Use of Polygonatum sibiricum flavonoids extract in preparing drugs for treating colorectal cancer

Abstract

The present application provides the use of a flavonoid extract of Polygonatum sibiricum in the preparation of drugs for treating colorectal cancer, and belongs to the field of biomedicine technology. The flavonoid extract of Polygonatum sibiricum and the high-isoflavonoid compounds of the present application exert excellent anti-cancer effects by inhibiting cancer cell proliferation, inducing cancer cell apoptosis and DNA damage. The above-mentioned drugs are highly safe, low-cost, and have good anti-cancer effects. In addition, the high-isoflavonoid compounds can also be used in combination with traditional chemotherapy drugs (such as 5-FU) to exert a synergistic and effective effect, with excellent results. The present application has good clinical application prospects.

Description

Technical Field

[0001] The present application belongs to the field of biomedicine technology, and specifically relates to the use of a flavonoid extract of Polygonatum sibiricum in the preparation of drugs for treating colorectal cancer. Background Art

[0002] Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies worldwide, with high morbidity and mortality, posing a serious threat to human health. Currently, first-line chemotherapy regimens primarily include 5-fluorouracil (5-FU), oxaliplatin, and irinotecan, but their efficacy is limited by significant side effects and acquired drug resistance. In recent years, targeted therapies (such as anti-EGFR monoclonal antibodies) and immune checkpoint inhibitors (such as PD-1 / PD-L1 antibodies) have made progress in the treatment of CRC, but their applicability is limited and they are prone to secondary drug resistance. Therefore, the development of anti-CRC compounds with natural origin, high safety, and novel mechanisms of action is a key focus of current anti-tumor drug research.

[0003] Natural products, due to their structural diversity and excellent biological activity, are important resources for the development of anti-tumor drugs. Polygonatum plants are widely used in traditional medicine. Modern pharmacological research has revealed that they are rich in polysaccharides, saponins, flavonoids, and isoflavonoids, exhibiting multiple activities, including antioxidant, anti-inflammatory, and immunomodulatory effects. Polygonatum kingianum, a member of the Polygonatum genus, is a unique and edible medicinal plant native to Yunnan Province. It boasts benefits such as tonifying qi and nourishing yin, strengthening the spleen, moistening the lungs, and benefiting the kidneys. Furthermore, Polygonatum kingianum contains a variety of bioactive components, including polysaccharides, steroidal saponins, flavonoids, phytosterols, volatile oils, and phenolic compounds. Flavonoids, among them, exhibit antioxidant, anti-inflammatory, and anti-tumor activities. However, the functional compounds within these compounds have not been systematically studied.

[0004] Therefore, isolating and identifying effective compounds from Polygonatum sibiricum and systematically evaluating their anti-colorectal cancer activity have important scientific significance and application value for the development of new natural anti-tumor drugs. Summary of the Invention

[0005] The purpose of this application is to provide the use of a flavonoid extract of Polygonatum sibiricum in the preparation of a drug for treating colorectal cancer.

[0006] The present application provides the use of a flavonoid extract of Polygonatum sibiricum in the preparation of a drug for preventing and / or treating colorectal cancer. The total flavonoid content in the Polygonatum sibiricum flavonoid extract is not less than 80 wt %, and the extract contains a high amount of isoflavone components.

[0007] Furthermore, the Polygonatum sibiricum flavonoid extract contains the compound represented by formula I:

[0008] ;

[0009] Formula I.

[0010] Furthermore, the preparation method of the Polygonatum sibiricum flavonoid extract comprises the following steps:

[0011] (1) Take the coarse powder of Polygonatum dahliae and extract it with ethanol-water solution;

[0012] (2) concentrating the extract and eluting and purifying the extract using high performance liquid chromatography to obtain an eluate;

[0013] (3) drying the eluate to obtain the Polygonatum sibiricum flavonoid extract;

[0014] In step (1), the weight ratio of the coarse powder of Polygonatum yunnanensis to the ethanol aqueous solution is 1: (8-10);

[0015] In step (1), the volume percentage of the ethanol aqueous solution is 60%;

[0016] In step (1), the extraction temperature is 60°C to 70°C, the extraction time is 30min to 60min, and the number of extractions is 1 to 3 times;

[0017] In step (2), the chromatographic column for elution and purification by high performance liquid chromatography is a C18YE chromatographic column, and the eluent is an ethanol aqueous solution with a volume fraction of 60%.

[0018] The above-mentioned drugs can be made into various dosage forms, including tablets, capsules, pills, granules, oral solutions and injections.

[0019] The recommended dosage of the Polygonatum sibiricum flavonoids extract in the anti-colorectal cancer drug of the present application is 100 μg / mL-500 μg / mL, and the preferred dosage is 200 μg / mL.

[0020] The present application also provides the use of a compound represented by Formula I or a salt thereof as the sole active ingredient in the preparation of a drug for preventing and / or treating colorectal cancer:

[0021] ;

[0022] Formula I.

[0023] Furthermore, the drug is a drug that upregulates the expression of proteins Cleaved-Caspase-3, Cleaved-Caspase-8 and / or γ-H2AX.

[0024] Furthermore, the dosage form of the drug is one of the following dosage forms: tablets, capsules, pills, granules, oral liquid or injection.

[0025] The recommended dosage of the compound represented by formula I or its salt in the anti-colorectal cancer drug is 1 μM-10 μM, and the preferred dosage is 4 μM.

[0026] The compound represented by formula I or its salt can be obtained from commercial products or prepared in-house. The method for preparing the compound in-house is to purify the above-mentioned Polygonatum sibiricum flavonoid extract by high performance liquid chromatography (HPLC).

[0027] The present application also provides a pharmaceutical composition for preventing and / or treating colorectal cancer, which is composed of a compound represented by Formula I or a salt thereof and 5-fluorouracil:

[0028] ;

[0029] Formula I

[0030] The mass ratio of the compound represented by formula I or its salt to 5-fluorouracil is (1-5):1.

[0031] Furthermore, the mass ratio of the compound represented by formula I or its salt to 5-fluorouracil is 4:1.

[0032] The present application also provides the use of a compound represented by Formula I or a salt thereof in combination with 5-fluorouracil in the preparation of a drug for preventing and / or treating colorectal cancer:

[0033] ;

[0034] Formula I

[0035] The mass ratio of the compound represented by formula I or its salt to 5-fluorouracil is (1-5):1.

[0036] Furthermore, the mass ratio of the compound represented by formula I or its salt to 5-fluorouracil is 4:1.

[0037] The excipients in the dosage form of this application include the following ingredients:

[0038] Binder: starch paste, carboxymethyl cellulose, hydroxypropyl cellulose or ethyl cellulose;

[0039] Bulking agents: starch, dextrin, or lactose;

[0040] Lubricants: micronized silica gel, fumed silica gel, talc or magnesium stearate.

[0041] Compared with the prior art, the present invention has the following advantages:

[0042] (1) The flavonoid extract of Polygonatum sibiricum provided in this application and its key component, high isoflavone compounds, can significantly inhibit the proliferation of colorectal cancer cells, induce cell apoptosis and DNA damage, have good anti-cancer activity, and are suitable for the prevention and treatment of colorectal cancer;

[0043] (2) The high-isoflavonoid compound of this application is derived from the medicinal and edible plant Polygonatum sibiricum, has high safety, low toxicity and side effects, is suitable for long-term use, and has strong clinical operability;

[0044] (3) The high isoflavone compound of the present application can be used alone as the sole active ingredient or in combination with traditional chemotherapy drugs (such as 5-fluorouracil), which has a synergistic anti-cancer effect and is conducive to reducing drug dosage and drug toxicity;

[0045] (4) The acquisition cost of the Yunnan Polygonatum flavonoid extract and high isoflavone compounds in this application is low, which is conducive to reducing the diagnosis and treatment costs of patients and medical institutions and improving the survival rate and quality of life of colorectal cancer patients;

[0046] (5) This application clarifies that the flavonoid extracts of Polygonatum sibiricum and its isoflavone compounds exert anti-tumor effects by upregulating the expression of apoptotic proteins such as Cleaved-Caspase-3 and Cleaved-Caspase-8, providing a theoretical basis and practical basis for the development of new natural medicines for the treatment of colorectal cancer and other related malignant tumors.

[0047] In summary, the present application provides a use of a Polygonatum sibiricum flavonoid extract and the high isoflavone compounds present therein in the preparation of a drug for preventing and / or treating colorectal cancer. The Polygonatum sibiricum flavonoid extract and the high isoflavone compounds exhibit excellent anti-cancer effects by inhibiting cancer cell proliferation, inducing cancer cell apoptosis, and DNA damage. The above-mentioned drugs are highly safe, low-cost, and have good anti-cancer effects. In addition, the high isoflavone compounds can also be used in combination with traditional chemotherapy drugs (such as 5-FU) to exert a synergistic effect and achieve excellent anti-cancer effects. The present application has good clinical application prospects.

[0048] Obviously, based on the above content of this application, in accordance with common technical knowledge and customary means in this field, without departing from the above basic technical ideas of this application, various other forms of modifications, replacements or changes can be made.

[0049] The following is a detailed description of the above content of this application through specific implementation methods in the form of examples. However, this should not be construed as limiting the scope of the above subject matter of this application to the following examples. All technologies implemented based on the above content of this application fall within the scope of this application. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] Figure 1This is the nuclear magnetic resonance hydrogen spectrum of high isoflavonoid compounds (HIF).

[0051] Figure 2 This is the carbon NMR spectrum of high isoflavone compounds (HIF).

[0052] Figure 3 This is the result of CCK-8 assay to detect the effect of different concentrations of Polygonatum sibiricum flavonoids extract (PKF) on the survival rate of HCT15 cells.

[0053] Figure 4 This is the result of CCK-8 assay to detect the effect of different concentrations of Polygonatum sibiricum flavonoids extract (PKF) on the survival rate of HCT116 cells.

[0054] Figure 5 The results of CCK-8 assay to detect the effects of different concentrations of high isoflavone compounds (HIF) on the survival rate of HCT116 and HCT15 cells and the IC 50 Value result graph.

[0055] Figure 6 This figure shows the results of Western Blot detection of the effects of different concentrations of Polygonatum sibiricum flavonoid extract (PKF) on the expression of Cleaved-Caspase-3 and Cleaved-Caspase-8 apoptosis proteins in HCT15 cells.

[0056] Figure 7 This figure shows the results of Western Blot detection of the effects of different concentrations of Polygonatum sibiricum flavonoid extract (PKF) on the expression of Cleaved-Caspase-3 and Cleaved-Caspase-8 apoptosis proteins in HCT116 cells.

[0057] Figure 8 This is the result of Western Blot detection of the effects of different concentrations of Polygonatum sibiricum flavonoids extract (PKF) on the expression of γ-H2AX protein in HCT15 cells.

[0058] Figure 9 This is the result of Western Blot detection of the effects of different concentrations of Polygonatum sibiricum flavonoids extract (PKF) on the expression of γ-H2AX protein in HCT116 cells.

[0059] Figure 10 This figure shows the results of Western Blot detection of the effects of different concentrations of high isoflavone compounds (HIF) on the expression of Cleaved-Caspase-3 and Cleaved-Caspase-8 apoptosis proteins in HCT15 cells.

[0060] Figure 11This figure shows the results of Western Blot detection of the effects of different concentrations of high isoflavone compounds (HIF) on the expression of Cleaved-Caspase-3 and Cleaved-Caspase-8 apoptosis proteins in HCT116 cells.

[0061] Figure 12 This figure shows the results of Western Blot detection of the effects of different concentrations of high isoflavone compounds (HIF) on the expression of γ-H2AX protein in HCT15 cells.

[0062] Figure 13 This figure shows the results of Western Blot detection of the effects of different concentrations of high isoflavonoid compounds (HIF) on the expression of γ-H2AX protein in HCT116 cells.

[0063] Figure 14 This is a graph showing the changes in tumor volume over time in the subcutaneous tumor model of mice in different PKF treatment groups.

[0064] Figure 15 The final tumor entity images of mice in different PKF treatment groups.

[0065] Figure 16 This is a statistical graph of the final tumor weights of mice in different PKF treatment groups.

[0066] Figure 17 This is a graph showing the changes in tumor volume over time in the subcutaneous tumor model of mice in different HIF treatment groups.

[0067] Figure 18 The final tumor entity images of mice in different HIF treatment groups.

[0068] Figure 19 This is a statistical graph of the final tumor weights of mice in different HIF treatment groups. DETAILED DESCRIPTION

[0069] The raw materials and experimental equipment used in the implementation of this application are all commercially available products and can be purchased through regular channels.

[0070] Example 1. Preparation of Polygonatum sibiricum Flavonoid Extract and Identification of High-Isoflavonoid Compounds

[0071] The crude powder of Polygonatum dahliae was placed in a 60% ethanol-water solution (10 times its weight) and extracted at 60°C for 30 minutes. The extraction was repeated three times, and the extracts were collected after each extraction. The extracts were combined and concentrated to obtain a concentrate. A C18YE column was used for chromatography, pre-equilibrated with a 60% ethanol-water solution. The concentrate was loaded and eluted with a 60% ethanol-water solution. The eluate was collected and the ethanol was recovered under reduced pressure. Finally, the eluate was dried to obtain the Polygonatum dahliae flavonoid extract (PKF).

[0072] A standard curve was constructed using rutin as the standard, and the total flavonoid content of the obtained Polygonatum cyrtonema flavonoid extract (PKF) was determined to be approximately 83 wt%. HPLC separation and analysis revealed the presence of high isoflavone components in the Polygonatum cyrtonema flavonoid extract (PKF), and nuclear magnetic resonance imaging revealed a high isoflavone compound (HIF) with the following structure:

[0073] ;

[0074] High isoflavonoids (HIF).

[0075] The nuclear magnetic resonance hydrogen spectrum of the above-mentioned high isoflavone compound (HIF) is as follows Figure 1 As shown, the carbon NMR spectrum is as follows Figure 2 The CAS number of HIF identified from PKF in this application is 189264-18-4, which can be obtained by purchasing commercial products. The HIF used in the following examples of this application was purchased from BLDpham.

[0076] Example 2: Study on the inhibitory effect of Polygonatum sibiricum flavonoid extract (PKF) and high isoflavonoid compounds (HIF) on the activity of human colorectal cancer cells

[0077] 1. Culture of HCT116 and HCT15 cells

[0078] Remove RPMI 1640 complete medium (containing 10% fetal bovine serum and 0.1% penicillin-streptomycin, purchased from Gibco) from a 4°C refrigerator 30 minutes in advance and bring to room temperature. HCT116 and HCT15 cells (human colorectal cancer cell lines, purchased from the Cell Bank of the Chinese Academy of Sciences) were seeded in this complete medium and cultured at 37°C in 5% CO2. The medium was changed every 48 hours, and cells were harvested after reaching the logarithmic growth phase.

[0079] 2. CCK-8 (Ce1l Counting Kit-8) cell proliferation activity detection

[0080] To evaluate the effects of Polygonatum yunnanensis flavonoid extract (PKF) and high isoflavonoid compounds (HIF) on the proliferation activity of HCT116 and HCT15 cells, the following experiments were performed.

[0081] 2.1 Polygonatum sibiricum Flavonoids Extract (PKF)

[0082] HCT116 and HCT15 cells were digested and seeded into 96-well plates, with six replicates per group. When the cell density reached approximately 50%–60%, the cells were treated with different concentrations of PKF (0 μg / mL, 10 μg / mL, 50 μg / mL, 100 μg / mL, 200 μg / mL, and 400 μg / mL, in DMSO) for 24 hours. After 24 hours, 10 μL of CCK-8 reagent was added to each well. The cells were incubated at 37°C for 2 hours, and the absorbance (OD) was measured at a wavelength of 450 nm using a microplate reader. The cell viability was calculated according to the following formula:

[0083]

[0084] Among them, the experimental group was treated with different concentrations of Yunnan Polygonatum flavonoid extract; the blank group was a group that only added CCK8 reagent without cells; and the control group was a pure cell group that added CCK8 reagent without any drug treatment.

[0085] The results of the effects of different concentrations of Yunnan Polygonatum flavonoids extract (PKF) on the survival rate of HCT15 cells are as follows Figure 3 The results of the effects on HCT116 cell survival are shown in Figure 4 As shown. Figure 3 and Figure 4 It can be seen that PKF has a significant inhibitory effect on the proliferation of HCT116 cells and HCT15 cells in a dose-dependent manner.

[0086] 2.2 High isoflavonoids (HIF)

[0087] According to the method shown in "2.1", different concentrations of PKF were replaced with different concentrations of high isoflavone compounds (solvent is DMSO) to obtain the survival rate of HCT116 cells and HCT15 cells under different concentrations of HIF. The curve was drawn according to the cell survival rate at different concentrations, and then the data was fitted to finally calculate the IC of HIF on HCT116 cells and HCT15 cells. 50 value.

[0088] The results are as follows Figure 5 As shown: HIF has a significant inhibitory effect on the proliferation of HCT116 cells and HCT15 cells, especially the IC 50 The value is 4.6 μM, and the IC for HCT116 cells 50 The value is 6.7 μM.

[0089] The above experimental results showed that both PKF and HIF could significantly inhibit the proliferation activity of HCT116 cells and HCT15 cells, and the effect of HIF was significantly better than that of PKF.

[0090] 3. Western Blot

[0091] To evaluate the effects of Polygonatum yunnanensis flavonoid extract (PKF) and high isoflavonoid compounds (HIF) on the expression of apoptosis-related proteins in HCT116 and HCT15 cells, Western Blot analysis was performed as follows.

[0092] HCT116 and HCT15 cells were divided equally into three groups. After digestion with 0.25% trypsin, they were seeded into 6-well plates with six replicate wells per group. When the cell density reached 50%-60%, the following treatments were performed:

[0093] Group 1 (control group): Cells were not treated with any drugs. Total protein was extracted using RIPA lysis buffer, and protein concentration was determined using a BCA assay kit. After quantification, the protein was mixed with 5× loading buffer and boiled in a 100°C water bath for 10 minutes. Samples were subjected to SDS-PAGE electrophoresis and transferred to a membrane (current 200 mA, 90 minutes, on ice). The membrane was then blocked in PBS containing 5% nonfat dry milk for 1 hour. The membrane was washed three times with TBST (10 minutes each time) and incubated overnight at 4°C with specific antibodies (cleaved-Caspase-3, cleaved-Caspase-8, γ-H2AX, GAPDH). The membrane was washed three more times with TBST the following day and exposed to ECL developer.

[0094] Group 2 (PKF 50 μg / mL or HIF 2 μM): Cells were treated with 50 μg / mL PKF or 2 μM HIF (DMSO as solvent) for 24 hours and then treated as in Group 1.

[0095] Group 3 (PKF 100 μg / mL or HIF 4 μM): cells were treated with PKF at a concentration of 100 μg / mL or HIF at a concentration of 4 μM (DMSO as solvent) for 24 hours, and then treated with the same procedures as group 1.

[0096] Figure 6 and Figure 7 The results show the effects of different concentrations of PKF on the expression of Cleaved-Caspase-3 and Cleaved-Caspase-8 apoptosis proteins in HCT15 and HCT116 cells; Figure 8 and Figure 9 The results show the effects of different concentrations of PKF on the expression of γ-H2AX protein in HCT15 and HCT116 cells; Figure 10 and Figure 11The results show the effects of different concentrations of HIF on the expression of Cleaved-Caspase-3 and Cleaved-Caspase-8 apoptosis proteins in HCT15 and HCT116 cells; Figure 12 and Figure 13 The results show the effects of different concentrations of HIF on the expression of γ-H2AX protein in HCT15 and HCT116 cells. Figures 6 to 13 Results showed that compared with the control group, all concentrations of PKF and HIF significantly upregulated the expression levels of cleaved-Caspase-3, cleaved-Caspase-8, and the DNA damage marker protein γ-H2AX in human colorectal cancer cell lines. This suggests that both PKF and HIF induce DNA damage and promote apoptosis in human colorectal cancer cell lines. HIF was significantly more effective than PKF, achieving these effects at a lower drug dose.

[0097] Example 3: Detection experiment of subcutaneous tumor model of mice using PKF and HIF

[0098] To evaluate the inhibitory effects of Polygonatum yunnanensis flavonoid extract (PKF) and high isoflavonoid compounds (HIF) on colorectal cancer, a subcutaneous tumor-bearing mouse model of HCT116 cells was used. The specific experimental steps are as follows:

[0099] The HCT116 cells cultured in Example 2 were treated with 0.25% trypsin and inoculated subcutaneously in mice. Each mouse was injected with 1×10 6 HCT116 cells. SPF female C57BL / 6J mice were randomly divided into groups according to body weight, with n=5 per group:

[0100] Blank control group: The mice did not receive any drug intervention, and the tumor growth was continuously recorded.

[0101] Pentofluorouracil group (positive control group): When the subcutaneous tumor volume reached about 50 mm 3 At 4 hr, 5-fluorouracil (5-FU) 10 mg / kg was injected intraperitoneally daily, and the treatment was continued and the tumor growth was recorded until the end of the experiment.

[0102] PKF low-dose group (PKF 10 mg / kg): When the subcutaneous tumor volume reached about 50 mm 3 At 4 hr, PKF 10 mg / kg was injected intraperitoneally daily and the treatment was continued until the end of the experiment. The tumor growth was recorded.

[0103] PKF medium dose group (PKF 30mg / kg): When the subcutaneous tumor volume reached about 50mm 3At 4 hr, PKF was intraperitoneally injected at 30 mg / kg daily, and the treatment was continued and the tumor growth was recorded until the end of the experiment.

[0104] PKF high-dose group (PKF 90 mg / kg): When the subcutaneous tumor volume reached about 50 mm 3 At 4 hr, PKF was intraperitoneally injected at 90 mg / kg daily, and the treatment was continued and the tumor growth was recorded until the end of the experiment.

[0105] PKF+pentafluorouracil group (PKF 90mg / kg + 5-FU 10mg / kg): When the subcutaneous tumor volume reached about 50mm 3 At 4 hr, mice were intraperitoneally injected with PKF 90 mg / kg and 5-FU 10 mg / kg daily, and the treatment was continued and the tumor growth was recorded until the end of the experiment.

[0106] HIF group (40 mg / kg): When the subcutaneous tumor volume reached about 50 mm 3 At 4 hr, HIF 40 mg / kg was injected intraperitoneally daily, and the treatment was continued and the tumor growth was recorded until the end of the experiment.

[0107] HIF+pentafluorouracil group (HIF 40 mg / kg + 5-FU 10 mg / kg): When the subcutaneous tumor volume reached about 50 mm 3 At 4h, HIF 40mg / kg and 5-FU 10mg / kg were intraperitoneally injected daily, and the treatment was continued and the tumor growth was recorded until the end of the experiment.

[0108] The tumor growth of each PKF group was as follows Figures 14 to 16 As shown, Figure 14 The results of the changes in tumor volume over time in each group are shown in Figure 2. Figure 15 The solid images of tumors obtained after mice were killed on the last day of the experiment in each group. Figure 16 The figure shows the tumor weight of mice in each group on the last day of the experiment. Figures 14 to 16 The results show that PKF can significantly inhibit the growth of subcutaneous tumors induced by HCT116 cells in a dose-dependent manner, with the degree of tumor growth inhibition gradually increasing with increasing dose. Furthermore, the combination of PKF and 5-FU can also effectively inhibit tumor growth.

[0109] The tumor growth of each HIF group was as follows Figures 17 to 19 As shown, Figure 17 The results of the changes in tumor volume over time in each group are shown in Figure 2. Figure 18 The solid images of tumors obtained after mice were killed on the last day of the experiment in each group. Figure 19 The figure shows the tumor weight of mice in each group on the last day of the experiment. Figures 17 to 19 It can be seen that HIF can significantly inhibit the growth of subcutaneous tumors induced by HCT116 cells. In addition, the combination of HIF and 5-FU can exert a synergistic effect in inhibiting tumor growth.

[0110] The present application has been described in detail above with reference to the preferred embodiments. It should be understood that these specific embodiments are for illustrative purposes only and are not intended to limit the scope of protection of the present application. Without departing from the spirit and claims of the present application, those skilled in the art may make various equivalent substitutions, improvements or modifications to the technical contents thereof, which shall all be deemed to fall within the scope of protection of the present application.

Claims

1. A pharmaceutical composition for treating colorectal cancer, characterized in that: It consists of a compound shown in formula I or a salt thereof and 5-fluorouracil: Formula I, The mass ratio of the compound represented by formula I or its salt to 5-fluorouracil is (1-5):

1.

2. The pharmaceutical composition according to claim 1, wherein: The mass ratio of the compound represented by formula I or its salt to 5-fluorouracil is 4:

1.

3. Use of the compound represented by Formula I or its salt in combination with 5-fluorouracil in the preparation of a medicament for treating colorectal cancer: Formula I, The mass ratio of the compound represented by formula I or its salt to 5-fluorouracil is (1-5):

1.

4. The use according to claim 3, characterized in that: The mass ratio of the compound represented by formula I or its salt to 5-fluorouracil is 4:1.

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