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Pharmaceutical composition for treating liver cancer and application thereof

A technology for treating liver cancer and drugs, which is applied in drug combinations, medical preparations containing active ingredients, anti-tumor drugs, etc., to achieve the effects of reducing treatment costs, affirming curative effects, and good curative effects

Inactive Publication Date: 2020-04-14
THE SECOND AFFILIATED HOSPITAL OF GUANGZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Chinese patent document CN105879049A discloses a clathrate formed with regorafenib as the active ingredient of the drug and β-cyclodextrin as the host molecule (host) at a molar ratio of 1:1. The bioavailability is greatly improved, and the preparation The method is simple and easy, the conditions are mild, and it is suitable for industrial production. The prepared clathrate has excellent pertinence for colon cancer targeted drug delivery, and has good safety. It can effectively overcome the poor water solubility and bioavailability of regorafenib itself. Disadvantages of low degree
But there is no report about a pharmaceutical composition for the treatment of liver cancer of the present invention and its combined application

Method used

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  • Pharmaceutical composition for treating liver cancer and application thereof
  • Pharmaceutical composition for treating liver cancer and application thereof
  • Pharmaceutical composition for treating liver cancer and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] 1. Experimental purpose: select liver cancer cell lines SMMC-7721, Hep3B and SK-Hep1 to detect the inhibitory effect of regorafenib and BMS-1 ​​alone on liver cancer cells.

[0039] 2. Spread the liver cancer cell lines SMMC-7721, Hep3B and SK-Hep1 on a 96-well plate, and add different concentrations of regorafenib (0.75, 1.5, 3, 6, 12, 24, 48 μM) and BMS after 24 hours. -1 (3.25, 7.5, 15, 30, 60, 120, 240μM), after 36 hours of culture, the CCK-8 test method was used to detect the effects of regorafenib and BMS-1 ​​on the activity of three liver cancer cell lines. According to OD Draw the growth inhibition rate curve and calculate the IC of the two drugs corresponding to the three liver cancer cell lines 50 .

[0040] 3. Experimental method: CCK8 detects the activity of drugs on cells

[0041] ①Select the liver cancer cells that are in good condition and proliferate and grow to a density of 70%-85%, digest with trypsin, centrifuge horizontally, resuspend them in fresh medium,...

Embodiment 2

[0048] 1. Experimental purpose: select liver cancer cell lines SMMC-7721, Hep3B and SK-Hep1 to detect the inhibitory effect of regorafenib combined with BMS-1 ​​on liver cancer cells.

[0049] 2. Spread the liver cancer cell lines SMMC-7721, Hep3B and SK-Hep1 on a 96-well plate, add different concentrations of regorafenib (2, 4, 6μM) and BMS-1 ​​(30, 40μM) after 24h, After 36 hours of culture, the CCK-8 experimental method was used to detect the effects of regorafenib and BMS-1 ​​combined treatment and single treatment on the viability of three liver cancer cells.

[0050] 3. Experimental method: CCK8 detects the activity of drugs on cells

[0051] ①Select the liver cancer cells that are in good condition and proliferate and grow to a density of 70%-85%, digest with trypsin, centrifuge horizontally, resuspend them in fresh medium, and use a cytometer to count 5×10^3 / well in 96 Seed uniformly in the well plate, set 4 duplicate wells / group, and place in the 37°C incubator overnight.

...

Embodiment 3

[0058] 1. Experimental purpose: select liver cancer cell lines SMMC-7721, Hep3B and SK-Hep1 to detect the proliferation inhibitory effect of regorafenib combined with BMS-1 ​​on liver cancer cells.

[0059] 2. EdU staining was used to detect the staining of cells in the S phase of the interphase of cell division after 36 hours of treatment of liver cancer cells in different treatment groups.

[0060] 3. Experimental method: EdU staining to detect cell proliferation experiment

[0061] According to the staining method of EdU kit (purchased from Guangzhou Ruibo Biotechnology Co., Ltd., article number: C10310-1), the cells treated with different drugs were stained with EdU, and then the proliferation of the cells was observed.

[0062] ① Select liver cancer cells that are in good condition and proliferate and grow to a density of 70%-85%, digest with trypsin, centrifuge horizontally, and resuspend them in fresh medium, and use a cytometer to count 1×10^4 / well in 96 Seed uniformly in the ...

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Abstract

The invention discloses an application of combined use of regorafenib and a PD-1 / PD-L1 inhibitor in preparation of a medicine for treating liver cancer. The pharmaceutical composition (regorafenib andthe PD-1 / PD-L1 inhibitor) provided by the invention can generate a synergistic anti-liver cancer effect; according to the scheme of combined administration of the two, the sensitivity of liver cancercells to the regorafenib can be improved, the inhibition effect on the liver cancer cells is improved, the dosage of the regorafenib can be reduced, the treatment cost of each liver cancer patient isdirectly reduced, and more liver cancer patients are benefited; the pharmaceutical composition is low in price, high in safety and affirmative in curative effect; the pharmaceutical composition disclosed by the invention is convenient to produce, convenient for large-scale production, good in curative effect and low in cost, and is also beneficial to social public interests.

Description

Technical field [0001] The present invention relates to the technical field of liver cancer treatment, in particular to a drug combination for the treatment of liver cancer and its application, in particular to the application of regorafenib combined with PD-1 / PD-L1 inhibitor BMS-1 ​​in the preparation of drugs for the treatment of liver cancer . Background technique [0002] Primary hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. It develops insidiously and rapidly. According to the global cancer statistics in 2018, the incidence of liver cancer ranks 6th among malignant tumors, and the mortality rate ranks among malignant tumors. No. 4 tumor-related deaths [1] . my country is an area with a high incidence of liver cancer. The latest data show that in 2015, the incidence of liver cancer in my country ranked 4th among tumor-related diseases, and the mortality rate ranked 3rd among malignant tumors. Both the incidence and mortality exceeded more th...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K31/44A61K31/445A61P1/16A61P35/00
CPCA61K31/44A61K31/445A61K45/06A61P1/16A61P35/00A61K2300/00
Inventor 杨辉王坤元余柑祥徐扬志古诚鑫林嘉恩王芝蕾
Owner THE SECOND AFFILIATED HOSPITAL OF GUANGZHOU MEDICAL UNIV
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