A traditional Chinese medicine composition for treating recurrent colorectal adenomatous polyps, its preparation method and application

Abstract

This invention discloses a traditional Chinese medicine composition for treating recurrent colorectal adenomatous polyps, its preparation method, and its application. The traditional Chinese medicine composition comprises the following components by weight: 2 parts Codonopsis pilosula, 2 parts stir-fried Atractylodes macrocephala, 2 parts stir-fried Paeonia lactiflora, 2 parts Corydalis yanhusuo, 3 parts Scutellaria barbata, 3 parts Agrimonia pilosa, 3 parts Hedyotis diffusa, 1.2 parts Angelica sinensis, and 0.6 parts prepared Glycyrrhiza uralensis. This invention has achieved satisfactory therapeutic effects in treating recurrent colorectal adenomatous polyps using the Codonopsis pilosula-Atractylodes macrocephala ...

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, and specifically relates to a traditional Chinese medicine composition for treating recurrent colorectal adenomatous polyps, its preparation method, and its application. Background Technology

[0002] Colorectal adenomatous polyps are benign tumors occurring in the colonic mucosal epithelium and are considered one of the precancerous lesions of colorectal cancer. Endoscopic polypectomy is currently the primary treatment for this disease and effectively reduces the incidence of colorectal cancer. However, many patients still experience symptoms such as abdominal pain, diarrhea, or constipation after polyp removal, and the recurrence rate of adenomatous polyps is high. Studies have shown that the recurrence rate of colorectal adenomatous polyps 3-5 years after endoscopic resection reaches 20%-50%. Western medicine often treats related intestinal symptoms and adenoma recurrence with oral probiotics and compound glutamine, but the efficacy is often unsatisfactory and can easily increase the economic and psychological burden on patients. Therefore, actively exploring new treatment options to effectively improve related intestinal symptoms and effectively reduce the recurrence rate of adenomatous polyps is an urgent problem to be solved in clinical practice. These ideas coincide with the traditional Chinese medicine theory of "preventing disease before it occurs." By applying the important concept of "preventing disease before it occurs and preventing its progression after it occurs," the recurrence of colorectal adenomatous polyps after surgery can be prevented, providing new diagnostic and treatment approaches for this disease in clinical practice.

[0003] Previous studies have investigated clinical predictive models for the recurrence of colorectal adenomatous polyps, assessed the risk of recurrence, and demonstrated the ability to prevent recurrence by inhibiting overactivation of the Wnt / β-catenin signaling pathway and regulating the transcription and protein expression of downstream related genes. Previous research has primarily focused on basic laboratory studies, with limited reports on clinical studies combining traditional Chinese and Western medicine and reducing postoperative recurrence of polyps. Therefore, this invention explores the clinical efficacy of the Shenshu Xianlian formula in patients after surgery for colorectal adenomatous polyps, aiming to provide strong data support and clinical evidence for traditional Chinese medicine compound treatment. Summary of the Invention

[0004] This invention provides a traditional Chinese medicine composition for treating recurrent colorectal adenomatous polyps, its preparation method, and its application, in order to solve the problems in the prior art.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A traditional Chinese medicine composition for treating recurrent colorectal adenomatous polyps comprises the following components by weight: Codonopsis pilosula 1.5–2.5 parts, stir-fried Atractylodes macrocephala 1.5–2.5 parts, stir-fried Paeonia lactiflora 1.5–2.5 parts, Corydalis yanhusuo 1.5–2.5 parts, Scutellaria barbata 2.5–3.5 parts, Agrimonia pilosa 2.5–3.5 parts, Hedyotis diffusa 2.5–3.5 parts, Angelica sinensis 1.0–1.5 parts, and prepared Glycyrrhiza uralensis 0.5–1.0 parts.

[0006] Preferably, the ingredients include the following components by weight: 2 parts Codonopsis pilosula, 2 parts stir-fried Atractylodes macrocephala, 2 parts stir-fried Paeonia lactiflora, 2 parts Corydalis yanhusuo, 3 parts Scutellaria barbata, 3 parts Agrimonia pilosa, 3 parts Hedyotis diffusa, 1.2 parts Angelica sinensis, and 0.6 parts prepared Glycyrrhiza uralensis.

[0007] Furthermore, the traditional Chinese medicine composition is a decoction, oral liquid, granules, capsules, tablets, or pills.

[0008] A method for preparing a traditional Chinese medicine composition for treating recurrent colorectal adenomatous polyps includes the following steps: Add water to Codonopsis pilosula, stir-fried Atractylodes macrocephala, stir-fried Paeonia lactiflora, Corydalis yanhusuo, Scutellaria barbata, Agrimonia pilosa, Hedyotis diffusa, Angelica sinensis, and prepared Glycyrrhiza uralensis, decoct, combine the decoctions, let stand, filter, and concentrate the filtrate to obtain the final product.

[0009] Furthermore, each raw material is decocted twice with water, the two decoctions are combined, and the mixture is allowed to stand for more than 15 hours. After filtration, the filtrate is concentrated to a relative density of 1.05 to 1.10 to obtain the final product.

[0010] A method for preparing a traditional Chinese medicine decoction for treating recurrent colorectal adenomatous polyps includes the following steps: S1. Extraction: Close and lock the bottom cover of the extraction tank, open the top cover, and put the pre-crushed medicinal materials from the feeding area into the extraction tank: 2 parts of Codonopsis pilosula, 3 parts of Agrimonia pilosa, 2 parts of stir-fried Atractylodes macrocephala, 2 parts of stir-fried Paeonia lactiflora, 1.2 parts of Angelica sinensis, 2 parts of Corydalis yanhusuo, 0.6 parts of prepared Glycyrrhiza uralensis, 3 parts of Hedyotis diffusa, and 3 parts of Scutellaria barbata.

[0011] First extraction: Open the drinking water valve and add 522.4L of water to the extraction tank, then close the lid. Soak for 30 minutes, then open the steam valve to heat the extraction tank. When the temperature reaches 100℃, close the steam valve and start timing to maintain the temperature at 100 ± 5℃ for 1 hour. The operator should adjust the steam pressure according to the extraction situation (steam pressure ≤ 0.1 MPa). The first extraction is then complete. First, close the steam valve to stop heating, then open the liquid outlet valve. After filtering the extract through the filter, use a vacuum to transfer the extract to the medicine storage tank.

[0012] Second extraction: Open the drinking water valve and add 522.4L of water to the extraction tank, then close the lid. Open the steam valve to heat the extraction tank. When the temperature reaches 100℃, close the steam valve and start timing to maintain the temperature at 100 ± 5℃ for 1 hour. The operator should adjust the steam pressure (steam pressure ≤ 0.1MPa) according to the extraction situation. The second extraction is then complete.

[0013] First, close the steam valve to stop heating, then open the liquid outlet valve. After the extract is filtered, use a vacuum to pump the extract into the drug storage tank.

[0014] Static filtration: Let stand for more than 15 hours, then pass through a 180-mesh filter cloth.

[0015] S2. Concentration: Open the vacuum valve of the single-effect external circulation concentrator. When the vacuum degree is controlled at -0.04 to -0.08 MPa, open the liquid feed valve. Vacuum suck in the liquid after it has been filtered through a 350-mesh filter cloth. Open the steam valve to start heating and concentrating. During the concentration process, the steam pressure should be ≤ 0.10 MPa, the concentration temperature should be controlled at 60 to 80℃, and the vacuum degree should be controlled at -0.06 to -0.10 MPa. During the concentration process, add material as needed according to the amount of clear paste in the equipment until all the liquid is sucked into the equipment. Concentrate the liquid to a relative density of 1.05 to 1.10 (80℃), then turn off the steam and vacuum, stop the concentration, release the clear paste, filter it while it is still hot (through a 180-mesh filter cloth), put it in a sterilized clean container, label it, and put it into storage.

[0016] S3. Dispensing and Sterilization: Cool to 40-50℃ and dispense into pharmaceutical glass bottles. Place the dispensed medicines into an open pot, add water to submerge them, and boil for at least 30 minutes.

[0017] S4. Storage of medicines: The packaged and sterilized medicines are stored in the medicine warehouse for future use. The temperature of the medicine warehouse is 18-26℃ and the humidity is 45%-65%. The storage time is 3 months.

[0018] Application of a traditional Chinese medicine composition in the preparation of a drug for treating colorectal adenomatous polyps.

[0019] Application of a traditional Chinese medicine composition in the preparation of a drug for preventing recurrence of colorectal adenomatous polyps after surgery.

[0020] Application of a traditional Chinese medicine composition in the preparation of a drug for improving the TCM syndrome of patients after surgery for colorectal adenomatous polyps.

[0021] The use of a traditional Chinese medicine composition in the preparation of a drug for reducing the levels of inflammatory factors in patients after surgery for colorectal adenomatous polyps, wherein the inflammatory factors are TNF-α and / or IL-17.

[0022] The application of a traditional Chinese medicine composition in the preparation of a drug for regulating the brain-gut peptide levels in patients after surgery for colorectal adenomatous polyps, wherein the brain-gut peptides are vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP) and / or somatostatin (SS).

[0023] Compared with the prior art, the present invention has the following beneficial effects: The Ginseng, Atractylodes, and Lotus Formula of this invention can significantly improve various clinical symptoms of patients when applied in clinical practice. It has significant efficacy in treating TCM syndromes, can significantly reduce the level of inflammatory factors, improve intestinal inflammatory response, and can also significantly improve the level of brain-gut peptides before treatment, thus achieving good clinical efficacy.

[0024] This invention has achieved satisfactory results in treating recurrent colorectal adenomatous polyps using the Shenshu Xianlian formula, with few adverse reactions. It was also found that regulating the levels of inflammatory factors and brain-gut peptides is an important mechanism by which this formula reduces polyp recurrence. Attached Figure Description

[0025] Figure 1 This invention compares the differences in TCM syndrome scores between two groups of patients before and after treatment. Figure 2 This invention compares the differences in inflammatory factors and brain-gut peptide levels before and after treatment in two groups of patients. Detailed Implementation

[0026] The present invention will be further described below with reference to embodiments.

[0027] Example 1: A traditional Chinese medicine composition for treating recurrent colorectal adenomatous polyps, comprising the following components by weight: Codonopsis pilosula 1.5-2.5 parts, stir-fried Atractylodes macrocephala 1.5-2.5 parts, stir-fried Paeonia lactiflora 1.5-2.5 parts, Corydalis yanhusuo 1.5-2.5 parts, Scutellaria barbata 2.5-3.5 parts, Agrimonia pilosa 2.5-3.5 parts, Hedyotis diffusa 2.5-3.5 parts, Angelica sinensis 1.0-1.5 parts, and prepared Glycyrrhiza uralensis 0.5-1.0 parts.

[0028] Example 2: A traditional Chinese medicine composition for treating recurrence of colorectal adenomatous polyps, comprising the following components by weight: 2 parts Codonopsis pilosula, 2 parts stir-fried Atractylodes macrocephala, 2 parts stir-fried Paeonia lactiflora, 2 parts Corydalis yanhusuo, 3 parts Scutellaria barbata, 3 parts Agrimonia pilosa, 3 parts Hedyotis diffusa, 1.2 parts Angelica sinensis, and 0.6 parts prepared Glycyrrhiza uralensis.

[0029] Example 3: Preparation method of a traditional Chinese medicine decoction for treating recurrent colorectal adenomatous polyps: 2 kg each of Codonopsis pilosula, stir-fried Atractylodes macrocephala, stir-fried Paeonia lactiflora, and Corydalis yanhusuo; 3 kg each of Scutellaria barbata, Agrimonia pilosa, and Hedyotis diffusa; 1.2 kg of Angelica sinensis; and 0.6 kg of prepared Glycyrrhiza uralensis. Add water and decoct twice. Combine the two decoctions, let stand for at least 15 hours, filter, concentrate the filtrate to a relative density of 1.05-1.10, cool, and dispense into 100 ml bottles. Sterilize. This method yields 200 bottles at a time. Usage of the traditional Chinese medicine decoction: Patients should take 25 ml orally twice a day, morning and evening, for 3 consecutive months.

[0030] To improve the accuracy of water addition in the water extraction experiment of medicinal slices, ensure the dissolution rate of effective components in the medicinal slices, and improve the quality of concentrated decoction of ginseng, atractylodes, angelica, and lotus, the water absorption rate of the medicinal slices in the prescription was investigated.

[0031] Orthogonal design method was used to study the active ingredient baicalin in Scutellaria barbata. Content and yield were the evaluation indicators. The three factors considered were water addition, extraction time, and number of extractions, according to L9(3).４ An orthogonal array was used to conduct experiments to select the optimal extraction process for the concentrated decoction of Ginseng, Atractylodes macrocephala, and Ligusticum sinense.

[0032] Factor Level Table

[0033] Example 4: A method for preparing a traditional Chinese medicine decoction for treating recurrent colorectal adenomatous polyps, comprising the following steps: S1. Extraction: Close and lock the bottom cover of the extraction tank, open the top cover, and put the pre-crushed medicinal materials from the feeding area into the extraction tank: 2 parts of Codonopsis pilosula, 3 parts of Agrimonia pilosa, 2 parts of stir-fried Atractylodes macrocephala, 2 parts of stir-fried Paeonia lactiflora, 1.2 parts of Angelica sinensis, 2 parts of Corydalis yanhusuo, 0.6 parts of prepared Glycyrrhiza uralensis, 3 parts of Hedyotis diffusa, and 3 parts of Scutellaria barbata.

[0034] First extraction: Open the drinking water valve and add 522.4L of water to the extraction tank, then close the lid. Soak for 30 minutes, then open the steam valve to heat the extraction tank. When the temperature reaches 100℃, close the steam valve and start timing to maintain the temperature at 100 ± 5℃ for 1 hour. The operator should adjust the steam pressure according to the extraction situation (steam pressure ≤ 0.1 MPa). The first extraction is then complete. First, close the steam valve to stop heating, then open the liquid outlet valve. After filtering the extract through the filter, use a vacuum to transfer the extract to the medicine storage tank.

[0035] Second extraction: Open the drinking water valve and add 522.4L of water to the extraction tank, then close the lid. Open the steam valve to heat the extraction tank. When the temperature reaches 100℃, close the steam valve and start timing to maintain the temperature at 100 ± 5℃ for 1 hour. The operator should adjust the steam pressure (steam pressure ≤ 0.1MPa) according to the extraction situation. The second extraction is then complete.

[0036] First, close the steam valve to stop heating, then open the liquid outlet valve. After the extract is filtered, use a vacuum to pump the extract into the drug storage tank.

[0037] Static filtration: Let stand for more than 15 hours, then pass through a 180-mesh filter cloth.

[0038] S2. Concentration: Open the vacuum valve of the single-effect external circulation concentrator. When the vacuum degree is controlled at -0.04 to -0.08 MPa, open the liquid feed valve. Vacuum suck in the liquid after it has been filtered through a 350-mesh filter cloth. Open the steam valve to start heating and concentrating. During the concentration process, the steam pressure should be ≤ 0.10 MPa, the concentration temperature should be controlled at 60 to 80℃, and the vacuum degree should be controlled at -0.06 to -0.10 MPa. During the concentration process, add material as needed according to the amount of clear paste in the equipment until all the liquid is sucked into the equipment. Concentrate the liquid to a relative density of 1.05 to 1.10 (80℃), then turn off the steam and vacuum, stop the concentration, release the clear paste, filter it while it is still hot (through a 180-mesh filter cloth), put it in a sterilized clean container, label it, and put it into storage.

[0039] S3. Dispensing and Sterilization: Cool to 40-50℃ and dispense into pharmaceutical glass bottles. Place the dispensed medicines into an open pot, add water to submerge them, and boil for at least 30 minutes.

[0040] S4. Storage of medicines: The packaged and sterilized medicines are stored in the medicine warehouse for future use. The temperature of the medicine warehouse is 18-26℃ and the humidity is 45%-65%. The storage time is 3 months.

[0041] Example 5: A traditional Chinese medicine composition for treating recurrent colorectal adenomatous polyps, which can also be prepared as oral liquid, granules, capsules, tablets or pills.

[0042] Example 6: Observation of the efficacy and safety of Shenshu Xianlian formula in treating colorectal adenomatous polyps after surgery. Methods: A randomized controlled clinical trial was conducted, enrolling 144 patients who underwent colorectal adenomatous polyp surgery. Patients were randomly divided into an observation group (n=72) and a control group (n=72) using a random number table at a 1:1 ratio. The control group received compound Lactobacillus acidophilus tablets, while the observation group received Shenshu Xianlian formula. The treatment course was 3 months. Changes in TCM syndrome efficacy, TCM syndrome scores, inflammatory factors (TNF-α, IL-17), and brain-gut peptides [vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), somatostatin (SS)] before and after treatment were compared between the two groups. The incidence of adverse reactions and the polyp recurrence rate at 1 and 2 years post-surgery were also assessed. Results: A total of 130 patients completed the study, including 66 in the observation group and 64 in the control group. The total effective rate in the observation group was 92.42%, significantly higher than the 68.75% in the control group. P <0.05). After treatment, the scores for loose or mucous stools, constipation, abdominal pain and distension, loss of appetite, nausea and vomiting, borborygmus, and total TCM syndrome scores decreased in both groups, with a more significant decrease in the observation group. P<0.05); Comparison of differences before and after treatment between groups showed that the observation group had significantly better improvement in scores for loose or mucous stools, constipation, abdominal pain and bloating, loss of appetite, dry and sticky mouth, fatigue and lethargy, nausea and vomiting, as well as the total score of TCM syndromes than the control group. P <0.05), there were no significant differences between the two groups in scores for heaviness and fatigue, borborygmus, and acne or eczema. P >0.05). After treatment, the levels of inflammatory factors and brain-gut peptides decreased in both groups, with a more significant decrease in the observation group. P <0.05); Comparing the differences before and after treatment between groups, the observation group showed significantly better improvement in inflammatory factors and brain-gut peptide levels than the control group ( P <0.05). The polyp recurrence rate at 1 and 2 years post-surgery was significantly lower in the observation group than in the control group. P <0.05). There were no statistically significant differences in blood routine tests and liver and kidney function before and after treatment between the two groups. P >0.05). Conclusion: Shenshu Xianlian formula can effectively improve the clinical symptoms of patients after surgery for colorectal adenomatous polyps and reduce the recurrence rate of polyps. It can also reduce the inflammatory response and lower the level of brain-gut peptides, and has high safety, providing a basis for the clinical application of traditional Chinese medicine.

[0043] 1. Clinical Data 101. Research Subjects 144 patients who underwent surgery for colorectal adenomatous polyps and visited the Department of Gastroenterology at Nanjing Integrated Traditional Chinese and Western Medicine Hospital affiliated with Nanjing University of Traditional Chinese Medicine between August 2023 and May 2024 were selected. A random number table was generated beforehand, and the patients were randomly divided into an observation group (72 cases) and a control group (72 cases) at a 1:1 ratio. Six patients dropped out of the observation group, and eight dropped out of the control group, resulting in a total of 130 patients completing the study. The control group consisted of 35 males and 29 females, aged 21-64 years (mean 43.64±10.63 years), with a disease duration of 1-8 years (mean 3.77±1.77 years). The observation group consisted of 36 males and 30 females, aged 22-65 years (mean 43.71±10.67 years), with a disease duration of 1-9 years (mean 4.46±1.94 years).

[0044] 102. Ethical Review This research project has been approved by the Ethics Committee of Nanjing Integrated Traditional Chinese and Western Medicine Hospital affiliated to Nanjing University of Chinese Medicine, and all patients signed informed consent forms before the start of the study.

[0045] 103. Diagnostic Criteria (1) Western medicine diagnostic criteria: Based on the relevant diagnostic criteria of the Clinical Practice Guidelines: Digestive System Diseases, the Consensus Opinion on the Prevention of Colorectal Cancer in China (2016, Shanghai), and the Pathological Diagnosis Consensus on Gastrointestinal Adenomas and Benign Epithelial Polyps, the following Western medicine diagnostic criteria were formulated: (1) Clinical manifestations include abdominal pain, abdominal distension, loose stools, constipation and other related symptoms; (2) Pathological histological examination confirms that it is a colorectal adenomatous polyp.

[0046] (2) Traditional Chinese Medicine (TCM) Diagnosis Criteria: Based on the "TCM Diagnosis and Treatment Plans for 105 Diseases in 24 Specialties (Combined Edition, Trial Version)" and the "Guiding Principles for Clinical Research of New Chinese Medicine Drugs (Trial Implementation)," the diagnosis criteria for spleen deficiency and blood stasis syndrome are summarized. Main symptoms: Loose or mucous stools, constipation, abdominal pain and distension, loss of appetite, dry and sticky mouth; Secondary symptoms: Fatigue, lethargy, nausea, vomiting, borborygmus, acne or eczema. Tongue and pulse: Pale, swollen, and dark tongue with petechiae or ecchymosis; wiry, slippery, or hesitant pulse. Diagnosis can be made by possessing two main symptoms and three secondary symptoms, combined with tongue coating and pulse.

[0047] 104. Inclusion Criteria (1) Meets the diagnostic criteria under “1.3”; (2) Age between 18 and 65 years old, gender not limited; (3) Within one month before enrollment, the patient has undergone colorectal polyp biopsy and clipping or endoscopic polyp removal by senior attending physicians or above in the Department of Gastroenterology of our hospital, and the pathology confirms that it is an adenoma; (4) The patient understands this study and signs the informed consent form.

[0048] 105. Exclusion Criteria (1) Those with other intestinal diseases such as colon cancer or intestinal tuberculosis; (2) Those with serious blood or immune system diseases; (3) Those with psychological dysfunction or mental illness; (4) Pregnant or lactating women; (5) Those who cannot follow the doctor's advice for treatment; (6) Those who are participating in other clinical research projects.

[0049] 106. Standards for Shedding and Rejection (1) Those with incomplete medical records; (2) Those who did not follow the treatment plan of the observation group and the control group for the whole course of treatment; (3) Those who had received other Chinese and Western medicine treatments for colorectal polyps within 3 months; (4) Those who were lost to follow-up.

[0050] 2. Method 201. Sample size calculation A randomized controlled trial was conducted. Based on previous efficacy statistics for colorectal adenomatous polyps and findings from our team's earlier clinical studies, the overall effective rate was projected to be approximately 90% in the observation group and approximately 70% in the control group. The sample size was determined using the following statistical formula: n= , in:Q 1. Q 2 represents the proportion of the two groups in the total sample. When the groups are divided in a 1:1 ratio... Q 1= Q 2 = 0.5; n is the sample size per group (when grouped equally). Q 1= Q 2=0.5). π 1 represents the expected efficacy rate of the observation group (90% = 0.9). π 2 represents the expected efficacy rate of the control group (70% = 0.7). π c = Q 1 π 1+ Q 2 π 2 represents the consolidation rate; Z α / 2 The number of digits in the standard normal distribution for a two-tailed test ( α =0.05, take 1.96); Z β To test the corresponding quantiles of the power (0.84 for 80% power and 1.28 for 90% power); Calculate the number of patients included and set... α =0.05, β =0.20, Q 1= Q 2 = 0.50, π c = Q 1 π 1+ Q 2 π 2. Considering that the dropout rate is ≤20%, the minimum estimated sample size for each group is 72 cases. Therefore, 144 patients were included, including 72 patients in the treatment group and 72 patients in the control group.

[0051] 202. Grouping Method Following the standardized operating procedures for double-blind clinical trials, a randomization table was created using SPSS 26.0 software at a 1:1 ratio. Randomization cards were then made from this table and placed inside sealed spheres. Patients were grouped according to their enrollment order, with each sphere bearing the same number. The resulting groupings formed the first layer of blinding (Group ① or Group ②). The second layer of blinding consisted of the corresponding treatment regimens for the two groups (observation group and control group). After screening eligible patients, the investigational drug administrator administered the medications sequentially according to the patients' enrollment order and drug serial numbers. Each coded drug was accompanied by a corresponding emergency letter for unblinding in case of an emergency. All letters were collected after the trial, and the blinding records were kept by the trial personnel, ensuring that both doctors and patients remained blinded to the medications used. Upon completion of the trial, the blinding was lifted, with Group ① serving as the observation group and Group ② as the control group.

[0052] 203. Treatment Plan The control group was treated with compound Lactobacillus acidophilus tablets (Tonghua Jinma Pharmaceutical Group Co., Ltd., National Drug Approval Number H10940114, 0.5g / tablet), 1g three times a day after meals, for three consecutive months.

[0053] The observation group was treated with the Shenshu Xianlian formula, which consisted of 2 kg each of Codonopsis pilosula, stir-fried Atractylodes macrocephala, stir-fried Paeonia lactiflora, and Corydalis yanhusuo; 3 kg each of Scutellaria barbata, Agrimonia pilosa, and Hedyotis diffusa; 1.2 kg of Angelica sinensis; and 0.6 kg of prepared Glycyrrhiza uralensis. All the herbs were decocted twice with water, the two decoctions were combined, and the mixture was allowed to stand for at least 15 hours. After filtration, the filtrate was concentrated to a relative density of 1.05-1.10, cooled, and dispensed into 100ml bottles. Sterilization was then performed. This process yielded 200 bottles at a time. The production process of the Shenshu Xianlian formula was verified by Associate Chief Pharmacist Wang of the hospital's pharmacy department to comply with the relevant provisions of the 2020 edition of the Pharmacopoeia of the People's Republic of China. Patients took 25ml orally twice a day, after breakfast and dinner, for three consecutive months.

[0054] 204. Detection Indicators and Efficacy Assessment Main efficacy indicators: (1) TCM syndrome score before treatment and 3 months after treatment: According to the TCM syndrome differentiation criteria, the main symptoms and secondary symptoms are scored as 0, 1, 2 and 3 points respectively for none, mild, moderate and severe. The score is positively correlated with the severity of the symptoms. (2) TCM syndrome efficacy before treatment and 3 months after treatment: The TCM syndrome efficacy judgment criteria are formulated with reference to the "Guiding Principles for Clinical Research of New Chinese Medicines (Trial)". Efficacy index = (score before treatment - score after 3 months of treatment) / score before enrollment × 100%. Complete cure: efficacy index ≥ 95%, clinical symptoms disappear or basically disappear; significant effect: 70% ≤ efficacy index < 95%, clinical symptoms significantly improve; effective: 30% ≤ efficacy index < 70%, clinical symptoms improve; ineffective: efficacy index < 30%, clinical symptoms do not improve or even worsen. Total effective rate = total number of effective cases (cured + significant effect + effective) / total number of cases × 100%.

[0055] Secondary efficacy endpoints: Before treatment and the day after 3 months of treatment, 10 mL of fasting venous blood was drawn from both groups of patients in the morning. After standing, the blood was centrifuged at 2000 r / min for 10 min with a centrifugation radius of 10 cm. The serum was separated and the levels of inflammatory factors [tumor necrosis factor-α (TNF-α) batch number: JL10208, interleukin-17 (IL-17) batch number: JL19256] and brain-gut peptides [vasoactive intestinal peptide (VIP) batch number: JL12727, substance P (SP) batch number: JL11060, calcitonin gene-related peptide (CGRP) batch number: JL11472, somatostatin (SS) batch number: JL10866] were detected by enzyme-linked immunosorbent assay (ELISA) on a Spark10 M multifunctional microplate reader [Diken (Shanghai) Laboratory Equipment Co., Ltd.]. All test kits were provided by Shanghai Jianglai Biotechnology Co., Ltd.

[0056] Recurrence of adenomatous polyps: In all cases, the polyps had been completely removed or excised at the time of enrollment, but new colorectal polyps (pathologically adenomatous) reappeared during follow-up colonoscopy, which was considered a recurrence of colorectal adenomatous polyps. Colonoscopies were performed 1 and 2 years after polyp removal or excision to calculate the recurrence rate.

[0057] Safety indicators and incidence of adverse reactions: During the treatment, adverse reactions in both groups of patients were recorded in detail and their incidence was statistically analyzed. Blood routine and liver and kidney function tests were performed on both groups of patients before treatment and after the study was completed.

[0058] 205. Statistical Methods The results were statistically analyzed using SPSS 26.0 and Graphpad Prism 10.1.2. Quantitative data that conformed to a normal distribution and had homogeneity of variance were expressed as mean ± standard deviation. To indicate, paired samples were used for comparisons within the group before and after treatment. t Independent samples are used for intergroup comparisons. t Test; for data that do not conform to a normal distribution or homogeneity of variance, use the median (interquartiles). M (P 25 P 75 Data are expressed as percentages (%), and nonparametric tests are used for comparisons within and between groups. Count data are expressed as number of cases (percentage, %), and comparisons between groups are performed using... Test. Rank-sum test is used for ordinal data. P <0.05 indicates a statistically significant difference.

[0059] 3. Results This study included 144 patients with colorectal adenomatous polyps, of whom 14 dropped out (6 in the observation group, including 4 lost to follow-up and 2 who refused to continue medication; 8 in the control group, including 5 lost to follow-up and 3 who refused to continue medication). A total of 130 patients completed the study: 66 in the observation group (36 males and 30 females) and 64 in the control group (35 males and 29 females). The age range in the observation group was 22-65 years, with a mean age of (43.71±10.67) years; the disease duration ranged from 1 to 9 years, with a mean duration of (4.46±1.94) years. 25 patients in the observation group had a single polyp, and 41 had multiple polyps. The age range in the control group was 21-64 years, with a mean age of (43.64±10.63) years; the disease duration ranged from 1 to 8 years, with a mean duration of (3.77±1.77) years; 26 patients in the control group had a single polyp, and 38 had multiple polyps. There were no statistically significant differences between the two groups of patients in terms of gender, age, disease duration, and number of polyps. P (>0.05), making them comparable.

[0060] Comparison of clinical efficacy between the two groups: As shown in Table 1, after 3 months of treatment, the total effective rate in the observation group (66 patients) was 92.42%, while the total effective rate in the control group (64 patients) was 68.75%. The difference between the two groups was statistically significant. =11.72, P <0.05).

[0061] Table 1. Comparison of clinical efficacy between the two groups of patients [n(%)]

[0062] Note: a) Compared with the control group, P <0.05.

[0063] Comparison of TCM syndrome scores between the two groups: As shown in Table 2, there were no statistically significant differences in the scores of each item and the total TCM syndrome score between the two groups before treatment. P >0.05). After treatment, the scores for loose or mucous stools, constipation, abdominal pain and bloating, loss of appetite, nausea and vomiting, borborygmus, and total TCM syndrome scores decreased in both groups, with a more significant decrease in the observation group. P <0.05). As shown in Table 2 and Figure 1 As shown, the difference between the groups before and after treatment was significantly better in the observation group than in the control group in terms of scores for loose or mucous stools, constipation, abdominal pain and bloating, loss of appetite, dry and sticky mouth, fatigue and lethargy, nausea and vomiting, as well as the total score of TCM syndrome. P <0.05), there was no statistically significant difference in the scores of heaviness and fatigue, borborygmus, and acne or eczema between the two groups. P >0.05).

[0064] Table 2 Comparison of TCM syndrome scores between the two groups of patients [score, M (P25 P 75 ) / )]

[0065] Note: a) Compared with the group before treatment P <0.05; b) The difference after treatment compared with the control group, P <0.05.

[0066] Figure 1 In the diagram, the x-axis represents each syndrome group, and the y-axis represents the syndrome score; black bars represent the observation group, and gray bars represent the control group; black dots in the bars represent the median or mean of the observation group; black squares in the bars represent the median or mean of the control group; T represents the quartile or standard deviation; * represents... P <0.05.

[0067] Comparison of inflammatory factors and brain-gut peptide levels between the two groups: As shown in Table 3, there was no statistically significant difference in the levels of inflammatory factors and brain-gut peptides between the two groups before treatment. P >0.05). After treatment, the levels of inflammatory factors and brain-gut peptides decreased in both groups, with a more significant decrease in the observation group. P <0.05). As shown in Table 3 and Figure 2 As shown, comparing the differences before and after treatment between groups, the observation group showed significantly better improvement in inflammatory factors and brain-gut peptide levels than the control group. P <0.05).

[0068] Table 3 Comparison of inflammatory factors and brain-gut peptide levels between the two groups of patients [ M (P 25 P 75 ) / ]

[0069] Note: TNF-α, tumor necrosis factor-α; IL-17, interleukin-17; VIP, vasoactive intestinal peptide; SP, substance P; CGRP, calcitonin gene-related peptide; SS, somatostatin.

[0070] a) Compared with the group before treatment P <0.05; b) The difference after treatment compared with the control group, P <0.05.

[0071] Figure 2In the diagram: The x-axis represents the observed indicators: TNF-α (tumor necrosis factor-α); IL-17 (interleukin-17); VIP (vasoactive intestinal peptide); SP (substance P); CGRP (calcitonin gene-related peptide); SS (somatostatin). The y-axis represents the units of the observed indicators; black bars represent the observation group, and gray bars represent the control group; black dots in the bars represent the median or mean of the observation group; black squares in the bars represent the median or mean of the control group; T represents the quartile or standard deviation; * represents... P <0.05.

[0072] Comparison of polyp recurrence rates between the two groups: As shown in Table 4, the total polyp recurrence rate one year after surgery was 7.6% in the observation group and 25% in the control group, with a statistically significant difference. =7.28, P <0.05); the total polyp recurrence rate 2 years after surgery was 22.73% in the observation group and 48.4% in the control group, and the difference was statistically significant. =9.39, P <0.05).

[0073] Table 4. Comparison of polyp recurrence rates between the two groups [n(%)]

[0074] Note: a) Compared with the control group, P <0.05.

[0075] Safety indicators: There were no statistically significant differences in blood routine tests and liver and kidney function between the two groups before and after treatment. P >0.05), no drug-related adverse reactions occurred.

[0076] Currently, the main Western medical treatment for colorectal adenomatous polyps is endoscopic polypectomy. However, the challenge lies in the difficulty in effectively and quickly improving patients' clinical symptoms after polyp removal, and polyp recurrence is very common in clinical practice. Therefore, it is necessary to establish a scientific and effective treatment plan to improve the prognosis of patients after colorectal adenomatous polyp surgery.

[0077] Colorectal adenomatous polyps fall under the categories of "intestinal fungus," "visceral toxins," and "intestinal obstruction" in Traditional Chinese Medicine (TCM). This disease is often caused by improper diet, excessive consumption of rich and fatty foods, damaging the spleen and stomach; or by emotional imbalance, overwork, or excessive rest, leading to stagnation of Qi, which then affects the spleen, causing impaired spleen function, abnormal digestion, accumulation of dampness, stagnation of Qi and blood, and the formation of toxins. The pathological factors are a prolonged combination of deficiency, dampness, blood stasis, and toxins, with the underlying cause being impaired spleen function and the manifestation being internal accumulation of blood stasis and toxins. The Ginseng, Atractylodes, and Lotus Seed Formula uses Codonopsis pilosula and Scutellaria barbata as the principal herbs. Codonopsis pilosula tonifies Qi and strengthens the spleen, with a mild effect that does not cause Qi stagnation; Scutellaria barbata clears heat, promotes diuresis, resolves blood stasis, detoxifies, heals sores, and disperses nodules. The combination of these two herbs, one tonifying and the other purging, eliminates pathogenic factors without harming the body's vital energy. Stir-fried Atractylodes macrocephala tonifies Qi and strengthens the spleen, dries dampness and promotes diuresis. Combined with Codonopsis pilosula, it not only strengthens the spleen and replenishes Qi, but also dries dampness, promotes diuresis, and stops diarrhea. Stir-fried Paeonia lactiflora softens the liver, relieves spasms and pain, and combined with stir-fried Atractylodes macrocephala, it regulates the liver and spleen, eliminates dampness, and stops diarrhea. Agrimonia pilosa tonifies deficiency, stops diarrhea, detoxifies, and astringes sores. Hedyotis diffusa clears heat, detoxifies, and disperses nodules. These four herbs are assistant herbs, used together to achieve a balance of warming and cooling properties, and a combination of tonifying and purging effects. Angelica sinensis and Corydalis yanhusuo are adjuvant herbs, which can promote Qi circulation, disperse nodules, relieve pain, invigorate blood, remove blood stasis, and detoxify, treating both Qi and blood. Prepared Glycyrrhiza uralensis is the guiding herb; combined with stir-fried Paeonia lactiflora, it relieves spasms and pain; combined with stir-fried Atractylodes macrocephala, it tonifies Qi and strengthens the spleen; combined with Scutellaria barbata and Hedyotis diffusa, it clears heat and detoxifies, and also harmonizes the other herbs in the formula. The entire formula works synergistically to tonify Qi and strengthen the spleen, eliminate dampness and detoxify, disperse nodules, and unblock the meridians.

[0078] This invention found that the observation group showed significantly improved clinical efficacy, improved TCM syndromes, and reduced inflammatory factor levels, thereby more effectively reducing the recurrence rate of polyps. This may be due to the strong anti-fatigue and anti-inflammatory effects of Codonopsis pilosula polysaccharides contained in the Shenshu Xianlian formula, combined with the total flavonoids of Scutellaria barbata, which can significantly inhibit the growth activity of HCT-116 colon cancer cells and exert an immunomodulatory effect. The extract of Atractylodes macrocephala and Paeonia lactiflora exerts anti-inflammatory effects by inhibiting the MAPK and NF-κB signaling pathways and downregulating the expression of inflammatory factors; luteolin, quercetin, and other components in the extracts of Agrimonia pilosa and Hedyotis diffusa have significant inhibitory effects on Escherichia coli and tumor cells.

[0079] Domestic and international scholars have reported a significant increase in *Escherichia coli* in the intestines of patients with colorectal polyps, releasing large amounts of endotoxins and bacterial toxins. This activates neutrophils and hepatic macrophages, leading to increased secretion of inflammatory factors such as TNF-α and IL-17, and promoting malignant transformation of polyps. Previous studies have shown that abnormal activation of the Wnt / β-catenin signaling pathway promotes the expression of downstream target genes such as MMP, c-Myc, and Cyclin D1, triggering an inflammatory response, promoting abnormal proliferation of colon cells, and ultimately leading to colorectal adenomas. This invention found that after treatment, the expression of TNF-α and IL-17 in the observation group was lower than that in the control group, suggesting that the Shenshu Xianlian formula may reduce the recurrence rate of polyps by reducing intestinal inflammation and inhibiting the abnormal activation of the Wnt / β-catenin signaling pathway in the colonic tissue.

[0080] In existing technologies, SS and VIP in brain-gut peptides have certain neurotransmitter and hormone-like effects, stimulating the release of inflammatory mediators and vasodilation, and are closely related to inflammatory bowel symptoms such as abdominal pain and diarrhea, and participate in the occurrence and development of colorectal polyps; CGRP and SP promote intestinal smooth muscle contraction and intestinal peristalsis, leading to increased intestinal mucus secretion and diarrhea. Animal experiments have shown that CGRP and SP are significantly elevated in rats during the active phase of intestinal inflammation. This invention found that the observation group can effectively regulate the levels of SP, VIP, CGRP, and SS, which is an important mechanism by which this formula improves clinical symptoms and reduces the recurrence rate of polyps.

[0081] In summary, patients with colorectal adenomatous polyps after surgery present with complex clinical symptoms, high polyp recurrence rates, and unsatisfactory efficacy with Western medicine. However, the Shenshu Xianlian formula of this invention has achieved satisfactory results with few adverse reactions. Furthermore, it has been found that regulating inflammatory factors and brain-gut peptide levels is an important mechanism by which this formula reduces polyp recurrence.

[0082] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition for treating recurrent colorectal adenomatous polyps, characterized in that, The following components are included in parts by weight: Codonopsis pilosula 1.5–2.5 parts, stir-fried Atractylodes macrocephala 1.5–2.5 parts, stir-fried Paeonia lactiflora 1.5–2.5 parts, Corydalis yanhusuo 1.5–2.5 parts, Scutellaria barbata 2.5–3.5 parts, Agrimonia pilosa 2.5–3.5 parts, Hedyotis diffusa 2.5–3.5 parts, Angelica sinensis 1.0–1.5 parts, prepared Glycyrrhiza uralensis 0.5–1.0 parts.

2. The traditional Chinese medicine composition for treating recurrent colorectal adenomatous polyps according to claim 1, characterized in that, The following components are included in parts by weight: Codonopsis pilosula 2 parts, stir-fried Atractylodes macrocephala 2 parts, stir-fried Paeonia lactiflora 2 parts, Corydalis yanhusuo 2 parts, Scutellaria barbata 3 parts, Agrimonia pilosa 3 parts, Hedyotis diffusa 3 parts, Angelica sinensis 1.2 parts, and prepared Glycyrrhiza uralensis 0.6 parts.

3. The traditional Chinese medicine composition for treating recurrent colorectal adenomatous polyps according to claim 1, characterized in that, The traditional Chinese medicine composition is in the form of decoction, oral liquid, granules, capsules, tablets or pills.

4. The method for preparing the traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, Includes the following steps: Add water to Codonopsis pilosula, stir-fried Atractylodes macrocephala, stir-fried Paeonia lactiflora, Corydalis yanhusuo, Scutellaria barbata, Agrimonia pilosa, Hedyotis diffusa, Angelica sinensis, and prepared Glycyrrhiza uralensis, decoct, combine the decoctions, let stand, filter, and concentrate the filtrate to obtain the final product.

5. The preparation method according to claim 4, characterized in that, Includes the following steps: S1. Feeding: Put the pitted medicinal materials from the feeding area into the extraction tank; S2. First extraction: Add water to the extraction tank, soak, heat the extraction tank to boiling, start timing and keep warm, maintain the temperature and decoct, stop heating, filter the extract through the filter and pump the extract into the medicine storage tank; S3. Second extraction: Add water to the extraction tank, heat the extraction tank to boiling, start timing and keep warm, maintain the temperature for decoction, stop heating, filter the extract through the filter, and pump the extract into the medicine storage tank. S4. Static filtration; S5. Concentration: Open the vacuum valve of the single-effect external circulation concentrator. When the vacuum degree is controlled at -0.04 to -0.08 MPa, open the liquid feed valve and vacuum-inhale the liquid after it has been filtered through the filter cloth. Open the steam valve to start heating and concentrating. During the concentration process, the steam pressure should be ≤0.10 MPa, the concentration temperature should be controlled at 60 to 80℃, and the vacuum degree should be controlled at -0.06 to -0.10 MPa. During the concentration process, when all the liquid is drawn into the equipment, concentrate it to a liquid with a relative density of 1.05 to 1.

10. Then, turn off the steam and the vacuum, stop the concentration, release the clear paste, filter it while it is still hot, put it in a sterilized clean container, label it, and put it into storage.

6. The use of the traditional Chinese medicine composition according to any one of claims 1-3 in the preparation of a medicament for treating colorectal adenomatous polyps.

7. The use of the traditional Chinese medicine composition according to any one of claims 1-3 in the preparation of a medicament for preventing recurrence of colorectal adenomatous polyps after surgery.

8. The use of the traditional Chinese medicine composition according to any one of claims 1-3 in the preparation of a medicine for improving the TCM syndrome of patients after surgery for colorectal adenomatous polyps.

9. The use of the traditional Chinese medicine composition according to any one of claims 1-3 in the preparation of a medicament for reducing the level of inflammatory factors in patients after surgery for colorectal adenomatous polyps, wherein the inflammatory factors are TNF-α and / or IL-17.

10. The use of the traditional Chinese medicine composition according to any one of claims 1-3 in the preparation of a drug for regulating the brain-gut peptide levels in patients after surgery for colorectal adenomatous polyps, wherein the brain-gut peptides are vasoactive intestinal peptide VIP, substance P SP, calcitonin gene-related peptide CGRP and / or somatostatin SS.

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