A traditional Chinese medicine composition, a preparation method therefor and application thereof

Abstract

The present application relates to a kind of traditional Chinese medicine composition for ulcerative colitis, by weight ratio, the traditional Chinese medicine composition includes: 1-100 portions of white head, 1-80 portions of poria cocos, 1-70 portions of mace, 1-80 portions of white atractylodes, 1-60 portions of phellodendron, 1-50 portions of schisandra chinensis, 1-50 portions of Terminalia chebula, 1-50 portions of pomegranate peel, 1-70 portions of broadleaf patchouli, 1-100 portions of Portulaca oleracea.This party can be used to treat spleen deficiency dampness ulcerative colitis of syndrome.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, and relates to a traditional Chinese medicine composition, its preparation method and application. Background Technology

[0002] Ulcerative colitis (UC) is a chronic, nonspecific inflammatory bowel disease characterized by continuous, diffuse inflammation of the colorectal mucosa. Clinical manifestations include persistent or recurrent diarrhea, bloody and purulent stools accompanied by abdominal pain, tenesmus, and varying degrees of systemic symptoms. Clinical treatment primarily focuses on repairing the intestinal mucosal barrier, regulating immunity, and modulating the gut microbiota to reduce the inflammatory response and prevent complications. Currently, Western medicine treatments for ulcerative colitis utilize aminosalicylic acid derivatives, glucocorticoids, immunosuppressants, and biologics.

[0003] However, these medications can cause significant side effects. For example, steroids and immunosuppressants may increase the risk of infection, osteoporosis, and gastrointestinal discomfort. Patients may need to take medication long-term to maintain remission, and relapse is common after discontinuation. Moreover, individual differences may not be adequately considered, leading to poor outcomes for some patients. Furthermore, this treatment tends to relieve symptoms rather than address the underlying cause.

[0004] Traditional Chinese medicine (TCM) emphasizes "holistic conditioning," employing syndrome differentiation and treatment to comprehensively consider factors such as the patient's constitution and environment to develop personalized treatment plans. It also has fewer side effects, alleviating patient discomfort during treatment while regulating the immune system and enhancing the body's self-healing abilities, thereby reducing recurrence rates. TCM offers a comprehensive and gentle approach to treating ulcerative colitis, suitable for long-term conditioning and health maintenance. Summary of the Invention

[0005] In view of this, the present invention provides a traditional Chinese medicine composition for ulcerative colitis, comprising, by weight: 1-100 parts Pulsatilla chinensis, 1-80 parts Poria cocos, 1-70 parts roasted Myristica fragrans, 1-80 parts Atractylodes macrocephala, 1-60 parts Phellodendron chinense, 1-50 parts vinegar-processed Schisandra chinensis, 1-50 parts roasted Terminalia chebula, 1-50 parts Punica granatum peel, 1-70 parts Pogostemon cablin, and 1-100 parts Portulaca oleracea.

[0006] As a preferred embodiment, the above-mentioned traditional Chinese medicine composition comprises, by weight, 1-50 parts of Pulsatilla chinensis, 1-40 parts of Poria cocos, 1-40 parts of roasted Myristica fragrans, 1-40 parts of Atractylodes macrocephala, 1-30 parts of Phellodendron chinense, 1-30 parts of vinegar-processed Schisandra chinensis, 1-30 parts of roasted Terminalia chebula, 1-30 parts of Punica granatum peel, 1-40 parts of Pogostemon cablin, and 1-50 parts of Portulaca oleracea.

[0007] More preferably, the traditional Chinese medicine composition includes: 5-15 parts of Pulsatilla chinensis, 5-15 parts of Portulaca oleracea, 4-12 parts of Atractylodes macrocephala, 4-12 parts of Poria cocos, 3-9 parts of roasted Myristica fragrans, 3-9 parts of Pogostemon cablin, 2-6 parts of Phellodendron chinense, 1-3 parts of roasted Terminalia chebula, 1-3 parts of Punica granatum peel, and 1-3 parts of vinegar-processed Schisandra chinensis.

[0008] More preferably, the traditional Chinese medicine composition includes: 13-15 parts of Pulsatilla chinensis, 13-15 parts of Portulaca oleracea, 10-12 parts of Atractylodes macrocephala, 10-12 parts of Poria cocos, 8-9 parts of roasted Myristica fragrans, 8-9 parts of Pogostemon cablin, 5-6 parts of Phellodendron chinense, 2.5-3 parts of roasted Terminalia chebula, 2.5-3 parts of Punica granatum peel, and 2.5-3 parts of vinegar-processed Schisandra chinensis.

[0009] Most preferably, the traditional Chinese medicine composition includes: 15 parts of Pulsatilla chinensis, 15 parts of Portulaca oleracea, 12 parts of Atractylodes macrocephala, 12 parts of Poria cocos, 9 parts of roasted Myristica fragrans, 9 parts of Pogostemon cablin, 6 parts of Phellodendron chinense, 3 parts of roasted Terminalia chebula, 3 parts of pomegranate peel, and 3 parts of vinegar-processed Schisandra chinensis.

[0010] The above-mentioned composition can be made by directly grinding raw materials into powder and mixing, or it can be an extract or other form obtained by conventional means. The raw materials used can also be used by directly grinding them into powder, extracting them, or using other processed forms.

[0011] The present invention also proposes a method for preparing any of the aforementioned traditional Chinese medicine compositions, the method comprising: Take Pulsatilla chinensis, Portulaca oleracea, Atractylodes macrocephala, Poria cocos, roasted nutmeg, Pogostemon cablin, Phellodendron chinense, roasted Terminalia chebula, pomegranate peel, and vinegar-processed Schisandra chinensis, add water and reflux twice. The first extraction is with 10 times the amount of water for 1.5 hours, and the second extraction is with 8 times the amount of water for 1 hour. Filter, concentrate under reduced pressure at 60~70℃ to a density of 1.10-1.15, and dry under reduced pressure at 60~70℃.

[0012] The present invention also proposes the application of any of the foregoing traditional Chinese medicine compositions in the preparation of a medicament for ulcerative colitis.

[0013] Specifically, the treatment for the ulcerative colitis may include: (1) Reduce rectal bleeding and frequency of bowel movements; and / or, (2) Improve inflammation levels; and / or, (3) Improve or alleviate intestinal mucosal damage, colonic atrophy, inflammatory cell infiltration, ulceration degree, mucosal fibrosis and other colonic tissue lesions.

[0014] Furthermore, the ulcerative colitis is chronic ulcerative colitis; in particular, it is progressive chronic ulcerative colitis, such as fibrotic ulcerative colitis.

[0015] The present invention also proposes a drug, characterized in that the drug is prepared from any of the aforementioned traditional Chinese medicine compositions and pharmaceutically acceptable excipients or additives.

[0016] Optionally, the drug is selected from decoctions, granules, capsules, tablets, pills, oral liquids, tinctures, syrups, suppositories, gels, sprays, and injections.

[0017] This invention does not specifically limit the type of excipients; those skilled in the art can adjust them according to the dosage form. The term "used for" can refer to any method beneficial to improving the corresponding symptoms of the patient, including treatment or prevention.

[0018] When the traditional Chinese medicine composition provided by the present invention is made into granules, the extracts of each raw material, lactose, and magnesium stearate are mixed evenly, granulated, dried, and made into granules.

[0019] When the traditional Chinese medicine composition provided by this invention is made into an oral liquid, the extracts of each raw material are dissolved in distilled water, filtered, syrup is added, and the pH value is adjusted to make the oral liquid.

[0020] When the traditional Chinese medicine composition provided by the present invention is made into tablets, the raw materials, lactose, and magnesium stearate are mixed evenly, granulated, and then compressed into tablets.

[0021] Other dosage forms described in this invention can be prepared using conventional pharmacopoeia methods.

[0022] This invention also proposes a method for preparing traditional Chinese medicine granules. The preparation method is as follows: 15 parts of Pulsatilla chinensis, 15 parts of Portulaca oleracea, 12 parts of Atractylodes macrocephala, 12 parts of Poria cocos, 9 parts of roasted Myristica fragrans, 9 parts of Pogostemon cablin, 6 parts of Phellodendron chinense, 3 parts of roasted Terminalia chebula, 3 parts of pomegranate peel, and 3 parts of vinegar-processed Schisandra chinensis. Water is added and refluxed twice. The first extraction is with 10 times the amount of water for 1.5 hours, and the second extraction is with 8 times the amount of water for 1 hour. The extract is filtered, concentrated under reduced pressure at 60-70℃ to a density of 1.10-1.15 (65℃), and dried under reduced pressure at 60-70℃ to obtain an extract powder. Maltodextrin is added, and granules are obtained by dry granulation.

[0023] This invention utilizes the following ingredients: Pulsatilla chinensis, Portulaca oleracea, and Phellodendron chinense to clear heat, dry dampness, cool the blood, and detoxify; Atractylodes macrocephala and Poria cocos to strengthen the spleen and resolve dampness; Myristica fragrans (prepared) to warm the middle jiao and promote qi circulation; Pogostemon cablin (prepared) to aromatically resolve dampness, harmonize the stomach, and stop vomiting; Terminalia chebula (prepared) and Punica granatum peel (prepared) to astringe the intestines and stop diarrhea; and Schisandra chinensis (prepared) to replenish qi, generate fluids, and astringe and consolidate. The key functions are strengthening the spleen and resolving dampness, replenishing qi and harmonizing the middle jiao, and astringing the intestines to stop diarrhea. This formula can be used to treat ulcerative colitis with spleen deficiency and dampness accumulation. The entire formula addresses both the root cause and symptoms, strengthens the spleen and resolves dampness, has a clear target, a simple composition, and does not contain expensive or rare herbs, thus possessing significant medicinal value. Compared with existing technologies, the herbal composition of this invention can significantly improve mucosal damage and ulceration to varying degrees, reduce colon length and disease activity index (DAI), improve intestinal function, and delay the progression of colonic fibrosis, achieving significant therapeutic effects. Detailed Implementation

[0024] Ulcerative colitis is a chronic, nonspecific inflammatory bowel disease with a protracted and recurring course, severely impacting patients' quality of life. Its pathogenesis is not fully understood, and clinical treatment primarily focuses on controlling acute inflammation and relieving symptoms, failing to effectively improve progressive pathological damage such as intestinal fibrosis. Traditional Chinese medicine (TCM) possesses unique advantages in treating ulcerative colitis, offering holistic regulation and addressing both the root cause and symptoms, making it a research hotspot in this field in recent years. Furthermore, the difficulty of treating chronic ulcerative colitis increases significantly with disease progression, especially in moderate to severe ulcerative colitis accompanied by colonic fibrosis, granuloma formation, intestinal wall thickening, and crypt destruction. The lesions can reach the muscular layer and even the serosa, resulting in complex pathological damage with low reversibility, making effective intervention difficult with conventional TCM treatments. Therefore, this invention aims to provide a TCM composition for ulcerative colitis. The following will describe the specific experimental findings.

[0025] Unless otherwise specified, all experiments in the following experiments were conducted under standard conditions or conditions recommended by the manufacturer. Active pharmaceutical ingredients (APIs) or excipients, as well as reagents or instruments whose manufacturers are not specified, are all commercially available products. Unless otherwise stated, all percentages, ratios, proportions, or parts are by weight.

[0026] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as are familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to this invention. Example 1: Preparation of granules of traditional Chinese medicine composition

[0027] Formula: 15 parts Pulsatilla chinensis, 15 parts Portulaca oleracea, 12 parts Atractylodes macrocephala, 12 parts Poria cocos, 9 parts roasted Myristica fragrans, 9 parts Pogostemon cablin, 6 parts Phellodendron chinense, 3 parts roasted Terminalia chebula, 3 parts pomegranate peel, and 3 parts vinegar-processed Schisandra chinensis.

[0028] Preparation method of the granules of this traditional Chinese medicine composition: Take the above-mentioned medicinal materials, add water and reflux extract twice. The first extraction is with 10 times the amount of water for 1.5 hours, and the second extraction is with 8 times the amount of water for 1 hour. Filter, concentrate under reduced pressure at 60~70℃ to a density of 1.10-1.15 (65℃), dry under reduced pressure at 60~70℃ to obtain extract powder, add maltodextrin, and granulate by dry granulation to obtain granules. Example 2: Preparation of oral liquid of traditional Chinese medicine composition

[0029] Formula: Take 15 parts of Pulsatilla chinensis, 15 parts of Portulaca oleracea, 12 parts of Atractylodes macrocephala, 12 parts of Poria cocos, 9 parts of roasted Myristica fragrans, 9 parts of Pogostemon cablin, 6 parts of Phellodendron chinense, 3 parts of roasted Terminalia chebula, 3 parts of pomegranate peel, and 3 parts of vinegar-processed Schisandra chinensis.

[0030] Preparation method of the capsule form of this traditional Chinese medicine composition: Take the above-mentioned medicinal materials, add water and reflux extract twice. The first extraction is with 10 times the amount of water for 1.5 hours, and the second extraction is with 8 times the amount of water for 1 hour. Filter, concentrate under reduced pressure at 60~70℃ to a density of 1.10-1.15 (65℃), dry under reduced pressure at 60~70℃ to obtain extract powder, add distilled water and syrup, adjust the pH value, and fill into oral liquid. Example 3: Preparation of tablets based on traditional Chinese medicine composition

[0031] Formula: 15 parts Pulsatilla chinensis, 15 parts Portulaca oleracea, 12 parts Atractylodes macrocephala, 12 parts Poria cocos, 9 parts roasted Myristica fragrans, 9 parts Pogostemon cablin, 6 parts Phellodendron chinense, 3 parts roasted Terminalia chebula, 3 parts pomegranate peel, and 3 parts vinegar-processed Schisandra chinensis.

[0032] Preparation method of this traditional Chinese medicine composition tablet: Take the above-mentioned medicinal materials, add water and reflux extract twice. The first extraction is with 10 times the amount of water for 1.5 hours, and the second extraction is with 8 times the amount of water for 1 hour. Filter, concentrate under reduced pressure at 60~70℃ to a density of 1.10-1.15 (65℃), and dry under reduced pressure at 60℃~70℃ to obtain extract powder. Add excipients such as microcrystalline cellulose to make tablets. Example 4: Pharmacodynamic experiment of traditional Chinese medicine composition on DSS-induced chronic ulcerative colitis model in mice.

[0033] 1. Experimental Materials 1.1 Preparation of the test drug 15 parts of Pulsatilla chinensis, 15 parts of Portulaca oleracea, 12 parts of Atractylodes macrocephala, 12 parts of Poria cocos, 9 parts of roasted Myristica fragrans, 9 parts of Pogostemon cablin, 6 parts of Phellodendron chinense, 3 parts of roasted Terminalia chebula, 3 parts of pomegranate peel, and 3 parts of vinegar-processed Schisandra chinensis were extracted twice by reflux with water. The first extraction was carried out with 10 times the amount of water for 1.5 hours, and the second extraction was carried out with 8 times the amount of water for 1 hour. The mixture was filtered and concentrated under reduced pressure at 60-70℃ to a density of 1.10-1.15 (65℃). The mixture was then dried under reduced pressure at 60-70℃.

[0034] 1.2 Comparative Example 1: Preparation of Test Drug 15 parts of Pulsatilla chinensis, 15 parts of Portulaca oleracea, 9 parts of roasted nutmeg, 9 parts of Pogostemon cablin, 6 parts of Phellodendron chinense, 3 parts of roasted Terminalia chebula, 3 parts of pomegranate peel, and 3 parts of vinegar-processed Schisandra chinensis were extracted twice by reflux with water. The first extraction was carried out with 10 times the amount of water for 1.5 hours, and the second extraction was carried out with 8 times the amount of water for 1 hour. The mixture was filtered and concentrated under reduced pressure at 60-70℃ to a density of 1.10-1.15 (65℃). The mixture was then dried under reduced pressure at 60-70℃.

[0035] 1.3 Comparative Example 2: Preparation of Test Drugs Prepare the drug for Comparative Example 2 according to the formula and its preparation method with the patent application number CN200910228405.X. The specific formula is as follows: Realgar 10 Kg, Pogostemon cablin 10 Kg, Pulsatilla chinensis 10 Kg, Talc 10 Kg, Coptis quinquesecta 10 Kg, Terminalia chebula 10 Kg, Portulaca oleracea 10 Kg, Phellodendron amurense 20 Kg, Effervescent agent 8 Kg, Lubricant 2 Kg; The above effervescent agent is composed of 4 Kg of citric acid and 4 Kg of sodium bicarbonate, and the lubricant is magnesium stearate. The preparation method steps of the test drug are as follows: (1) Weigh realgar and talc according to the weight ratio, crush them and all pass through an 80-mesh sieve; (2) Weigh 172 weights of Pogostemon cablin, Pulsatilla chinensis, Coptis quinquesecta, Terminalia chebula, Portulaca oleracea, and Phellodendron amurense according to the weight ratio, crush them and all pass through an 80-mesh sieve, and decoct and filter the remaining 1 / 2 weight of Pogostemon cablin, Pulsatilla chinensis, Coptis quinquesecta, Terminalia chebula, Portulaca oleracea, and Phellodendron amurense residues. Concentrate the filtrate into a paste, add the sieved Pogostemon cablin, Pulsatilla chinensis, Coptis quinquesecta, Terminalia chebula, Portulaca oleracea, and Phellodendron amurense, mix well, and all pass through an 80-mesh sieve to obtain mixture A; (3) Weigh the effervescent agent and lubricant according to the weight ratio, crush them respectively and all pass through an 80-mesh sieve, mix them well with mixture A and the sieved realgar and talc to obtain mixture B; (4) Use a 50% ethanol solution of 2% PVP as a binder to make a soft material from mixture B, pass the soft material through a 10-mesh sieve to make granules, dry them by ventilation at 50 °C, and then pass them through a 20-mesh sieve to make whole granules. Press tablets to obtain a finished effervescent traditional Chinese medicine composition with the function of astringing the intestine and stopping dysentery.

[0036] 1.4 Experimental animals C57BL / 6 mice, male, 8 - 9 weeks old, weighing 22 - 24 g, purchased from Beijing SPF Biotechnology Co., Ltd., license number: SCXK (Beijing) 2019 - 0010, animal certificate number: NO.110324221106451047.

[0037] 1.5 Instruments and reagents Instruments: Electronic balance (Sartorius, Germany, BS224S), weighing scale (Changshu Shuangjie Testing Instrument Factory, TC3K), centrifuge (Eppendorf, Germany, 5804R), microplate reader (Molecular Devices, Flexstation 3) Reagents: Sodium chloride (Shanghai Reagent Co., Ltd. of China National Pharmaceutical Group, 20171221), formaldehyde (Shanghai Reagent Co., Ltd. of China National Pharmaceutical Group, 20180313), dextran sulfate (DSS) (MP Biomedicals, USA, S7102).

[0038] 2 Experimental methods 2.1 Dose design The composition sample of this invention, based on a daily oral dose, is equivalent to 58 g of crude drug, which, based on an adult body weight of 60 kg, is 0.97 g crude drug / kg / day. This translates to an equivalent dose of 12 g / kg / day for mice. In the experiment, mice were administered three dose groups: 24 g crude drug / kg (high dose), 12 g crude drug / kg (medium dose), and 6 g crude drug / kg (low dose) (equivalent to twice, equal, and half the human clinical dose, respectively), via gavage at a dose of 20 mL / kg per day. Comparative Example 1 and Comparative Example 2 were both administered at a dose of 24 g crude drug / kg.

[0039] 2.2 Grouping and Modeling Purchased mice were randomly divided into 5 groups: a normal control group (n=10), a model control group (n=10), a high-dose composition group (n=10), a medium-dose composition group (n=10), a low-dose composition group (n=10), a control group 1 (n=10), and a control group 2 (n=10). DSS was dissolved in double-distilled water to prepare a 2% solution, which was given to the mice for free drinking (except for the normal control group). Fresh solutions were prepared every two days. After drinking the 2% DSS solution for 5 days, the mice were switched to double-distilled water for 14 days, and this cycle was repeated twice. Then, the mice continued to drink the 2% DSS solution for 5 days, for a total modeling period of 43 days. From day 1 of the experiment, each group was administered the corresponding drug by gavage at a dose of 20 mL / kg. The normal control and model control groups received the same amount of double-distilled water. During the period of free drinking of DSS solution, the mice were weighed and their condition observed daily. During the period of free drinking of double-distilled water, the mice were weighed and their condition observed daily for the first 4 days, and then weighed every 2 days thereafter.

[0040] 3. Efficacy evaluation indicators 3.1 Disease Activity Index (DAI) Mice were given 2% DSS in drinking water for days 1-5, 20-24, and 39-43, and double-distilled water for days 6-19 and 25-38. During the DSS period, mouse weight, stool characteristics, and bloody stool were recorded daily and scored. During the double-distilled water period, mouse weight, stool characteristics, and bloody stool were recorded daily for four days immediately after modeling and every two days starting from day six. Scores were also recorded, and the criteria are shown in Table 1. The highest score was 10.

[0041] Table 1 DAI Scoring Criteria

[0042] Note: Normal stool: formed stool; loose stool: pasty or semi-formed stool that adheres to the anus; loose stool: watery stool that can adhere to the anus.

[0043] 3.2 Colon length and mucosal damage index (CMDI) After the experiment, the colon was examined by laparotomy. The colon from the anus to the ileocecal junction was taken and its length was measured. The colon was then cut open along the mesentery side, rinsed with saline, and the colon's ulceration and inflammation, as well as the mucosal adhesion, were observed and scored. The scoring criteria are shown in Table 2.

[0044] Table 2 CMDI Scoring Criteria

[0045] 3.3 Data Analysis Quantifiable data are expressed as mean ± standard deviation (X±SD). Comparisons between groups were performed using analysis of variance and t-tests. p <0.05 indicates that the difference is statistically significant.

[0046] 4. Experimental Results 4.1 Disease Activity Index (DAI) Except for the normal group mice which had a normal diet and no diarrhea or bloody stools, all groups of mice showed varying degrees of weight loss, diarrhea, and bloody stools, as shown in Tables 3 and 4. After the modeling was completed on day 44, the model group mice had decreased weight and increased disease activity index, which improved after drug administration. Among them, compared with the model group, the weight of mice in the medium-dose group and the high-dose group of the traditional Chinese medicine composition was significantly different. p <0.01, p <0.0001, the disease activity index of mice in each dose group of the traditional Chinese medicine composition decreased significantly ( p <0.0001).

[0047] Table 3 Effects of the traditional Chinese medicine composition on mouse body weight from 0 to 21 days

[0048]

[0049] Table 3 (Continued) Effects of the traditional Chinese medicine composition on mouse body weight from day 25 to 44

[0050]

[0051] (Compared with the model group, ****) p <0.0001, *** p <0.001,** p <0.01, * p <0.05 indicates a statistically significant difference (the same applies below).

[0052] Table 4. Effects of the traditional Chinese medicine composition on the disease activity index in mice from 0 to 21 days.

[0053]

[0054] Table 4 (Continued) Effects of Traditional Chinese Medicine Composition on Disease Activity Index in Mice from Day 25 to 44

[0055] 4.2 Colon length and mucosal damage index (CMDI) As shown in Table 5, compared with the model group, the colon length of the high-dose group and the medium-dose group was significantly increased ( p <0.01); the ulcer and inflammation scores in each treatment group were significantly lower than those in the model group ( p <0.05); the mucosal adhesion score was significantly reduced in the high-dose group ( p <0.0001); the mucosal adhesion scores of the low, medium, and high dosage groups of the traditional Chinese medicine composition were also significantly reduced to varying degrees compared with the model group. p <0.01, p <0.05, p <0.001).

[0056] Table 5. Effects of Traditional Chinese Medicine Compositions on Colon Length and Mucosal Injury Index

[0057]

[0058] 5. Experimental Conclusions In summary, based on the above experimental results, the traditional Chinese medicine composition of this invention was used to establish a chronic ulcerative colitis model in C57BL6 / J mice by allowing them free access to 2% DSS solution, in order to verify its efficacy. Compared with the normal group, all mice in the model group showed ulcers, inflammatory cell infiltration, and lesions extending to the submucosa, indicating that the model was successfully established.

[0059] The short-term goal of ulcerative colitis treatment is to achieve a clinical response (defined as a patient-reported outcome of at least a 50% reduction in rectal bleeding and defecation frequency). The medium-term goal is clinical remission and normalization of inflammatory markers. The long-term goal is to achieve mucosal healing. Based on this experiment, both medium and high doses of the herbal composition of this invention can significantly improve (…). p <0.01), and the results of efficacy evaluation by visual observation of the colon also showed that each dose group could significantly improve the degree of mucosal damage and ulceration to varying degrees. Combined with colon length and disease activity index (DAI) results, the traditional Chinese medicine composition mentioned in this invention can achieve significant therapeutic effects when administered to mice at clinically equivalent doses. Example 5: Pharmacodynamic experiment of traditional Chinese medicine composition on TNBS-induced chronic ulcerative colitis model in SD rats.

[0060] 1. Experimental Materials 1.1 Preparation of test drug: Same as in Example 4.

[0061] 1.2 Laboratory Animals Male SD rats, 6-9 weeks old, weighing 226.18-264.24 g, were purchased from Sichuan Vitonlihua Laboratory Animal Technology Co., Ltd., license number: SCXK (Sichuan) 2023-0040, animal qualification certificate number: No. 511215600018002.

[0062] 1.5 Instruments and Reagents Instruments: Electronic balance (METTLLER TOLEDO, ML2001), centrifuge (Eppendorf, 5424R), microplate reader (METTLLER TOLEDO, ML2001), ELISA reader (METTLLER TOLEDO, Flexstation 3). Reagents: 0.9% sodium chloride injection (Sichuan Kelun Pharmaceutical Co., Ltd., G124040606), TNBS (Shanghai Jizhi Biochemical Technology Co., Ltd., T7223AD12), anhydrous ethanol (Chengdu Kelong Chemical Co., Ltd., 2023102301).

[0063] 2 Experimental Methods 2.1 Dosage Design The composition sample of this invention, based on a daily oral dose, is equivalent to 58 g of crude drug, which, based on an adult body weight of 60 kg, is 0.97 g crude drug / kg / day. This translates to an equivalent rat dose of 6 g / kg / day. In the experiment, rats were administered three dose groups: 12 g crude drug / kg (high dose), 6 g crude drug / kg (medium dose), and 3 g crude drug / kg (low dose) (equivalent to 2 times, 1 / 2 times, and 1 / 2 times the human clinical dose, respectively), via gavage at a dose of 20 mL / kg per day. Mesalazine enteric-coated tablets (from Jiamusi Luling Pharmaceutical Co., Ltd., Sunflower Pharmaceutical Group) were selected as the positive control drug in this study, at a dose of 30 mg / kg.

[0064] 2.2 Grouping and Modeling Animals that passed the adaptation period screening were randomly divided into six groups based on their body weight: normal control group (n=10), model control group (n=10), mesalazine group (n=10), low-dose group (n=10), medium-dose group (n=10), and high-dose group (n=10). On the day of model induction, except for the normal control group which received a 37.5% ethanol aqueous solution, all other experimental groups were administered TNBS ethanol solution (37.5% ethanol-2.5% TNBS mixed solution) via enema. The TNBS dosage was 30 mg / animal, and the enema depth was 8 cm from the anus. Two weeks (14 days) later, the same procedure was repeated to induce the model, for a total of two times. All animals in the groups were fasted for 16 hours before model induction. During the experimental period, all experimental group animals were provided with normal drinking water and food, and were weighed and observed daily.

[0065] 3. Efficacy evaluation indicators

[0066] 3.1 Disease Activity Index (DAI) After model induction, the animals were administered the medication once daily for 28 consecutive days. The disease activity index of each group of experimental animals was scored based on animal weight, fecal morphology and characteristics, and fecal blood loss. The scoring criteria are shown in Table 6 below.

[0067] Table 6 DAI Scoring Criteria

[0068] 3.2 Gross damage, length, and weight of the colon At the end of the experiment, the colon was dissected and its appearance observed. A section of the colon from the anus to the ileocecal junction was harvested. After collecting the colonic tissue, it was immediately rinsed clean of feces with physiological saline, and excess water was quickly blotted dry with filter paper. A gross colonic injury assessment was performed, measuring length and weight, and calculating the colonic weight / length ratio. The colon was then dissected along its axis, laid flat on filter paper, and the area of ​​intestinal ulcer foci was calculated. The scoring criteria are shown in Table 7.

[0069] Table 7 Scoring criteria for gross morphological features of the colon

[0070] 3.3 Colonic histopathological examination At the experimental endpoint, tissue from the anus to the ileocecal junction was collected, fixed in 10% formaldehyde, embedded in paraffin, and cut into 3 μm thick sections. These sections were then dewaxed in xylene, graded-wise ethanol hydration, stained with H&E and Masson staining, dehydrated, cleared, and sealed. Histopathological changes in the colonic tissue were observed and photographed under a microscope. Based on the colonic H&E staining results, colonic inflammation and colonic ulceration in each experimental group were analyzed (diagnostic criteria are shown in Table 8). Based on the colonic Masson staining results, colonic fibrosis in each experimental group was analyzed. ImageJ was used to calculate the colonic collagen volume fraction (CVF%) in each experimental group to analyze the effect of the test sample on the colonic fibrosis process in the model animals.

[0071] Table 8 Scoring criteria for colonic histological injury

[0072] 3.4 Data Analysis Quantifiable data are expressed as mean ± standard deviation (X±SD). Comparisons between groups were performed using analysis of variance and t-tests. p <0.05 indicates that the difference is statistically significant.

[0073] 4. Experimental Results 4.1 Disease Activity Index (DAI) As shown in Tables 9 and 10, the animals in the normal control group showed normal weight gain, normal fecal characteristics, and no abnormalities in the perianal area or activity level. The animals in the model control group, after TNBS enema induction, exhibited typical symptoms of chronic ulcerative colitis, specifically significant weight loss, perianal inflammation and swelling, pasty and thin feces, and decreased activity levels, but no obvious bleeding or occult blood was observed. Under the established treatment regimen, the weight loss in the low- and high-dose traditional Chinese medicine combination groups and the positive control drug mesalazine group was significantly improved. p <0.05, p <0.0001, p <0.05), the fecal pathological characteristics of animals in the low, medium, and high dose traditional Chinese medicine combination groups and the positive drug mesalazine group were significantly alleviated, and the mean DAI score showed a significant decrease. p <0.05).

[0074] Table 9. Effects of Traditional Chinese Medicine Compositions on Body Weight Changes in Model Animals

[0075]

[0076] Note: Compared with the normal control group **** P <0.0001; compared with the model control group # P <0.05, ### P <0.001, #### P <0.0001.

[0077] Table 10 Effects of Traditional Chinese Medicine Compositions on DAI Scores in Model Animals

[0078]

[0079] Note: Compared with the normal control group **** P <0.0001; compared with the model control group # P <0.05, ## P <0.01, ### P <0.001.

[0080] 4.2 Gross morphological damage to the colon, area of ​​ulceration and weight / length ratio As shown in Table 11, the colonic structure of the normal control group animals was intact, with no obvious abnormalities. The colonic structure of the model control group animals exhibited obvious characteristics of chronic ulcerative colitis, mainly manifested as colonic atrophy and deformation, significant thickening of the intestinal wall, and ulceration. The ulcers showed multifocal and confluent distribution, adhering to surrounding tissues, with significant connective tissue hyperplasia at the adhesion sites, most severely affected in the middle and lower segments of the colon. Simultaneously, significant segmental lesions were observed in the middle and lower segments of the colon, with intestinal narrowing at the lesion sites, fecal accumulation leading to swelling, and a significant increase in the longitudinal axis of the intestine. When the intestine was dissected and laid flat on filter paper, obvious ulcer lesions were visible, showing signs of intestinal tissue erosion. Under the established treatment regimen, the low, medium, and high dose traditional Chinese medicine combination groups and the positive control drug mesalazine group showed a significant decrease in the degree of damage such as colonic atrophy, ulceration, and colonic adhesions, as well as the colonic weight / length ratio. p <0.05).

[0081] Table 11 Effects of Traditional Chinese Medicine Compositions on Gross Colonic Injury, Ulcer Area, and Colon Weight / Length Ratio in Model Animals

[0082]

[0083] Note: Compared with the normal control group **** P <0.0001; compared with the model control group # P <0.05, ## P <0.01, ### P <0.001, #### P <0.0001.

[0084] 4.3 Colonic histopathology As shown in Tables 12 and 13, the colonic structure of the normal control group animals was normal, with no obvious histological abnormalities such as inflammation, ulceration, or vascular damage. The colonic structure of the model control group animals, after two rounds of TNBS induction, showed obvious characteristics of chronic ulcerative colitis. The histopathological features mainly included typical ulcer foci (containing granulomatous foci) and colonic fibrosis. The main manifestations were significant thickening of the colonic wall, the formation of fissure-like ulcer foci on the mucosal surface, typical granulomas in the submucosa and muscularis propria, accompanied by inflammatory cell infiltration mainly composed of lymphocytes and plasma cells, small vessel proliferation, small vessel arterial endarteritis, and fibroblast proliferation. Destruction of crypt structures and hemorrhage were observed around the ulcer foci. The lesion depth could reach the muscularis propria, and in some animals, the damage could extend to the serosa. Significant and extensive connective tissue proliferation and fibrosis were observed in the submucosa and muscularis propria, with fibers distributed in bundles. The lesion depth reached the muscularis propria, and in some cases, the serosa. Under the established treatment plan, the degree of histological damage to the colon in animals in the low, medium, and high dose traditional Chinese medicine combination groups and the positive control drug mesalazine group was significantly alleviated, and the degree of colonic ulceration, crypt damage, inflammatory infiltration, and colonic fibrosis all showed a significant decrease. p <0.05).

[0085] Table 12 Effects of Traditional Chinese Medicine Compositions on Colonic Ulcers, Crypt Injuries, and Inflammatory Infiltration in Model Animals

[0086]

[0087] Note: Compared with the normal control group **** P <0.0001; compared with the model control group # P <0.05, ## P <0.01, ### P <0.001.

[0088] Table 13 Effects of Traditional Chinese Medicine Compositions on the Degree of Colonic Fibrosis in Model Animals

[0089]

[0090] Note: Compared with the normal control group **** P <0.0001; compared with the model control group # P <0.05, ## P <0.01, ### P <0.001, #### P<0.0001.

[0091] 5. Experimental Conclusions In summary, this experiment established a rat model of chronic ulcerative colitis that conforms to clinical pathogenesis, and the efficacy evaluation results of the traditional Chinese medicine composition in this model showed that it has significant therapeutic effects.

[0092] The above description of the embodiments is provided to enable those skilled in the art to understand and use the invention. It will be apparent to those skilled in the art that various modifications can be made to these embodiments, and the general principles described herein can be applied to other embodiments without inventive effort. Therefore, the present invention is not limited to the above embodiments, and any improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the invention should be within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition, characterized in that, By weight ratio, the traditional Chinese medicine composition includes: 1-100 parts Pulsatilla chinensis, 1-80 parts Poria cocos, 1-70 parts Myristica fragrans, 1-80 parts Atractylodes macrocephala, 1-60 parts Phellodendron chinense, 1-50 parts Schisandra chinensis, 1-50 parts Terminalia chebula, 1-50 parts Punica granatum peel, 1-70 parts Pogostemon cablin, and 1-100 parts Portulaca oleracea.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition includes: 1-50 parts Pulsatilla chinensis, 1-40 parts Poria cocos, 1-40 parts Myristica fragrans, 1-40 parts Atractylodes macrocephala, 1-30 parts Phellodendron chinense, 1-30 parts Schisandra chinensis, 1-30 parts Terminalia chebula, 1-30 parts Punica granatum peel, 1-40 parts Pogostemon cablin, and 1-50 parts Portulaca oleracea.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition includes: 5-15 parts of Pulsatilla chinensis, 5-15 parts of Portulaca oleracea, 4-12 parts of Atractylodes macrocephala, 4-12 parts of Poria cocos, 3-9 parts of Myristica fragrans, 3-9 parts of Pogostemon cablin, 2-6 parts of Phellodendron chinense, 1-3 parts of Terminalia chebula, 1-3 parts of Punica granatum peel, and 1-3 parts of Schisandra chinensis.

4. The traditional Chinese medicine composition according to claim 2, characterized in that, The traditional Chinese medicine composition includes: 15 parts of Pulsatilla chinensis, 15 parts of Portulaca oleracea, 12 parts of Atractylodes macrocephala, 12 parts of Poria cocos, 9 parts of Myristica fragrans, 9 parts of Pogostemon cablin, 6 parts of Phellodendron chinense, 3 parts of Terminalia chebula, 3 parts of Punica granatum peel, and 3 parts of Schisandra chinensis.

5. A method for preparing a traditional Chinese medicine composition as described in any one of claims 1-4, characterized in that, The method for preparing the traditional Chinese medicine composition includes: Take Pulsatilla chinensis, Portulaca oleracea, Atractylodes macrocephala, Poria cocos, Myristica fragrans, Pogostemon cablin, Phellodendron chinense, Terminalia chebula, Punica granatum peel, and Schisandra chinensis, add water and reflux twice. The first extraction is with 10 times the amount of water for 1.5 hours, and the second extraction is with 8 times the amount of water for 1 hour. Filter, concentrate under reduced pressure at 60~70℃ to a density of 1.10-1.15, and dry under reduced pressure at 60~70℃.

6. The use of the traditional Chinese medicine composition according to any one of claims 1-4 in the preparation of a medicament for ulcerative colitis.

7. A drug, characterized in that, The drug is prepared from the traditional Chinese medicine composition according to any one of claims 1-4 and pharmaceutically acceptable excipients or additives.

8. The medicament according to claim 7, characterized in that, The drug is selected from decoctions, granules, capsules, tablets, pills, oral liquids, tinctures, syrups, suppositories, gels, sprays, and injections.

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