Application of 7-hydroxycoumarin and structural analogue or derivative thereof in preparation of medicine for treating intestinal cancer
By using pharmaceutical formulations prepared from 7-hydroxycoumarin and its derivatives, the problems of high incidence and high cost of colorectal cancer treatment have been solved, and significant tumor inhibition effects have been achieved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-12
- Publication Date
- 2026-04-14
AI Technical Summary
Colorectal cancer has a high incidence and mortality rate, immunotherapy is costly, and chemotherapy is not very effective.
7-hydroxycoumarin and its derivatives are used as anti-colon cancer drugs, and appropriate drug formulations are prepared for the treatment of colon cancer.
It significantly inhibited tumor growth in the CT-26 colon cancer cell model, demonstrating a significant therapeutic effect, with a relative tumor proliferation rate of less than 40% and no significant change in body weight.
Smart Images
Figure FT_1 
Figure FT_2 
Figure SMS_1
Abstract
Description
Technical Field
[0001] This invention relates to the field of colorectal cancer treatment and prevention technology, specifically to the application of structural analogs based on 7-hydroxycoumarin and their derivatives in the field of colorectal cancer treatment or prevention technology. Background Technology
[0002] Colorectal cancer is one of the most common malignant tumors, ranking among the top three in both incidence and mortality. Its pathogenesis is a multifactorial, multi-step, and progressive process. In recent years, the emergence of targeted therapies and immunotherapies such as bevacizumab, cetuximab, and pembrolizumab has significantly improved the quality of life and 5-year survival rate of colorectal cancer patients. However, due to its high cost, chemotherapy remains one of the main treatment methods for colorectal cancer.
[0003] Coumarins are a class of aromatic natural products with a benzo-α-pyranone core. They are lactone compounds widely found in nature, first isolated from coumarins, and have been proven to have extensive medicinal value. Most coumarins have an oxygen-containing functional group at C-7; 7-hydroxycoumarin can be considered the parent compound of the coumarin class. Their structures are as follows: Summary of the Invention
[0004] To address the problems of high incidence and mortality rates of colorectal cancer, high costs of immunotherapy, and unsatisfactory efficacy of chemotherapy, this invention provides a method for treating or preventing colorectal cancer based on structural analogs and derivatives of 7-hydroxycoumarin (Umbelliferone).
[0005] The experimental results of this invention show that, based on tumor growth curves and relative tumor proliferation rate (T / C) data, 7-hydroxycoumarin can significantly inhibit tumor growth in a BALB / c mouse subcutaneous tumor model constructed from CT-26 colon cancer cells, demonstrating a very significant therapeutic effect. This indicates that 7-hydroxycoumarin has anti-colon cancer activity and can be used to prepare drugs for treating colon cancer. Detailed Implementation
[0007] The present invention will be further described below through specific embodiments.
[0008] The present invention will be further described below. The embodiments given below are for illustrative purposes only and are not intended to limit the scope of the present invention. Any modifications or substitutions made based on the present invention shall fall within the protection scope of the present invention.
[0009] Example 1
[0010] 7-Hydroxycoumarin (CAS No.: 93-35-6) was purchased from Sigma-Aldrich, USA, catalog number: H24003-25G. Animals were purchased from SPAFE (Beijing) Biotechnology Co., Ltd., laboratory animal quality certificate number: 110324241104586385.
[0011] Cell culture: CT-26 cells were removed from the liquid nitrogen container, thawed at 37°C, washed with 10 ml of PBS, centrifuged at 1000 rpm, and the supernatant was discarded. The cells were resuspended in 2 ml of 1640 medium and gently agitated in a culture dish. The culture dish was pre-filled with 6 ml of 1640 medium containing 10% fetal bovine serum. Cell growth was observed and recorded daily, with the medium changed every 48 hours and passaged every 72 hours. After sufficient cell number was reached, a suspension of ten million cells per milliliter was prepared for later use.
[0012] Animal Model Preparation: Establishment of a BALB / c mouse subcutaneous tumor model: Before the experiment, mice were acclimatized for 7 days. Cultured CT-26 cells were counted and prepared into a suspension of 10 million cells per milliliter. 0.1 ml of the mixed cell suspension was subcutaneously injected into the flank of each mouse. After 5 days of growth at the injection site, when the tumor cells reached a volume of 100 cubic millimeters, mice with tumors that were nearly elliptical in shape and without rupture were selected and grouped. Grouping followed a randomization principle.
[0013] Animal grouping: Animals were randomly divided into three groups: a model control group (Control), a positive drug treatment group (Paclitaxel), and a 7-hydroxycoumarin treatment group (Umbelliferone). The positive drug treatment group received a tail vein injection at a dose of 10 mg / kg, with a single administration volume of 50 μL per 10 g body weight, twice weekly. The 7-hydroxycoumarin treatment group received a dose of 30 mg / kg, with a single administration volume of 100 μL per 10 g body weight, once daily.
[0014] Drug preparation: Weigh 18 mg of paclitaxel powder and dissolve it in 900 μL of DMSO to prepare a stock solution with a concentration of 20 mg / mL. Complete dissolution is required before proceeding to the next step. Use ultrasound to aid dissolution. Take 900 μL of the stock solution, add 3600 μL of PEG300, mix thoroughly until clear, add 450 μL of Tween 80, mix thoroughly until clear, add 4050 μL of physiological saline, mix well, and dispense into 6 portions, 1.5 ml each. Store at -80°C, thawing one portion before each use. Weigh 30 mg of 7-hydroxycoumarin and dissolve it in 1 ml of DMSO. After complete dissolution, add 9 ml of physiological saline. Prepare the solution and dispense into portions for use.
[0015] Tumor volume measurement: The mouse was restrained with the left hand, and the long and short diameters of the tumor were measured with calipers in the right hand. The formula for calculating the tumor volume is: 1 / 2 × L × W × W, where L is the long diameter of the tumor and W is the short diameter of the tumor.
[0016] Experimental results: such as Figure 1 As shown, all mice maintained normal body weight during the treatment period;
[0017] like Figure 2 As shown, compared with the model group, the tumor growth rate of both the positive control group and the 7-hydroxycoumarin treatment group was significantly reduced, with the 7-hydroxycoumarin treatment group showing the most significant slowdown in tumor growth rate. The relative tumor proliferation rate (T / C%) of the positive control group was calculated to be 30.13%; the relative tumor proliferation rate (T / C%) of the 7-hydroxycoumarin treatment group was 13.76%, P<0.05. The relative tumor proliferation rate (T / C%) of both the positive control group and the 7-hydroxycoumarin treatment group was <40%, indicating a definite anti-cancer effect.
[0018] Figure 1 Mouse weight gain curve during treatment:
[0019] Figure 2 Tumor growth curves in mice during treatment.
Claims
1. Application of 7-hydroxycoumarin in the preparation of drugs for treating colorectal cancer. Application of 2,7-hydroxycoumarin structural analogs or derivatives thereof in the preparation of drugs for treating colorectal cancer.
3. A novel drug for treating colon cancer, characterized in that, The active ingredient of the drug is one or more structural analogs and derivatives of 7-hydroxycoumarin.
4. The use of the component according to any one of claims 1 to 3 in the preparation of a combined treatment method for colorectal cancer.
5. The use of the ingredient according to any one of claims 1 to 3 in the treatment of other tumors that have the same therapeutic target as colon cancer.
6. Based on the pathogenesis of tumors and the results of 7-hydroxycoumarin inhibiting colon cancer growth as disclosed in this invention, this patent claims the use of 7-hydroxycoumarin and its structural analogs or derivatives in the preparation of drugs or foods for the prevention of colon cancer.