GlcNAc suppository for preventing colorectal cancer and preparation method thereof

Abstract

The invention discloses a GlcNAc suppository for preventing colorectal cancer and a preparation method of the GlcNAc suppository, and belongs to the technical field of medicines. The GlcNAc suppository can obviously inhibit and reduce the sizes of colorectal cancer tumors and polyps, and the prevention and treatment effect of the GlcNAc suppository is better than that of a galactose suppository; meanwhile, the suppository is used for administration, so that the medicine can directly act on tumors, and the bioavailability is high. Moreover, compared with other formula suppositories for colorectal cancer, the GlcNAc used in the suppository disclosed by the invention is good in safety as glucosamine, and experiments prove that the GlcNAc basically has no adverse reaction after being used for a long time, is higher in safety and has less influence on the living quality of patients with colorectal cancer.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and particularly relates to a GlcNAc suppository for preventing colorectal cancer and a preparation method thereof. Background Art

[0002] Colorectal cancer is a common malignant tumor of the gastrointestinal tract. Early symptoms are subtle, but as the tumor grows, symptoms develop, including changes in bowel habits, blood in the stool, diarrhea, alternating diarrhea and constipation, and localized abdominal pain. In the late stages, systemic symptoms such as anemia and weight loss appear. Currently, colorectal cancer prevention methods include the use of indomethacin suppositories combined with endoscopic high-frequency electrocautery for the treatment of colorectal adenomatous polyps. Clinical studies of this technique have demonstrated that endoscopic high-frequency electrocautery followed by indomethacin suppositories can reduce the incidence of colorectal cancer, the incidence of mid- to late-stage colorectal cancer, and mortality. However, this technique often has side effects, including gastrointestinal discomfort, central nervous system reactions, and skin reactions, and it does not directly target the tumor.

[0003] In addition, other suppositories are used to prevent colorectal cancer recurrence. For example, a multicenter randomized controlled trial evaluated the feasibility and recurrence prevention effects of Tegafur suppositories after preoperative intravenous and oral fluoropyrimidine administration in patients with resectable stage II or III colorectal cancer. The trial found that Tegafur suppositories significantly improved survival in patients with colorectal cancer. However, the following disadvantages exist: 1. Irritation and adverse reactions: Tegafur suppositories are somewhat irritating and may have adverse effects on the patient's body. After using Tegafur suppositories, patients may experience discomfort such as itching, redness, swelling, and pain around the anus. Furthermore, long-term use may cause gastrointestinal reactions such as nausea and vomiting, and in severe cases, may even lead to serious conditions such as bone marrow suppression and leukopenia. 2. Hepatotoxicity: Tegafur suppositories are metabolized by the liver and excreted by the kidneys, and long-term use can damage liver and kidney function. This side effect increases the patient's health risk, especially when used concurrently with other drugs that may cause hepatotoxicity and renal toxicity. 3. Peripheral neuropathy: Long-term use of tegafur suppositories may also cause peripheral neuropathy, manifesting as numbness and tingling in the hands and feet. This not only affects the patient's quality of life but may also negatively impact treatment.

[0004] In addition, the prior art “Streptococcus thermophilus inhibits colorectal tumorigenesis through secreting β-galactosidase” discloses that galactose can be used to prevent and treat colorectal cancer. However, the present invention finds that the preventive and therapeutic effect of N-acetylglucosamine is better than that of galactose. Summary of the Invention

[0005] Technical issues

[0006] Currently, some treatments for preventing and treating colorectal cancer have disadvantages such as adverse reactions and weak prevention and treatment effects. Therefore, it is necessary to develop a method for preventing colorectal cancer that has good effects, excellent safety, and few adverse reactions when taken for a long time.

[0007] Technical content

[0008] In order to solve the above problems, the present invention provides a compound for use in preparing a drug for preventing and / or treating colorectal cancer. The structural formula of the compound is shown in Formula I below:

[0009]

[0010] wherein R1 is -CH2-, -CH2-CH2- or -CH2-CH2-CH2-, and R2 is -CH3, -CH2-CH3 or -CH2-CH2-CH3.

[0011] Furthermore, in the formula, R1 is -CH2- or -CH2-CH2-.

[0012] Furthermore, in the formula, R2 is -CH3 or -CH2-CH3.

[0013] Specifically, optionally, R1 in the formula is -CH2-.

[0014] Specifically, optionally, R2 in the formula is -CH3.

[0015] Furthermore, the drug is administered through the anus.

[0016] Furthermore, the medicine includes suppositories, gels, ointments or enemas.

[0017] The present invention also provides the use of N-acetylglucosamine in preparing drugs for preventing and / or treating colorectal cancer.

[0018] Furthermore, the structural formula of the N-acetylglucosamine is shown in Formula II below:

[0019]

[0020] Furthermore, the drug is administered through the anus.

[0021] Furthermore, the medicine includes suppositories, gels, ointments or enemas.

[0022] The present invention also provides a suppository for preventing and / or treating colorectal cancer, wherein the preparation method of the suppository comprises:

[0023] Melt the semi-synthetic fatty acid glyceride, then add Tween 80 and stir evenly to obtain a matrix solution, pour the matrix solution into a mold and place a rod-shaped object to form a hollow suppository after the matrix solution cools;

[0024] Prepare N-acetylglucosamine solution, pour it into the hollow suppository shell, then pour in the matrix solution to seal the shell, and take it out after cooling to obtain a suppository for preventing and / or treating colorectal cancer.

[0025] In one embodiment of the present invention, the added amount of Tween 80 is 2-8 wt% of the mass of the semi-synthetic fatty acid glyceride.

[0026] In one embodiment of the present invention, the concentration of N-acetylglucosamine in the N-acetylglucosamine solution is 1 to 1000 mg / mL.

[0027] In one embodiment of the present invention, the solvent in the N-acetylglucosamine solution is water.

[0028] In one embodiment of the present invention, the amount of N-acetylglucosamine solution added is 1 to 1000 μL.

[0029] Beneficial effects

[0030] 1. Good inhibitory effect: The GlcNAc suppository of the present invention can significantly inhibit and reduce the size of colorectal cancer tumors and polyps, and its preventive and therapeutic effect is better than that of galactose suppositories. At the same time, administration via suppository allows the drug to act directly on the tumor, with high bioavailability.

[0031] 2. High safety: Compared with colorectal cancer suppositories, the GlcNAc used in the present invention is a kind of glucosamine with good safety. Experiments have shown that it has basically no adverse reactions when used, is safer, and has less impact on the quality of life of colorectal cancer patients. DETAILED DESCRIPTION

[0032] Source of raw materials

[0033] N-acetylglucosamine (GlcNAc) was purchased from Shanghai MacLean Biochemical Technology Co., Ltd., and its chemical formula is C8H 15 NO6, with a purity of 98%, has the following structure:

[0034]

[0035] Galactose was purchased from Shanghai MacLean Biochemical Technology Co., Ltd., and its chemical formula is C6H 12 O6, purity 98%; semi-synthetic fatty acid glycerides were purchased from Shanghai Zhouyuan Biotechnology Co., Ltd.

[0036] Example 1: Preparation of suppositories

[0037] Semi-synthetic fatty acid glyceride was melted in a 60°C water bath, and then 4 wt% Tween 80 relative to the semi-synthetic fatty acid glyceride was added and stirred to obtain a matrix solution. The matrix solution was poured into a 0.6 g bullet-shaped plug mold (do not fill it to the brim; pour 0.5 g). After it was slightly cooled, a glycerol-coated plastic rod was vertically inserted into the matrix to secure it. After the matrix cooled, the plastic rod was removed to obtain a hollow plug shell.

[0038] Then, 50 μL of drug solution (containing 15 mg GlcNAc or 15 mg Galactose, respectively) with water as the dispersion medium was injected, and finally the matrix solution was poured in to seal the tail. After cooling, the mold was opened to obtain GlcNAc suppositories and Galactose suppositories.

[0039] Example 2

[0040] 1. Mouse Experiment

[0041] Data related to the number of colon tumors, colon tumor volume, and number of small intestinal polyps in mice obtained using suppositories of two different components (GlcNAc and Galactose) at different doses.

[0042] The experiment used C57BL / 6J-APCMin / + mice, with dosing frequency of every two days at a dose of 0.05 mL per mouse per day, i.e., one suppository per mouse per day. The amount of GlcNAc or Galactose in the suppository was calculated based on the mouse's body weight and the different dosages and adjusted according to the preparation steps in Example 1. The mice were fasted one day before dosing. The prepared GlcNAc and Galactose suppositories were administered by inserting them into the anus. After 42 days, the mice were sacrificed and autopsied.

[0043] The number of colon tumors and small intestinal polyps was determined by post-mortem counting. Colon tumor volume was calculated by summing the length and width of each tumor after dissection using the formula (longest diameter × width²) / 2. Tumor volume was calculated by summing the volumes of each tumor. The results are shown in Tables 1-15 below.

[0044] (1) Number of colon tumors

[0045] Table 1 Number of colon tumors using two suppositories with different compositions at a dose of 125 mg / kg

[0046]

[0047] Table 2 Number of colon tumors using two suppositories with different compositions at a dose of 250 mg / kg

[0048]

[0049] Table 3 Number of colon tumors using two suppositories with different compositions at a dose of 500 mg / kg

[0050]

[0051]

[0052] Table 4 Number of colon tumors using two suppositories with different compositions at a dose of 750 mg / kg

[0053]

[0054] Table 5 Number of colon tumors using two suppositories with different compositions at a dose of 1000 mg / kg

[0055]

[0056] (2) Colon tumor volume

[0057] Table 6 Colon tumor volume / mm using two suppositories with different compositions at a dose of 125 mg / kg 3

[0058]

[0059] Table 7 Colon tumor volume / mm using two suppositories with different compositions at a dose of 250 mg / kg 3

[0060]

[0061] Table 8 Colon tumor volume / mm using two suppositories with different compositions at a dose of 500 mg / kg 3

[0062]

[0063] Table 9 Colon tumor volume / mm using two suppositories with different compositions at a dose of 750 mg / kg 3

[0064]

[0065] Table 10 Colon tumor volume / mm using two suppositories with different compositions at a dose of 1000 mg / kg 3

[0066]

[0067]

[0068] (3) Number of small intestinal polyps

[0069] Table 11 Number of small intestinal polyps using two suppositories with different compositions at a dose of 125 mg / kg

[0070]

[0071] Table 12 Number of small intestinal polyps using two suppositories with different compositions at a dose of 250 mg / kg

[0072]

[0073] Table 13 Number of small intestinal polyps using two suppositories with different compositions at a dose of 500 mg / kg

[0074]

[0075] Table 14 Number of small intestinal polyps using two suppositories with different compositions at a dose of 750 mg / kg

[0076]

[0077] Table 15 Number of small intestinal polyps using two suppositories with different compositions at a dose of 1000 mg / kg

[0078]

[0079] As can be seen from Tables 1 to 15 above, GlcNAc suppositories at doses ranging from 125 to 1000 mg / kg have a good inhibitory effect on colon tumors, and the inhibitory effect increases with increasing dose. The best inhibitory effect is achieved at a dose of 1000 mg / kg.

[0080] 2. Human Experiments

[0081] The experiment was conducted in 12 patients with colorectal cancer. Four patients received blank suppositories as controls. Of the remaining eight patients, four received GlcNAc suppositories at a dose of 125 mg / kg, and four received GlcNAc suppositories at a dose of 1000 mg / kg. The volume of the drug solution in the suppositories and the amount of GlcNAc used were adjusted according to the preparation steps in Example 1 based on the patient's weight and the different doses. The number of suppositories used could also be adjusted based on actual conditions. CT scans were performed 60 days later to examine rectal tumor volume.

[0082] Patient tumor volume (cm 3 ) are compared as shown in Table 16 below:

[0083] Table 16

[0084]

[0085]

[0086] As shown in Table 16, both 125 and 1000 mg / kg doses of GlcNAc inhibited colon tumors, with the 1000 mg / kg dose generally showing greater inhibitory effects. Furthermore, no patients who used the GlcNAc suppositories exhibited any adverse reactions throughout the entire administration process, nor did they experience any adverse reactions within two weeks after the end of administration. This demonstrates that the GlcNAc suppositories of the present invention are human-friendly in inhibiting colon tumors, do not produce any negative effects, and have minimal impact on patients' lives.

[0087] The embodiments provided above are not intended to limit the scope of the present invention, nor are the steps described to limit their execution order. Any obvious improvements to the present invention made by those skilled in the art in combination with existing common knowledge shall fall within the scope of protection defined by the claims of the present invention.

Claims

1. Use of a compound in the preparation of a drug for preventing and / or treating colorectal cancer, characterized in that: The structural formula of the compound is shown in Formula I below: wherein R1 is -CH2-, -CH2-CH2- or -CH2-CH2-CH2-, and R2 is -CH3, -CH2-CH3 or -CH2-CH2-CH3.

2. The use according to claim 1, characterized in that Wherein R1 is -CH2- or -CH2-CH2-.

3. The use according to claim 1, characterized in that Wherein R2 is -CH3 or -CH2-CH3.

4. Use of N-acetylglucosamine in the preparation of a drug for preventing and / or treating colorectal cancer, characterized in that: The structural formula of the N-acetylglucosamine is shown in Formula II below:

5. The use according to claim 4, characterized in that The drug is administered through the anus.

6. The use according to claim 4, characterized in that The medication includes suppositories, gels, ointments or enemas.

7. A suppository for preventing and / or treating colorectal cancer, characterized in that: The preparation method of the suppository comprises: Melt the semi-synthetic fatty acid glyceride, then add Tween 80 and stir evenly to obtain a matrix solution, pour the matrix solution into a mold and place a rod-shaped object to form a hollow suppository after the matrix solution cools; Prepare N-acetylglucosamine solution, pour it into the hollow suppository shell, then pour in the matrix solution to seal the shell, and take it out after cooling to obtain a suppository for preventing and / or treating colorectal cancer.

8. The suppository according to claim 7, characterized in that The added amount of Tween 80 is 2-8 wt% of the mass of the semi-synthetic fatty acid glyceride.

9. The suppository according to claim 7, characterized in that The concentration of N-acetylglucosamine in the N-acetylglucosamine solution is 1 to 1000 mg / mL.

10. The suppository according to claim 7, characterized in that The amount of N-acetylglucosamine solution added is 1 to 1000 μL.

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