Traditional Chinese medicine formula for treating mastitis tumors in non-lactation period and preparation method of traditional Chinese medicine formula

Abstract

A preparation method of the traditional Chinese medicine comprises the following steps: taking 13 traditional Chinese medicinal materials in required parts by weight, adding water in an amount which is 2 times that of the required parts by weight of the traditional Chinese medicinal materials, soaking the medicinal materials in water for about 20 minutes, and boiling with strong fire; keeping boiling with slow fire but not excessive boiling for 30 minutes; filtering out the first decocted liquid medicine, adding water which submerges the medicinal materials, decocting for the second time, and boiling with strong fire (big fire); keeping boiling for 30 minutes without excessive boiling by using slow fire (soft fire); the invention provides a traditional Chinese medicine formula for treating non-lactation period mastitis tumors and a preparation method thereof, the traditional Chinese medicine formula has the advantages that the traditional Chinese medicine formula is remarkable in curative effect, good in safety, free of toxic and side effects, free of toxic and side effects, free of toxic and side effects and free of toxic and side effects, and can be used for treating non-lactation period mastitis tumors. And the traditional Chinese medicine composition has the advantages in the aspects of improving symptoms, reducing lumps, relieving pains and reducing surgical treatment requirements.

Description

Technical Field

[0001] The invention relates to the field of medicine, in particular to a traditional Chinese medicine formula for treating non-lactation mastitis tumors and a preparation method thereof. Background Art

[0002] Non-lactational mastitis is a chronic inflammatory disease of the breast with unknown etiology, which belongs to the category of "acne mastitis" in traditional Chinese medicine. In recent years, the incidence of this disease has increased year by year, and the disease has a wide range of lesions and many skin injuries, making it difficult to achieve ideal treatment effects through conventional lesion excision. The initial mass stage of this disease accounts for about 38% to 43%. In this stage, the lesions are mostly manifested as breast lumps, with a hard texture and unclear boundaries. Steroid hormones are an important adjuvant treatment for non-lactational mastitis in the mass stage, but long-term use of steroids can lead to glucose intolerance and Cushing's symptoms, such as weight gain, depression, osteoporosis and increased susceptibility to infection. Some patients may rebound after stopping the drug. If the scope of surgery in the mass stage is too large, it will seriously damage the appearance of the breast, thereby bringing additional psychological burden to the patient. If the scope of excision is too small, it may miss small lesions and lead to the risk of disease recurrence. Therefore, if a method can be found to reduce the breast lesions early and promote the internal elimination of the lumps or to quickly surround and aggregate the lumps to limit the lesions, the pain of ulceration and the changes in breast appearance caused by surgery can be greatly reduced. In view of this, it is necessary to invent a Chinese medicine formula that can treat early non-lactation mastitis to help patients with this disease receive drug treatment as soon as possible and control the progression of the disease. Summary of the invention

[0003] The technical problem to be solved by the present invention is to provide a Chinese medicine formula for treating non-lactation mastitis tumors and a preparation method thereof, which can effectively solve the problems raised in the above-mentioned background technology.

[0004] To solve the above problems, the technical solution adopted by the present invention is: a traditional Chinese medicine formula for treating non-lactation mastitis tumors, which is prepared from the following raw materials in parts by weight: 9 parts of bupleurum, 9 parts of scutellaria, 9 parts of angelica, 15 parts of red peony root, 30 parts of dandelion, 15 parts of smilax china, 12 parts of whole trichosanthes, 9 parts of forsythia, 18 parts of gleditsia thorn, 9 parts of siler, 9 parts of tangerine peel, 6 parts of green peel and 6 parts of liquorice.

[0005] As a further preferred embodiment of the present invention, the bupleurum 9g, scutellaria 9g, angelica 9g, red peony root 15g, dandelion 30g, smilax china 15g, whole trichosanthes 12g, forsythia suspensa 9g, gleditsia thorn 18g, siler 9g, tangerine peel 9g, green peel 6g and liquorice 6g.

[0006] Also included is a method for preparing a Chinese medicine formula, based on the above Chinese medicine formula for treating non-lactation mastitis tumors, comprising the following steps:

[0007] S1. Prepare the formula amount of Bupleurum, Scutellaria, Angelica, Red Peony Root, Taraxacum, Smilax, Trichosanthes, Forsythia, Gleditsia, Saposhnikovia, Tangerine Peel, Green Peel and Licorice, add twice the amount of water of the raw material formula, soak the raw material in water for about 20 minutes, boil with high heat, change to low heat and keep boiling for 30 minutes, then filter out the first decoction;

[0008] S2. Add water that has covered the herbs, boil for the second time, boil over high heat, then simmer for 30 minutes and filter out the second decoction;

[0009] S3. Mix the first decoction and the second decoction. If the mixed liquid is larger than 200 ml, continue to boil the liquid over low heat to evaporate the water and concentrate it to 200 ml.

[0010] Compared with the prior art, the present invention provides a Chinese medicine formula for treating non-lactation breast inflammatory tumors and a preparation method thereof, which has significant therapeutic effects and good safety, and shows advantages in improving symptoms, reducing tumors, alleviating pain and reducing the need for surgical treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 Schematic diagram of the preparation of the GLM model of the embodiment;

[0012] Figure 2 This is a schematic diagram of a lump rupture and nipple inversion in the embodiment;

[0013] Figure 3 This is a comparison diagram of the difference in tumor size in the embodiment;

[0014] Figure 4 HE staining (100X) of the example

[0015] Figure 5 For example, immunofluorescence staining (50X)

[0016] Figure 6 Westen blot indicator comparison diagram for example

[0017] Figure 7 It is a schematic diagram for comparing and verifying the embodiments;

[0018] Figure 8 It is a schematic diagram for comparing and verifying the embodiments;

[0019] Fig. 9 It is a schematic diagram for comparing and verifying the embodiments;

[0020] Fig.10 It is a schematic diagram for comparing and verifying the embodiments; DETAILED DESCRIPTION

[0021] If "and / or" or "and / or" appears in the full text, its meaning includes three parallel options. Taking "A and / or B" as an example, it includes option A, or option B, or a option in which both A and B are satisfied.

[0022] In addition, the technical solutions between the various embodiments can be combined with each other, but it must be based on the fact that ordinary technicians in the field can implement it. When the combination of technical solutions is contradictory or cannot be implemented, it should be deemed that such combination of technical solutions does not exist and is not within the scope of protection required by the present invention.

[0023] In the early stage of the disease, Professor Chen Hongfeng, a famous Chinese medicine doctor in Shanghai, adhered to the guiding ideology of TCM surgical ulcers that the most important thing is to eliminate them. According to the etiology and pathogenesis of the early stage of "heat accumulation in the liver meridian and the failure of the nutrient qi", he often used the prescription of Chaiqin Xiaoyong Yin, which is "soothing the liver, clearing heat, dispersing knots and reducing swelling", to treat the disease. Chaiqin Xiaoyong Yin is modified from the classic ancient prescription Chaihu Qinggan Decoction. The whole prescription is composed of 13 herbs, including 9 grams of Bupleurum, 9 grams of Scutellaria, 9 grams of Angelica, 15 grams of Red Peony, 30 grams of Taraxacum, 15 grams of Smilax, 12 grams of Trichosanthes, 9 grams of Forsythia, 18 grams of Gleditsia sinensis, 9 grams of Saposhnikovia divaricata, 9 grams of Tangerine peel, 6 grams of Citrus aurantium, and 6 grams of Licorice.

[0024] The whole formula uses Bupleurum as the bitter and cool nature, which has the effects of soothing the liver and relieving depression, clearing the liver and reducing fever, and raising yang and qi; Scutellaria baicalensis can clear away heat and detoxify, reduce swelling and discharge pus, and is compatible with Bupleurum. The two are the main ingredients, which can not only soothe the evil in the semi-exterior of Shaoyang, but also clear the heat in the semi-interior of Shaoyang, and enter the Shaoyang liver and gallbladder meridian to make the qi flow smoothly, and together they can achieve the effect of soothing the stagnant heat in the liver and gallbladder.

[0025] Red peony root is bitter, slightly cold, and enters the liver meridian. It has the effects of cooling blood, eliminating carbuncle, removing blood stasis and relieving pain.

[0026] Angelica sinensis can dispel blood stasis, promote new blood circulation, and nourish blood. When used together with red peony root, it can increase the effect of promoting blood circulation and unblocking collaterals, thus achieving the effect of dispersing blood stasis, removing rot and promoting new blood circulation.

[0027] Dandelion combined with Smilax china can cool blood, invigorate blood circulation, remove dampness and turbidity, detoxify and disperse blood stasis, and together play the role of clearing away heat and dispersing stagnation, inhibiting the spread of pus;

[0028] The thorns of soapberry can penetrate pus and eliminate carbuncles. The above ingredients are all ministerial medicines.

[0029] The whole Trichosanthes root can clear away heat and resolve phlegm, dredge meridians and disperse stagnation, and can transfer the medicinal power to the liver meridian to clear away the stagnant heat in the liver meridian.

[0030] Lianqiao clears away heat and detoxifies, dissipates stagnation and eliminates carbuncle. The combination of the two can clear the heat of the liver meridian and resolve the pus and toxins in the milk network.

[0031] Tangerine peel has the functions of regulating qi and strengthening the spleen, drying dampness and resolving phlegm. When combined with green peel, it can enhance its ability to strengthen the spleen and regulate qi. The above four medicines are collectively adjuvants.

[0032] Saposhnikovia divaricata belongs to the category of wind medicines, with pungent, sweet and slightly warm nature and flavor. It is known as the "moisturizing agent among wind medicines" and enters the liver, spleen, lung and bladder meridians. It can dispel wind and relieve exterior symptoms, overcome dampness and relieve pain. It can promote the circulation of qi, blood and body fluids inside and outside the body, so that qi and blood can flow smoothly throughout the body and circulate throughout the body without stagnation. Licorice harmonizes all medicines, and these two medicines are guiding medicines.

[0033] The whole formula is compatible with the harmony of yin and yang, and together they have the effects of soothing the liver, clearing away heat, dispersing nodules and reducing swelling.

[0034] As a specific embodiment of the invention:

[0035] A traditional Chinese medicine formula for treating non-lactation mastitis, which consists of 9 grams of bupleurum, 9 grams of scutellaria, 9 grams of angelica, 15 grams of red peony root, 30 grams of dandelion, 15 grams of smilax china, 12 grams of trichosanthes, 9 grams of forsythia, 18 grams of gleditsia thorn, 9 grams of siler, 9 grams of tangerine peel, 6 grams of green peel, and 6 grams of liquorice.

[0036] The decoction is prepared by:

[0037] (1) Take the required weight portions of 13 Chinese medicinal materials, add 2 times the weight portions of water, soak the medicinal materials in water for about 20 minutes, and then boil them over high heat; then change to low heat and keep boiling but not over-boiling for 30 minutes; and filter out the first decoction.

[0038] (2) Add enough water to cover the herbs and boil for the second time over high heat. Then switch to low heat and keep the water boiling but not over-boiling for 30 minutes.

[0039] Combine the decoctions obtained in step (1) and step (2). If there is a lot of liquid, continue to boil the decoction over low heat to evaporate the water and concentrate it to 200 ml.

[0040] As a further improvement of the present invention, the step of adding pharmaceutical excipients to prepare granules, oral liquids, pills, pills, pastes and powders is also included, such as:

[0041] 1. Production process: Extract Chinese herbal medicine slices with water, concentrate into extract with a certain specific gravity, spray dry, dry granulate and package.

[0042] Inspection: Inspection is carried out in accordance with the provisions of the Chinese Pharmacopoeia under the granules.

[0043] 2. Mixed formula production steps:

[0044] 1. Extraction: The Chinese herbal medicine pieces used in the prescription are extracted with water, concentrated and spray-dried.

[0045] 2. Mixing: Collect single extracts according to the prescription and mix them evenly.

[0046] 3. Granulation: The mixture is prepared into granules by dry granulation.

[0047] 4. Packaging: Pack the granules into small aluminum foil bags according to specifications.

[0048] Finished granule inspection items: properties, solubility, moisture, particle size, filling volume difference, microbial limit, etc. (Testing is based on Part IV of the 2020 edition of the Chinese Pharmacopoeia).

[0049] Clinical trial as a specific embodiment of the present invention

[0050] 1. Research design

[0051] This trial adopts a randomized, double-blind, placebo-controlled clinical trial design. The sample size calculation method of the superiority test of the two-group rate comparison is adopted. According to the results of the preliminary small sample experiment, the treatment group Pt = 0.91, the control group Pc = 0.44, and the superiority limit Δ = 0.15. The significance test level of the difference test between the two groups is set as α = 0.025, the test power (1-β) is 0.9, and a one-sided test is adopted. The treatment group and the control group are allocated 1:1, analyzed according to the PASS15 software, and approximate calculations are performed based on the t distribution. The sample size correction is based on the Pooled varance method, and n = 43 is calculated. If the loss rate is controlled to be ≤ 20%, 54 cases are required in each group, a total of 108 cases, and they are respectively entered into the treatment group and the control group. This trial adopts the method of completely random grouping. First, 108 random numbers are generated by SPSS statistical software. The random numbers that can be divided by 2 are set as the treatment group, and those that cannot be divided by 2 are set as the control group. The 108 numbers and corresponding groupings were handed over to Tianjiang Pharmaceutical Co., Ltd. to number and mark all the drugs. This study adopted a double-blind method, and both the researchers and the subjects were blinded, and the drugs were distributed according to the order of the subjects' visits. The blind bottom was kept in Tianjiang Pharmaceutical Co., Ltd. If a serious adverse event occurs during the study, the researcher must be given an emergency envelope for emergency unblinding for storage.

[0052] 2. Medication and treatment course

[0053] Treatment group: Chaiqin Xiaoyong Yin granules were taken orally. Composition: 9g of Bupleurum, 9g of Scutellaria, 9g of Angelica, 15g of Red Peony Root, 30g of Taraxacum, 15g of Smilax, 12g of Trichosanthes, 9g of Forsythia, 18g of Gleditsia sinensis, 9g of Saposhnikovia, 9g of Tangerine Peel, 6g of Citrus Aurantifolia, and 6g of Licorice.

[0054] Control group: Placebo granules for oral administration: Made of starch, dextrin and bittering agent, the appearance is the same as the test drug, containing excipients and <5% of the drug ingredients of Chaiqin Xiaoyong Yin. The appearance and packaging of the placebo are the same as those of Chaiqin Xiaoyong Yin granules, both of which are produced and provided by Tianjiang Pharmaceutical Co., Ltd., with drug production batch number: 2208309. All patients took it orally twice a day, 3 bags each time, brewed with 200ml warm water, and continued for 14 days.

[0055] 3. Observation indicators and methods

[0056] 3.1 Main efficacy indicators: Disease effectiveness rate: (clinical cure + marked effect + effective number of patients) / total number of patients*100%.

[0057] The standard for judging the efficacy based on the TCM symptom and sign score is based on the Guidelines for Clinical Research of New Chinese Medicines and the TCM symptoms and signs of acne mastitis with heat accumulation in the liver meridian in the Guidelines for Clinical Diagnosis and Treatment of TCM Surgery / Compiled by the Chinese Association of Traditional Chinese Medicine: a. Clinical cure: clinical symptoms and signs disappear or basically disappear, and the efficacy index is ≥90%; b. Marked effect: clinical symptoms and signs are significantly improved, and the efficacy index is ≥70%; c. Effective: clinical symptoms and signs are improved, and the efficacy index is reduced by ≥30%; d. Ineffective: clinical symptoms and signs are significantly improved or even aggravated, and the efficacy index is reduced by less than 30%. Referring to the relevant symptoms of "Modern Breast Diseases of Traditional Chinese Medicine" and "Standards for Diagnosis and Efficacy of TCM Diseases and Syndromes", combined with the experience of the instructor, dry mouth, chest and flank distension, irritability, and fever were defined as the main symptoms, and 0, 2, 4, and 6 points were given according to their presence and severity; depression, anxiety, fatigue, and poor sleep were defined as auxiliary symptoms, and 0, 1, 2, and 3 points were given according to their severity, and the TCM symptom score was calculated. Efficacy index = (pre-treatment score - post-treatment score) / pre-treatment score × 100%.

[0058] 3.2 Secondary efficacy indicators ① Breast pain degree: Visual analogue scale (VAS) was used to evaluate the local pain of the patient; ② Lump size: The long diameter (cm) and short diameter (cm) of the largest lump were measured by ruler during physical examination. ③ Laboratory observation indicators: a. Systemic Immune-inflammation Index (SII); b. Blood routine test including white blood cell count (WBC); c. Serum C-reactive protein (CRP); d. Serum prolactin (PRL).

[0059] 3.3 Other observation indicators After the 14-day trial, all patients continued to receive Gu's comprehensive surgical treatment. Breast shear wave elastic ultrasound detection was completed every 28 days. The hardness of the lesion was evaluated based on the maximum elastic hardness value of the lesion. Patients with a hardness reduction range of less than 10kpa for three consecutive times and breast enhanced MRI indicating 4a-level lesions or patients with severe complications during treatment (such as erythema nodosum, joint pain, cough, severe headache, etc.) were recommended to undergo surgical treatment. The proportion of surgical treatment in our center was followed up for half a year. Telephone follow-up was used to record whether or not surgical treatment was chosen for this disease.

[0060] 3.4 Safety indicators: ① Blood and urine routine tests, liver and kidney function tests, etc., are recorded before treatment and 14 days after treatment. ② Observe and record any adverse reactions that occur after the patient takes the medicine at any time.

[0061] 4. Results

[0062] A total of 120 patients with liver meridian heat accumulation type acne-like mastitis who met the inclusion and exclusion criteria were recruited in this study, 12 cases were excluded, and there were 54 cases in each group after unblinding. Among them, 2 cases dropped out of the treatment group, 1 case stopped taking the medicine on its own due to epigastric discomfort after taking the medicine, and 1 case dropped out because of failure to follow up on time; 4 cases dropped out of the control group, all of whom dropped out due to failure to cooperate with the treatment and follow-up on time. No adverse reactions occurred in both groups, so the actual number of completed cases in the two groups was 52 cases in the treatment group and 50 cases in the control group.

[0063] 4.1 Evaluation of the effective rate of treatment in the two groups

[0064] Before treatment, the TCM symptom and sign scores of the treatment group were 30.19±2.14, and the TCM symptom and sign scores of the control group were 30.16±1.95. The nonparametric Mann-Whitney U test showed that P>0.05 between the two groups. The baselines of the two groups before treatment were consistent and comparable. After 7 days of treatment with Chaiqin Xiaoyan and placebo granules, the TCM symptom and sign scores of the treatment group were 18.79±2.54, and the TCM symptom and sign scores of the control group were 27.22±2.59; after 14 days of treatment, the TCM symptom and sign scores of the treatment group were 15.33±3.77, and the TCM symptom and sign scores of the control group after treatment were 25.62±3.73. In the intra-group comparison, the TCM syndrome score of the treatment group after treatment was significantly lower than that before treatment, and the TCM symptom scores of the two groups after 7 and 14 days of treatment were significantly lower than those of the control group, and P was less than 0.05. According to statistics, after 14 days of treatment, 6 cases in the treatment group showed marked effect, 41 cases were effective, 5 cases were ineffective, and the total effective rate was 90.38%; in the control group, 0 cases showed marked effect, 18 cases were effective, 32 cases were ineffective, and the total effective rate was 36.00%; compared between the two groups, the overall effective rate of the treatment group was significantly higher than that of the control group, and the difference was statistically significant, P < 0.05. See Table 2-3.

[0065] Table 2 Comparison of TCM symptom and sign scores between the two groups before and after treatment

[0066]

[0067] Note: Comparison between groups at each time point compared with the control group *P<0.05; comparison within the group compared with before treatment # P<0.05.

[0068] Table 3 Comparison of clinical efficacy between the two groups of patients

[0069]

[0070] Note: Comparison between groups *P<0.01

[0071] 4.2 VAS pain scores in the two groups before and after treatment

[0072] Before treatment, the VAS score of the treatment group was 5.38±0.89, and that of the control group was 5.28±0.70. The nonparametric Mann-Whitney U test was used to compare the two groups, and P>0.05 was obtained, and there was no significant difference at baseline. After 7 days of oral Chaiqin Xiaoyan Yin treatment, the VAS score of the treatment group was 3.92±0.95, and that of the control group was 5.08±0.60. After 14 days of treatment, the VAS score of the treatment group was 2.27±1.43, and that of the control group was 4.74±0.66; after 7 and 14 days of treatment, the pain index of the treatment group was significantly lower than that of the control group, and the P value was 0.000. In the intra-group comparison, the Mann-Whitney U test was used to compare the treatment group with the pre-treatment after 7 and 14 days of treatment, and the control group with the pre-treatment after 14 days of treatment. The P values ​​were all <0.05, and the differences were statistically significant. See Table 4.

[0073] Table 4 Comparison of VAS pain scores between the two groups before and after treatment

[0074]

[0075] Note: Inter-group comparison, each time point compared with the control group *P<0.05; intra-group comparison compared with before treatment # P<0.05.

[0076] 4.3 Evaluation of serum WBC and CRP in the two groups

[0077] Before treatment, the mean WBC in the treatment group was 10.02±3.69*10^9 / L, and the control group was 10.78±3.89*10^9 / L; the mean CRP was 15.77±5.81mg / L, and the control group was 15.85±6.04; the P between the disease groups was greater than 0.05, and the difference between the two groups was not significant, which was comparable. After 14 days of treatment with Chaiqin Xiaoyong Yin and placebo, the mean WBC in the treatment group was 7.12±2.21, and the mean in the control group was 10.65±3.08; the mean CRP in the treatment group was 8.28±3.00mg / L, and the mean in the control group was 14.28±5.10mg / L; after treatment, the intergroup comparison was P<0.05; the intergroup comparison between the treatment groups was P<0.05. See Table 5.

[0078] Table 5 Comparison of WBC and CRP content between the two groups

[0079]

[0080] Note: Comparison before and after treatment in each group *P<0.05; comparison between groups ▲P<0.05.

[0081] 4.4 Comparison of systemic immune inflammatory factors (SII) between the two groups

[0082] Before treatment, the mean serum SII of the treatment group was 1421.80±626.16, and the mean of the control group was 1493.05±891.62, and the intergroup comparison was P>0.05. After 14 days of treatment with Chaiqin Xiaoyong Yin, the mean SII of the treatment group was 818.72±488.07, and the mean of the control group was 1330.29±678.66. After treatment, the intergroup comparison between the two groups was P<0.05; the intragroup comparison before and after the treatment group was P<0.05. See Table 6.

[0083] Table 6 Changes in the levels of systemic immune inflammatory factors (SII) in the two groups

[0084]

[0085] Note: Comparison before and after treatment in each group *P<0.05; comparison between groups ▲ P<0.05.

[0086] 4.5 Evaluation of tumor size before and after treatment in the two groups

[0087] The maximum long diameter and short diameter of the target mass on the body surface were measured before treatment. The average long diameter of the mass in the treatment group was 6.33±2.03cm, and the average short diameter was 3.65±1.19mm; the average long diameter of the mass in the control group was 6.21±2.64mm, and the average short diameter was 3.46±1.36cm. The statistical analysis of the MannWhitney U test in the non-parametric test showed that there was no significant difference in the long diameter and short diameter of the target mass between the two groups before treatment (P>0.05). After 14 days of treatment, the maximum long diameter of the target mass in the treatment group was 4.46±1.84cm, and the short diameter was 2.28±1.42cm; the maximum long diameter of the target mass in the control group was 6.95±2.97cm, and the short diameter was 3.06±1.81cm. In the treatment group, the inter-group comparison was P<0.05; the intra-group comparison before and after treatment in the two groups showed that after 14 days of treatment, the maximum long diameter and the maximum short diameter in the treatment group were both lower than those in the control group, P<0.05, and the difference was significant. See Table 7.

[0088] Table 7 Comparison of tumor size between the two groups before and after treatment

[0089]

[0090] Note: Comparison between groups ▲ P<0.05; intra-group comparison # P<0.05.

[0091] 4.6 Proportion of patients who underwent surgery after six months of follow-up in both groups

[0092] After completing 14 days of randomized controlled treatment, both groups were treated with Gu's surgical comprehensive therapy. During this period, breast ultrasound shear wave elastic imaging examinations were regularly followed up. According to the trend of the maximum ultrasound shear wave elastic hardness value of the lesion, surgical treatment was recommended for patients with a decrease index of less than 10kpa for three consecutive assessments and MRI indicating a 4a grade lesion. After six months of follow-up, the proportion of patients undergoing surgery in the two groups was as follows. See Table 8.

[0093] Table 8 Proportion of surgical treatment in the two groups of patients

[0094]

[0095] Note: Comparison between groups *P<0.01

[0096] 4.7 Safety evaluation

[0097] A total of 102 subjects were included in this study. During the implementation of the experiment, 2 patients in the treatment group had mild diarrhea after taking Chinese medicine, which was relieved by themselves, and no other adverse reactions were shown during the period. By comparing the blood routine, liver and kidney function, urine routine tests and electrocardiogram tests of the 102 GLM patients before and after enrollment, no abnormalities in the hematopoietic system, circulatory system, liver and kidney function, etc. occurred in the patients.

[0098] Animal experiments

[0099] 1. Preparation of non-lactation mastitis GLM (granulomatous mastitis) rat model

[0100] The model was established according to the GLM modeling method studied in the previous experiments of the research group. Milk was mixed with Freund's complete adjuvant and Freund's incomplete adjuvant in a ratio of 1:1 to prepare a milky white suspension for later use. Each rat was subcutaneously injected with metoclopramide at a dose of 30 mg / kg daily for 2 consecutive weeks. At the same time, on the first day, each rat was injected with 0.2 ml of milk + complete Freund's adjuvant suspension through the 3rd and 4th pairs of mammary glands, and 0.2 ml of milk + incomplete Freund's adjuvant suspension was injected again on the 7th and 14th days. Figure 1 .

[0101] 2. Macrophage polarization phenotypes at different stages of the GLM model and the role of the TLR4 / NF-κB signaling pathway

[0102] Twenty 6-week-old Wistar rats, each weighing about 160-170 g, were selected. After one week of adaptive feeding, 14 rats were randomly selected to establish the GLM rat model according to the method in 1.1. One rat was selected for identification of the model and the tissue was kept for later use. The remaining model rats were randomly divided into the model group, the model + LPS group, the model + RS09 (Toll-like receptor agonist) group, and the model + TAK242 (Toll-like receptor inhibitor) group, with 3 rats in each group. Each rat in the model + LPS group was intraperitoneally injected with LPS at 1 mg / kg once, each rat in the model + RS09 group was intraperitoneally injected with RS09 at 1 mg / kg once, and each rat in the model + TAK242 group was intraperitoneally injected with TAK242 at 2.1 mg / kg for 2 consecutive days. One rat was taken on the 3rd, 7th, and 14th day after modeling for subsequent index detection, and the remaining one model rat and two normal rats were raised until the 30th day for sampling and detection.

[0103] 3. Tumor and overall condition of rats

[0104] 3.1 Overall Situation

[0105] After the injection of metoclopramide, the model rats were more irritable than normal rats and often licked and scratched the lumps. Two of the rats had unformed stools, and the stools of the remaining model rats were soft. All model rats had lumps, and some of the lumps had sunken and ulcerated nipples, such as Figure 2 .

[0106] 3.2 Modeling mass

[0107] The sizes of the tumors of the rats were measured with a vernier caliper on days 0, 3, 7, and 14 of the modeling. The differences between the changes on days 3, 7, and 14 and 0 were compared. On day 3 after modeling, the tumor size of the model + TAK242 group was smaller than that of the model + LPS group and the model + RS09 group, and the difference was statistically significant, P<0.01. On day 7 after modeling, the tumor in the model group was smaller than that in the model + LPS group, and the difference was statistically significant, P<0.05; the tumor size of the model + TAK242 group was smaller than that of the model + LPS group and the model + RS09 group, and the difference was statistically significant, P<0.05. On day 14 after modeling, the tumor size of the model + TAK242 group was smaller than that of the model group, the model + LPS group, and the model + RS09 group, and the difference was statistically significant, P<0.05, see Figure 3 .

[0108] 3.3HE staining and immunofluorescence

[0109] On the 3rd, 7th and 14th days after modeling, tissues of rats in each group were taken to prepare paraffin sections and stained with HE. The normal group rats were mainly composed of mammary stroma, which was composed of fat and collagen, and scattered double-layer cells of mammary duct-lobular system were seen. The mammary duct-lobular system of GLM rats was destroyed, and a large number of inflammatory cells infiltrated the mammary stroma, and multiple granulomas of varying sizes were seen.

[0110] Paraffin sections of rats in each group were taken on the 7th day after modeling and immunofluorescence staining was performed, which showed that the normal group rats were mainly composed of M2 macrophages. There were a large number of M1 macrophages around the granulomas of rats in each model, and a small number of M2 macrophages infiltrated in the periphery.

[0111] 3.4Westen blot detection

[0112] On the 3rd, 7th and 14th days after modeling, the mammary gland tissues of rats in each group were homogenized, proteins were extracted, and electrophoresis, membrane transfer and development were performed. According to the results of the bands, the expression of TLR4, MyD88, NF-κB, IKK-α, INOS and Arg-1 in the normal group was lower than that in the GLM rats; the expression of TLR4, NF-κB, IKK-α, INOS and Arg-1 in the model+TAK242 group was lower than that in the model group, model+LPS group and model+RS09 group; the expression of TLR4, NF-κB, MyD88, IKK-α, INOS and Arg-1 in the model+LPS group and model+RS09 group was higher than that in the model group.

[0113] 4. The medication method and results are as follows:

[0114] 4.1 Medication method: The model rats were given Chaiqin Xiaoyong Decoction (14.04 g / kg / d), Chaiqin Xiaoyong Decoction combined with TAK242 (3 mg / kg / d), and methylprednisolone (2.1 mg / kg / d) once a day for 14 days, and equal numbers of rats were randomly selected for testing on the 0th, 7th, and 14th days.

[0115] 4.2 Experimental results:

[0116] (I) CQXYY has a significant therapeutic effect on reducing local tumors and lowering skin temperature in rats. Figure 7 It can be seen that the nipples of the normal control group were not sunken, but lumps or ulcers appeared around the nipples of the rats after modeling, and some nipples were sunken. After CQXYY treatment, the size and weight of the lumps around the nipples of the rats were reduced, and the skin temperature was reduced. Figure 8 HE staining confirmed the above results. It can be observed that in the GLM model, there is lymphocyte infiltration in the lobules, the intralobular ducts disappear, and the degree of lymphocyte infiltration around the interstitial capillaries varies. Inflammatory granulomatous lesions are distributed along the mammary lobules, some lesions are fused, and the glandular ducts in the lobules are reduced or disappeared ( Fig. 9After CQXYY treatment, inflammation was reduced and some normal ducts were visible, but inflammation was still present compared to the control group, suggesting that XSGSJT may lead to reduced inflammation in the GLM model.

[0117] (ii) CQXYY reversed the activation of the TLR4 / NF-κB pathway caused by the mastitis model. As shown by PCR, the mastitis model activated TLR4 / NF-κB and upregulated the expression of pathway-related mRNAs such as TLR4, MyD88, and NF-κB. At the same time, the expression of pro-inflammatory factors increased, such as TNF-α, IL-1β, IL-6, and IL-12 mRNA, while the expression of TGF-β and IL-10 mRNA decreased. After treatment, CQXYY inhibited the activation of the TLR4 / NF-κB pathway and downregulated the mRNA of pro-inflammatory factors, such as Fig.10 .

[0118] (III) No adverse reactions were observed in rats during the experiment.

[0119] In summary, the Chinese herbal prescription used in the treatment group showed significant efficacy in the treatment of non-lactation mastitis, with good safety, and showed advantages in improving symptoms, reducing lumps, alleviating pain, and reducing the need for surgical treatment.

[0120] The above description is only a preferred embodiment of the present invention, and does not limit the patent scope of the present invention. All equivalent structural changes made by using the contents of the present invention specification and drawings under the inventive concept of the present invention, or directly / indirectly applied in other related technical fields are included in the patent protection scope of the present invention.

Claims

1. A Chinese medicine formula for treating non-lactational mastitis tumors, characterized in that: The medicine is prepared from the following raw materials in parts by weight: 9 parts of bupleurum, 9 parts of scutellaria, 9 parts of angelica, 15 parts of red peony root, 30 parts of dandelion, 15 parts of smilax china, 12 parts of whole trichosanthes, 9 parts of forsythia, 18 parts of gleditsia thorn, 9 parts of siler, 9 parts of dried tangerine peel, 6 parts of green tangerine peel and 6 parts of liquorice.

2. The Chinese medicine prescription for treating non-lactational mastitis tumors according to claim 1, characterized in that: The ingredients include 9g of bupleurum, 9g of scutellaria, 9g of angelica, 15g of red peony root, 30g of dandelion, 15g of smilax china, 12g of whole trichosanthes, 9g of forsythia, 18g of gleditsia thorn, 9g of siler, 9g of dried tangerine peel, 6g of green tangerine peel and 6g of liquorice.

3. A method for preparing a Chinese medicine prescription, comprising the Chinese medicine prescription for treating non-lactational mastitis tumors as claimed in claim 1 or 2, characterized in that: The following steps are involved: S1. Prepare the formula amount of Bupleurum, Scutellaria, Angelica, Red Peony Root, Taraxacum, Smilax, Trichosanthes, Forsythia, Gleditsia, Saposhnikovia, Tangerine Peel, Green Peel and Licorice, add twice the amount of water of the raw material formula, soak the raw material in water for about 20 minutes, boil with high heat, change to low heat and keep boiling for 30 minutes, then filter out the first decoction; S2. Add water to cover the herbs, boil for the second time, boil over high heat, then simmer for 30 minutes and filter out the second decoction; S3. Mix the first decoction and the second decoction. If the mixed liquid is larger than 200 ml, continue to boil the liquid over low heat to evaporate the water and concentrate it to 200 ml.

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