CN-121971442-A - Berberine and glabridin combined use, preparation of self-assembled preparation and application of self-assembled preparation in colorectal cancer resistance

Abstract

The invention belongs to the field of biology, and in particular relates to a berberine and glabridin combined use and application of self-assembled preparations thereof in anti-colorectal cancer treatment. According to the invention, firstly, a large amount of screening discovers that the combination of berberine hydrochloride and glabridin can obviously inhibit proliferation of colorectal cancer cells, particularly has obvious inhibition effect on colorectal cancer infected by clostridium nucleatum and has a synergistic effect, and secondly, the berberine hydrochloride and glabridin molecules form a nanoparticle preparation through a self-assembly process, the nanoparticles do not need exogenous carriers and have uniform particle size, the anti-colorectal cancer effect is superior to that of a composition of berberine and glabridin free molecules under the same dosage, the solubility and the delivery efficiency of medicines can be improved, and a new candidate strategy is provided for clinical treatment.

Inventors

• CHEN PENG
• LI YONGYUAN
• ZHOU ZHONGKUN
• MA YUNHAO
• Zhang Baizhuo

Assignees

• 兰州大学

Dates

Publication Date

20260505

Application Date

20260313

Claims (10)

1. 1. A pharmaceutical composition for the treatment of colorectal cancer, characterized in that the active ingredient of the pharmaceutical composition consists of berberine or a pharmaceutically acceptable salt thereof and glabridin or a pharmaceutically acceptable salt thereof.
2. 2. The pharmaceutical composition of claim 1, wherein the molar ratio of berberine to glabridin is from 1:1 to 1:5.
3. 3. The pharmaceutical composition of claim 2, wherein, the pharmaceutical composition also comprises pharmaceutically acceptable auxiliary materials.
4. 4. A self-assembled nanoparticle formulation, wherein the self-assembled nanoparticle is self-assembled from berberine or a pharmaceutically acceptable salt thereof and glabridin or a pharmaceutically acceptable salt thereof.
5. 5. The self-assembled nanoparticle formulation of claim 4, wherein the self-assembled nanoparticle is self-assembled from berberine hydrochloride and glabridin.
6. 6. The self-assembled nanoparticle formulation of claim 5, wherein the molar ratio of berberine to glabridin is from 3:1 to 1:3.
7. 7. The self-assembled nanoparticle formulation of claim 6, wherein the method of preparing the self-assembled nanoparticle formulation comprises the steps of: S1, weighing berberine hydrochloride and glabridin according to a molar ratio, and dissolving in methanol; S2, slowly dripping the methanol mixed solution into deionized water at a final concentration; s3, rapidly stirring for 0.5-1 h at a constant temperature of 60-90 ℃; S4, after the solution is cooled, performing ultrasonic treatment for 10 minutes under 50-100W; S5, obtaining self-assembled nano particles after dialysis for 6 hours.
8. 8. The self-assembled nanoparticle formulation of claim 7, wherein the berberine hydrochloride and glabridin are at a concentration of 0.1-1 mM and 0.1-1 mM, respectively.
9. 9. Use of a pharmaceutical composition according to any one of claims 1-3 or a self-assembled nanoparticle formulation according to any one of claims 4-7 for the preparation of a medicament for the treatment of colorectal cancer.
10. 10. The use according to claim 9, wherein the colorectal cancer is colorectal cancer combined with a fusobacterium nucleatum infection.

Description

Berberine and glabridin combined use, preparation of self-assembled preparation and application of self-assembled preparation in colorectal cancer resistance Technical Field The invention belongs to the field of biological medicine, and particularly discloses a berberine and glabridin combined use, preparation of a self-assembled preparation and application thereof in colorectal cancer resistance. Background Colorectal cancer is a global high-grade malignancy whose occurrence and development are closely related to dysbacteriosis in the intestinal tract. Among them, the specific enrichment of F.nucleatum in colorectal cancer tissues and its carcinomatous effect have been widely demonstrated. The bacteria can promote tumor progression by activating inflammation, promoting proliferation, and remodelling host cell metabolism. At present, the clinical chemotherapeutic drugs have great toxic and side effects and are easy to generate drug resistance, so that the development of a novel treatment strategy with high efficiency and low toxicity is quite important. Berberine and glabridin are two natural products with various biological activities, but the problems of poor water solubility and low bioavailability limit the clinical application of the berberine and glabridin. In order to overcome the problems, the invention provides a combined drug and preparation scheme which has high efficiency and low toxicity, can simultaneously exert synergistic curative effects and overcome the bioavailability problem. Disclosure of Invention Aiming at the technical problems, the invention provides application of berberine and glabridin in preparing medicines for resisting colorectal cancer, in particular application in preparing medicines for treating colorectal cancer related to Fusobacterium nucleatum infection. The method specifically comprises the following steps: in a first aspect, the present invention provides a pharmaceutical composition for the treatment of colorectal cancer, the active ingredients of which consist of berberine or a pharmaceutically acceptable salt thereof and glabridin or a pharmaceutically acceptable salt thereof. Preferably, the molar ratio of berberine to glabridin is 1:1 to 1:5. Preferably, the molar ratio of berberine to glabridin is 1:3. Preferably, the berberine or a pharmaceutically acceptable salt thereof is administered at a concentration ranging from 10 μm to 20 μm, and the glabridin or a pharmaceutically acceptable salt thereof is administered at a concentration ranging from 30 μm to 50 μm. Preferably, the pharmaceutical composition further comprises pharmaceutically acceptable excipients. In a second aspect, the invention provides the use of a pharmaceutical composition according to the first aspect above for the manufacture of a medicament for the treatment of colorectal cancer. Preferably, the colorectal cancer is colorectal cancer combined with a fusobacterium nucleatum infection. In a third aspect, the present invention provides a self-assembled nanoparticle formulation, the self-assembled nanoparticle being obtained from self-assembly of berberine or a pharmaceutically acceptable salt thereof and glabridin or a pharmaceutically acceptable salt thereof. Preferably, the self-assembled nanoparticle is obtained by self-assembly of berberine hydrochloride and glabridin. Preferably, the molar ratio of berberine to glabridin is 3:1 to 1:3. Preferably, the molar ratio of berberine to glabridin is 1:1. Preferably, the preparation method of the self-assembled nanoparticle preparation comprises the following steps: S1, weighing berberine hydrochloride and glabridin according to a molar ratio, and dissolving in methanol; S2, slowly dripping the methanol mixed solution into deionized water at a final concentration; s3, rapidly stirring for 0.5-1 h at a constant temperature of 60-90 ℃; S4, after the solution is cooled, performing ultrasonic treatment for 10 minutes under 50-100W; S5, obtaining self-assembled nano particles after dialysis for 6 hours. Preferably, the concentrations of berberine hydrochloride and glabridin are 0.1-1 mM and 0.1-1 mM respectively. Preferably, the concentrations of berberine hydrochloride and glabridin are 0.5 mM and 0.5 mM, respectively. Preferably, the S3 is stirred at a constant temperature and a rapid speed of 30 minutes under the condition of 65 ℃ and the rotating speed is 600-1000 rpm. Preferably, the step S4 is that after the solution is cooled, the solution is sonicated for 10 minutes at 50W. In a fourth aspect, the present invention provides the use of a self-assembled nanoparticle formulation as described in the second aspect above in the manufacture of a medicament for the treatment of colorectal cancer. Preferably, the colorectal cancer is colorectal cancer combined with a fusobacterium nucleatum infection. The invention has the beneficial effects that the combined drug combination of berberine and glabridin can effectively inhibit proliferation of colorectal