Traditional Chinese medicine composition for preventing and treating relapse of colorectal adenoma and preparation method thereof

Abstract

The invention discloses a traditional Chinese medicine composition for preventing and treating relapse of colorectal adenoma, which is prepared from the following raw material medicines: coptis chinensis, mangnolia officinalis, rhizoma acori graminei, fructus amomi, raw coix seed, curcuma zedoary, edible tulip, roasted rhizoma atractylodis macrocephalae and raw astragalus mongholicus, and a preparation method and application of the traditional Chinese medicine composition. The traditional Chinese medicine composition disclosed by the invention can effectively improve clinical symptoms of patients with colorectal adenoma, effectively reduce the recurrence rate of endoscopically removed patients with colorectal adenoma, and play a role in inhibiting colorectal adenoma by adjusting a polyunsaturated fatty acid metabolic pathway of mice with colorectal adenoma.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition for preventing and treating recurrence of colorectal adenoma and a preparation method thereof. Background Art

[0002] Colorectal adenoma refers to a tumor with abnormal proliferation of colorectal mucosal epithelium, and is the most common benign tumor among colorectal tumors. Colorectal cancer is a malignant tumor that ranks among the top three in terms of incidence and mortality worldwide. Colorectal adenoma accounts for 85% to 90% of the precancerous lesions of colorectal cancer, and it is the leading cause. The canceration rate of adenomatous polyps is approximately 1.4% to 20.4%. The evolution process from low-grade adenoma to high-grade adenoma takes about 10 years. Early detection and treatment of colorectal adenoma is the key to reducing the incidence of colorectal cancer. At present, endoscopic treatment is the first-line treatment for colorectal adenoma, but it still has a high recurrence rate after resection. According to statistics, the recurrence rates of colorectal polyps in my country in the first and second years after surgery are 38.1% and 78.2%, respectively. This ratio is positively correlated with the patient's age, the number of adenomas, and the malignancy of adenomas. That is, as these factors increase, the recurrence rate also increases.

[0003] Currently, there is no drug on the market that can prevent the recurrence and malignant transformation of colorectal adenomas. The main treatment for colorectal adenomas is endoscopic resection, but the risk of recurrence is higher after adenomatous polyps are removed. Repeated endoscopic examinations and endoscopic treatments also bring great psychological and economic burdens to patients. Therefore, preventing and treating the recurrence of colorectal polyps after surgery is the key to reducing the incidence of colorectal cancer and improving the quality of life of patients with colorectal polyps. The use of traditional Chinese medicine to prevent and treat the recurrence of colorectal polyps after surgery has a good effect and shows good prospects.

[0004] The treatment of colorectal adenoma with traditional Chinese medicine compound is mainly reflected in improving the quality of life of patients with adenoma and reducing the recurrence of adenoma. Studies have shown that combined treatment with traditional Chinese medicine after endoscopic surgery can reduce the recurrence rate of colorectal adenoma, and the effect is better than simple endoscopic treatment, providing patients with a new treatment approach. At present, there are no drugs for the prevention and treatment of colorectal adenoma at home and abroad, and such products are urgently needed to fill the gap. Summary of the invention

[0005] The purpose of the present invention is to provide a Chinese medicine composition for preventing and treating recurrence of colorectal adenoma and a preparation method thereof.

[0006] To achieve this object, the present invention adopts the following technical scheme: a traditional Chinese medicine composition for preventing and treating the recurrence of colorectal adenoma, which is prepared by extracting the following traditional Chinese medicine pieces in parts by weight: 3-10 parts of coptis chinensis, 6-10 parts of magnolia bark, 5-10 parts of calamus, 2-4 parts of amomum villosum, 10-20 parts of raw coix seeds, 8-12 parts of zedoaria, 5-10 parts of trillium, 10-20 parts of stir-fried atractylodes, and 5-15 parts of raw astragalus.

[0007] The Chinese medicine composition for preventing and treating the recurrence of colorectal adenoma is prepared by extracting the following Chinese medicine pieces in parts by weight: 5 parts of coptis root, 6 parts of magnolia bark, 10 parts of calamus, 4 parts of amomum villosum, 15 parts of raw coix seeds, 10 parts of zedoaria, 5 parts of trillium, 15 parts of stir-fried atractylodes, and 10 parts of raw astragalus.

[0008] The Chinese medicine composition for preventing and treating the recurrence of colorectal adenoma is prepared by extracting the following Chinese medicine pieces in parts by weight: 3 parts of coptis root, 10 parts of magnolia bark, 5 parts of calamus, 4 parts of amomum, 10 parts of raw coix seeds, 12 parts of zedoaria, 5 parts of trillium, 20 parts of stir-fried atractylodes, and 5 parts of raw astragalus.

[0009] The Chinese medicine composition for preventing and treating the recurrence of colorectal adenoma is prepared by extracting the following Chinese medicine pieces in parts by weight: 10 parts of coptis root, 6 parts of magnolia bark, 10 parts of calamus, 2 parts of amomum villosum, 20 parts of raw coix seeds, 8 parts of zedoaria, 10 parts of trifoliate osmanthus, 10 parts of stir-fried atractylodes, and 15 parts of raw astragalus.

[0010] The Chinese medicine composition for preventing and treating the recurrence of colorectal adenoma is in the form of an oral dosage form.

[0011] The Chinese medicinal composition for preventing and treating the recurrence of colorectal adenoma has an oral dosage form of tablets, capsules, granules and oral liquid.

[0012] The preparation method of the Chinese medicine composition for preventing and treating recurrence of colorectal adenoma comprises the following steps:

[0013] (1) Weighing the various Chinese herbal medicine slices, mixing, decocting with water, filtering, collecting the filtrate, concentrating the obtained medicinal solution, adding ethanol for alcohol precipitation, centrifuging, collecting the supernatant, and concentrating into an extract with a density of 1.20-1.30 g / mL;

[0014] (2) spray-drying the extract prepared in step (1), adding auxiliary materials, and preparing it into one of tablets, capsules, and granules.

[0015] The preparation method of the Chinese medicine composition for preventing and treating recurrence of colorectal adenoma comprises the following steps:

[0016] (1) Weighing the various Chinese herbal medicine slices, mixing, decocting with water, filtering, collecting the filtrate, concentrating the obtained medicinal solution, adding ethanol for alcohol precipitation, centrifuging, collecting the supernatant, and concentrating into an extract with a density of 1.20-1.30 g / mL;

[0017] (2) Take the extract prepared in step (1), add sucrose, and prepare an oral solution.

[0018] The Chinese medicine composition for preventing and treating the recurrence of colorectal adenoma is used in the preparation of a drug for preventing and treating the recurrence of colorectal adenoma, and colorectal adenoma belongs to the syndrome of spleen deficiency, dampness and blood stasis.

[0019] Coptis chinensis: bitter in taste, cold in nature, and enters the heart, stomach, liver, and large intestine meridians. It clears away heat and dampness, purges fire and detoxifies, and is used to treat damp-heat fullness, damp-heat symptoms such as diarrhea and abdominal pain. Ingredients in Coptis chinensis, such as berberine, can inhibit tumor cell proliferation, induce apoptosis, enhance the activity of immune cells such as T lymphocytes and NK cells, and promote cytokine secretion, thereby helping to fight tumor cells.

[0020] Magnolia officinalis: bitter and pungent in taste, warm in nature, enters the spleen, stomach, lung, and large intestine meridians. It can dry dampness and eliminate phlegm, relieve qi and relieve fullness, and is used for dampness stagnation, abdominal distension, vomiting and diarrhea, food accumulation and qi stagnation, abdominal distension and constipation, etc. The active ingredients in Magnolia officinalis, such as magnolol, have the function of regulating cell cycle-related proteins and apoptosis signaling pathways, and can inhibit the invasion and metastasis of tumor cells to exert anti-cancer effects; in terms of immunity, Magnolia officinalis can regulate the body's immune function, enhance the phagocytic activity of macrophages, promote the secretion of immune cytokines, and regulate the differentiation and proliferation of immune cells.

[0021] Acorus calamus: pungent and bitter in taste, warm in nature, and enters the heart and stomach meridians. It can open the mind and dissipate phlegm, wake up the mind and improve intelligence, remove dampness and stimulate appetite. It is used for symptoms such as abdominal distension without hunger, and dysentery with a closed mouth. Acorus calamus can promote gastrointestinal peristalsis, stimulate the contraction of gastrointestinal smooth muscles, help improve gastrointestinal motility, and relieve symptoms such as indigestion and gastrointestinal distension.

[0022] Amomum villosum: pungent in taste, warm in nature, and enters the spleen, stomach, and kidney meridians. It has the effects of removing dampness and stimulating appetite, warming the spleen and stopping diarrhea, regulating qi and calming the fetus. It is often used for symptoms such as dampness and turbidity blocking the middle part of the body, abdominal distension without hunger, vomiting and diarrhea. In terms of the pharmacological effects on colon adenoma and adenocarcinoma, the volatile oil components in Amomum villosum, such as bornyl acetate, may inhibit the proliferation of tumor cells and induce apoptosis by regulating the intracellular signal transduction pathway.

[0023] Raw coix seed: cool in nature, sweet and light in taste, and enters the spleen, stomach, and lung meridians. It can promote diuresis and eliminate dampness, strengthen the spleen and stop diarrhea, remove numbness, discharge pus, detoxify and disperse knots, and is often used for spleen deficiency diarrhea, dampness and numbness cramps, intestinal carbuncle, cancer and other diseases. In terms of colon adenoma and adenocarcinoma, the ingredients such as coix lacrymate and coix seed oil in raw coix seed have potential anti-cancer activity, which may play a role by interfering with the metabolic process of tumor cells, inducing tumor cell apoptosis, and inhibiting the invasion and metastasis of tumor cells. It can enhance the phagocytic activity of macrophages and stimulate the proliferation and differentiation of T lymphocytes and B lymphocytes.

[0024] Curcuma: Spicy and bitter in taste, warm in nature, enters the liver and spleen meridians. It can promote blood circulation and qi, eliminate accumulation and relieve pain, and is often used for blood stasis, amenorrhea, chest pain, heart pain, stagnation, abdominal distension and pain, etc. The active ingredients contained in Curcuma, such as curcumol and curcumone, can inhibit the proliferation of tumor cells, induce their apoptosis, inhibit tumor angiogenesis, activate immune cells such as macrophages and NK cells, enhance their phagocytic ability and killing activity, and increase the secretion level of cytokines such as interleukins and interferons.

[0025] Trillium: Sweet, slightly spicy, cool in nature, enters the liver and spleen meridians. It has the effects of clearing away heat and detoxifying, resolving phlegm and dispersing nodules, and is often used for carbuncle, furuncle, scrofula, phlegm nodules, masses and lumps. Colchicine and other ingredients in Trillium may inhibit the mitosis of tumor cells, interfere with the proliferation process of tumor cells, induce tumor cell apoptosis, and thus inhibit the transformation of colon adenoma to adenocarcinoma and the further development of adenocarcinoma.

[0026] Stir-fried Atractylodes macrocephala: warm in nature, bitter and sweet in taste, and enters the spleen and stomach meridians. It strengthens the spleen and replenishes qi, dries dampness and promotes diuresis, and is often used for symptoms such as spleen deficiency, poor appetite, abdominal distension and diarrhea. In terms of colon adenoma and adenocarcinoma, the ingredients such as atractylodesone and atractylodes alcohol contained in stir-fried Atractylodes macrocephala may play a role in multiple ways. For example, it may regulate cell proliferation and apoptosis-related signaling pathways, inhibit the abnormal proliferation of colon tumor cells, and induce apoptosis of cancer cells, thereby hindering the development of tumors; at the same time, stir-fried Atractylodes macrocephala can also enhance the phagocytic ability of macrophages, promote the proliferation and differentiation of lymphocytes, and increase the secretion level of cytokines such as interleukins and interferons, thereby enhancing the body's immune surveillance and killing of colon tumor cells.

[0027] Astragalus: sweet in taste, slightly warm in nature, and enters the spleen and lung meridians. It can replenish qi and raise yang, strengthen the body's defense system, remove toxins and promote tissue regeneration, and promote diuresis and reduce swelling. It is used for fatigue, loss of appetite, and loose stools caused by spleen deficiency. Astragalus can inhibit tumor cell proliferation, induce tumor cell apoptosis, and enhance the activity of immune cells such as T lymphocytes and NK cells.

[0028] There is no such disease name as "colonic adenoma" in traditional Chinese medicine. The clinical symptoms of colonic adenoma vary, and can be manifested as abdominal pain, abdominal distension and discomfort, diarrhea, constipation, mucus stool and even bloody stool. According to its clinical manifestations, it can be classified into the categories of "intestinal tumor", "intestinal accumulation", "intestinal fungus", "diarrhea" and "constipation". Regarding the cause of colonic adenoma, most people believe that it is caused by the six exogenous pathogens, improper diet, emotional injury, and insufficient congenital endowment, which lead to the loss of spleen and stomach transportation and transformation, and the sticky and heavy dampness, which easily hinders the movement of qi. In the intestines and other parts, dampness stagnates and affects the normal conduction function of the intestines. At the same time, dampness and heat evil fight each other, and heat evil boils body fluids, causing body fluids to condense into phlegm, and phlegm and heat are combined, further aggravating the pathological products in the body. In the colon and other parts, dampness, heat and phlegm evil condense, qi and blood flow is not smooth, qi and blood stagnate in the intestines, blood stasis is not removed, and new blood is not generated. Over time, it will form lumps and lead to "intestinal tumor" or "intestinal fungus". The "Expert Consensus on the Diagnosis and Treatment of Large Colorectal Adenomas and Early Colorectal Cancer with Integrated Traditional Chinese and Western Medicine" formulated by the Chinese Society of Integrated Traditional Chinese and Western Medicine in 2021 divides colorectal adenomas into five syndromes: cold-dampness obstruction syndrome, damp-heat accumulation syndrome, spleen deficiency-dampness stasis syndrome, qi stagnation and blood stasis syndrome, and spleen deficiency syndrome. In clinical practice, spleen deficiency-dampness stasis syndrome is the most common.

[0029] In general, dampness, heat, phlegm, and blood stasis are the main pathogenesis of colon adenoma caused by spleen deficiency, dampness, and blood stasis. First of all, dampness, heat, phlegm, and blood stasis are important factors in the formation of colon polyps. Excessive consumption of stimulating foods such as fatty, sweet, and spicy alcohol can easily breed dampness and heat in the body. For example, eating a lot of barbecue, fried foods, and strong alcohol can cause damage to the spleen and stomach's transportation and transformation functions. The spleen and stomach cannot normally transport and transform the essence of water and grain, and water and dampness accumulate, and dampness accumulates and turns into heat, forming dampness and heat. Dampness and heat accumulate in the large intestine, which will affect the large intestine's conduction function and the circulation of qi and blood. The large intestine mucosa is burned by dampness and heat for a long time, and the local qi and blood are stagnant. Dampness and blood stasis are stuck together, which can easily lead to abnormal proliferation of colon mucosal tissue, thereby causing colon adenoma. In a humid and hot environment, the human body is easily affected by dampness and heat from the outside world. For example, in the plum rain season in the south, the humidity is heavy. If the human body lacks positive energy, dampness and heat will take the opportunity to invade the human body and directly attack the large intestine. Or after being infected with exogenous dampness, due to physical factors, dampness quickly turns into heat in the body, and dampness and heat accumulate in the intestine. This external dampness and heat will disrupt the normal physiological environment of the large intestine, causing the large intestine mucosa to be in an inflammatory pathological state. Inflammation repeatedly stimulates the mucosa, causing excessive proliferation of mucosal cells and increasing the risk of colon adenoma. Secondly, dampness, heat, phlegm and blood stasis are the pathological mechanisms that lead to colon polyps. Stagnation of qi and blood and dampness and heat are intertwined. The accumulation of dampness and heat in the colon will hinder the movement of qi. When qi moves, blood moves, and when qi stagnates, blood stagnates. The poor qi movement caused by dampness and heat will cause blood stasis, and blood stasis and dampness and heat will fight each other. This state of qi and blood stagnation will cause obstruction of the microcirculation of the large intestine mucosa. The mucosa cannot be adequately nourished by qi and blood. At the same time, it is stimulated by dampness, heat and blood stasis. The balance of cell proliferation and apoptosis is broken, and the normal mucosal tissue will undergo abnormal hyperplasia and form adenoma. If dampness and heat accumulate in the body for a long time, it may also turn into poison. Toxic pathogens are more pathogenic and can further damage the cell structure and function of the colon mucosa. From the perspective of modern medicine, this toxicity may be related to the accumulation of toxins in the intestines and the metabolites of harmful microorganisms. When dampness and heat accumulate, the possibility of malignant transformation of colon polyps will also increase, because toxic pathogens can cause abnormal changes such as gene mutations in polyp cells, causing polyps to transform from benign to malignant.

[0030] In summary, the pathogenesis of colorectal adenoma with spleen deficiency and dampness stasis syndrome involves impaired spleen and stomach transportation and transformation function, accumulation of water and dampness, depression of dampness and heat, formation of damp-heat evil, condensation of water and dampness into phlegm, leading to disorder of qi mechanism, internal stasis of blood, phlegm and blood stasis, and formation of colon adenoma over time, so dampness, heat, phlegm and blood stasis run through the whole process of colorectal adenoma formation. The Chinese medicine composition of the present invention is a prescription for the prevention and treatment of colorectal adenoma, which is the most common syndrome type of Chinese medicine for colorectal adenoma, spleen deficiency and dampness stasis syndrome, and is derived from Lianpuyin, which is a prescription for the prevention and treatment of colorectal adenoma. Among them, Coptis chinensis, Magnolia bark, and Acorus gramineus are used as the main ingredients of Lianpuyin prescription. Coptis chinensis clears heat and dries dampness, purges fire and detoxifies, Magnolia bark dries dampness and eliminates phlegm, lowers qi and removes fullness, and Acorus gramineus removes dampness and stimulates appetite. The three are compatible, and play the functions of clearing heat and dampness, removing dampness and removing fullness, regulating qi and stimulating appetite, and effectively remove damp-heat evil in the body.

[0031] The spleen and stomach are the source of dampness, heat, phlegm and blood stasis. Their generation and dissipation are related to the spleen and stomach's transportation and transformation and qi movement. "The Theory of the Spleen and Stomach: The Theory of the Rise and Fall of Yin and Yang" states: "In humans, clear and turbid qi all come from the spleen and stomach, and the nourishing qi nourishes the body, which is transformed by the qi of water and grain." "The Four Sacred Heart Sources" points out that "when the middle qi is weak, the rise and fall are blocked..., blood disease causes stagnation and does not flow, and qi disease causes stagnation and does not clear. All diseases of the four dimensions are caused by the middle qi. The middle qi is the mechanism of harmonizing water and fire, and the axis of rising and falling metal and wood." It points out the key role of the spleen and stomach in the rise and fall of the human body's qi movement, and emphasizes that the spleen and stomach function is the root cause of many diseases including dampness, heat, phlegm and blood stasis. In the syndrome of spleen deficiency and dampness and blood stasis, the abnormal rise and fall of the spleen and stomach will lead to the disorder of the whole body's qi movement. By regulating the spleen and stomach qi movement and restoring its rise and fall function, the qi movement can be unobstructed, dampness and heat can be dissipated, and phlegm and blood stasis can be dissipated. The "Golden Chamber Essentials: Water Qi Disease Pulse Symptoms and Treatments" mentioned: "Once the atmosphere changes, the knot will be dispersed." The "atmosphere" here can be understood as the qi of the human body. When the qi is unobstructed, it can dissipate pathological products including damp heat, phlegm and blood stasis. At the same time, damp heat, phlegm and blood stasis block the meridians and qi and blood. Regulating the spleen and stomach qi can improve the symptoms of poor meridian qi and blood caused by damp heat, phlegm and blood stasis. Li Diangui, a master of traditional Chinese medicine, believes that turbidity and toxins are the main cause of colon polyps. Turbidity and toxins stay inside, hindering the flow of qi, blood and body fluids, and can change into phlegm and turbidity. Phlegm and turbidity and blood stasis are intertwined and blocked in the intestines, leading to the occurrence of polyps. Professor Zhou Bin called digestive tract polyps "intracavitary masses", believing that they are based on insufficient spleen qi and deficiency of body qi, generating phlegm and dampness turbidity, which stays in the large intestine for a long time and forms "phlegm and turbidity" is the root cause of the disease. Zhang Tao et al. proposed that the deterioration of adenomatous colorectal polyps is related to phlegm and toxins, and phlegm is involved in the entire process of polyp-adenoma-cancer sequence evolution. The present invention uses Amomum villosum, Coix seeds, Curcuma zedoaria and Psoralea corylifolia as ministerial drugs. The Compendium of Materia Medica states that Amomum villosum "awakens the spleen, regulates the vital energy, unblocks stagnant qi, dispels cold and phlegm, chokes and vomits", and the Compendium of Materia Medica states that Amomum villosum "harmonises the middle and replenishes qi, warms the stomach and digests food", and Zhang Yuansu states that Amomum villosum "treats stagnation of qi in the spleen and stomach". Amomum villosum "awakens the spleen", "regulates the vital energy, unblocks stagnant qi", "harmonises the middle and replenishes qi", and "treats stagnation of qi", has the effects of harmonizing the spleen and stomach, unblocking qi mechanism and helping the spleen and stomach to transport and transform, and its pungent and dispersing nature helps to eliminate dampness, so that dampness can be transported and transformed, and heat evil is alleviated accordingly. By restoring the normal rise and fall and transportation of spleen and stomach qi, the source of phlegm is eliminated. At the same time, "qi is the commander of blood, and blood flows when qi flows". Amomum villosum regulates spleen and stomach qi, promotes the circulation of qi, prevents the formation of blood stasis, and is used with blood-activating and stasis-removing drugs to enhance the effect of blood-activating and stasis-removing. Coix seed removes dampness and promotes diuresis. When used together with Acorus calamus, it strengthens the effects of invigorating the spleen and appetizing, removing dampness and promoting qi. Curcuma zedoaria and Tripterygium wilfordii are also components of the ministerial medicine. Curcuma zedoaria can break blood and promote qi, eliminate accumulation and relieve pain, while Tripterygium wilfordii can clear heat and detoxify, resolve phlegm and disperse knots. The combination of the two can not only activate blood and eliminate accumulation, but also detoxify, resolve phlegm and disperse knots. It can be used to treat lumps and masses caused by internal blood stasis and phlegm and toxicity. Compared with using Curcuma zedoaria alone, adding Trillium gracile has a better effect on phlegm diseases. Chen Shiduo's "New Edition of Materia Medica" says: "Most strange diseases are caused by phlegm. Trillium gracile is the holy medicine for eliminating phlegm. If the phlegm is treated, the strange diseases will naturally be eliminated."Psoralea corylifolia-curcuma zedoaria is a typical representative drug pair of the method of resolving phlegm and eliminating blood stasis. Damp heat refines liquid into phlegm, which moves with qi and can circulate throughout the body. Over time, it affects the blood, causing blood stasis, and phlegm and blood stasis, which eventually lead to colon adenoma and even cancer. In the anti-tumor medical records of Zhou Zhongying, a master of traditional Chinese medicine, the most frequently used Chinese medicine is Psoralea corylifolia, which is close to 77.29%. Pharmacological studies have found that Psoralea corylifolia has the effects of inhibiting tumor cell proliferation and metastasis, regulating the body's immune system, and protecting nerves. Curcuma zedoaria is pungent and bitter in taste and warm in nature. It has the functions of eliminating lumps, breaking blood stasis, dispersing blood stasis, treating heartache, and eliminating abdominal pain. In modern pharmacological studies of Curcuma zedoaria, it is often believed that it has anti-tumor, anti-platelet aggregation and thrombosis, liver protection, antioxidant, and antiviral effects. The combination of Psoralea corylifolia and Curcuma zedoaria can not only disperse stagnation, eliminate phlegm and detoxify, but also break blood, remove blood stasis and promote qi. The invention selects Amomum villosum, Coix seeds, Curcuma zedoaria and Psoralea corylifolia as the assistant drugs, and promotes the effects of the main drugs Rhizoma Coptidis, Magnolia officinalis and Acorus calamus on clearing away heat and dampness, removing dampness and eliminating fullness, regulating qi and stimulating appetite.

[0032] Spleen deficiency can lead to insufficient positive energy in the body, which is an important force for the human body to resist disease. By strengthening the positive energy, the spleen and stomach functions can be enhanced, the body's disease resistance can be improved, and thus the body can better resist and eliminate pathogenic factors. Eliminating pathogenic factors to eliminate pathological factors: dampness and blood stasis are the main pathological factors leading to spleen deficiency dampness and stasis syndrome. The purpose of eliminating pathogenic factors is to eliminate these pathological factors by methods such as removing dampness and activating blood circulation, thereby alleviating symptoms and promoting recovery of the disease. Strengthening the positive energy and eliminating pathogenic factors are two aspects that complement each other. Strengthening the positive energy can enhance the body's disease resistance and help eliminate pathogenic factors; while eliminating pathogenic factors can reduce the damage of pathogenic factors to positive energy, which is conducive to the recovery of positive energy. Spleen deficiency dampness and stasis syndrome is a syndrome of mixed deficiency and excess, with both deficiency symptoms of insufficient positive energy and excess symptoms of dampness and blood stasis. Therefore, stir-fried Atractylodes macrocephala and raw Astragalus membranaceus are used as adjuvants to strengthen the positive energy and eliminate pathogenic factors. Damp-heat, phlegm and stasis will last for a long time, and the spleen and stomach will be weak. The two can strengthen the spleen and replenish qi, and cooperate with the drugs for eliminating pathogenic factors to restore the positive energy and remove the pathogenic factors easily.

[0033] The whole formula works together to eliminate dampness and heat, strengthen the body and eliminate symptoms, and has a definite therapeutic effect on preventing the recurrence of colorectal adenoma.

[0034] Clinical data show that the recurrence rate of colon adenoma in the treatment of spleen deficiency, dampness and stasis syndrome in the Chinese medicine composition group is 17.4%, and the recurrence rate in the control group is 33.3%, indicating that the Chinese medicine composition of the present invention can effectively reduce the recurrence rate of patients with endoscopic removal of colon adenomas, and significantly reduce the number and size of adenomas in mice with colon adenoma. Mechanism studies have shown that the present invention affects the fatty acid metabolic pathway in mice with colorectal adenoma. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 :The Chinese medicine composition of the present invention inhibits colon adenoma induced by AOM+DSS. (A) Experimental schematic diagram of colon adenoma model establishment and drug treatment; (B) Changes in mouse body weight; (C) Number of colon adenomas; (D) Size (area) of colon adenoma.

[0036] Figure 2 :Metabolomics screening of the action pathways of colon adenoma and analysis of the volcano plot of the two groups of differential metabolites. DETAILED DESCRIPTION

[0037] The technical solution of the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only for exemplary description and explanation of the present invention and should not be construed as limiting the scope of protection of the present invention.

[0038] Embodiment 1: Take 500g of Coptis chinensis, 600g of Magnolia officinalis, 1000g of Acorus calamus, 400g of Amomum villosum, 1500g of raw Coix seeds, 1000g of Curcuma zedoaria, 500g of Psoralea corylifolia, 1500g of stir-fried Atractylodes macrocephala, and 1000g of raw Astragalus, and the preparation method comprises the following steps:

[0039] (1) Weighing the various Chinese herbal medicine slices, mixing, decocting twice with water, each time adding water in an amount of 10 times the weight of the Chinese herbal medicine slices, filtering, collecting the filtrate, combining, concentrating the resulting liquid, adding 95% ethanol for alcohol precipitation to make the ethanol content in the liquid 75%, centrifuging, collecting the supernatant, and concentrating to an extract with a density of 1.25 g / mL;

[0040] (2) spray-drying the extract prepared in step (1), adding starch, and preparing granules.

[0041] Example 2: Take 300g of Coptis chinensis, 1000g of Magnolia officinalis, 500g of Acorus calamus, 400g of Amomum villosum, 1000g of raw Coix seeds, 1200g of Curcuma zedoaria, 500g of Trillium, 2000g of stir-fried Atractylodes macrocephala, and 500g of raw Astragalus. The preparation method comprises the following steps:

[0042] (1) Weighing the various Chinese herbal medicine slices, mixing them, decocting them twice with water, with the amount of water added each time being 10 times the weight of the Chinese herbal medicine slices, filtering, collecting the filtrate, combining, concentrating the resulting medicinal solution, adding 95% ethanol for alcohol precipitation to make the ethanol content in the medicinal solution 75%, centrifuging, collecting the supernatant, and concentrating it into an extract with a density of 1.20 g / mL;

[0043] (2) spray-drying the extract prepared in step (1), adding dextrin, and preparing into tablets.

[0044] Example 3: Take 1000g of Coptis chinensis, 600g of Magnolia officinalis, 1000g of Acorus calamus, 200g of Amomum villosum, 2000g of raw Coix seeds, 800g of Curcuma zedoaria, 1000g of Psoralea corylifolia, 1000g of stir-fried Atractylodes macrocephala, and 1500g of raw Astragalus. The preparation method comprises the following steps:

[0045] (1) Weighing the various Chinese herbal medicine slices, mixing them, decocting them twice with water, with the amount of water added each time being 10 times the weight of the Chinese herbal medicine slices, filtering, collecting the filtrate, combining, concentrating the resulting medicinal solution, adding 95% ethanol for alcohol precipitation to make the ethanol content in the medicinal solution 75%, centrifuging, collecting the supernatant, and concentrating it into an extract with a density of 1.30 g / mL;

[0046] (2) spray-drying the extract prepared in step (1), adding starch, and preparing capsules.

[0047] Example 4: Take 500g of Coptis chinensis, 600g of Magnolia officinalis, 1000g of Acorus calamus, 400g of Amomum villosum, 1500g of raw Coix seeds, 1000g of Curcuma zedoaria, 500g of Psoralea corylifolia, 1500g of stir-fried Atractylodes macrocephala, and 1000g of raw Astragalus. The preparation method comprises the following steps:

[0048] (1) Weighing the various Chinese herbal medicine slices, mixing, decocting twice with water, with the amount of water added each time being 10 times the weight of the Chinese herbal medicine slices, filtering, collecting the filtrate, concentrating the resulting medicinal solution into a first extract with a density of 1.15 g / mL, adding ethanol for alcohol precipitation, centrifuging, collecting the supernatant, and concentrating into a second extract with a density of 1.25 g / mL;

[0049] (2) Take the extract prepared in step (1), add sucrose, and prepare an oral solution.

[0050] Example 5: Clinical study

[0051] 1. Inclusion criteria: (1) Meet the diagnostic criteria of colorectal adenoma and TCM syndrome differentiation criteria. (2) Aged 18-75 years (inclusive), regardless of gender. (3) Patients volunteer to participate in the study and sign the informed consent form. The process of obtaining the informed consent form should comply with ethical principles.

[0052] 2. Western medicine diagnostic standards: refer to the Chinese Consensus on Endoscopic Diagnosis and Treatment of Colorectal Cancer and Precancerous Lesions (2023, Guangzhou), the Chinese Expert Consensus on Early Diagnosis and Treatment of Colorectal Cancer (2023 Edition) and the 2023 "Guidelines for the Prevention and Treatment of Colorectal Adenomas with Integrated Traditional Chinese and Western Medicine". Clinical manifestations: Some patients may experience symptoms such as abdominal distension and pain, difficult defecation, diarrhea, mucus stool, and blood in the stool. Some patients do not have the above clinical symptoms. The diagnosis of this disease is mainly based on endoscopic and pathological examinations. Pathological histological diagnosis: The pathological diagnostic criteria for colorectal adenoma can be divided into ① tubular adenoma (villous structure component less than 25%), ② villous adenoma (villous structure component more than 75%), and ③ tubular-villous adenoma (villous structure component between 25% and 75%) according to the adenoma structure. Those with tubular adenomas (villous structure component less than 25%) are included.

[0053] 3. TCM diagnostic and differentiation standards: Refer to the "Expert Consensus on the Diagnosis and Treatment of Colorectal Adenoma and Early Colorectal Cancer with Integrated Traditional Chinese and Western Medicine" formulated by the Chinese Society of Integrated Traditional Chinese and Western Medicine in 2021. Spleen deficiency, dampness and blood stasis syndrome: The main symptoms include abdominal fullness, even abdominal distension and pain, or stabbing pain, constipation or loose stools, tenesmus, and secondary symptoms include shortness of breath, laziness to speak, limb fatigue, poor appetite, pale and dark tongue, white or greasy tongue coating, and thin and wiry pulse.

[0054] 4. Exclusion criteria: (1) Patients diagnosed with familial adenomatous polyposis, Peutz-Jeghers polyposis, or Turcot syndrome; (2) Patients whose adenomas have been pathologically confirmed to have become malignant (including high-grade intraepithelial neoplasia); (3) Patients with a Boston score of <6 for bowel preparation during colonoscopy; (4) Patients with severe primary diseases of the heart, brain, liver, kidney, and hematopoietic system, as well as mental illness; (5) Women who are pregnant or preparing to become pregnant, or women who are breastfeeding. (6) Suspected or confirmed history of alcohol or drug abuse; (7) Participants in other clinical trials or deemed unsuitable by the investigators for this trial; (8) Allergic constitution, such as those with a history of allergies to two or more drugs or foods; or those known to be allergic to the ingredients of this drug; (9) Those currently taking or need to take drugs during the study that may affect the effectiveness evaluation of the trial drug: lipid-lowering drugs, metformin, non-steroidal anti-inflammatory drugs (such as aspirin, ibuprofen, diclofenac, etc.), cyclooxygenase 2 inhibitors (such as celecoxib, etc.) and other traditional Chinese medicines, etc. (10) Other reasons that, according to the investigators' judgment, reduce the possibility of enrollment or complicate enrollment, such as frequent changes in work environment, which may easily lead to loss of follow-up.

[0055] 5. Treatment methods: (1) The treatment group of the present invention: In addition to the routine treatment after colorectal polypectomy, the granules prepared in Example 1 of the present invention were given after the resumption of diet, with a daily dosage of 5g of Coptis chinensis, 6g of Magnolia officinalis, 10g of Acorus calamus, 4g of Amomum villosum, 15g of raw Coix seeds, 10g of Curcuma zedoaria, 5g of Trillium, 15g of stir-fried Atractylodes macrocephala, and 10g of raw Astragalus membranaceus, taken warm after meals in the morning and evening. The course of treatment was 12 weeks, and colonoscopy was repeated one year after surgery. (2) Non-traditional Chinese medicine treatment group: In addition to the routine treatment after colorectal polypectomy, no other oral Chinese medicine treatment was given, and colonoscopy was repeated one year after surgery.

[0056] 6. Observation indicators: (1) Main efficacy indicator: adenoma recurrence rate. (2) Observation time: The two groups of patients underwent colonoscopy one year after endoscopic treatment. Both colonoscopy operations were performed by senior doctors. If the patient had adenoma recurrence, all of them were removed, and the location, size, number, pathological type, etc. of the removed adenoma were recorded. The adenoma recurrence in the two groups was statistically analyzed.

[0057] 7. Efficacy indicators: Recurrence rate: The definition of recurrence rate is formulated according to the "Standards for Diagnosis and Efficacy of Chinese Medicine Diseases". In the case where all colorectal polyps have been removed, a colonoscopy review is scheduled one year after surgery. If one or more polyps reappear in the original or other parts, and the histological pathological type is the same or different from that of the primary colorectal polyps, it is collectively referred to as recurrence, which is the percentage of the number of recurrences in each group to the total number of cases in each group.

[0058] 8. Statistical methods: SPSS 26.0 software was used to analyze the data. Measurement data that did not conform to normal distribution were expressed as medians or quartiles [M (P25, P75)] and tested using the rank sum test. Count data were expressed as numbers or percentages and tested using the chi-square test.

[0059] 9. Results: Patients with colorectal adenoma who visited the outpatient department of the Department of Spleen and Stomach of Nanjing Hospital of Traditional Chinese Medicine or were hospitalized from May 2021 to December 2024 were collected. Patients were screened according to the diagnostic criteria, inclusion criteria, exclusion criteria, termination and dropout criteria. A total of 23 patients with colorectal adenoma were included in the Chinese medicine treatment group. There were 15 patients in the control group. All patients underwent colorectal polypectomy before enrollment and signed informed consent. The clinical research plan has been approved by the Ethics Committee of Nanjing Hospital of Traditional Chinese Medicine. The results are shown in Table 1:.

[0060] Table 1 Analysis of recurrence of colorectal adenomas in the two groups

[0061]

[0062] As can be seen from Table 1, the Chinese medicine composition of the present invention can eliminate dampness and heat, strengthen the body and eliminate symptoms, and achieve the purpose of preventing and treating the recurrence of colorectal adenoma. It has a significant effect on preventing and treating the recurrence of colorectal adenoma of damp-heat, phlegm and blood stasis type, and is easily accepted by patients.

[0063] Example 6: Study on the effect of the present invention on the number and size of adenomas in mice with colon adenoma induced by AOM+DSS

[0064] Twenty-five male C57BL / 6J mice were randomly divided into five groups: a blank control group, a model group, a low-dose group of the Chinese medicine composition of Example 1 of the present invention (5.27 g / kg), a high-dose group of the Chinese medicine composition of Example 1 of the present invention (21.06 g / kg), and a berberine positive control group. Except for the blank control group, the rest used AOM+DSS to establish a mouse colon adenoma model. In the first week, except for the control group, the mice in other groups were intraperitoneally injected with 12.5 mg / kg AOM, and the blank control group was injected with an equal volume of normal saline. Subsequently, except for the blank control group, all mice were given drinking water containing 1% dextran sulfate sodium (DSS) to drink freely. Starting from the third week, the mice in each treatment group were given the corresponding drugs by gavage every day until the end of the experiment, for a total of 14 weeks. After the mice were killed, the colon polyps were dissected, and the number and size of colon adenomas in each group were calculated. The results are shown in Tables 2 and Figure 1 .

[0065] Table 2 Effect of the present invention on the number and size of adenomas in mice with colon adenoma

[0066]

[0067] Note: Compared with the model group. *P<0.05, **P<0.01, ***P<0.001 Compared with the control group, #P<0.001

[0068] From Table 2 and Figure 1 It can be seen that the high-dose group of the Chinese medicine composition of the present invention can significantly increase the body weight of mice with colon adenoma induced by AOM+DSS, and the low-dose group and high-dose group of the Chinese medicine composition of the present invention can reduce the number and size of adenomas in mice with colon adenoma induced by AOM+DSS (P<0.05), and the therapeutic effect of the high-dose group of the Chinese medicine composition of the present invention is better than that of the positive control group (berberine), indicating that this product can effectively prevent the recurrence of colorectal adenoma.

[0069] Example 7: Study on the effect of the Chinese medicine composition of the present invention on lipid metabolism in mice with colon adenoma induced by AOM+DSS

[0070] 25 male C57BL / 6J mice were randomly divided into 5 groups: control group, model group, low-dose group of Chinese medicine composition in Example 1 of the present invention (5.27 g / kg), high-dose group of Chinese medicine composition in Example 1 of the present invention (21.06 g / kg), and berberine positive control group. Except for the control group, the rest used AOM+DSS to establish a mouse colon adenoma model. In the first week, except for the control group, the mice in other groups were intraperitoneally injected with 12.5 mg / kg AOM, and the control group was injected with an equal volume of normal saline. Subsequently, except for the control group, drinking water containing 1% dextran sulfate sodium (DSS) was given to drink freely. From the third week, mice in each treatment group were given corresponding drugs by gavage every day until the end of the experiment, for a total of 14 weeks. After the experiment, intestinal fecal samples of each group of mice were retained and stored in liquid nitrogen. Liquid chromatography-mass spectrometry (LC-MS) non-targeted metabolomics technology was used. In the sample pretreatment stage, metabolites were extracted using organic solvents or special kits, and then impurities were removed by centrifugation, filtration and other operations to obtain a pure metabolite solution. Then, liquid chromatography (LC) separation was performed, and the pretreated samples were injected into the LC system. Based on the polarity, molecular weight and other characteristics of the metabolites, separation was achieved under the interaction between the mobile phase and the stationary phase, and different metabolites were eluted in sequence. The separated metabolites were sequentially detected by mass spectrometry (MS), ionized in MS to form charged ions, and recorded according to the mass-to-charge ratio to obtain the original mass spectrometry data. In OPLS-DA analysis, the variable weight value (VIP) can be used to measure the influence and explanatory power of the expression pattern of each metabolite on the classification and discrimination of each group of samples. The differential metabolites were obtained according to the VIP value of the first principal component of the OPLS-DA model>1 and the P<0.05 of the T test. The volcano map was drawn using the online bioinformatics analysis drawing tool, see Table 3 and Figure 2 .

[0071] Table 3 List of differential metabolites

[0072]

[0073]

[0074] From Table 3 and Figure 2 It can be seen that the Chinese medicine composition of the present invention can significantly promote the fatty acid metabolic pathway, especially the biosynthesis pathway of polyunsaturated fatty acids, which may be the key mechanism for the Chinese medicine composition of the present invention to produce the adenoma-inhibiting effect.

[0075] The above is an explanation of the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A Chinese medicine composition for preventing and treating recurrence of colorectal adenoma, characterized in that: The invention is prepared by extracting the following Chinese medicinal pieces in parts by weight: 3-10 parts of coptis root, 6-10 parts of magnolia bark, 5-10 parts of calamus, 2-4 parts of amomum villosum, 10-20 parts of raw coix seeds, 8-12 parts of zedoaria, 5-10 parts of trillium, 10-20 parts of stir-fried atractylodes and 5-15 parts of raw astragalus.

2. The Chinese medicine composition for preventing and treating recurrence of colorectal adenoma according to claim 1, characterized in that: The preparation method is prepared by extracting the following Chinese herbal medicine pieces in parts by weight: 5 parts of coptis root, 6 parts of magnolia bark, 10 parts of calamus, 4 parts of amomum villosum, 15 parts of raw coix seeds, 10 parts of zedoaria, 5 parts of trillium, 15 parts of stir-fried atractylodes, and 10 parts of raw astragalus.

3. The Chinese medicine composition for preventing and treating recurrence of colorectal adenoma according to claim 1, characterized in that: The medicine is prepared by extracting the following Chinese herbal medicine pieces in parts by weight: 3 parts of coptis root, 10 parts of magnolia bark, 5 parts of calamus, 4 parts of amomum villosum, 10 parts of raw coix seeds, 12 parts of zedoaria, 5 parts of trillium, 20 parts of stir-fried atractylodes, and 5 parts of raw astragalus.

4. The Chinese medicinal composition for preventing and treating recurrence of colorectal adenoma according to claim 1, characterized in that: The preparation method is prepared by extracting the following Chinese herbal medicine pieces in parts by weight: 10 parts of coptis root, 6 parts of magnolia bark, 10 parts of calamus, 2 parts of amomum villosum, 20 parts of raw coix seeds, 8 parts of zedoaria, 10 parts of trillium, 10 parts of stir-fried atractylodes, and 15 parts of raw astragalus.

5. The Chinese medicinal composition for preventing and treating recurrence of colorectal adenoma according to claim 1, characterized in that: The dosage form of the Chinese medicine composition is an oral dosage form.

6. The Chinese medicinal composition for preventing and treating recurrence of colorectal adenoma according to claim 5, characterized in that: The oral dosage form is one of tablets, capsules, granules, and oral liquid.

7. The Chinese medicinal composition for preventing and treating recurrence of colorectal adenoma according to claim 1, characterized in that: The preparation method comprises the following steps: (1) Weighing the various Chinese herbal medicine slices, mixing, decocting with water, filtering, collecting the filtrate, concentrating the obtained medicinal solution, adding ethanol for alcohol precipitation, centrifuging, collecting the supernatant, and concentrating into an extract with a density of 1.20-1.30 g / mL; (2) spray-drying the extract prepared in step (1), adding auxiliary materials, and preparing it into one of tablets, capsules, and granules.

8. The Chinese medicinal composition for preventing and treating recurrence of colorectal adenoma according to claim 1, characterized in that: The preparation method comprises the following steps: (1) Weighing the various Chinese herbal medicine slices, mixing, decocting with water, filtering, collecting the filtrate, concentrating the obtained medicinal solution, adding ethanol for alcohol precipitation, centrifuging, collecting the supernatant, and concentrating into an extract with a density of 1.20-1.30 g / mL; (2) Take the extract prepared in step (1), add sucrose, and prepare an oral solution.

9. Use of the Chinese medicinal composition for preventing and treating recurrence of colorectal adenoma according to claim 1 in the preparation of a drug for preventing and treating recurrence of colorectal adenoma, wherein the colorectal adenoma belongs to the syndrome of spleen deficiency, dampness and blood stasis.

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