A traditional Chinese medicine composition for treating ulcerative colitis, its preparation method, combined drugs, and applications.

Abstract

This invention discloses a traditional Chinese medicine composition for treating ulcerative colitis, its preparation method, combined drugs, and applications. The traditional Chinese medicine composition for treating ulcerative colitis of this invention is made from the following raw materials in parts by weight: Astragalus membranaceus 13-26 parts, Lonicera japonica 10-20 parts, Sargentodoxa cuneata 10-20 parts, Prunus mume 8-16 parts, Agrimonia pilosa 8-16 parts, Allium macrostemon 6-12 parts, Platycodon grandiflorus 6-12 parts, Coptis chinensis 3-6 parts, and Panax notoginseng powder 1-3 parts. An animal model of ulcerative colitis was constructed using DSS induction, and the results showed that the traditional Chinese medicine composition of this invention has a certain therapeutic effect on ulcerative colitis. Clinical studies showed that the traditional Chinese medicine composition of this invention, used in combination with mesalazine enteric-coated tablets, can reduce the modified Mayo score and serum inflammatory markers in patients with active ulcerative colitis, improve colonic mucosal inflammation and gastrointestinal symptoms, and effectively treat active ulcerative colitis of the damp-heat type.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine composition technology, and in particular to a traditional Chinese medicine composition for treating ulcerative colitis, its preparation method, combined drugs, and applications. Background Technology

[0002] Ulcerative colitis (UC) is a chronic, nonspecific inflammatory bowel disease characterized by continuous, diffuse inflammation of the colorectal mucosa. The lesions are primarily confined to the colorectal mucosa and submucosa. Clinical manifestations of UC include diarrhea, bloody and mucous stools, and abdominal pain, varying in severity. Patients often experience a recurrent, chronic course characterized by alternating remissions and relapses. Based on its clinical presentation, Traditional Chinese Medicine (TCM) classifies UC under categories such as "chronic dysentery," "intestinal bleeding," or "diarrhea." Although the prevalence of UC in Asia is relatively low compared to Europe and the United States, its actual incidence has shown a year-on-year upward trend in recent years.

[0003] Current treatment strategies for ulcerative colitis (UC) primarily focus on rapidly inducing remission during the active phase and maintaining long-term remission, while preventing complications such as cancer. Commonly used medications include 5-aminosalicylic acid (mesalazine), glucocorticoids, immunosuppressants, and biologics, employed in a step-up therapy approach. However, these medications have limitations, such as unstable efficacy, high relapse rates after discontinuation, side effects like liver and kidney damage and even bone marrow suppression, increased risk of infection, and high treatment costs. Clinical studies based on evidence-based medicine show that Traditional Chinese Medicine (TCM) has unique advantages in improving UC clinical symptoms, inducing remission, preventing relapse, improving quality of life, and reducing complications. Furthermore, combining TCM with Western medicine in UC treatment can achieve a "synergistic effect and reduced toxicity," making the study of TCM and its combined use in the prevention, treatment, and efficacy research of UC significant. Basic research has also confirmed that TCM can intervene in UC through multiple mechanisms, including anti-inflammation, immune regulation, and mucosal repair. Therefore, there is an urgent need to develop TCM compositions with significant efficacy against ulcerative colitis and combined TCM and Western medicine treatments with fewer side effects. Summary of the Invention

[0004] The purpose of this invention is to provide a traditional Chinese medicine composition for treating ulcerative colitis, its preparation method, combined drugs, and applications. This traditional Chinese medicine composition and combined drugs are safe and effective for treating active ulcerative colitis.

[0005] To achieve the above objectives, the present invention adopts the following technical solution:

[0006] In a first aspect, the present invention provides a traditional Chinese medicine composition for treating ulcerative colitis, which is made from the following raw materials in parts by weight: Astragalus membranaceus 13-26 parts, Lonicera japonica 10-20 parts, Sargentodoxa cuneata 10-20 parts, Prunus mume 8-16 parts, Agrimonia pilosa 8-16 parts, Allium macrostemon 6-12 parts, Platycodon grandiflorus 6-12 parts, Coptis chinensis 3-6 parts, and Panax notoginseng powder 1-3 parts.

[0007] Astragalus is the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge., belonging to the Fabaceae family. Astragalus has the effects of tonifying qi and raising yang, consolidating the exterior and stopping sweating, promoting diuresis and reducing swelling, generating fluids and nourishing blood, promoting circulation and relieving pain, promoting detoxification and draining pus, and astringing sores and promoting tissue regeneration.

[0008] Honeysuckle is the dried flower bud or newly opened flower of Lonicera japonica Thunb., a plant of the Caprifoliaceae family; honeysuckle has the effects of clearing heat and detoxifying, and dispersing wind-heat.

[0009] Sargentodoxa cuneata is the dried stem of Sargentodoxa cuneata (Oliv.) Rehd. et Wils., a plant in the Lardizabalaceae family. Sargentodoxa cuneata has the effects of clearing heat and detoxifying, promoting blood circulation, dispelling wind and relieving pain.

[0010] Ume is the dried, nearly mature fruit of Prunus mume (Sieb.) Sieb. et Zucc., a plant in the Rosaceae family. Ume has the effects of astringing the lungs, astringing the intestines, promoting the production of body fluids, and expelling roundworms.

[0011] Agrimony is the dried aerial part of Agrimonia pilosa Ledeb., a plant in the Rosaceae family. Agrimony has the effects of astringing and stopping bleeding, treating malaria, stopping dysentery, detoxifying, and tonifying deficiency.

[0012] Allium macrostemon Bge. or Allium chinense G.Don, both belonging to the Liliaceae family, are dried bulbs. Allium macrostemon has the effects of promoting yang, dispersing stagnation, regulating qi, and relieving stagnation.

[0013] Platycodon grandiflorum (Jacq.) A.DC., a plant in the Campanulaceae family, is a plant that is dried. Platycodon grandiflorum has the effects of clearing the lungs, relieving sore throat, eliminating phlegm, and draining pus.

[0014] Coptis chinensis is the dried rhizome of Coptis chinensis Franch., Coptis deltoidea CYCheng et Hsiao, or Coptis teeta Wall., all belonging to the Ranunculaceae family. Coptis chinensis has the effects of clearing heat and drying dampness, purging fire and detoxifying.

[0015] Panax notoginseng is the dried root and rhizome of Panax notoginseng (Burk.) FHChen, a plant belonging to the Araliaceae family. Panax notoginseng powder has the effects of dispersing blood stasis, stopping bleeding, reducing swelling, and relieving pain.

[0016] Based on the above technical solutions, the traditional Chinese medicine composition of this invention uses Astragalus membranaceus to exert its function of strengthening the spleen and replenishing qi, promoting tissue regeneration and detoxification; Lonicera japonica, Sargentodoxa cuneata, and Coptis chinensis to clear heat and dry dampness, cool blood and detoxify, and promote blood circulation and unblock collaterals; Prunus mume is sour and warm, astringes the intestines and stops diarrhea, nourishes yin and generates fluids; Agrimonia pilosa is astringent and nourishing, and stops diarrhea while promoting circulation, thus treating both the root cause and the symptoms; Allium macrostemon and Platycodon grandiflorus are added to open the lung qi and unblock the bowel qi, treat diarrhea and tenesmus, and at the same time promote the flow of qi and enhance the function of pus drainage.

[0017] As an example, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 20 parts Astragalus membranaceus, 15 parts Lonicera japonica, 15 parts Sargentodoxa cuneata, 12 parts Prunus mume, 12 parts Agrimonia pilosa, 10 parts Allium macrostemon, 10 parts Platycodon grandiflorus, 5 parts Coptis chinensis, and 1.5 parts Panax notoginseng powder.

[0018] Furthermore, the traditional Chinese medicine composition may be a decoction. It is understood that any dosage form of the traditional Chinese medicine composition made from the above-mentioned raw materials is within the scope of protection of this invention.

[0019] Secondly, the present invention provides a method for preparing a traditional Chinese medicine composition for treating ulcerative colitis as described in any of the above claims, comprising the following steps: mixing the raw materials used to prepare the traditional Chinese medicine composition according to the stated mass proportions, soaking them in water and then decocting them, collecting the decoction to obtain the aqueous decoction.

[0020] In the above preparation method, the soaking time can be 20 to 30 minutes, such as 20 minutes;

[0021] The decoction time is controlled so that for every 100.5g of raw material, 1000-1500mL of water is used to decoct until the remaining liquid is 150-300ml, such as 200mL.

[0022] The decoction is prepared twice, and the decoction liquids are combined after the decoction is completed.

[0023] Thirdly, the present invention provides the application of the aforementioned traditional Chinese medicine composition in the preparation of a medicament for treating ulcerative colitis.

[0024] In the above applications, the treatment of ulcerative colitis specifically manifests in at least one of the following: 1) reducing weight loss caused by ulcerative colitis; 2) protecting or repairing damage to the colonic mucosa; 3) reducing inflammation of the colonic tissue.

[0025] In the above applications, the traditional Chinese medicine composition is used to treat humans or mammals (such as mice). In this invention, male c57bl / 6 mice were administered the traditional Chinese medicine composition by gavage at doses of 13.1 g / kg / d and 26.2 g / kg / d. The results showed that the 26.2 g / kg / d dose was more effective (superior to the mesalazine group).

[0026] Fourthly, the present invention provides a medicament for the combined treatment of ulcerative colitis, comprising the traditional Chinese medicine composition as described in any one of the preceding claims and mesalazine enteric-coated tablets.

[0027] In the aforementioned drugs, the dosage of the traditional Chinese medicine composition is a decoction, one dose per day, twice a day, 200 mL each time; the dosage of the mesalazine enteric-coated tablets is 3 g / day.

[0028] Fifthly, the present invention provides the use of the described drug in the preparation of a medicament for treating ulcerative colitis.

[0029] In the above applications, the ulcerative colitis refers to the active phase of ulcerative colitis; and / or,

[0030] The ulcerative colitis mentioned is a type of ulcerative colitis caused by intestinal damp-heat.

[0031] Specifically, the activity period is mild, moderate, or severe, such as mild-to-moderate activity period or moderate-to-severe activity period.

[0032] The treatment for ulcerative colitis specifically includes at least one of the following: 1) reducing the modified Mayo score; 2) reducing C-reactive protein; 3) reducing erythrocyte sedimentation rate; and 4) reducing white blood cell count.

[0033] The diagnostic criteria for intestinal damp-heat syndrome are as follows: (1) Primary symptoms: ① Diarrhea with mucus and bloody stools. ② Tenesmus; (2) Secondary symptoms: ① Dry mouth and bitter taste. ② Burning sensation in the anus. ③ Short and dark urine; (3) Tongue and pulse: Yellow, thick and greasy tongue coating, slippery and rapid or soft and rapid pulse; (4) Syndrome identification: The diagnosis can be made by having two primary symptoms (items 1 and 2 are required) plus one secondary symptom, and referring to the tongue and pulse.

[0034] Furthermore, the use of the drug in the preparation of a drug for reducing the syndrome score of damp-heat in the intestines of patients with ulcerative colitis or improving the symptoms of damp-heat in the intestines of patients with ulcerative colitis is also within the scope of protection of this invention.

[0035] The present invention has the following beneficial effects:

[0036] (1) The present invention constructs an animal model of ulcerative colitis by inducing dextran sulfate sodium salt (DSS). The results show that the traditional Chinese medicine composition of the present invention has a certain therapeutic effect on ulcerative colitis, specifically by reducing weight loss caused by ulcerative colitis, reducing inflammation of colon tissue, and protecting or repairing damage to colon mucosa.

[0037] (2) The combination of the traditional Chinese medicine composition of the present invention with mesalazine can reduce the modified Mayo score and serum inflammatory markers in patients with active ulcerative colitis, improve colonic mucosal inflammation and gastrointestinal symptoms, and the total effective rate of treatment for patients with active ulcerative colitis is 85.19%.

[0038] (3) The combination of the traditional Chinese medicine composition of the present invention with mesalazine can effectively improve active ulcerative colitis of the intestinal damp-heat type. According to the TCM symptom score of gastrointestinal diseases, the efficacy rate was 14.81% and the effective rate was 81.48%. Attached Figure Description

[0039] Figure 1 The figures show the weight changes of mice in the normal group, model group, low-dose group of traditional Chinese medicine composition, and high-dose group of traditional Chinese medicine composition in Example 3 of this invention.

[0040] Figure 2A HE staining images of mouse colon tissues from the normal group, model group, low-dose group of traditional Chinese medicine composition, and high-dose group of traditional Chinese medicine composition in Example 3 of this invention, and RILEY scores for each group; Figure 2B This is the RILEY rating sheet.

[0041] Figure 3 The expression levels of inflammatory factors (IL-6 and IL-1β) in the colon tissues of mice in the normal group, model group, low-dose group of traditional Chinese medicine composition, and high-dose group of traditional Chinese medicine composition in Example 3 of the present invention.

[0042] Figure 4 This is the intestinal mucosa condition under endoscopy before treatment in a typical clinical case in Example 4 of the present invention.

[0043] Figure 5 This is an endoscopic view of the intestinal mucosa after treatment in a typical clinical case in Example 4 of the present invention. Detailed Implementation

[0044] The present invention will now be described in further detail with reference to specific embodiments. The given embodiments are merely illustrative of the invention and not intended to limit its scope. The embodiments provided below can serve as a guide for further improvements by those skilled in the art and do not constitute a limitation on the invention in any way.

[0045] Unless otherwise specified, the methods used in the following embodiments are conventional methods, performed according to the techniques or conditions described in the literature in this field or according to the product instructions. Unless otherwise specified, the materials and reagents used in the following embodiments are commercially available.

[0046] The Chinese medicinal materials used in the following examples all comply with the relevant provisions of the Chinese Pharmacopoeia (2020 Edition), Part I, under the respective medicinal materials section. Before addition of materials, each medicinal material was identified, and the actual product matched the name, and the quality met the standards.

[0047] Example 1: Preparation of a traditional Chinese medicine composition (decoction) for treating active ulcerative colitis.

[0048] 1. Raw material formula

[0049] The traditional Chinese medicine composition for treating active ulcerative colitis provided in this embodiment is made from the following raw materials: Astragalus membranaceus 20g, Lonicera japonica 15g, Sargentodoxa cuneata 15g, Prunus mume 12g, Agrimonia pilosa 12g, Allium macrostemon 10g, Platycodon grandiflorus 10g, Coptis chinensis 5g, and Panax notoginseng powder 1.5g.

[0050] 2. Preparation method

[0051] The preparation method of the traditional Chinese medicine composition for treating active ulcerative colitis provided in this embodiment is as follows: Weigh and mix the above raw materials according to the above formula, add water to submerge and exceed the surface of the raw materials by more than 1 / 3 (1200mL), soak for 20 minutes, then bring to a boil over high heat, and then simmer over low heat until the remaining liquid is 200ml. Repeat the above simmering process twice, mix the obtained medicinal juice and divide it into two portions, each about 200ml, to obtain the traditional Chinese medicine composition.

[0052] 3. Usage and Dosage

[0053] The dosage and administration of the traditional Chinese medicine composition in this example are as follows: one dose per day, twice a day, 200 mL each time.

[0054] Example 2: Preparation of a traditional Chinese medicine composition (granules) for treating active ulcerative colitis.

[0055] 1. Raw material formula

[0056] The traditional Chinese medicine composition for treating active ulcerative colitis provided in this embodiment is made from the following raw materials: Astragalus membranaceus 20g, Lonicera japonica 15g, Sargentodoxa cuneata 15g, Prunus mume 12g, Agrimonia pilosa 12g, Allium macrostemon 10g, Platycodon grandiflorus 10g, Coptis chinensis 5g, and Panax notoginseng powder 1.5g.

[0057] 2. Preparation method

[0058] The method for preparing a traditional Chinese medicine composition for treating active ulcerative colitis provided in this embodiment includes the following steps: The water-extractable granules of the above-mentioned raw materials are weighed according to the above formula and mixed evenly to obtain the traditional Chinese medicine composition (granules). The granules of each raw material can be obtained commercially.

[0059] 3. Usage and Dosage

[0060] The dosage and administration of the traditional Chinese medicine composition in this example are as follows: Dissolve the traditional Chinese medicine composition in boiling water before taking it. Dissolve 100.5g of raw materials into granules in 150mL of boiling water, and take one dose daily.

[0061] Example 3: Animal experimental study on the treatment of active ulcerative colitis with traditional Chinese medicine composition.

[0062] 1. Research Methods

[0063] 1.1. Grouping and treatment of laboratory animals

[0064] Fifty male c57bl / 6 mice aged 5-7 weeks were housed in a standardized clean animal room, fed with regular feed, and given free access to water. After one week of acclimatization, 50 male c57bl / 6 mice aged 6-8 weeks were randomly divided into four groups using a random number table: normal group, model group, mesalazine control group, low-dose group of traditional Chinese medicine composition, and high-dose group of traditional Chinese medicine composition, with 10 mice in each group. The mice were given free access to distilled water, free access to 2.5% DSS, free access to 2.5% DSS plus mesalazine 200 mg / kg / day (calculated based on adult standard dose and mouse body surface area, dissolved in distilled water), free access to 2.5% DSS plus traditional Chinese medicine composition 13.1 g / kg / day (based on the total weight of the raw materials of the traditional Chinese medicine composition, calculated based on adult standard dose and mouse body surface area), and free access to 2.5% DSS plus traditional Chinese medicine composition 26.2 g / kg / day (calculated based on twice the adult dose and mouse body surface area). The mice were administered the medicine once daily by gavage for one week. Daily changes in mouse weight were observed. After one week, the mice were sacrificed, and colon tissue was collected.

[0065] 1.2. Observation Indicators

[0066] Body weight, colon pathology HE staining and pathological score.

[0067] 1.3 Statistical Methods

[0068] SPSS 22.0 software was used for statistical analysis. Quantitative data were expressed as mean ± standard deviation. ANOVA was used to compare differences between groups; a two-tailed test was employed. P <0.05 was considered statistically significant; multiple comparisons between groups were performed using the LSD test, with a two-tailed test. P<0.05 indicates a statistically significant difference.

[0069] 2. Research Results

[0070] 2.1 Comparison of mouse body weight

[0071] like Figure 1 As shown, the body weight of mice in the model group was significantly lower than that of mice in other groups, and the differences were statistically significant. The body weight of the high-dose group of the traditional Chinese medicine composition was higher than that of the mesalazine control group and higher than that of the low-dose group of the traditional Chinese medicine composition. The above results suggest that the traditional Chinese medicine composition of the present invention, at the dosage calculated based on the adult standard dose and the mouse body surface area, can alleviate the weight loss caused by ulcerative colitis.

[0072] 2.1 Mouse colon pathology HE staining and scoring

[0073] like Figure 2A As shown, the colonic mucosa of the normal mice was intact, the epithelial cells were neatly arranged and morphologically normal, the crypt structure was intact, and no obvious inflammatory cell infiltration was observed. The colonic mucosa of the model group showed more epithelial cell shedding, abnormal epithelial cell morphology and structure, disordered crypt structure, and extensive inflammatory cell infiltration in the submucosa and lamina propria. Compared with the model group, the colonic mucosa of each treatment group was relatively intact, the epithelial cell shedding and crypt structure abnormalities were improved, and the number of infiltrating inflammatory cells was reduced.

[0074] Furthermore, based on the modified RILEY score of pathological histology ( Figure 2B The pathological results of each group were scored. Compared with the normal group, the pathological score of the model group was significantly higher. P <0.01), the pathological scores of each treatment group were significantly lower than those of the model group ( P <0.01), among which, the high-dose group of the traditional Chinese medicine composition showed better therapeutic effects than the mesalazine group and better than the low-dose group of the traditional Chinese medicine. The above experimental results indicate that the drug of the present invention can significantly alleviate the symptoms of colonic lesions, has a good protective and repairing effect on colonic mucosal damage, and can be used to treat ulcerative colitis.

[0075] 2.3 Levels of inflammatory factors in mouse colon tissue

[0076] like Figure 3 As shown, compared with the normal group, the levels of two inflammatory factors, IL-6 and IL-1β, in the colon tissue of the model group mice were significantly increased ( P <0.01), the levels of the two inflammatory factors in each treatment group were significantly lower than those in the model group ( P<0.05), wherein the high-dose group of the traditional Chinese medicine composition showed better therapeutic effects in reducing IL-6 than the low-dose group and the mesalazine group; the high-dose group of the traditional Chinese medicine composition showed better therapeutic effects in reducing IL-1β than the mesalazine group and the low-dose group. The above experimental results indicate that the drug of the present invention can significantly reduce colonic tissue inflammation and can be used to treat ulcerative colitis.

[0077] Example 4: Clinical study of the traditional Chinese medicine composition of the present invention in the treatment of active ulcerative colitis.

[0078] 1. Materials and Methods

[0079] This prospective study analyzed the efficacy of the herbal composition of this invention in patients with active ulcerative colitis who visited the Beijing Anorectal Hospital between June 2023 and March 2024 for 12 weeks. This study was approved by the Ethics Committee of Beijing University of Chinese Medicine (Approval No.: 2023BZYLL1105).

[0080] 1.1. Selection Criteria

[0081] The enrolled patients were those with mild to moderate active ulcerative colitis, diagnosed with intestinal damp-heat syndrome according to traditional Chinese medicine, aged 18-75 years (inclusive), regardless of gender or ethnicity, and who voluntarily signed the informed consent form.

[0082] The Western medicine diagnostic criteria for ulcerative colitis refer to the "Consensus Opinion on Diagnosis and Treatment of Inflammatory Bowel Disease" issued by the Inflammatory Bowel Disease Group of the Chinese Society of Gastroenterology in 2018 and the "Technical Guidelines for Clinical Trials of Drugs for the Treatment of Ulcerative Colitis" issued by the Center for Drug Evaluation of the National Medical Products Administration in 2021. A comprehensive assessment is made based on the patient's clinical symptoms and signs, laboratory tests, imaging examinations, colonoscopy, and histopathological results. At least 3 months should have elapsed since symptom onset at enrollment. If the diagnosis is uncertain, endoscopic and histopathological re-examinations should be performed after a certain period (generally 6 months). Crohn's disease, intestinal tuberculosis, other chronic intestinal infectious diseases, and intestinal malignancies should be excluded. Evidence of disease activity should be provided using the modified Mayo Criterion, with 3-5 indicating mild activity, 6-10 indicating moderate activity, and 11-12 indicating severe activity.

[0083] The diagnostic criteria for UC are based on the "Guiding Principles for Clinical Research of New Chinese Medicines" and the "Expert Consensus Opinions on the Diagnosis and Treatment of Ulcerative Colitis with Traditional Chinese Medicine (2017)" issued by the Spleen and Stomach Diseases Branch of the Chinese Association of Traditional Chinese Medicine. For those diagnosed with intestinal damp-heat syndrome: (1) Primary symptoms: ① Diarrhea with mucus and bloody stools. ② Tenesmus; (2) Secondary symptoms: ① Dry mouth and bitter taste. ② Burning sensation in the anus. ③ Short and dark urine; (3) Tongue and pulse: Thick and greasy yellow tongue coating, slippery and rapid or soft and rapid pulse; (4) Syndrome determination: Two primary symptoms (the first and second are required) plus one secondary symptom, and the diagnosis can be made by referring to the tongue and pulse.

[0084] 1.2. Exclusion Criteria

[0085] Those with serious complications, such as toxic megacolon, intestinal obstruction, intestinal perforation, massive bleeding, or colorectal cancer; those with other intestinal diseases, such as bacterial dysentery, intestinal tuberculosis, or Crohn's disease; those who are pregnant, breastfeeding, or planning to become pregnant; those with serious primary diseases of the heart, brain, lungs, kidneys, liver, hematopoietic system, or malignant tumors; those who are allergic to or have contraindications to any of the components of the herbal composition of this invention; those who have participated in other clinical trials within the past 4 weeks; and other individuals deemed unsuitable by the researchers.

[0086] 1.3. Treatment

[0087] Patients with ulcerative colitis meeting the inclusion criteria were enrolled consecutively according to their consultation order and treatment preferences. Patients treated with traditional Chinese medicine combined with mesalazine enteric-coated tablets were included in the combined group, while those treated with mesalazine enteric-coated tablets were included in the mesalazine group. Once the first patient was enrolled, continuous enrollment was mandatory. The combined group received the traditional Chinese medicine composition described in Example 1. One dose was taken twice daily (before breakfast and dinner), 200 mL each time. Both groups received mesalazine enteric-coated tablets (Salfour, Losan Pharma GmbH, Germany) 0.5 g / tablet, 2 tablets (total 1 g), orally three times daily. Both groups were treated for 12 weeks. For patients previously treated with traditional Chinese medicine, a 2-week washout period was provided; those newly starting traditional Chinese medicine could be directly enrolled. During treatment, the use of other traditional Chinese medicines and Western medicines with similar or identical efficacy should be avoided as much as possible. For example, β-lactam antibiotics, nonsteroidal antipyretics, analgesics, and anti-inflammatory drugs, as well as traditional Chinese medicines such as Wuwei Kushen enteric-coated capsules and Xianglian tablets, are considered ineffective if intravenous or oral hormones are added during treatment due to the severity of UC. Furthermore, during medication, patients should avoid spicy, cold, and high-fiber foods (such as celery), dairy products, and soy milk, and avoid staying up late and fatigue.

[0088] 1.4. Observation Indicators

[0089] Clinical observation indicators included modified Mayo score, Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), and platelet count (PLT).

[0090] Effectiveness was defined as a reduction of ≥30% and ≥3 points in the modified Mayo score relative to baseline after 12 weeks of treatment, with a reduction of ≥1 point in the hematochezia sub-score, or a score of 0 or 1 for that sub-score.

[0091] The TCM syndrome evaluation was conducted using the TCM Symptom Scoring Scale for Gastrointestinal Diseases, formulated by the Digestive System Diseases Professional Committee of the China Association of Integrative Medicine in 2011. Clinical syndrome efficacy was assessed using the following formula: Efficacy Score = (Total Syndrome Score Before Treatment - Total Syndrome Score After Treatment) / (Total Syndrome Score Before Treatment) × 100%. Specifically: Clinically cured: Syndrome essentially disappeared, with a score reduction of ≥ 95%; Significantly effective: Syndrome effectiveness rate reduced by > 75% compared to before treatment; Effective: Syndrome effectiveness rate reduced by ≥ 50% compared to before treatment; Ineffective: Syndrome effectiveness rate reduced by < 50% compared to before treatment.

[0092] 1.5. Statistical Methods

[0093] Statistical analysis was performed on the data using R Studio 4.3.2 and SPSS Statistics 27.0 software. Quantitative data were expressed as mean ± standard deviation or interquartile range. Comparisons between two groups were performed using the t-test or the Mann-Whitney U test. Categorical data were expressed as frequency (%), unordered data were analyzed using the Pearson chi-square test, and ordinal data were analyzed using the nonparametric Wilcoxon two-sample rank-sum test.

[0094] 2. Research Results

[0095] 2.1 Comparison of the two sets of basic data

[0096] This study observed the therapeutic effects of mesalazine combined with traditional Chinese medicine in 220 patients with active ulcerative colitis. The observation group (n=80) and the control group (n=120) were treated with mesalazine alone. In terms of gender, the observation group consisted of 56 males (70%) and 24 females (30%), while the control group consisted of 85 males (60.71%) and 55 females (39.29%). Regarding age, the mean age in the observation group was 58.5 years (range 51.00-68.00 years), and the mean age in the control group was 59.00 years (range 48.00-65.00 years).

[0097] 2.2 Comparison of clinical indicators after treatment

[0098] After treatment, the modified Mayo Criteria (including frequency of bowel movements, rectal bleeding, endoscopic findings, and physician's overall evaluation) all decreased compared to before treatment, and the differences were statistically significant. P< 0.05). The modified Mayo score in the observation group (2.00, 1.25-3.00) was lower than that in the control group (3.00, 2.00-4.00), and the difference was statistically significant. P < 0.05), indicating that the improvement in the modified Mayo score in the observation group was better than that in the control group (Table 1).

[0099] Table 1 Comparison of Modified Mayo Scores Before and After Treatment

[0100]

[0101] After treatment, the UCEIS scores of both groups decreased compared with those before treatment, and the difference was statistically significant. P < 0.05). After treatment, the UCEIS score in the observation group (1.00 - 2.00) was lower than that in the control group (3.00 - 3.25), and the difference was statistically significant. P < 0.05), indicating that the observation group showed better improvement in UCEIS scores than the control group (see Table 2).

[0102] Table 2 Comparison of UCEIS scores before and after treatment

[0103]

[0104] After treatment, the CRP level in both groups decreased compared to before treatment, and the difference was statistically significant. P < 0.05 (Table 3). During the same treatment period, the CRP decrease rate in the observation group was higher than that in the control group ( Figure 1 ).

[0105] Table 3 Comparison of CRP levels before and after treatment

[0106]

[0107] After treatment, the ESR index in both groups decreased compared to before treatment, and the difference was statistically significant. P < 0.05 (Table 4).

[0108] Table 4 Comparison of ESR indices before and after treatment

[0109]

[0110] After treatment, the WBC count in both groups decreased compared to before treatment, and the difference was statistically significant. P < 0.05). After treatment, the WBC count in the observation group was 5.66 ± 1.58, which was lower than that in the control group (6.43 ± 1.69), and the difference was statistically significant. P<0.05), indicating that the improvement of WBC in the observation group was better than that in the control group (see Table 5).

[0111] Table 5 Comparison of WBC levels before and after treatment

[0112]

[0113] After treatment, the PLT index in both groups decreased compared to before treatment, and the difference was statistically significant. P < 0.05. After treatment, the PLT index in the observation group (211.00 - 249.00) was lower than that in the control group (239.00 - 276.75), and the difference was statistically significant. P < 0.05), indicating that the improvement of PLT in the observation group was better than that in the control group (see Table 6).

[0114] Table 6 Comparison of PLT indices before and after treatment

[0115]

[0116] The results above show that the traditional Chinese medicine composition of the present invention can reduce the modified Mayo score and serum inflammatory markers in patients with active ulcerative colitis of the intestinal damp-heat type, and improve colonic mucosal inflammation and gastrointestinal symptoms.

[0117] 2.3 Evaluation of therapeutic effect

[0118] Clinical efficacy was assessed based on the modified Mayo Cognitive Assessment (MCA) score. At week 12, the effective rate in the observation group was 85.19%, and the ineffective rate was 14.81%; in the control group, the effective rate was 68.52%, and the ineffective rate was 31.48%. The clinical efficacy of the observation group was significantly higher than that of the control group. The clinical efficacy of the observation group was superior to that of the control group, and the difference in clinical efficacy between the two groups was statistically significant. P < 0.05 (see Table 7).

[0119] Table 7 Comparison of Clinical Efficacy

[0120]

[0121] 2.4 Evaluation of Traditional Chinese Medicine Syndromes

[0122] The scoring was conducted using the Traditional Chinese Medicine Symptom Scoring Scale for Gastrointestinal Diseases, formulated in 2011 by the Digestive System Diseases Professional Committee of the China Association of Integrative Medicine. Clinical efficacy was assessed using the following formula: Efficacy Score = (Total Symptom Score Before Treatment - Total Symptom Score After Treatment) / (Total Symptom Score Before Treatment) × 100%. Criteria were categorized as follows: Clinically Cured: Symptoms essentially disappeared, with a score reduction of ≥ 95%; Significantly Effective: The effective rate of symptoms decreased by > 75% compared to before treatment; Effective: The effective rate of symptoms decreased by ≥ 50% compared to before treatment; Ineffective: The effective rate of symptoms decreased by < 50% compared to before treatment.

[0123] Based on the TCM symptom scoring system for gastrointestinal diseases, the clinical efficacy was assessed. In the observation group, at week 12 of treatment, the clinical efficacy rate was 14.81%, the effective rate was 81.48%, and the ineffective rate was 4.70%. In the control group, the clinical efficacy rate was 1.85%, the effective rate was 62.96%, and the ineffective rate was 35.19%. The efficacy of the observation group was significantly higher than that of the control group. The difference in efficacy between the two groups was statistically significant. P < 0.01 (see Table 8).

[0124] Table 8 Clinical syndrome efficacy

[0125]

[0126] 2.5 Typical Case Analysis

[0127] Ms. Fang, female, 73 years old, was admitted to the hospital due to "intermittent abdominal pain, diarrhea, and bloody mucus stools for over a year." Over a year prior, she developed diarrhea and small amounts of fresh blood after defecation without any obvious cause, accompanied by mild abdominal pain. Previous treatments with mesalazine, hydrocortisone butyrate sodium succinate, and prednisolone acetate tablets were ineffective or resulted in bilateral lower extremity edema and palpitations (considered a hormonal reaction). On December 29, 2022, an electronic colonoscopy revealed: the cecum, ileocecal junction, and ascending colon mucosa were smooth, with clear vascular pathways. The mid-transverse colon to descending colon (40cm from the anal verge) showed congestion, edema, erosion, and roughness of the mucosa, with scattered punctate bleeding points and shallow ulcer formation, some of which merged into patches, and obliteration of vascular pathways. The sigmoid colon (25cm-15cm from the anal verge) showed congestion and edema of the mucosa, with scattered patchy erosions. The rectal mucosa was relatively smooth, with clear vascular pathways. Endoscopic diagnosis: Ulcerative colitis, extensive colonic type, active phase, Mayo Cognitive Impairment score 3 (see [link to endoscopy]). Figure 4The patient's modified Mayo Cognitive Index (MCI) score was 8, and their UCEIS score was 8. The Western medicine diagnosis was moderate to severe active ulcerative colitis; the Traditional Chinese Medicine diagnosis was chronic dysentery with intestinal damp-heat syndrome. Treatment was based on consideration of the patient's hormone dependence and hormonal response. The patient was given the herbal composition of this invention, granules (Example 2), a fixed prescription, one dose per day, combined with mesalazine enteric-coated tablets (Salfo) 1g (2 tablets, 0.5g / tablet), three times daily, orally, for 12 weeks. Follow-up visits were conducted at weeks 4 and 8 after treatment. The patient had 1-2 bowel movements per day, soft stools, no visible mucus or blood, and no abdominal pain. No adverse reactions were observed during this period. A follow-up examination at week 8 showed 2-3 bowel movements per day, occasional mild abdominal pain, and no visible bloody stools. The modified Mayo Cognitive Index (MCI) score was 4. Treatment continued until week 12. Bowel movements were twice daily, without mucus or blood, and there was no abdominal pain. Physical examination of the heart, lungs, and abdomen was unremarkable. There was no edema in the lower extremities. Weight was monitored at 66 kg. A repeat electronic colonoscopy revealed: smooth terminal ileum mucosa with visible ileocecal valve and appendiceal opening. The entire colon showed rough, atrophic mucosa. Scattered inflammatory polyps were observed in the ascending and transverse colon, with shallowed mucosal folds and some white, scar-like changes. The mucosa further 40 cm from the anus was rough and edematous, with some mucosal erosion but no shallow ulcers. Vascular course was obliterated, and the lesions were continuously distributed. The Mayo endoscopic score was 2 (see...). Figure 5 The modified Mayo Cognitive Assessment (MCA) score was 3, and the UCEIS score was 2. No adverse reactions were reported during treatment.

[0128] 2.6. Adverse Reactions

[0129] No serious adverse reactions were observed in any of the patients treated with the herbal composition of this invention.

[0130] In summary, the herbal composition of this invention can significantly alleviate the symptoms and inflammation of colonic lesions, and has a good protective and repairing effect on colonic mucosal damage, and can be used to treat ulcerative colitis. The combined use of the herbal composition of this invention and mesalazine can reduce the modified Mayo score and serum inflammatory markers in patients with active ulcerative colitis of the damp-heat type, improve colonic mucosal inflammation and gastrointestinal symptoms. The clinical efficacy of the observation group was better than that of the control group, and the difference in clinical efficacy between the two groups was statistically significant.

[0131] The present invention has been described in detail above. Those skilled in the art will recognize that the invention can be practiced in a wide range of ways with equivalent parameters, concentrations, and conditions without departing from its spirit and scope. While specific embodiments have been provided, it should be understood that further modifications can be made to the invention. In summary, according to the principles of the invention, this application is intended to include any changes, uses, or improvements to the invention, including modifications made using conventional techniques known in the art that depart from the scope disclosed herein.

Claims

1. A traditional Chinese medicine composition for treating active ulcerative colitis of the damp-heat type in the intestine, characterized in that, Made from the following parts by weight of raw materials: Astragalus membranaceus 13-26 parts, Lonicera japonica 10-20 parts, Sargentodoxa cuneata 10-20 parts, Prunus mume 8-16 parts, Agrimonia pilosa 8-16 parts, Allium macrostemon 6-12 parts, Platycodon grandiflorus 6-12 parts, Coptis chinensis 3-6 parts, Panax notoginseng powder 1-3 parts.

2. The traditional Chinese medicine composition for treating active ulcerative colitis of the damp-heat type according to claim 1, characterized in that: The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 20 parts Astragalus membranaceus, 15 parts Lonicera japonica, 15 parts Sargentodoxa cuneata, 12 parts Prunus mume, 12 parts Agrimonia pilosa, 10 parts Allium macrostemon, 10 parts Platycodon grandiflorus, 5 parts Coptis chinensis, and 1.5 parts Panax notoginseng powder.

3. The traditional Chinese medicine composition for treating active ulcerative colitis of the damp-heat type according to any one of claims 1-2, characterized in that: The traditional Chinese medicine composition is a decoction.

4. The method for preparing the traditional Chinese medicine composition for treating active ulcerative colitis of the damp-heat type intestinal region as described in claim 3, characterized in that, The process includes the following steps: mixing the raw materials used to prepare the traditional Chinese medicine composition according to the stated mass proportions, soaking them in water and then decocting them, collecting the decoction to obtain the aqueous decoction.

5. The method for preparing the traditional Chinese medicine composition for treating active ulcerative colitis of the damp-heat type according to claim 4, characterized in that: The soaking time is 20 to 30 minutes; The decoction time is controlled so that for every 100.5g of raw material, 1000-1500mL of water is used to decoct until the remaining liquid is 150-300ml. The decoction is prepared twice, and the decoction liquids are combined after the decoction is completed.

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 active ulcerative colitis of the intestinal damp-heat type.

7. A drug for combined treatment of active ulcerative colitis of the damp-heat type in the intestine, characterized in that, The traditional Chinese medicine composition according to any one of claims 1-3 and mesalazine enteric-coated tablets are included.

8. The use of the medicament according to claim 7 in the preparation of a medicament for treating active ulcerative colitis of the intestinal damp-heat type.

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