancerous ulcers or tuberculous ulcers; ③Those who have used immunosuppressants within the past month; ④ Patients with serious primary diseases, severe infections, or mental or legal disabilities; ⑤ Those with abnormal laboratory indicators (clinically significant abnormalities in complete blood count, liver and kidney function, and electrocardiogram); ⑥ Individuals allergic to the drugs used in this study.

[0087] (3) Criteria for shedding and rejection: ① Patients whose poor compliance during clinical trials affected the evaluation of clinical efficacy; ② A serious adverse event occurred during the trial, making it unsuitable for continued treatment; ③ The patient voluntarily withdrew from the trial for personal reasons. 3. Research Methods Patients meeting the inclusion criteria were randomly divided into an experimental group (hereinafter referred to as the experimental group) and a control group (hereinafter referred to as the control group) using the traditional Chinese medicine composition described in Example 6. Both groups of patients were given the modified Qingxiao formula orally. The main ingredients of this formula are: Bupleurum chinense 6g, Atractylodes macrocephala 15g, Smilax glabra 15g, Hedyotis diffusa 30g, Crataegus pinnatifida 15g, Pyrola rotundifolia 15g, Curcuma longa 12g, Camellia sinensis root 30g, Taraxacum mongolicum 30g, Solanum nigrum 30g, Scutellaria barbata 30g, and Semiaquilegia adoxoides 15g. In addition, the experimental group received a decoction of the traditional Chinese medicine composition from the herbal medicine pharmacy of Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine for external application. The method of application was as follows: each time, take about 50ml of the decoction, soak a sterile gauze in it, wring it out until it is not dripping wet, and cover it on the wound. Each wet compress lasted for 15 minutes, 3 times a day. The control group received external application of Kangfuxin Liquid (ingredients: dried American cockroach body extract) from Sichuan Good Doctor Panxi Pharmaceutical Co., Ltd. (National Drug Approval Number Z51021834), using the same application method as the experimental group. Both groups were treated for 2 months.

[0088] 4. Observation Indicators Clinical data of patients were collected and analyzed before treatment and at weeks 2, 4, 6 and 8 after treatment.

[0089] (1) Patient baseline information: age, time from onset to postpartum, duration of breastfeeding, time from onset to ulceration, treatment at other hospitals, number of ulcers, initial area of ​​breast wound, initial area of ​​lump.

[0090] (2) Main therapeutic indicators ①Cure rate: From the start of enrollment, the percentage of cured patients in each group was counted every two cycles until the 8th week of treatment, for a total of 4 counts.

[0091] ②Scar area: The area of ​​the scar formed after the wound heals is collected at the end of the follow-up period. The scar area is measured in cm. 2 Units.

[0092] (3) Secondary efficacy indicators ① Wound exudation assessment: The assessment is based on the number of gauze layers soaked through during dressing changes. If the patient changes the gauze dressing themselves, they should be instructed to observe and record the findings, as detailed in Table 10. Table 10. Scoring Criteria for Exudation Status

[0093] ② Wound granulation tissue scoring: The condition of the wound granulation tissue was scored during follow-up, as detailed in Table 11: Table 11. Grafting Tissue Condition Scoring Criteria

[0094] Note: Standard for the amount of new granulation tissue: based on the ratio of the area of ​​the wound: all, large (>75%), moderate (>25%≤75%), small (≤25%).

[0095] ③ Wound VAS Pain Score: The Visual Analogue Scale (VAS) was used as the pain standard. The pain score ranged from 0 (no pain) to 10 (the most severe, unbearable pain). Patients selected the score that corresponded to their experience. Details are as follows (Table 12): Table 12. VAS Pain Score Criteria for Wounds

[0096] (4) Safety indicators: skin allergy (see Table 13); blood routine, liver and kidney function.

[0097] Table 13. Allergic Reaction Record Sheet

[0098] 5. Efficacy evaluation criteria: The standard for evaluating efficacy is the "Standards for Diagnosis and Efficacy of Diseases and Syndromes in Traditional Chinese Medicine" issued by the State Administration of Traditional Chinese Medicine in 2012 (see Table 14).

[0099] Table 14. Evaluation Criteria for Local Wound Therapy

[0100] 6. Methods for measuring wound area and scar area: The film tracing method is used. A plastic film is placed over the ulcerated wound on the breast skin, and the outline is recorded with a black marker. The outline of the film is copied onto transparent area measurement paper, and the wound area is calculated. The scar area is measured in the same way.

[0101] 7. Statistical Methods: SPSS 27.0 software was used for data analysis in this study. Continuous variables, including baseline clinical characteristics, scar area, and healing time, were described as mean ± standard deviation. Independent samples t-tests were used for variables conforming to a normal distribution; nonparametric tests were used for those not conforming to a normal distribution. Chi-square tests were used for cure rates. Categorical variables were described as frequency / percentage (n / (%)), and chi-square tests were used for comparisons between groups. Local wound scores (wound size, exudate, granulation tissue) are repeated measures continuous variables, with multiple observations for the same patient. These repeated observations showed significant internal correlation, meaning they changed over time. Since this did not meet the internal correlation requirement of generalized linear regression, the Generalized Estimated Equation (GEE) was used, treating time t as a continuous variable to analyze the difference in the weekly rate of change of the dependent variable between the experimental and control groups. The GEE equation is Yi = βi0 + β1. group+β2 t+β3 group t.

[0102] 8. Clinical data analysis and comparison The two groups initially included 76 patients. One patient dropped out of each group due to loss to follow-up, resulting in 37 patients in each group, for a total of 74 patients.

[0103] (1) The baseline of the two groups of patients was consistent. There were no statistically significant differences between the two groups of patients in terms of baseline data, age, time from postpartum to onset, duration of breastfeeding, time from onset to ulceration, treatment received at other hospitals, number of ulcers, initial area of ​​breast wound, and initial area of ​​mass. P >0.05).

[0104] (2) The cure rate of the Chinese medicine combination for relatively large wounds after GLM ulceration was significantly higher than that of the control group.

[0105] The efficacy of the two groups of patients was compared at 2, 4, 6, and 8 weeks of treatment (Table 15). It was found that the cure rate and effective rate of both groups gradually increased as the treatment stabilized, but there was no significant difference in the cure rate and effective rate between the two groups. P >0.05).

[0106] Table 15. Comparison of treatment efficacy between the two groups of GLM subjects

[0107] Considering the potential confounding factor of wound area, a stratified study was conducted at 8 weeks of treatment, using 8 cm² as the wound area boundary. The results showed no statistically significant difference in healing between the two groups for patients with wound area 2 ≤ 8 cm², but a higher healing rate in the experimental group for patients with wound area 8 ≤ 14 cm². P <0.05), indicating that the experimental group had better efficacy for large-area GLM wounds (see Table 16).

[0108] Table 16. Stratified analysis of recovery status in the two groups at 8 weeks of treatment

[0109] Notice: represent P <0.05.

[0110] (3) The scar area of ​​the ulcerated wound after treatment with the Chinese medicine composition was smaller than that of the control group.

[0111] The average scar area after wound healing in the experimental group was 1.09 ± 0.59 cm². 2 The control group had a measurement of 1.58 ± 0.69 cm. 2 The experimental group had a smaller average scar area. P <0.05 (see Table 17).

[0112] Table 17. Comparison of scar area after healing between the two groups of GLM patients (cm²) 2 )

[0113] Notice: represent P <0.05.

[0114] (4) The Chinese medicine combination treatment for GLM ulceration showed better results than the control group in terms of exudation, granulation tissue and perilesional pain.

[0115] Using generalized estimating equations to analyze wound exudate, granulation tissue, and pain scores in the two groups of patients, it was found that the scores decreased more rapidly in the experimental group, and the difference was statistically significant. P <0.05), indicating that the traditional Chinese medicine composition significantly reduces exudation and improves granulation tissue condition in post-GLM ulceration treatment (see Tables 18-20). Figure 10-12 ).

[0116] Table 18. Comparison of wound exudation between the two groups of GLM patients

[0117] Notice: represent P <0.05.

[0118] Table 19. Comparison of granulation tissue in the wounds of the two groups of GLM patients

[0119] Notice: represent P <0.05.

[0120] Table 20. Comparison of wound pain between the two groups of GLM patients

[0121] Notice: represent P <0.05.

[0122] (5) The traditional Chinese medicine composition has good safety in treating post-ulceration wounds of GLM. During the treatment period of this study, one patient in the experimental group developed symptoms of skin itching and rashes around the wound one week after wet compress treatment, with an allergy symptom score of 2. The symptoms subsided after 3 days of discontinuation of treatment. No abnormalities in vital signs such as heart rate, blood pressure, respiration, and pulse were observed in either the experimental or control groups during the treatment process, and no other adverse reactions such as burning or stinging occurred during the topical application period.

Claims

1. A traditional Chinese medicine composition for treating ulcerated wounds of granulomatous lobular mastitis, characterized in that, It is made from the following raw materials in parts by weight: 5-15 parts of yam, 5-15 parts of raw Sanguisorba officinalis, 5-15 parts of dandelion, 3-10 parts of Salvia miltiorrhiza, and 3-6 parts of Gallnut.

2. The traditional Chinese medicine composition for treating ulcerated wounds of granulomatous lobular mastitis as described in claim 1, characterized in that, The weights of each raw material are as follows: 10 parts yam, 10 parts raw Sanguisorba officinalis, 10 parts dandelion, 10 parts salvia miltiorrhiza, and 5 parts gallnut.

3. The traditional Chinese medicine composition for treating ulcerated wounds of granulomatous lobular mastitis according to claim 1 or 2, characterized in that, Prepare clinically acceptable topical drug formulations according to conventional Chinese medicine preparation methods.

4. The traditional Chinese medicine composition for treating ulcerated wounds of granulomatous lobular mastitis according to claim 3, characterized in that, The external pharmaceutical preparations include liquid preparations, ointments, gel preparations, powders, or granules.

5. The method for preparing the traditional Chinese medicine composition for treating ulcerated wounds of granulomatous lobular mastitis as described in claim 4, characterized in that, The process includes the following steps: Weigh the raw materials according to the following proportions: yam, raw rehmannia root, dandelion, salvia miltiorrhiza and gallnut. Add 10 times the amount of water and decoct twice, the first time for 60 minutes and the second time for 40 minutes. Filter the decoction, combine the filtrates, let stand for no less than 12 hours, and take the supernatant and concentrate it to a relative density of 1.02-1.06 (60℃).

6. Use of the traditional Chinese medicine composition according to any one of claims 1-4 in the preparation of a medicament for treating ulcerated wounds of granulomatous lobular mastitis.

7. The use according to claim 6, characterized in that, For external use only. Take 50ml of the medication, soak a sterile gauze pad, wring it out until it is no longer dripping wet, apply it to the wound, and then cover it with a medical waterproof membrane to prevent the medication from evaporating too quickly. Apply for 0.5 hours each time, once a day. Before removing the gauze, moisten the dried gauze with saline solution, and then slowly peel it off. Remember not to forcefully remove it to prevent secondary damage to the wound.

Images