Traditional Chinese medicine effective component compound preparation for inhibiting transformation of colitis and proctitis cancer and application of traditional Chinese medicine effective component compound preparation

Abstract

The invention discloses a traditional Chinese medicine effective component compound preparation for inhibiting colorectal cancer transformation, which is composed of palmatine, berberine, coptisine and aesculin, and the mass ratio of the palmatine to the berberine to the coptisine to the aesculin is 3: 3: 1: 3. The traditional Chinese medicine active ingredient compound preparation can be prepared into clinical common preparations including granules, capsules or oral liquid according to a conventional method. The traditional Chinese medicine effective component compound preparation disclosed by the invention is proved to be capable of inhibiting intestinal inflammation, improving the intestinal barrier function and remarkably inhibiting colorectal tumor in an inflammatory state by intervening a mouse DSS induced chronic colitis model and an AOM / DSS combined induced colitis and proctitis cancer transformation model.

Description

Technical Field

[0001] The invention relates to a traditional Chinese medicine effective component compound preparation for effectively inhibiting colorectal cancer transformation and application thereof. Background Art

[0002] Colorectal cancer (CRC) has become the third most common tumor and the second most common cause of cancer death in the world, and the incidence and mortality rates in men are higher than those in women. Most CRCs are sporadic, and common causative factors include: lack of physical exercise, unhealthy diet, obesity, drinking and smoking. At present, the treatment of CRC is mainly based on surgery, chemotherapy and biological antibody therapy. Related adjuvant treatment methods include fluorouracil, oxaliplatin, etc., but they have obvious negative effects. In addition, there are reports that chronic inflammation is associated with an increased risk of CRC, and chronic inflammation of the colorectal mucosa is associated with the progression of CRC. It is particularly important to explore effective strategies to inhibit the progression of intestinal inflammation to tumors.

[0003] Disruption of intestinal microbial balance may affect the host's physiological functions and induce diseases. The microbiome has been identified as one of the new biomarkers of disease. Intestinal microorganisms are an important factor affecting the occurrence of CRC. Changes in the ratio of probiotics (such as bifidobacteria and lactic acid bacteria) to pathogenic bacteria (such as enterotoxigenic Bacteroides, Escherichia coli, and Clostridium difficile) will cause bacterial translocation and change intestinal mucosal permeability. It will also promote pathogenic bacteria to secrete a variety of toxic factors to damage the intestinal epithelial barrier, produce carcinogenic metabolites, reactive oxygen species and other free radicals, activate the innate and adaptive immune systems, lead to DNA damage and host cell mutations, and then induce chronic inflammatory responses and progress to CRC. In addition, the synergistic effects within fungi and the antagonistic effects between bacteria and fungi may also be the key to promoting CRC.

[0004] FMT (Fecal microbial transplantation, FMT) is the most direct way to regulate intestinal microorganisms. It transfers the entire intestinal microbial ecosystem to the recipient and benefits the host through the cooperation of multiple microorganisms. Studies have shown that the diversity of the intestinal flora of the recipient generally increases after FMT. The possible reason is that FMT reduces intestinal permeability and promotes the integrity of the epithelial barrier by increasing short-chain fatty acids (such as butyrate). In addition, the mucus secreted by goblet cells prevents bacteria from crossing the colonic epithelial barrier. Muc2 is the main component of colonic mucus, which separates bacteria from the colonic epithelium. Therefore, the lack of Muc2 increases susceptibility to intestinal inflammation, which emphasizes the importance of a strong intestinal barrier function. Summary of the invention

[0005] In view of the above-mentioned deficiencies in the prior art, according to an embodiment of the present invention, it is hoped to provide a compound preparation of effective ingredients of traditional Chinese medicine for inhibiting the transformation of colorectal inflammation into cancer. The DSS and AOM / DSS models are used to confirm a drug component that effectively inhibits the transformation of colorectal inflammation into cancer, and the FMT experiment shows that the protective effect is related to the regulation of intestinal flora.

[0006] The present invention demonstrates the effectiveness of a compound preparation of effective components of traditional Chinese medicine in inhibiting the transformation of colorectal cancer.

[0007] The invention discloses for the first time that the compound preparation of effective components of traditional Chinese medicine can inhibit the transformation of colorectal inflammation into cancer.

[0008] According to the embodiments, the present invention provides a compound preparation of effective ingredients of traditional Chinese medicine for inhibiting the transformation of colorectal inflammation into cancer, which is composed of flavonoids, berberine, coptisine and aesculin, and the mass ratio of flavonoids, berberine, coptisine and aesculin is 3:3:1:3.

[0009] The preparation method of the compound preparation of the effective components of traditional Chinese medicine of the present invention is not special and can be prepared into commonly used clinical preparations according to conventional methods, including granules, capsules or oral liquids.

[0010] The effective component compound preparation of Chinese medicine of the present invention is based on four Chinese medicines, namely, Pulsatilla striata, Fraxinus chinensis, Phellodendron chinense and Coptis chinensis, which are currently commonly used in the clinic to treat intestinal inflammation, and is composed of the main effective components of these four herbs. Traditional Chinese medicine compound focuses on holistic comprehensive treatment, and its mechanism of action is multi-target and multi-pathway. The unknown target has also become a bottleneck for the rapid development of Chinese medicine. Intestinal flora is an important target for Chinese medicine compound preparations to exert their efficacy, and is a hot spot and trend in the international development of Chinese medicine research. It is of great significance to the development of new drugs with fewer ingredients, controllable quality and clear mechanism.

[0011] In the present invention, we evaluated the protective effect of the compound preparation of effective ingredients of traditional Chinese medicine of the present invention on mice by using DSS-induced chronic colorectal inflammation and AOM / DSS-induced colorectal cancer transformation models, including improvement of intestinal barrier function and inhibition of inflammation. Further 16S rRNA analysis of fecal samples focused on the increase of Firmicutes / Bacteroidetes after the intervention of the compound preparation in the DSS model (compared with the model group), and focused on the decrease of Proteobacteria abundance after intervention in the AOM / DSS model (compared with the model group). In order to further explore whether the protective effect of Baitouweng Decoction is related to intestinal flora, we conducted an FMT experiment, and the results showed that in the recipient group, the intestinal barrier function and inflammation level of mice intervened by the compound preparation of effective ingredients of traditional Chinese medicine of the present invention were significantly reduced compared with the model group. Therefore, it is considered to be a promising drug that can effectively inhibit the transformation of colorectal cancer.

[0012] The results of the effective Chinese medicine compound preparation of the present invention in improving intestinal barrier function and inhibiting inflammation were verified in DSS and AOM / DSS models. The results confirmed that it can effectively inhibit the progression of colon inflammation to tumors, and its potential mechanism of action may be related to regulating intestinal flora. Therefore, the effective Chinese medicine compound preparation of the present invention has good application value in clinical prevention of colorectal cancer. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 It shows that the compound preparation of effective components of traditional Chinese medicine of the present invention can effectively improve the intestinal barrier function and inflammation of mice with chronic colitis.

[0014] Figure 2 It shows that the compound preparation of effective components of traditional Chinese medicine of the present invention can effectively improve the intestinal flora of mice with chronic colitis.

[0015] Figure 3 It shows that the compound preparation of effective components of traditional Chinese medicine of the present invention can effectively improve the intestinal barrier function and inflammation of mice transformed with colorectal cancer.

[0016] Figure 4 It shows that the compound preparation of effective components of traditional Chinese medicine of the present invention can effectively improve the intestinal flora of mice transformed with colorectal cancer.

[0017] Figure 5 The results show that fecal microbial transplantation of the compound preparation of effective ingredients of traditional Chinese medicine of the present invention can effectively improve the intestinal barrier function and inflammation of mice. DETAILED DESCRIPTION

[0018] The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments. These embodiments should be understood to be only used to illustrate the present invention and not to limit the scope of protection of the present invention. After reading the contents of the present invention, those skilled in the art may make various changes or modifications to the present invention, and these equivalent changes and modifications also fall within the scope defined by the claims of the present invention.

[0019] The following examples of the present invention are based on DSS-induced chronic colorectal inflammation and AOM / DSS-induced colorectal cancer transformation models to evaluate the protective effect of the compound preparation of effective ingredients of traditional Chinese medicine of the present invention on mice, and explore its potential mechanism of action through 16S rRNA analysis and FMT experiments.

[0020] 1. Introduction to experimental methods:

[0021] 1. Materials and Methods

[0022] 1.1 Preparation of compound preparations

[0023] The traditional Chinese medicine effective component compound preparation of the invention consists of flavonoids, berberine, coptisine and aesculin, and the mass ratio of flavonoids, berberine, coptisine and aesculin is 3:3:1:3.

[0024] 1.2 Animal models

[0025] Female C57BL / 6J mice (4-5 weeks old) were purchased from Jiangsu Jicui Yaokang Biotechnology Co., Ltd. The animal experiment protocol of this experiment was approved by the Experimental Ethics Committee of Shanghai University of Traditional Chinese Medicine (ethics number: PZSHUTCM2307050006). All mice were kept in a specific pathogen-free environment with a temperature of 25±2°C, a humidity of 45%-50%, a light / dark cycle of 12h, and free access to water and standard feed. After 3 days of adaptation to the experimental environment, the mice were randomly divided into 4 groups (n=8 / group). Dextran sulfate sodium (DSS, MP Biomedicals) modeling and intervention: The model group was given 2.5% DSS in drinking water for 4 days, and then changed to normal drinking water for 14 days. Every 18 days was a DSS cycle, and 5 cycles were repeated. Starting from the first day of DSS treatment, mice were gavaged with the compound preparation of the effective ingredients of the Chinese medicine of the present invention (0.15g / 0.1mL, 0.3g / 0.1mL) or an equivalent amount of 0.9% NaCl solution every day. After the experimental period, the entire colon was collected and cut longitudinally, the colon length was measured and the number of tumors was recorded. Azomethane AOM / DSS modeling and intervention: The model group was intraperitoneally injected with 12.5 mg / kg AOM and given 2.5% DSS in drinking water for 5 days, and then switched to normal drinking water for 16 days. Every 21 days was a DSS cycle, and 4 cycles were repeated. From the first day of AOM / DSS modeling, mice were gavaged with the compound preparation of the effective ingredients of the Chinese medicine of the present invention (0.15 g / 0.1 mL) or an equivalent amount of 0.9% NaCl solution every day. At the end of the experimental period, the entire colon was collected and cut longitudinally, the colon length was measured and the number of tumors was recorded.

[0026] 1.3 Fecal microbiota transplantation

[0027] To determine the direct effect of the compound preparation of effective Chinese medicinal ingredients of the present invention on the transformation of colorectal cancer, 6-8 week-old sterile C57BL / 6J mice were divided into 4 groups (8 mice in each group), induced to receive AOM / DSS, and simultaneously received FMT. Fecal samples of mice in the AOM model group treated with the compound preparation of effective Chinese medicinal ingredients of the present invention, the AOM / DSS model mouse group, the mouse group intervened with the compound preparation of effective Chinese medicinal ingredients of the present invention, and the phosphate buffered saline (PBS) control mouse group were collected, homogenized and suspended in 0.9% sterile saline (200 mg / 2 ml), and then centrifuged at 800 rpm for 3 minutes, sampled and stored at -80°C for further FMT.

[0028] 1.4 Disease Activity Index

[0029] During DSS, the clinical manifestations of mice were monitored daily using the disease activity index (DAI). The DAI was calculated based on the following indicators: weight loss (0 points, none; 1 point, <5%; 2 points, 5%-10%; 3 points, 10%-20%; 4 points, >20%), diarrhea (0 points, normal; 2 points, loose stools; 4 points, watery diarrhea), and rectal bleeding (0 points, no bleeding; 2 points, mild bleeding; 4 points, heavy bleeding).

[0030] 1.5 HE staining

[0031] The samples were embedded in paraffin and cut into 4-micron sections. The paraffin sections were dewaxed with xylene, dehydrated in serially diluted ethanol (95%, 80%, and 70%), and then stained with hematoxylin for 10 minutes and eosin for 3 minutes at room temperature. They were then rinsed with distilled water for 30 seconds. They were rinsed twice with 95% anhydrous ethanol (1 minute each) and three times with xylene (5 minutes each).

[0032] 1.6 Immunohistochemistry

[0033] The samples were embedded in paraffin and cut into 4 μm sections. The paraffin sections were immersed in xylene and absolute ethanol twice for 5 min each time, then treated with serially diluted ethanol (concentrations of 95%, 80%, and 70%) for 5 min and rinsed with distilled water for 5 min. The sections were treated with Tris EDTA antigen retrieval solution for 10 min, cooled to room temperature, and then washed three times with phosphate buffered saline (PBS, Servicebio, G4202) for 5 min each. The sections were then treated with 3% H2O2 for 15 min and washed three times with PBS for 5 min each. The sections were incubated in 5% BSA (BOSTER, Wuhan, China) at 37°C for 30 min. Primary antibodies Ki67 (CST, 12202S) and MUC-2 (Proteintech, 27675-1-AP) were added and incubated overnight at 4°C. The next day, the sections were washed three times with PBS for 5 minutes each time, followed by incubation with anti-rabbit IgG (BOSTER, Wuhan, China, SA1022) at 37°C for 30 minutes. The sections were washed three times with PBS for 5 minutes each time, incubated with diaminobenzidine (DAB) for 5 minutes, and then rinsed with water. The sections were counterstained with hematoxylin for 1 minute and then rinsed twice with running water (3 minutes each time). The sections were observed at ×200 magnification under a Nikon Eclipse 50i microscope (Nikon, Tokyo, Japan), and the positively stained cells were counted using Image J software.

[0034] 1.7 Immunofluorescence

[0035] The samples were embedded in paraffin and cut into 4 μm sections. Paraffin sections were immersed in xylene and absolute ethanol twice for 5 min each time, then treated with serially diluted ethanol (concentrations of 95%, 80%, and 70%) for 5 min and rinsed with distilled water for 5 min. They were treated with Tris EDTA antigen retrieval solution for 10 min, cooled to room temperature, and then washed three times with PBS for 5 min each. The sections were then treated with goat serum (Beyotime, C0265) for 30 min, and then primary antibodies ZO-1 (abcam, ab221541) and Occludin (CST, 91131S) were added and incubated overnight at 4°C. The next day, the sections were washed three times with PBS for 5 min each, followed by incubation with dropwise added secondary antibodies at 37°C for 1 h. They were then washed three times with PBS for 5 min each, stained with DAPI (BOSTER, Wuhan, China) for 5 min, and washed three times with PBS for 5 min each. Images were acquired using a laser confocal microscope.

[0036] 1.8 Real-time fluorescence quantitative PCR

[0037] Total RNA was isolated from colon tissue using TRIzol reagent (Ambion, USA). RNA was reverse transcribed using a reverse transcription kit (Accurate Biology, Shanghai, China) according to the manufacturer's instructions. mRNA expression was determined using SYBR Green PCR mixture (Thermo Fisher Scientific, Waltham, MA, USA). -ΔΔCt Data were analyzed and normalized to the gene expression of GAPDH. Primer sequences are shown below: Gapdh: 5'-AGGTCGGTGTGAACGGATTTG-3', 5'-TGTAGACCATGTAGTTGAGGTCA-3'; IL-6: 5'-GGAGAGGAGACTTCACAGAGGATACC-3', 5'-AAGTTGTTCTTCATGTACTCCAGGTAGC-3'; IL-1β: 5'-GCAACTGTTCCTGAACTCAACT-3', 5'-ATCTTTTGGGGTCCGTCAACT-3'TNF-α: 5'-CCC TCA CACTCA GAT CAT CTT CT-3', 5'-GCTACGACGTGGGCT ACAG-3'.

[0038] 1.9 Western blot analysis

[0039] Proteins from frozen colon tissues were extracted using RIPA buffer supplemented with protease and phosphatase inhibitors. Protein concentrations were quantified using a BCA kit (Epizyme, Shanghai, China). Proteins (15-20 μg) were electrophoresed on a 10% SDS-polyacrylamide gel and transferred to a 0.45 μm polyvinylidene fluoride (PVDF) membrane (Millipore, USA). After blocking with 5% BSA for 2 h at room temperature, the membranes were incubated with the corresponding primary antibody overnight at 4 °C and incubated with horseradish peroxidase-conjugated secondary antibodies (rabbit: CST, 7074S; mouse: CST, 7076S) at room temperature for 1 h the next day. Bands were visualized using an ECL chemiluminescent detection kit (WBKLS0500, Millipore, USA) and an enhanced chemiluminescence system (Tanon5200, Shanghai, China). The expression of β-actin was used as a control. ZO-1 (CST, 13663S), Occludin (CST, 91131S), Claudin3 (abcam, ab214487), Anti-TLR4 (CST, 14358S), MyD88 (abcam, ab219413), P65 (CST, 8242S), p-P65 (CST, 303S), IκB (CST, 4814S), p-IκB (CST, 2859S), PCNA (CST, 13110S) antibodies were diluted 1:1000. Anti-β-actin (HUABIO, ET1702-67) and secondary antibodies were diluted 1:5000. Finally, the density of protein bands was quantified and analyzed using ImageJ software.

[0040] 1.10 Statistical analysis

[0041] Statistical analysis was performed using Prism 8.0 software (version 8.0; Graphpad Software Inc., San Diego, CA, USA). Except for the analysis of intestinal microbiota, data are presented as mean ± SD. Statistical comparisons among multiple groups were performed by one-way analysis of variance (ANOVA), and comparisons between groups were performed using Dunnett's t test. P values ​​< 0.05 were considered statistically significant.

[0042] 2. Experimental Results

[0043] 2.1 The compound preparation of effective ingredients of traditional Chinese medicine of the present invention improved the intestinal barrier function and inflammation of mice with chronic colorectal inflammation.

[0044] In order to explore the protective effect of the compound preparation of effective components of traditional Chinese medicine on chronic colitis, we used 2.5% DSS ( Figure 1A) Induction for 5 cycles, and intervention with human and mouse equivalent doses and double doses. After the experimental cycle, the intestinal appearance of each group was observed ( Figure 1 B) Polyp / tumor ratio ( Figure 1 C) and disease activity index ( Figure 1 D). The results showed that the intervention of the compound preparation of effective ingredients of traditional Chinese medicine of the present invention significantly reduced the number of intestinal polyps / tumors in mice and reduced the disease activity index. At the same time, the degree of intestinal pathology was alleviated ( Figure 1 E), decreased tumor proliferation ( Figure 1 F, 1G). The expression of intestinal pro-inflammatory factor TNF-α was reduced ( Figure 1 H), serum pro-inflammatory factors IL-6, IL-1β ( Figure 1 I, 1J) decreased in expression. The expression of Muc2 was detected by Paneth staining, Alcian blue staining and immunohistochemistry ( Figure 1 K) showed that the intervention of the effective ingredients of traditional Chinese medicine compound preparation of the present invention improved the mucus barrier of the mouse intestine. Intestinal WB and immunofluorescence ( Figure 1 The results of L, 1M) showed that the physical barrier of the mouse intestine was improved to a certain extent after the intervention of the compound preparation of the effective ingredients of the traditional Chinese medicine of the present invention.

[0045] 2.2 The compound preparation of effective ingredients of traditional Chinese medicine of the present invention regulates the intestinal microbiota of mice with chronic colorectal inflammation.

[0046] 16S rRNA sequencing was performed on fecal samples of chronic colitis mice to compare the microbial composition of different groups. The Shannon index showed no significant changes in species diversity among the three groups ( Figure 2 A). Principal component analysis (PCoA) showed the differences among the three sample groups ( Figure 2 B). In addition, compared with the normal group, the abundance of Firmicutes / Bacteroidetes at the phylum level in the model group was significantly reduced, and the abundance of Helicobacter increased, while the intervention of the compound preparation of the effective ingredients of the traditional Chinese medicine of the present invention significantly reversed this trend ( Figure 2 C-2F). This indicates that the effect of the compound preparation of effective ingredients of traditional Chinese medicine on the intestinal microbiota of DSS-induced chronic colitis is reflected in the reduction of pathogenic bacteria abundance and the increase of beneficial bacteria abundance. LEfSe analysis showed the same results ( Figure 2 G, 2H). PICRUST function prediction suggests that the expression of LPS-synthesized lipoprotein is reduced after Baitouweng decoction intervention ( Figure 2 I).

[0047] 2.3 The compound preparation of effective ingredients of traditional Chinese medicine of the present invention improves the intestinal barrier function and inflammation of mice transformed with colorectal cancer.

[0048] In order to further explore the intervention effect of the effective Chinese medicine compound preparation of the present invention on the transformation of colorectal cancer, we used 12.5 mg / kg AOM and 2.5% DSS to induce 4 cycles ( Figure 3 A) The model was constructed and treated with the compound preparation of effective components of traditional Chinese medicine of the present invention at the equivalent dose of human and mouse. After the experimental period, we observed the intestinal appearance of each group ( Figure 3 B) Polyp / tumor ratio ( Figure 3 C) Ratio of polyps / tumors larger than 3 mm ( Figure 3 D) DAI score ( Figure 3 E). The results showed that the number of intestinal polyps / tumors in mice treated with the effective component compound preparation of the Chinese medicine of the present invention was significantly reduced, and the DAI score was significantly reduced. The degree of intestinal pathology was reduced ( Figure 3 F), decreased tumor proliferation ( Figure 3 G, 3H). Intestinal pro-inflammatory factor TNF-α ( Figure 3 I) and serum pro-inflammatory factors IL-6, IL-1β ( Figure 3 J, 3K) expression was significantly reduced. Pan's staining, Alcian blue staining and Muc2 immunohistochemistry ( Figure 3 L) showed that the intervention of the effective ingredients of traditional Chinese medicine compound preparation of the present invention improved the intestinal mucus barrier of mice. Intestinal WB and immunofluorescence experiments ( Figure 3 M, 3N) showed that after intervention with the compound preparation of effective ingredients of traditional Chinese medicine of the present invention, the physical barrier of the intestinal epithelium of mice was improved to a certain extent.

[0049] 2.4 The compound preparation of effective ingredients of traditional Chinese medicine of the present invention regulates the intestinal microbiota of mice transformed with colorectal cancer.

[0050] The microbial composition of the different groups was compared by 16S rRNA sequencing. Principal component analysis (PCoA) showed the differences among the three sample groups ( Figure 4 A). In addition, compared with the normal control group, the abundance of Proteobacteria at the phylum level in the model group increased significantly. After treatment with the compound preparation of the effective ingredients of the Chinese medicine of the present invention, this trend was significantly reversed ( Figure 4 B, 4C). LEfSe analysis showed the same results ( Figure 4 D, 4E). This indicates that the regulation of the intestinal microbiota of mice with colorectal cancer transformation by the effective Chinese medicine compound preparation of the present invention is reflected in the reduction of the abundance of pathogenic bacteria. PICRUST function prediction suggests that the expression level of LPS-synthesized lipoprotein is reduced after the intervention of Baitouweng Decoction ( Figure 4 F).

[0051] 2.6 Fecal microbiota transplantation improves intestinal barrier function and inflammation in mice.

[0052] To further explore whether the protective effect of the compound preparation of the effective ingredients of the Chinese medicine of the present invention on colorectal cancer transformation is mediated by the intestinal flora, we conducted a fecal microbial transplantation (FMT) experiment as described above ( Figure 5 A), after the experimental period, we observed the intestinal appearance of each group ( Figure 5 B) Colon length ( Figure 5 C) DAI score ( Figure 5 D), weight ( Figure 5 E). The results showed that the intestinal length and body weight of mice treated with BTW increased significantly, and the DAI score decreased significantly. The degree of intestinal pathology decreased ( Figure 5 F), decreased tumor proliferation ( Figure 5 G, 5H). Intestinal pro-inflammatory factors IL-6, IL-1β ( Figure 5 I, 5J) expression was significantly reduced. Colonoscopy showed that after BTW intervention, the degree of intestinal pathology was reduced, the tumor was significantly inhibited, and the intestinal wall was smooth and flat ( Figure 5 K). Pan's staining, Alcian blue staining and immunohistochemistry of Muc2 ( Figure 5 L) showed that fecal microbiota transplantation significantly improved the intestinal mucus barrier of mice. Intestinal WB and immunofluorescence experiment results ( Figure 5 M, 5N) showed that fecal microbiota transplantation significantly improved the physical barrier of the mouse intestine.

Claims

1. A compound preparation of effective ingredients of traditional Chinese medicine for inhibiting the transformation of colorectal cancer, characterized in that: It is composed of flavonoids, berberine, coptisine and aesculin, and the mass ratio of flavonoids, berberine, coptisine and aesculin is 3:3:1:

3.

2. The Chinese medicinal active ingredient compound preparation for inhibiting colorectal cancer transformation according to claim 1, characterized in that: The compound preparation is in the form of granules, capsules or oral solution.

3. Use of the compound preparation of effective ingredients of traditional Chinese medicine according to claim 1 or 2 in the preparation of a drug for inhibiting the transformation of colorectal inflammation into cancer.

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