A traditional Chinese medicine composition for treating endometriosis, a preparation method and application thereof

Abstract

This invention belongs to the technical field of traditional Chinese medicine compositions and preparations, specifically relating to a traditional Chinese medicine composition for treating endometriosis, its preparation method, and its application. The traditional Chinese medicine composition for treating endometriosis of this invention is made from components including the following raw materials: Salvia miltiorrhiza, Paeonia lactiflora, Curcuma zedoaria, Cinnamomum cassia, Corydalis yanhusuo, Hirudo medicinalis, Caesalpinia sappan, Litchi chinensis seed, Ostrea gigas, and Cremastra appendiculata. The traditional Chinese medicine composition of this invention has a clear formulation and standardized sources, taking into account the functions of breaking up blood stasis and eliminating masses, warming the meridians and dispelling cold, promoting qi circulation and relieving pain, and softening and dispersing masses, which is suitable for the pathogenesis characteristics of endometriosis (EM) characterized by "deficiency of the root and excess of the branch, with blood stasis as the main symptom." Compared with existing solutions that focus on simply relieving pain or warming the meridians and regulating menstruation, this invention can simultaneously cover multiple key aspects such as inflammation, pain, lesion growth, fibrosis, and hormone receptor abnormalities.

Description

Technical Field

[0001] This invention belongs to the technical field of traditional Chinese medicine compositions and preparations, specifically relating to a traditional Chinese medicine composition for treating endometriosis, its preparation method, and its application. Background Technology

[0002] Endometriosis (EMs) is a common chronic inflammatory disease in women of reproductive age. It is characterized by the presence of active endometrial glands and stroma outside the uterine cavity, leading to progressive dysmenorrhea, chronic pelvic pain, menstrual irregularities, and infertility. Current Western medical treatments primarily rely on surgical removal, gonadotropin-releasing hormone agonists, progestins, or oral contraceptives. However, these treatments generally suffer from high rates of recurrence after discontinuation or surgery, significant adverse reactions with long-term use, and substantial impacts on fertility and quality of life.

[0003] Traditional Chinese medicine (TCM) has advantages in the treatment of dysmenorrhea (EMS) including holistic regulation, multi-target intervention, and long-term management. Commonly used regimens include Sanjie Zhentong Capsules, Wenjing Decoction, and various blood-activating and stasis-removing compound formulas. While Sanjie Zhentong Capsules can alleviate dysmenorrhea to some extent, its comprehensive regulation of lesion proliferation, inflammatory networks, fibrosis, and recurrence control remains relatively limited.

[0004] Wenjing Decoction also has a certain therapeutic effect on EMs, but existing public research still has obvious shortcomings: First, basic research is mostly limited to the rat model of EMs, lacking multi-level verification at the cell-tissue-whole level; Second, the sample size of clinical studies is generally small, mostly single-center or combined with Western medicine regimens, making it difficult to evaluate the true contribution of Wenjing Decoction to lesion volume, fibrosis and recurrence control; Third, the lack of systematic toxicological and long-term safety evaluation limits its clinical promotion.

[0005] Furthermore, existing traditional Chinese medicine (TCM) compositions generally suffer from traditional ingredient combinations and insufficient synergistic coverage of pathological processes such as inflammatory responses, pain, angiogenesis, fibrosis, and hormone receptor imbalance. Therefore, there is an urgent need to provide a novel TCM composition with a clear formulation, rational compatibility, stable preparation, and the ability to comprehensively intervene in the EMS process at multiple stages. Summary of the Invention

[0006] The purpose of this invention is to provide a traditional Chinese medicine composition for treating endometriosis, its preparation method and application. This composition has the effects of promoting blood circulation and removing blood stasis, eliminating masses and dispersing nodules, warming the meridians and dispelling cold, and regulating qi and relieving pain. It can synergistically intervene in EMs from multiple aspects such as inflammatory response, lesion proliferation, fibrosis and hormone receptor imbalance.

[0007] The traditional Chinese medicine composition provided by this invention is also known as Danzhi Heterotope Formula (DZYWF), and the raw materials used include: Salvia miltiorrhiza, Paeonia lactiflora, Curcuma zedoaria, Cinnamomum cassia, Corydalis yanhusuo, Hirudo medicinalis, Sappanwood, Litchi chinensis seed, Ostrea gigas, and Cremastra appendiculata. Among them, "Hirudo medicinalis" and "Ostrea gigas" are the proper names of the medicinal materials; if processed products are used, the processing method can be specified in accordance with the pharmacopoeia specifications during implementation.

[0008] Preferably, the traditional Chinese medicine composition comprises, by weight, 10-15 parts of Salvia miltiorrhiza, 6-15 parts of Paeonia lactiflora, 6-10 parts of Curcuma zedoaria, 1-5 parts of Cinnamomum cassia, 3-10 parts of Corydalis yanhusuo, 1-3 parts of Hirudo medicinalis, 3-10 parts of Caesalpinia sappan, 5-15 parts of Litchi chinensis seed, 9-30 parts of Ostrea gigas, and 3-10 parts of Cremastra appendiculata. More preferably, the traditional Chinese medicine composition comprises: 12-15 parts of Salvia miltiorrhiza, 10-15 parts of Paeonia lactiflora, 8-10 parts of Curcuma zedoaria, 3-5 parts of Cinnamomum cassia, 8-10 parts of Corydalis yanhusuo, 2-3 parts of Hirudo medicinalis, 8-10 parts of Caesalpinia sappan, 10-15 parts of Litchi chinensis seed, 15-30 parts of Ostrea gigas, and 6-10 parts of Cremastra appendiculata. Most preferably, the composition of the traditional Chinese medicine composition is as follows: 15 parts of Salvia miltiorrhiza, 15 parts of Paeonia lactiflora, 10 parts of Curcuma zedoaria, 5 parts of Cinnamomum cassia, 10 parts of Corydalis yanhusuo, 3 parts of Hirudo medicinalis, 10 parts of Sappanwood, 15 parts of Litchi chinensis seed, 30 parts of Ostrea gigas and 10 parts of Cremastra appendiculata.

[0009] The functions and compatibility of each component in the traditional Chinese medicine composition of the present invention are as follows: Salvia miltiorrhiza: bitter, slightly cold, enters the heart and liver meridians. Its functions include promoting blood circulation and removing blood stasis, regulating menstruation and relieving pain, clearing the heart and relieving irritability, cooling the blood and eliminating carbuncles. It is mainly used to treat menstrual disorders, dysmenorrhea, amenorrhea, and postpartum abdominal pain caused by blood stasis; chest pain and heart pain due to blood stasis, abdominal pain, masses and accumulations, traumatic injuries, and pain due to heat; carbuncles and boils; and insomnia due to irritability.

[0010] Red peony root: bitter, slightly cold, enters the liver meridian. Its functions are to clear heat and cool the blood, disperse blood stasis and relieve pain. It is mainly used to treat heat entering the blood, febrile rashes, blood heat causing vomiting and nosebleeds; red and swollen eyes, carbuncles and sores; liver stagnation causing hypochondriac pain, amenorrhea and dysmenorrhea, abdominal masses and pain, and traumatic injuries.

[0011] Leech: Salty, bitter, neutral, slightly toxic, enters the liver meridian, its functions are to break up blood stasis and promote menstruation, remove blood stasis and eliminate masses; it is mainly used to treat amenorrhea due to blood stasis, abdominal masses; hemiplegia due to stroke, traumatic injuries, and abdominal pain due to blood stasis.

[0012] Curcuma zedoaria: pungent, bitter, and warm, it enters the liver and spleen meridians. Its functions include breaking up blood stasis, promoting qi circulation, eliminating stagnation, and relieving pain. It is mainly used to treat abdominal masses, amenorrhea due to blood stasis, chest pain, food stagnation and qi stagnation, and abdominal distension and pain.

[0013] Corydalis: pungent, bitter, and warm. It enters the liver, spleen, and heart meridians. Its functions are to invigorate blood, promote qi circulation, and relieve pain. It is mainly used to treat qi and blood stagnation, chest and rib pain, abdominal pain, chest pain, amenorrhea, dysmenorrhea, postpartum blood stasis, and swelling and pain from falls.

[0014] Cinnamon: pungent, sweet, and very hot in nature. It enters the kidney, spleen, heart, and liver meridians. Its functions include tonifying fire and assisting yang, dispelling cold and relieving pain, warming and unblocking the meridians, and guiding fire back to its source. It is mainly used to treat kidney yang deficiency, decline of the fire of the gate of life, impotence and cold uterus, cold pain in the waist and knees; cold pain in the heart and abdomen, vomiting and diarrhea due to deficiency and cold, abdominal pain due to cold hernia; dysmenorrhea and amenorrhea due to deficiency and cold of the Chong and Ren meridians and blood stasis due to cold, cold and damp bi syndrome, and yin carbuncles; asthma due to kidney deficiency, upward floating of deficient yang, dizziness and red eyes.

[0015] Lychee seeds: sweet, slightly bitter, warm, enter the liver and kidney meridians, and have the functions of promoting qi circulation and dispersing stagnation, dispelling cold and relieving pain; they are mainly used to treat abdominal pain due to cold hernia, testicular swelling and pain, stomach distension and pain, dysmenorrhea, and postpartum abdominal pain.

[0016] Mountain Cremastrae: Sweet, slightly pungent, cool, enters the liver and spleen meridians. Its functions are to clear heat and detoxify, eliminate carbuncles and dissipate nodules; it is mainly used to treat carbuncles, boils, scrofula, phlegm nodules, snake and insect bites; and abdominal masses.

[0017] Sappanwood: Sweet, salty, neutral; enters the heart, liver, and spleen meridians. Its functions include promoting blood circulation and removing blood stasis, reducing swelling and relieving pain. It is mainly used to treat traumatic injuries, muscle injuries and fractures, swelling and pain due to blood stasis, amenorrhea and dysmenorrhea due to blood stasis, postpartum blood stasis, chest and abdominal pain, and carbuncles and boils.

[0018] Oyster: Salty, slightly cold, enters the liver, gallbladder and kidney meridians. Its functions include calming yang and nourishing yin, sedating the mind and soothing the nerves, softening and dispersing nodules, astringing and consolidating, neutralizing acid and relieving pain. It is mainly used to treat liver yang hyperactivity, dizziness and tinnitus; restlessness, palpitations and insomnia; scrofula, phlegm nodules, abdominal masses; spontaneous sweating and night sweats, seminal emission and spermatorrhea, metrorrhagia and leukorrhea; stomach pain and acid regurgitation.

[0019] The formulation of this invention follows the principle of "principal, assistant, adjuvant, and guide" in traditional Chinese medicine. Danshen and leech are the principal herbs: Danshen invigorates blood and removes blood stasis without harming the body's vital energy, while leech has a strong effect in breaking up blood stasis and eliminating masses. The two herbs complement each other, which can not only enhance the effect of removing blood stasis and dispersing masses, but also avoid the excessively strong effect of using blood-breaking herbs alone.

[0020] Red peony root, turmeric, corydalis rhizome, and sappanwood are the assistant herbs. Red peony root cools the blood and disperses blood stasis, turmeric breaks up blood stasis and promotes qi circulation, corydalis rhizome invigorates blood and relieves pain, and sappanwood invigorates blood and reduces swelling. They work together to form a "blood-invigorating, qi-regulating, and pain-relieving" synergy, which helps to inhibit blood stasis, pain, and the progression of lesions.

[0021] Cinnamon and lychee seeds are used as adjuvants. Cinnamon warms the meridians, dispels cold, unblocks the channels, and relieves pain, while lychee seeds promote qi circulation, disperse stagnation, dispel cold, and relieve pain. The two work together to address common symptoms of EM such as cold stagnation, menstrual cramps, and lower abdominal pain.

[0022] Oyster shell and *Cremastra appendiculata* are used as adjuvant herbs. Oyster shell softens and disperses masses, and has a calming and sedative effect, while *Cremastra appendiculata* clears heat and detoxifies, and disperses masses and abscesses. The two herbs complement each other, enhancing their effect on softening and dispersing masses, cystic lesions, and inflammatory nodules. The entire formula combines warming and cooling properties, one breaking down lumps and the other harmonizing them, taking into account "promoting blood circulation and removing blood stasis, warming the meridians and dispelling cold, regulating qi and relieving pain, and softening and dispersing masses," achieving a balanced approach to both cold and heat, and a moderate attack and dissipation.

[0023] The traditional Chinese medicine composition of this invention has a clear formulation and standardized sources, and takes into account the functions of breaking up blood stasis and eliminating masses, warming the meridians and dispelling cold, promoting qi circulation and relieving pain, and softening and dispersing masses. It is suitable for the pathogenesis characteristics of EMs, which are "deficiency of the root and excess of the branch, with blood stasis as the main feature". Compared with existing solutions that focus on simply relieving pain or warming the meridians and regulating menstruation, this invention can simultaneously cover multiple key aspects such as inflammation, pain, lesion growth, fibrosis, and hormone receptor abnormalities.

[0024] From the perspective of drug compatibility, all the medicinal materials used in this invention are listed in the Chinese Pharmacopoeia. The drug compatibility does not involve any of the clearly contraindicated drug pairs in the traditional "Eighteen Incompatibilities" and "Nineteen Antagonisms". Through the layered combination of principal, assistant, adjuvant and guide drugs, the synergistic effects of mutual reinforcement and mutual assistance are brought into play, while avoiding the cancellation of efficacy or the increase of toxic side effects caused by mutual opposition and mutual incompatibility.

[0025] Component analysis revealed 105 chemical components in the leech extract, mainly including phenolic acids, flavonoids, terpenes / sesquiterpenes, and carboxylic acids. Representative components included tanshinone, salvianolic acid A / B, cryptotanshinone, paeoniflorin, curcumol / curcuminone, cinnamaldehyde, eugenol, corydalis alkaloids, and brassinolide, providing a pharmacodynamic material basis for the anti-inflammatory, analgesic, antithrombotic, antifibrotic, and immunomodulatory effects of the herbal composition of this invention.

[0026] Network pharmacology further revealed that this composition identified 163 potential active ingredients and 896 effective targets, with 167 overlapping with targets associated with EMs-related diseases. Core targets included TP53, STAT3, IL-6, EGFR, and TNF; the composition was significantly enriched in signaling pathways such as TNF, PI3K-Akt, MAPK, NF-κB, and JAK-STAT. Animal pharmacodynamic results showed a decrease in ectopic lesion volume, reduction in fibrosis, improvement in ER / PR, and downregulation of IL-6 / TNF-α in a rat EMs model, directly supporting the interventional effects of this invention on lesion growth, inflammation, and fibrosis.

[0027] On the other hand, the present invention also provides a method for preparing the above-mentioned traditional Chinese medicine composition, wherein the preparation method can produce conventional oral preparations such as pills, powders, decoctions, extracts, granules, tablets, capsules, oral liquids, or lyophilized preparations. The method includes: mixing the raw materials and then decocting and extracting them, or pulverizing them first and then mixing them, or mixing them and then extracting and further refining them to obtain the extract or effective fraction; the extraction solvent can be water or a pharmaceutically acceptable organic solvent.

[0028] The preparation of the above-mentioned conventional oral formulations requires the addition of commonly used pharmaceutically acceptable excipients, including: fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, and matrices. Fillers include: starch, pregelatinized starch, lactose, mannitol, chitosan, microcrystalline cellulose, sucrose, etc.; disintegrants include: starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, croscarmellose, low-substituted hydroxypropyl cellulose, croscarmellose sodium, etc.; lubricants include: magnesium stearate, sodium lauryl sulfate, talc, silica, etc.; suspending agents include: polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methylcellulose, etc.; binders include: starch paste, polyvinylpyrrolidone, hydroxypropyl methylcellulose, etc.

[0029] In some preferred embodiments, the preparation method includes the following steps: (1) weigh out the following ingredients according to the ratio: Salvia miltiorrhiza, Paeonia lactiflora, Curcuma zedoaria, Cinnamomum cassia, Corydalis yanhusuo, Hirudo medicinalis, Sappanwood, Litchi chinensis seed, Ostrea gigas and Cremastra appendiculata, mix them and soak for 30-60 minutes; (2) pre-decoct the Ostrea gigas with water for 30-60 minutes, then add the remaining medicinal materials, add 5-8 times the amount of water according to the total mass of the medicinal materials, decoct for 1.0-2.0 hours, filter, and obtain the first filtrate; (3) add 3-6 times the amount of water to the dregs after the first decoction, decoct for 0.5-1.5 hours, filter, and obtain the second filtrate; (4) combine the two filtrates, filter to remove impurities, and concentrate under reduced pressure at 55-65℃; if necessary, further dry under reduced pressure at 55-65℃ to obtain extract or freeze-dried powder.

[0030] The traditional Chinese medicine composition described in this invention can be used to prepare drugs for the prevention, relief and / or treatment of endometriosis, and is especially suitable for symptoms such as progressive dysmenorrhea, chronic pelvic pain, menstrual abnormalities, pelvic masses and infertility related to endometriosis.

[0031] The technical solution of the present invention has the following beneficial effects: (1) The traditional Chinese medicine composition for treating endometriosis provided by the present invention has readily available raw materials and mature production process. Through the synergistic effect of multiple traditional Chinese medicine components, it solves the technical problems of poor efficacy of current traditional Chinese medicine formulations, insufficient optimization of traditional Chinese medicine formulations, and high cost due to multiple traditional Chinese medicine components, thereby reducing the economic burden on patients.

[0032] (2) The traditional Chinese medicine composition for treating endometriosis provided by the present invention has been clinically observed to have a definite curative effect on treating EMs, with no obvious side effects, and animal experiments have proven that the efficacy is significant. Clinical cases show that the traditional Chinese medicine composition of the present invention can significantly relieve the pain symptoms of patients with endometriosis, reduce the size of lesions, and improve the quality of life of patients.

[0033] (3) The traditional Chinese medicine composition for treating endometriosis provided by the present invention is scientifically and rationally formulated. Clinical typical cases and animal experiments show that it can effectively treat EMs. It solves the shortcomings of existing technologies that can not cure the disease through surgical intervention and have limited efficacy of drug treatment. Furthermore, the preparation process is simple and easy to control, and the ingredients are widely available, which is conducive to large-scale production and can better meet clinical needs.

[0034] (4) The traditional Chinese medicine composition for treating endometriosis provided by the present invention, through precise selection and proportion of medicinal materials, integrates multiple mechanisms such as promoting blood circulation and removing blood stasis, regulating immunity, and anti-inflammation. It can not only effectively relieve symptoms such as pain and menstrual abnormalities caused by EMs, but also achieve the effect of controlling the condition and delaying the progression of the disease by regulating endocrine and immune functions. In addition, the present invention optimizes the proportion of the prescription and the preparation process of the drug, making the efficacy more stable, with fewer side effects, and high safety for long-term use. It is suitable for patients of different ages and has good clinical application prospects.

[0035] (5) Animal experiments show that the traditional Chinese medicine composition for treating endometriosis provided by the present invention can significantly reduce the volume of ectopic lesions, alleviate fibrosis, downregulate the expression of IL-6 and TNF-α and improve ER / PR imbalance, and has good safety. Detailed Implementation

[0036] To fully understand the purpose, features, and effects of this invention, the following detailed embodiments are provided. Except as described below, the process methods of this invention employ conventional methods or apparatus in the art. Unless otherwise specified, the terms and expressions used below have the meanings commonly understood by those skilled in the art.

[0037] Example 1 Formula: 15 parts Salvia miltiorrhiza, 15 parts Paeonia lactiflora, 10 parts Curcuma zedoaria, 5 parts Cinnamomum cassia, 10 parts Corydalis yanhusuo, 3 parts Hirudo medicinalis, 10 parts Sappanwood, 15 parts Litchi chinensis seed, 30 parts Ostrea gigas, 10 parts Cremastra appendiculata.

[0038] Preparation method: Weigh out the following ingredients according to the specified ratio: Salvia miltiorrhiza, Paeonia lactiflora, Curcuma zedoaria, Cinnamomum cassia, Corydalis yanhusuo, Hirudo medicinalis, Sappanwood, Litchi chinensis seed, Ostrea gigas, and Cremastra appendiculata. Mix well and soak for 30 minutes. First, pre-decoct the Ostrea gigas in water for 30 minutes, then add the remaining medicinal materials. Add 6 times the amount of water according to the total mass of the medicinal materials, decoct for 1.5 hours, filter, and obtain the first filtrate. Add 4 times the amount of water to the dregs after the first decoction, decoct for another hour, filter, and obtain the second filtrate. Combine the two filtrates, filter to remove impurities, concentrate under reduced pressure at 60-65℃, and dry under reduced pressure to obtain lyophilized powder.

[0039] Example 2 Formula: 10 parts Salvia miltiorrhiza, 12 parts Paeonia lactiflora, 9 parts Curcuma zedoaria, 3 parts Cinnamomum cassia, 10 parts Corydalis yanhusuo, 2 parts Hirudo medicinalis, 9 parts Sappanwood, 8 parts Litchi chinensis seed, 15 parts Ostrea gigas, and 6 parts Cremastra appendiculata.

[0040] Preparation method: Same as in Example 1.

[0041] Example 3 Formula: 13 parts Salvia miltiorrhiza, 9 parts Paeonia lactiflora, 6 parts Curcuma zedoaria, 5 parts Cinnamomum cassia, 8 parts Corydalis yanhusuo, 3 parts Hirudo medicinalis, 6 parts Sappanwood, 5 parts Litchi chinensis seed, 9 parts Ostrea gigas, and 9 parts Cremastra appendiculata.

[0042] Preparation method: Same as in Example 1.

[0043] Example 4 Formula: 15 parts of Salvia miltiorrhiza, 6 parts of Paeonia lactiflora, 8 parts of Curcuma zedoaria, 1 part of Cinnamomum cassia, 3 parts of Corydalis yanhusuo, 1 part of Hirudo medicinalis, 3 parts of Sappanwood, 10 parts of Litchi chinensis seed, 30 parts of Ostrea gigas, and 3 parts of Cremastra appendiculata.

[0044] Preparation method: Same as in Example 1.

[0045] Effect Experiment Example The following experimental examples illustrate the efficacy of the traditional Chinese medicine composition of this invention.

[0046] 1. Experimental Methods Experimental animals: Sixty 6-week-old SPF-grade female SD rats, weighing 160–180g, were selected. An ectopic cyst model was established using autologous transplantation: autologous uterine tissue was harvested from the rats, trimmed, and sutured to a highly vascularized area of ​​the abdominal wall. Postoperatively, estradiol benzoate was administered to promote lesion formation. On day 15 of model establishment, exploratory laparotomy revealed spherical or hemispherical ectopic cysts adhered to surrounding tissues and accompanied by neovascularization, indicating successful model establishment.

[0047] Grouping and administration: Except for the sham-operated group (Sham), successfully modeled rats were randomly divided into a model control group (Model), a dydrogesterone group (DQYT), and low, medium, and high dose groups of the herbal composition of this invention (DZYWF-L, DZYWF-M, and DZYWF-H), with 10 rats in each group. The DQYT group was administered dydrogesterone at 1.8 mg / kg by gavage; the DZYWF-L, DZYWF-M, and DZYWF-H groups were administered the lyophilized powder prepared in Example 1 at 1.1 g / kg, 2.21 g / kg, and 4.43 g / kg, respectively, by gavage; the Sham and Model groups were administered an equal volume of physiological saline by gavage. The intervention was carried out continuously for 28 days.

[0048] Observation indicators: record weight changes; measure the volume of ectopic lesions by laparotomy; observe the pathological changes of lesion tissue by HE staining and evaluate fibrosis by Masson staining; detect the expression of ER, PR, IL-6 and TNF-α in ectopic lesions by immunohistochemistry.

[0049] Table 1. Grouping and Dosing Regimens of Pharmacodynamic Experiments

[0050] 2. Experimental Results Safety: There was no statistically significant difference in the overall mean body weight of each group before and after administration, indicating that the herbal composition of the present invention did not show any obvious toxic side effects within the experimental dosage range.

[0051] Ectopic lesion volume: Compared with the Model group, the volume of ectopic lesions decreased in the low, medium and high dose groups of the traditional Chinese medicine composition of the present invention, with the medium and high dose groups showing better effects, suggesting that the traditional Chinese medicine composition of the present invention can significantly inhibit the growth of ectopic lesions.

[0052] Table 2 Comparison of ectopic lesion volume in each group

[0053] Pathological changes: HE staining showed that the cyst wall in the Model group was thicker, with glandular and inflammatory cell infiltration visible; after intervention with the traditional Chinese medicine composition of the present invention, the epithelium of the lesion thinned, the number of stromal cells decreased, the number of glands decreased or disappeared, and the inflammatory cell infiltration was reduced. Masson staining showed that the traditional Chinese medicine composition of the present invention can reduce the area of ​​collagen deposition and fibrosis, with the medium-dose group showing the most significant improvement.

[0054] Masson staining quantitative analysis showed that the fibrosis area in the Model group was 76.90 ± 1.40%, while in the DQYT, DZYWF-L, DZYWF-M, and DZYWF-H groups it was 49.24 ± 0.24%, 58.93 ± 0.26%, 47.97 ± 4.57%, and 67.52 ± 9.43%, respectively. The low- and medium-dose groups, as well as the dydrogesterone group, showed significant improvement compared to the Model group, with the medium-dose group showing the greatest improvement.

[0055] Immunohistochemistry: Compared with the Model group, the traditional Chinese medicine composition of this invention downregulated the expression of ER, IL-6, and TNF-α in ectopic lesions and upregulated the expression of PR, suggesting that it can improve local hormone receptor abnormalities and inhibit inflammatory responses. Combined with network pharmacology results, it is shown that its effects are related to the regulation of the TNF-α / IL-6 / STAT3 signaling axis.

[0056] Table 3 Immunohistochemical results of ER, PR, IL-6 and TNF-α in ectopic lesions ( ±s)

[0057] Western blot analysis revealed that the expression of TNF-α, IL-6, and p-STAT3 in the Model group was higher than that in the Sham group, suggesting an upregulation of inflammatory factor expression and related signaling pathway activation levels under ectopic lesion conditions. After intervention with the herbal composition of this invention, the expression of TNF-α / IL-6 / STAT3-related proteins in each dosage group showed an overall decreasing trend. This composition can inhibit the expression of TNF-α / IL-6 / STAT3-related proteins in ectopic lesion tissue to a certain extent, with the medium-dose group showing the best effect.

[0058] Table 4. Relative expression levels of TNF-α, IL-6, and p-STAT3 in ectopic lesion tissues ( ±s)

[0059] 3. Experimental Conclusions The above results indicate that the herbal composition of the present invention can significantly inhibit the growth of ectopic lesions of endometriosis, improve the histological morphology of the lesions, reduce fibrosis, regulate the ER / PR balance, and inhibit the abnormal expression of inflammatory factors such as IL-6 and TNF-α, and has the potential to be developed as a drug for the treatment of endometriosis.

[0060] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0061] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

[0062] Furthermore, various different embodiments of the present invention can be combined in any way, as long as they do not violate the spirit of the present invention, they should also be regarded as the content disclosed by the present invention.

Claims

1. A traditional Chinese medicine composition for treating endometriosis, characterized in that, The traditional Chinese medicine composition is made from the following ingredients: Salvia miltiorrhiza, Paeonia lactiflora, Curcuma zedoaria, Cinnamomum cassia, Corydalis yanhusuo, Hirudo medicinalis, Sappanwood, Litchi chinensis seed, Ostrea gigas and Cremastra appendiculata.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition comprises, by weight, 10-15 parts of Salvia miltiorrhiza, 6-15 parts of Paeonia lactiflora, 6-10 parts of Curcuma zedoaria, 1-5 parts of Cinnamomum cassia, 3-10 parts of Corydalis yanhusuo, 1-3 parts of Hirudo medicinalis, 3-10 parts of Caesalpinia sappan, 5-15 parts of Litchi chinensis seed, 9-30 parts of Ostrea gigas, and 3-10 parts of Cremastra appendiculata.

3. The traditional Chinese medicine composition according to claim 2, characterized in that, The traditional Chinese medicine composition comprises, by weight, 12-15 parts of Salvia miltiorrhiza, 10-15 parts of Paeonia lactiflora, 8-10 parts of Curcuma zedoaria, 3-5 parts of Cinnamomum cassia, 8-10 parts of Corydalis yanhusuo, 2-3 parts of Hirudo medicinalis, 8-10 parts of Caesalpinia sappan, 10-15 parts of Litchi chinensis seed, 15-30 parts of Ostrea gigas, and 6-10 parts of Cremastra appendiculata.

4. The traditional Chinese medicine composition according to any one of claims 1 to 3, characterized in that, The traditional Chinese medicine composition, by weight, consists of: 15 parts of Salvia miltiorrhiza, 15 parts of Paeonia lactiflora, 10 parts of Curcuma zedoaria, 5 parts of Cinnamomum cassia, 10 parts of Corydalis yanhusuo, 3 parts of Hirudo medicinalis, 10 parts of Sappanwood, 15 parts of Litchi chinensis seed, 30 parts of Ostrea gigas, and 10 parts of Cremastra appendiculata.

5. A method for preparing the traditional Chinese medicine composition according to any one of claims 1 to 4, characterized in that, Includes the following steps: The raw materials are mixed and then boiled for extraction, or they are first crushed and then mixed, or they are mixed and then extracted and further refined to obtain extracts or effective components.

6. The preparation method according to claim 5, characterized in that: Includes the following steps: After soaking the raw materials, the oysters are pre-decocted, and then the remaining medicinal materials are added for at least two decoctions. The filtrates are filtered and combined, and then concentrated under reduced pressure. If necessary, further concentration under reduced pressure and / or drying are performed to obtain an extract or lyophilized powder.

7. The preparation method according to claim 6, characterized in that: Soaking time is 30-60 minutes; oyster pre-decoction time is 30-60 minutes; for the first decoction, the amount of water added is 5-8 times the total mass of the medicinal materials, and the decoction is carried out for 1.0-2.0 hours; for the second decoction, the amount of water added is 3-6 times the total mass of the medicinal materials, and the decoction is carried out for 0.5-1.5 hours; the temperature for vacuum concentration and / or drying is 55-65℃.

8. The preparation method according to any one of claims 5 to 7, characterized in that, The traditional Chinese medicine composition is prepared into pills, powders, decoctions, extracts, granules, tablets, capsules, oral liquids, or freeze-dried preparations.

9. The use of the traditional Chinese medicine composition according to any one of claims 1 to 4 in the preparation of a drug for the prevention, relief and / or treatment of endometriosis.

10. The application according to claim 9, characterized in that, The symptoms associated with endometriosis include progressive dysmenorrhea, chronic pelvic pain, menstrual irregularities, pelvic masses, and / or infertility associated with endometriosis.

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