Traditional Chinese medicine composition for treating colorectal adenoma as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating colorectal adenoma and a preparation method and application thereof. The traditional Chinese medicine composition is prepared from fructus mume, herba patriniae, radix clematidis, radix codonopsis, spina gleditsiae, silkworm excrement, fried malt and hypericum perforatum. The traditional Chinese medicine components in the traditional Chinese medicine composition supplement each other and are combined with standardized western medicines for treatment, clinical symptoms of patients suffering from colorectal adenoma are improved, and the recurrence rate of endoscopic removal of the patients suffering from colorectal adenoma is reduced.

Description

Technical Field

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

[0002] Colorectal polyps refer to raised lesions that occur on the mucosa of the colon or rectum. They are usually discovered through colonoscopy. Colorectal polyps have always been a focus of medical research. This refers to a type of growth that protrudes from the mucosal tissue of the large intestine. Colorectal polyps are generally divided into common polyps such as hyperplastic polyps, inflammatory polyps, and adenomatous polyps. Among them, adenomatous polyps are closely related to the occurrence and development of colorectal cancer. They are the initial joint in the "tumor-cancer" transformation. Most colorectal polyps are benign, but some types of polyps have the potential risk of malignant transformation, especially adenomatous polyps, which are considered to be early lesions of colorectal cancer. Therefore, colorectal adenoma is an important precancerous lesion of colorectal cancer and needs to be given sufficient attention.

[0003] Endoscopic resection of colorectal adenomas is commonly performed in clinical practice. However, epidemiological studies suggest that 20% to 50% of patients will experience recurrence within 3 to 5 years after surgical resection. Therefore, effectively preventing and controlling postoperative recurrence of colorectal adenomas has become a major challenge in the medical field.

[0004] According to Traditional Chinese Medicine, the etiology and pathogenesis of colorectal adenomas stem from spleen and stomach weakness caused by external pathogens, dietary indiscriminateness, and emotional trauma. Alternatively, due to congenital deficiency, the spleen fails to function properly, leading to damp-heat, cold-dampness, and dampness turbidity stagnating in the intestines and obstructing Qi. Over time, this leads to blood stasis, which then binds and becomes entangled within the body, forming adenomas. Over time, this toxicity can develop into cancer. If only the visible tumor is removed, the pathological factors such as dampness and blood stasis remain stagnant and persistent, and when pathogens are encountered, they can regenerate into tumors, leading to recurrent attacks. Traditional Chinese Medicine (TCM) uses syndrome differentiation and treatment to formulate traditional Chinese medicine prescriptions to eliminate these persistent roots, reducing the recurrence rate and improving symptoms. Therefore, after colorectal adenoma and endoscopic resection, it is recommended that traditional Chinese medicine decoctions, combined with a comprehensive adjustment plan for postoperative lifestyle, be used to improve symptoms and reduce recurrence rates.

[0005] How to effectively treat adenomas and reduce postoperative recurrence rates has become a major challenge for the medical community. Traditional Chinese medicine offers unique advantages in treating colorectal polyps and adenomas, such as simplicity, effectiveness, and affordability. However, there are currently no unified treatment guidelines, and there is a lack of comprehensive Chinese herbal formulas for these conditions. Summary of the Invention

[0006] In view of the above problems, the purpose of the present invention is to provide a traditional Chinese medicine composition for treating colorectal adenoma, and its preparation method and application.

[0007] In order to achieve the above object, the present invention provides the following technical solutions:

[0008] A traditional Chinese medicine composition for treating colorectal adenoma. The traditional Chinese medicine components of the traditional Chinese medicine composition include black plum, Patrinia patriniae, clematis root, codonopsis pilosula, sapodilla thorn, silkworm excrement, roasted malt, and Hypericum perforatum.

[0009] Preferably, the traditional Chinese medicine composition comprises the following traditional Chinese medicine components in parts by weight: 14-16 parts of black plum, 14-16 parts of Patrinia chinensis, 9-11 parts of Clematidis, 9-11 parts of Codonopsis pilosula, 4-6 parts of Gleditsia chinensis, 4-6 parts of silkworm feces, 14-16 parts of roasted malt, and 7-9 parts of Hypericum perforatum.

[0010] Preferably, the traditional Chinese medicine composition comprises the following traditional Chinese medicine components in parts by weight: 15-16 parts of black plum, 15-16 parts of Patrinia chinensis, 10-11 parts of Clematidis, 10-11 parts of Codonopsis pilosula, 5-6 parts of Gleditsia chinensis, 5-6 parts of silkworm feces, 15-16 parts of roasted malt, and 8-9 parts of Hypericum perforatum.

[0011] Preferably, the traditional Chinese medicine composition comprises the following traditional Chinese medicine components in parts by weight: 15 parts of black plum, 15 parts of Patrinia chinensis, 10 parts of Clematidis, 10 parts of Codonopsis pilosula, 5 parts of Gleditsia chinensis, 5 parts of silkworm feces, 15 parts of roasted malt, and 8 parts of Hypericum perforatum.

[0012] The present invention also provides a method for preparing the traditional Chinese medicine composition for treating colorectal adenoma, comprising the following steps: powdering and mixing corresponding parts by weight of traditional Chinese medicine component raw materials, adding purified water for soaking; boiling over high heat after soaking, then decocting over low heat to obtain a decoction; filtering the decoction, taking the filtrate, and processing to obtain the traditional Chinese medicine composition.

[0013] Preferably, the soaking time is 30 to 50 minutes.

[0014] Preferably, the amount of pure water added is specifically as follows: the surface of the pure water is 1 to 2 cm higher than the surface of the traditional Chinese medicine component.

[0015] Preferably, the boiling time over high heat is 10 to 20 minutes; the decocting time over low heat is 20 to 40 minutes.

[0016] The third aspect of the present invention provides the use of the traditional Chinese medicine composition in the preparation of a drug for treating colorectal adenoma.

[0017] Preferably, the dosage form of the drug is tablet, capsule, granule or solution.

[0018] Compared with the prior art, the advantages and beneficial effects of the present invention are:

[0019] 1. The Chinese medicine composition of the present invention can improve the clinical symptoms of patients with colorectal adenoma and reduce the recurrence rate of patients who undergo endoscopic removal of colorectal adenoma.

[0020] 2. In the prescription of the present invention, Wumei and Patrinia are the main medicines, while Clematidis, silkworm feces, Chinese honey locust thorns and Hypericum perforatum are the ministerial medicines, Codonopsis pilosula and fried malt are the adjuvant medicines. The whole prescription has the effects of strengthening the spleen and removing dampness, clearing away heat and detoxifying, and reducing swelling and discharging pus. DETAILED DESCRIPTION

[0021] The following is a clear and complete description of the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts are within the scope of protection of the present invention.

[0022] The invention provides a traditional Chinese medicine composition for treating colorectal adenoma, wherein the traditional Chinese medicine components include black plum, patrinia herb, clematis root, codonopsis pilosula, sapodilla thorn, silkworm excrement, roasted malt and Hypericum perforatum.

[0023] The raw materials used in this invention are all included in the Chinese Pharmacopoeia (2020 edition).

[0024] Black plums are sour and astringent in nature, and can astringe the lungs to relieve coughs and astringe the intestines to relieve diarrhea. Modern research has shown that the ursolic acid in black plums can prevent tumor formation and induce tumor cell apoptosis. Black plums and their recurrence can also inhibit precancerous lesions and enhance immunity.

[0025] Patrinia salsa has a bitter and cold nature, can enter the gastrointestinal meridian, and has the effect of promoting blood circulation, eliminating carbuncles and discharging pus.

[0026] Both Clematidis and silkworm feces are warm in nature, can dispel rheumatism and dredge meridians. The use of this medicine is to treat the key pathological factor of "dampness" of colorectal polyps and to guide the medicine directly to the diseased area.

[0027] Codonopsis pilosula and fried malt are important medicines for strengthening the spleen and replenishing qi. The formation of colorectal polyps is still "deficiency at the root and excess at the superficial level". Whether from the perspective of treating adenomatous polyps or from the perspective of "prevention before illness", such qi-invigorating and strengthening medicines are needed to reduce the recurrence rate of colorectal adenomas.

[0028] Soapberry thorn is a special medicine for reducing swelling, draining pus and treating various carbuncle and tumor. Hypericum perforatum can relieve liver depression, clear away heat and dampness.

[0029] Black plum and Patrinia chinensis are the main medicines, Clematis chinensis, silkworm feces, Sophora japonica thorn, and Hypericum perforatum are the auxiliary medicines, and Codonopsis pilosula and roasted malt are the adjuvant medicines. The whole prescription has the effects of strengthening the spleen and removing dampness, clearing away heat and detoxifying, and reducing swelling and discharging pus.

[0030] In specific application scenarios, the weight ratio range of the above-mentioned traditional Chinese medicine components is specifically as follows: 14-16 parts of black plum, 14-16 parts of Patrinia herba, 9-11 parts of Clematidis, 9-11 parts of Codonopsis pilosula, 4-6 parts of Gleditsia chinensis, 4-6 parts of silkworm excrement, 14-16 parts of roasted malt, and 7-9 parts of Hypericum perforatum. The weight ratios of the above-mentioned traditional Chinese medicine components can be adjusted within the above ranges based on the actual diagnosis of the disease and the emphasis on efficacy. Such changes will not affect the scope of protection of the present invention.

[0031] Furthermore, the present invention provides a method for preparing the above-mentioned traditional Chinese medicine composition for treating colorectal adenoma, comprising the following steps:

[0032] (1) Preparation of medicinal materials: Weigh the above Chinese medicinal materials according to the corresponding weight parts, mix and grind into powder, sieve and set aside.

[0033] (2) Soaking: Add purified water to the medicinal powder. The amount of water added should be sufficient to cover the medicinal powder by one finger width. The duration of the soaking process is 30 to 50 minutes. In actual operation, the height of one finger width is about 1 to 2 cm. The height can be adjusted appropriately according to the diameter of the decoction dish. The medicinal powder can be fully immersed in water during the entire soaking process and the water consumption in the subsequent decoction process is sufficient. Reasonable changes in the specific height value do not affect the scope of protection of the present invention.

[0034] (3) Decoction: After soaking, boil over high heat, then simmer over low heat to obtain a decoction. During the decoction process, stir continuously with a bamboo spatula to prevent the bottom from sticking, so that it is evenly heated to obtain a decoction containing the medicinal powder. In specific application scenarios, the boiling time over high heat can be 10 to 20 minutes, and the decoction time over low heat can be 20 to 40 minutes. Depending on the difference in water content and dosage form requirements, the corresponding decoction time can be adjusted according to actual needs, and such changes will not affect the scope of protection of the present invention.

[0035] (4) Finished medicine: The decoction containing the medicinal powder is filtered through a 0.45 μm filter membrane, and the filtrate is taken and further processed to obtain a Chinese medicine composition. It should be noted that the Chinese medicine composition proposed in the present invention is for the preparation of a drug for treating colorectal adenoma. According to the difference in the dosage form requirements of the final drug, the final form of the corresponding Chinese medicine composition also needs to be changed accordingly, such as concentrated liquid or powder. Therefore, the purpose of the above-mentioned treatment of the filtrate is to remove excess water and transform the final physical form. The specific treatment content may include low-temperature distillation, crystallization, reduced pressure concentration, freeze drying and other treatment methods, all of which are adjusted to facilitate storage or match the final drug processing requirements. Such changes in the specific treatment method will not affect the scope of protection of the present invention.

[0036] Example 1

[0037] This embodiment provides a traditional Chinese medicine composition for treating colorectal adenoma, which comprises the following traditional Chinese medicine components in parts by weight: 15 parts of black plum, 15 parts of Patrinia herba, 10 parts of Clematidis, 10 parts of Codonopsis pilosula, 5 parts of Gleditsia chinensis, 5 parts of silkworm feces, 15 parts of roasted malt, and 8 parts of Hypericum perforatum.

[0038] The preparation method of a corresponding traditional Chinese medicine composition for treating colorectal adenoma comprises the following steps: taking corresponding parts by weight of the traditional Chinese medicine components, scoring and mixing them; adding purified water to the mixed medicinal powder, covering the medicinal powder by one finger width; soaking the mixture for 40 minutes; boiling over high heat for 15 minutes; then decocting over low heat for 30 minutes; cooling the decoction, filtering through a 0.45 μm filter membrane, collecting the filtrate, and concentrating it to obtain a concentrated solution of the traditional Chinese medicine composition.

[0039] Example 2

[0040] This embodiment provides another traditional Chinese medicine composition for treating colorectal adenoma, which comprises the following traditional Chinese medicine components in parts by weight: 15 parts of black plum, 16 parts of Patrinia herba, 10 parts of Clematidis, 11 parts of Codonopsis pilosula, 5 parts of Gleditsia chinensis, 6 parts of silkworm feces, 15 parts of roasted malt, and 9 parts of Hypericum perforatum.

[0041] The preparation method of the corresponding traditional Chinese medicine composition for treating colorectal adenoma comprises the following steps: powdering and mixing corresponding parts by weight of traditional Chinese medicine components, placing the mixture into a clay pot, adding purified water into the clay pot so that the water level covers the surface of the medicine by 1.5 cm, soaking for 45 minutes, heating the clay pot over high heat, boiling for 12 minutes, reducing heat to low and continuing to boil for 40 minutes, cooling the decoction, filtering with a 0.45 μm filter membrane, and performing low-temperature distillation on the filtrate to remove excess water to obtain a concentrated solution of the traditional Chinese medicine composition.

[0042] Example 3

[0043] This embodiment provides another traditional Chinese medicine composition for treating colorectal adenoma, which comprises the following traditional Chinese medicines in parts by weight: 16 parts of black plum, 15 parts of Patrinia herba, 11 parts of Clematidis, 10 parts of Codonopsis pilosula, 6 parts of Gleditsia chinensis, 5 parts of silkworm feces, 16 parts of roasted malt, and 8 parts of Hypericum perforatum.

[0044] The preparation method of the corresponding traditional Chinese medicine composition for treating colorectal adenoma comprises the following steps: powdering and mixing corresponding parts by weight of traditional Chinese medicine components, placing the mixture into a decoction vessel, adding purified water to cover the medicine surface by 1.2 cm, soaking for 50 minutes, heating over high heat, decocting for 14 minutes, then boiling, reducing heat to low and continuing to decoct for 35 minutes, filtering through a 0.45 μm filter membrane, and drying the filtrate to obtain powder particles of the traditional Chinese medicine composition.

[0045] clinical trials

[0046] 1 Study Design

[0047] The trial adopted a multicenter, randomized, double-blind, placebo-controlled clinical trial method. The trial drug was produced, packaged, and provided according to the random allocation and double-blind principle.

[0048] 2 Study population

[0049] 2.1 Diagnostic criteria

[0050] 2.1.1 Western medicine diagnostic criteria

[0051] The diagnosis of colorectal adenoma should comply with the diagnostic criteria of the Chinese Consensus on Endoscopic Diagnosis and Treatment of Colorectal Cancer and Precancerous Lesions (2023, Guangzhou). Colorectal adenoma: It is a benign tumor originating from the glandular epithelium of the colorectal mucosa, including colon adenoma and rectal adenoma, and is a common benign intestinal tumor. It is the most common precancerous lesion of the colorectum, and its incidence increases with age. It can be divided into tubular adenomas, tubular villous adenomas and villous adenomas through the classic "adenoma-adenocarcinoma" pathway. Villous adenomas have the highest cancerization rate, while tubular adenomas have the lowest. Sessile serrated lesions (SSL): A new term added by the World Health Organization in 2019. It was previously called sessile serrated adenomas / polyps. It appears flat and hidden under the endoscope and is easily missed. SSL is the most important precancerous lesion that becomes cancerous through the serrated pathway. Advanced adenoma: refers to an adenoma that meets one or more of the following criteria: ① diameter > 10 mm; ② villous or tubulovillous adenoma; ③ high-grade intraepithelial neoplasia. Most patients are asymptomatic. Symptoms are related to the size, location, and pathological nature of the adenoma. Symptomatic patients may have the following manifestations: abdominal discomfort and abdominal pain, which are mostly caused by large adenomas with intussusception and intestinal obstruction; (2) changes in bowel habits, including constipation, diarrhea, and tenesmus; (3) blood in the stool, most commonly intermittent blood in the stool; (4) Some large, pedunculated adenomas located in the rectum may fall off or protrude outside the anus during defecation.

[0052] 2.1.2 Traditional Chinese Medicine Diagnostic Criteria

[0053] The standards developed with reference to the expert consensus on the diagnosis and treatment of colorectal adenoma and early colorectal cancer using integrated traditional Chinese and Western medicine (2021):

[0054] (1) Cold-dampness obstruction syndrome

[0055] Characteristics of the syndrome: abdominal distension and loss of appetite, dull abdominal pain, aggravated by cold and relieved by warmth, bland mouth without thirst, cold body and limbs, clear and long urine, watery or hard stools, intestinal rumbling, tenesmus, pale tongue with white or greasy tongue coating, and deep and tight pulse.

[0056] (2) Damp-heat accumulation syndrome

[0057] Characteristics of symptoms: abdominal distension or pain, dry and bitter mouth, thirst leading to drinking, or uncomfortable diarrhea, yellow-brown and foul-smelling stool, burning sensation in the anus, tenesmus, or constipation, short and dark urine, red tongue with yellow and greasy coating, and stringy or slippery and rapid pulse.

[0058] (3) Qi stagnation and blood stasis syndrome

[0059] Symptom characteristics: abdominal pain, distension, or stabbing pain, which comes and goes, frequent belching, aggravated by bad mood, intestinal rumbling and flatulence, dry and hard stools, or loose stools, tenesmus, dark tongue or ecchymosis, thin white tongue coating, and wiry or astringent pulse.

[0060] (4) Spleen deficiency, dampness and stasis syndrome

[0061] Characteristics of the syndrome: shortness of breath, laziness to speak, fatigue of limbs, poor appetite, abdominal fullness and stuffiness, even abdominal distension and pain, or stabbing pain, constipation or loose stools, tenesmus, pale and dark tongue, white or greasy tongue coating, and thin and wiry pulse.

[0062] (5) Spleen deficiency syndrome

[0063] Characteristics of the syndrome: fatigue, sallow complexion, poor appetite, abdominal distension or dull abdominal pain, loose stools with undigested food residues, or light blood in the stools, dry and hard stools, weak bowel movements, pale tongue with white fur, and a thready and weak pulse.

[0064] 2.2 Inclusion criteria

[0065] Patients who meet the following six criteria can be included in this study:

[0066] 1) Ages 18 to 75, gender not limited.

[0067] 2) Patients diagnosed with advanced colorectal adenomas (including villous adenomas, tubulovillous adenomas, tubular adenomas, and serrated adenomas) by colonoscopy and completely removed by endoscopic pathology within the past 6 months, and with 1 to 6 colorectal adenomas confirmed by histology.

[0068] 3) With or without constipation, diarrhea, abdominal distension and other symptoms.

[0069] 4) Boston score for intestinal cleanliness ≥6 points.

[0070] 5) Familial colorectal adenoma or polyposis has been ruled out by inquiring into medical and family history.

[0071] 6) Volunteers who participated in the study and signed the informed consent form.

[0072] 2.3 Exclusion criteria

[0073] Patients who meet one or more of the following criteria should be excluded:

[0074] 1) The adenoma was not completely removed during the previous colonoscopy.

[0075] 2) Patients with polyps that have already become cancerous, familial adenomatous polyposis or inflammatory bowel disease.

[0076] 3) Long-term use of aspirin, nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors, vitamin D and calcium supplements, and long-term maintenance of systemic immunotherapy.

[0077] 4) Those who cannot tolerate colonoscopy.

[0078] 5) Patients with poor bowel preparation for colonoscopy or examination time less than 6 minutes.

[0079] 6) Patients with severe cardiovascular and cerebrovascular diseases, liver and kidney diseases, severe postoperative complications, and other acute and chronic diseases that may seriously affect treatment and prognosis.

[0080] 7) Women who are pregnant or planning to become pregnant, and breastfeeding women.

[0081] 8) Those who are allergic to or have contraindications to related drugs.

[0082] 9) Those who have mental illness and are unable to cooperate with the trial.

[0083] 10) Patients with other malignant tumors.

[0084] 11) Patients who are undergoing other clinical trials within 1 month.

[0085] 12) Other situations that the researchers consider inappropriate for inclusion.

[0086] 2.4 Subject Withdrawal and Termination of Treatment

[0087] 2.4.1 Investigator-determined withdrawal

[0088] (1) During the study, if the patient's condition worsens rapidly, regardless of whether there is a predisposing factor, the study medication should be stopped immediately.

[0089] (2) During the clinical study, the subject develops certain comorbidities, complications and special physiological changes and is not suitable for continued study.

[0090] (3) The use of other prohibited combined treatments or drugs, which may affect the effectiveness and safety assessment.

[0091] (4) Subjects who have experienced adverse events or serious adverse events and are not suitable to continue the study.

[0092] (5) Subjects who do not return for follow-up on time or are lost to follow-up and have poor compliance.

[0093] 2.4.2 Subjects voluntarily withdraw from the study

[0094] (1) The patient perceives that the treatment effect is poor.

[0095] (2) Finding it difficult to tolerate certain adverse reactions.

[0096] (3) Unable to continue clinical research due to any reasons.

[0097] (4) Lost to follow-up due to unknown reasons.

[0098] 2.4.3 Regardless of the reason, for cases that withdraw from the study, their case records should be retained, and their last test results should be transferred as the final results, and a full data analysis of their efficacy and adverse reactions should be conducted.

[0099] 3. Number of cases and grouping method

[0100] This study used the reduction in the 1-year recurrence rate of colorectal adenoma after surgery as the primary efficacy indicator and counting data. The sample size was estimated using the sample size formula for comparing two rates, as follows:

[0101]

[0102] Wherein, n is the calculated sample size of one group, P1 and P2 are the recurrence rates of the experimental group and the control group, according to the literature reports: (1. Gao QY, Chen HM, Sheng JQ, et al. The first-year follow-up after colorectal denoma polypectomy is important: a multiple center study in symptomatic hospital-based individuals in China. Front Med China 2010; 4:436-42. 2. Higurashi T, Hosono K, Takahashi H, et al. Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomized phase 3trial. Lancet Oncol. 2016;17:475-83.), P1 = 30%, P2 = 50%, α = 0.05, β = 0.20, and substituting these values into the formula yields: n ≈ 332. This means that 166 patients are required per group. Considering a 20% dropout rate and a 1:1 ratio of subjects per group, the sample size for the experimental and control groups was determined to be 210, respectively, for a total sample size of 420.

[0103] 4 Experimental drugs

[0104] 4.1 Name and Specification of Test Drug and Control Drug

[0105] Test drug: Xianmei Xiaoliu Fang granules. This granule is a traditional Chinese medicine composition prepared using the method proposed in the examples of the present invention (drug composition: 15g of Prunus mume, 15g of Patrinia chinensis, 10g of Clematidis, 10g of Codonopsis pilosula, 5g of Gleditsia sinensis, 5g of Silkworm excrement, 15g of roasted malt, and 8g of Hypericum perforatum). It is taken orally, one packet each time, about 15g, twice a day.

[0106] Control drug: Chinese medicine granule simulant, with the same specifications, usage and dosage as the test drug.

[0107] 4.2 Treatment options

[0108] Experimental group: Oral administration of the above experimental drugs, 1 packet each time, 2 times a day, for 3 months.

[0109] Control group: Oral Chinese medicine granule simulant, with the same specifications, usage, and dosage as the test drug. This simulant has the same appearance, smell, taste, specifications, and packaging as the Chinese medicine composition prepared in Example 1, meeting the requirements of a placebo in a placebo-controlled randomized clinical trial. The oral method, treatment course, and follow-up were the same as those of the test group.

[0110] 5 Research steps and related inspections

[0111] 5.1 Visit 1: Screening and Enrollment Period (Days -7 to 0)

[0112] (1) Sign the informed consent form.

[0113] (2) Demographic data.

[0114] (3) Record general information and medical history.

[0115] (4) Physical examination.

[0116] (5) Examination of main symptoms and vital signs.

[0117] (6) Clinical symptom assessment: pathological score and mucosal efficacy assessment.

[0118] (7) Safety examination: routine blood test, routine urine test; liver function test (ALT, AST), kidney function test (BUN, Cr), routine stool test.

[0119] (8) Colonoscopy.

[0120] (9) Issue log cards.

[0121] (10) Record concomitant medication.

[0122] (11) Evaluate the examination results and review the inclusion and exclusion criteria.

[0123] 5.2 Visit 2: Baseline Period (Day 0)

[0124] (1) Examination of main symptoms and vital signs.

[0125] (2) Clinical symptom assessment: pathological score, mucosal efficacy assessment, TCM symptom score, and TCM syndrome score.

[0126] (3) Collect the log cards and review the inclusion and exclusion criteria.

[0127] (4) Random grouping.

[0128] (5) Distribute trial drugs and log cards.

[0129] (6) Record concomitant medication.

[0130] (7) Make an appointment for the next visit.

[0131] 5.3 Visit 3: Treatment period (3 months ± 1 week after medication)

[0132] (1) Examination of main symptoms and vital signs.

[0133] (2) Clinical symptom assessment: TCM symptom score and TCM syndrome score.

[0134] (3) Record concomitant medication.

[0135] (4) Record adverse events.

[0136] (5) Safety examination review: routine blood test, routine urine test; liver function test (ALT, AST), kidney function test (BUN, Cr), routine stool test.

[0137] (6) Recover medications and log cards.

[0138] (7) Make an appointment for the next visit.

[0139] 5.4 Visit 4: Follow-up period (± 2 weeks after 1 year of medication)

[0140] (1) Examination of main symptoms and vital signs.

[0141] (2) Clinical symptom assessment: pathological score, mucosal efficacy assessment, TCM symptom score, and TCM syndrome score.

[0142] (3) Record concomitant medication.

[0143] (4) Record adverse events.

[0144] (5) Safety examination review: routine blood test, routine urine test; liver function test (ALT, AST), kidney function test (BUN, Cr), routine stool test.

[0145] (6) Colonoscopy.

[0146] (7) Record trial completion and compliance.

[0147] 6 Observation indicators

[0148] 6.1 Main efficacy indicators

[0149] Observation indicators: The primary outcome measure was the 1-year recurrence rate of colorectal adenoma after surgery.

[0150] Observation time points: before treatment, 3 months ± 1 week of treatment, and 1 year ± 2 weeks of follow-up.

[0151] Evaluation criteria: Advanced adenoma refers to adenoma that meets one or more of the following criteria: ① diameter >10 mm; ② villous or tubulovillous adenoma; ③ high-grade intraepithelial neoplasia.

[0152] The primary outcome measure was the 1-year recurrence rate of colorectal adenoma after surgery.

[0153] 6.2 Secondary efficacy indicators

[0154] Observation indicators: This study mainly established the TCM syndrome efficacy scale score for patients

[0155] Evaluation Criteria: The Traditional Chinese Medicine Syndrome Efficacy Scale score was calculated using the nimodipine method. The efficacy index = [(pre-treatment score - post-treatment score) / pre-treatment score] × 100%. Clinical cure: disappearance or near-disappearance of major symptoms and signs (efficacy index ≥ 95%); marked efficacy: significant improvement of major symptoms and signs (efficacy index 70% ≤ < 95%); effective: significant improvement of major symptoms and signs (efficacy index 30% ≤ < 70%); ineffective: no significant improvement or even worsening of major symptoms and signs (efficacy index < 30%). The SAS and SDS were used to assess anxiety and depression in the enrolled subjects, respectively. Scale scores were positively correlated with anxiety and depression status.

[0156] 6.3 Traditional Chinese Medicine Symptom Score

[0157] Observation indicators: The TCM symptom scores of the subjects were calculated at each time point.

[0158] Observation time points: observe and record once before treatment and each time when taking medicine.

[0159] Evaluation criteria: The TCM symptom grading and scoring method refers to the "Guiding Principles for Clinical Research of New Chinese Medicines (2002 Edition)". The primary symptoms are divided into four levels (0, 1, 2, 3) according to the severity of the symptoms, with scores of 0, 2, 4, and 6, respectively. The secondary symptoms are divided into four levels (0, 1, 2, 3) according to the severity of the symptoms, with scores of 0, 1, 2, and 3, respectively.

[0160] 6.4 Traditional Chinese Medicine Syndrome Scoring

[0161] Observation indicators: The TCM syndrome scores of the subjects were calculated at each time point.

[0162] Observation time points: observe and record once before treatment and each time when taking medicine.

[0163] Evaluation criteria: Symptoms are quantified using a symptom scoring scale, and tongue and pulse information are quantified using a tongue diagnosis instrument and a pulse diagnosis instrument.

[0164] 6.5 Safety Indicators

[0165] (1) Routine examinations: routine blood test, routine urine test, routine stool test + occult blood test, performed at the time of enrollment and at the end of the 12th week of treatment.

[0166] (2) Biochemical indicators: liver function (ALT, AST), renal function (BUN, Cr), performed at the time of enrollment and at the end of the 12th week of treatment.

[0167] (3) Adverse reaction log: if rash, diarrhea or other special symptoms occur, the patient should record it at any time.

[0168] Level 1: Safe, without any adverse reactions.

[0169] Level 2: Relatively safe. If any adverse reaction occurs, no treatment is required and the medication can continue.

[0170] Level 3: There are safety issues and moderate adverse reactions, but the drug can continue to be administered after treatment.

[0171] Grade 4: Discontinue the drug due to adverse reactions.

[0172] 7. Compliance Observation

[0173] Whether the patient can take medication on time and in the correct dosage: whether the patient takes other medications on their own. Medication compliance should be calculated by dividing the actual dosage by the required dosage x 100%. Good compliance is considered when medication is taken between 70% and 120%. Subjects should return unused medication and empty packaging at each follow-up visit. The investigator or designated personnel will count the number of returned medications. Records should be kept of lost or unreturned medications. If the subject's compliance is poor, the reasons should be investigated and documented. The investigator should record the amount of medication dispensed and returned in the appropriate section of the case report form.

[0174] 8. Combined medication

[0175] In addition to the trial medications, the use of other traditional Chinese medicines, Western medicines, and biopharmaceuticals with the potential to treat colorectal adenomas, colorectal cancer, or other anti-tumor therapies is prohibited during the observation period. Any concurrent illnesses or symptoms that require intervention after the start of the trial should have their interventions recorded in detail. Physicians should require patients to bring all medications / pill boxes they are currently taking to follow-up visits to review their concomitant medications. Any medications or other treatments that require continued use for concurrent illnesses must be recorded in the study medical record, along with the name (or other therapy name), dosage, frequency, and duration of use, for analysis and reporting purposes.

[0176] If a subject experiences worsening symptoms and cannot tolerate them during the study, researchers may administer additional symptomatic medications based on specific circumstances. However, detailed records of medication names, dosages, specifications, and timing must be kept to assess whether medications may have affected the study's results. During the baseline period before entering the clinical trial, patients will receive healthy lifestyle education and are advised to maintain stable living and dietary habits throughout the trial.

[0177] 9 Statistical analysis

[0178] SPSS 25.0 software was used. First, the quantitative data were checked to see if they followed a normal distribution and the homogeneity of variance was tested. The data were found to be normal with a t-test and the mean ± standard deviation was used. If the data did not follow a normal distribution, a rank sum test was used, and M (P25, P75) was used for descriptive analysis. For count data, the chi-square test was used for statistical analysis. Statistical significance was assumed to be statistic ally significant when P < 0.05.

[0179] Study Results

[0180] A total of 342 patients completed the study, including 169 patients in the treatment group who completed the study and 41 patients who did not complete the study (15 patients took less than 80% of the medication, 10 patients were lost to follow-up, and 16 patients did not undergo colonoscopy on time); 173 patients in the control group who completed the study and 37 patients who did not complete the study (13 patients were lost to follow-up, and 24 patients did not undergo colonoscopy on time). See Table 1 for details.

[0181] Table 1 The number of people who finally completed the study

[0182]

[0183] 1. Comparison of baseline characteristics

[0184] There was no statistically significant difference in gender, age, BMI level, smoking history, alcohol history, history of intestinal polyps, comorbidities, family history of colorectal cancer, and baseline characteristics of adenoma between the two groups of patients (P>0.05), and they were comparable (see Table 2).

[0185] Table 2 Comparison of baseline data of patients after colorectal adenoma surgery in the two groups

[0186]

[0187]

[0188] 2. Comparison of recurrence rates between the two groups one year after surgery

[0189] As shown in Table 3, one year after treatment, the recurrence rate of colorectal adenoma in the treatment group was 47.91% (81 / 169), and the recurrence rate in the control group was 63.01% (109 / 173). The difference in recurrence rate between the two groups was statistically significant (P < 0.05).

[0190] Table 3 Comparison of one-year recurrence rate in two groups of patients after colorectal adenoma surgery

[0191]

[0192] 3. Comparison of TCM symptom scores between the two groups of patients before and after treatment

[0193] As shown in Table 4, before treatment, 55.62% (94 / 169) of the patients in the treatment group had no obvious symptoms, while 52.02% (90 / 173) of the patients in the control group had no obvious symptoms (P>0.05, indicating no statistically significant difference). One year after surgery, 78.70% (133 / 169) of the patients in the treatment group had no obvious symptoms.

[0194] In the control group, 67.63% (117 / 173) of patients had no obvious symptoms (P=0.02<0.05), and the difference was statistically significant. Compared with before treatment, the number of patients without symptoms increased significantly (P=<0.05).

[0195] There was no significant difference in symptom scores between the two groups before treatment. One year after surgery, the TCM syndrome scores in the treatment group were significantly lower than those in the control group (P < 0.05). One year after surgery, the syndrome scores in both the treatment and control groups decreased significantly compared with those before treatment (P = < 0.05).

[0196] Table 4 Comparison of one-year recurrence rate in two groups of patients after colorectal adenoma surgery

[0197]

[0198] Note: Compared with the control group, * p<0.05, ** p < 0.01;

[0199] Compared with before treatment, # p<0.05, ## p<0.01.

[0200] 4. Safety Observation Results

[0201] No obvious adverse reactions such as fever and rash were observed in the treatment group, and no patient developed liver or kidney function damage.

[0202] The above is a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A Chinese medicine composition for treating colorectal adenoma, characterized in that: The Chinese medicinal components of the Chinese medicinal composition include: Black plum, Patrinia chinensis, Clematis chinensis, Codonopsis pilosula, Sophora japonica thorn, silkworm feces, roasted malt, Hypericum perforatum.

2. The Chinese medicine composition according to claim 1, characterized in that The Chinese medicine composition comprises the following Chinese medicine components in parts by weight: 14-16 parts of black plums, 14-16 parts of Patrinia scabra, 9-11 parts of clematis root, 9-11 parts of Codonopsis pilosula, 4-6 parts of Gleditsia spinosa, 4-6 parts of silkworm excrement, 14-16 parts of roasted malt, and 7-9 parts of Hypericum perforatum.

3. The Chinese medicine composition according to claim 2, characterized in that The Chinese medicine composition comprises the following Chinese medicine components in parts by weight: 15-16 parts of black plums, 15-16 parts of Patrinia scabra, 10-11 parts of clematis root, 10-11 parts of Codonopsis pilosula, 5-6 parts of Gleditsia chinensis thorns, 5-6 parts of silkworm excrement, 15-16 parts of roasted malt, and 8-9 parts of Hypericum perforatum.

4. The Chinese medicine composition according to claim 3, characterized in that The Chinese medicine composition comprises the following Chinese medicine components in parts by weight: 15 parts of Plums, 15 parts of Herba Patriniae, 10 parts of Radix Clematidis, 10 parts of Codonopsis pilosula, 5 parts of Spina Gleditsiae, 5 parts of Silkworm Excrement, 15 parts of Roasted Malt, 8 parts of Hypericum perforatum.

5. A method for preparing the traditional Chinese medicine composition for treating colorectal adenoma according to any one of claims 1 to 4, characterized in that: The following steps are involved: Powder and mix the corresponding weight portions of Chinese medicinal component raw materials, and add purified water to soak; After soaking, boil over high heat, then simmer over low heat to obtain a decoction; The decoction is filtered, and the filtrate is taken and processed to obtain the traditional Chinese medicine composition.

6. The preparation method according to claim 5, characterized in that The soaking time is 30 to 50 minutes.

7. The preparation method according to claim 5, characterized in that The amount of pure water added is specifically as follows: the surface of the pure water is 1 to 2 cm higher than the surface of the traditional Chinese medicine component.

8. The preparation method according to claim 5, characterized in that The boiling time of the high fire is 10 to 20 minutes; The time for decocting over low heat is 20 to 40 minutes.

9. Use of the traditional Chinese medicine composition according to any one of claims 1 to 4 in preparing a medicament for treating colorectal adenoma.

10. Use of the traditional Chinese medicine composition according to claim 9 in preparing a drug for treating colorectal adenoma, characterized in that: The dosage form of the medicine is tablet, capsule, granule or solution.

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