A kind of anti-tumor combination drug and its application in the preparation of anti-cancer drug

An anti-tumor and drug technology, applied in the field of biomedicine, can solve the problems of limited curative effect, large toxic and side effects, etc.

Active Publication Date: 2021-03-09
SICHUAN JIUZHANG BIO TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, BCR-ABL inhibitors have problems such as high toxicity and side effects, which make their efficacy limited

Method used

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  • A kind of anti-tumor combination drug and its application in the preparation of anti-cancer drug
  • A kind of anti-tumor combination drug and its application in the preparation of anti-cancer drug
  • A kind of anti-tumor combination drug and its application in the preparation of anti-cancer drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1 MTT Determination of Proliferation Inhibition of Combination Drugs

[0031] 1.1 Test material

[0032] Test drugs: chlorogenic acid, imatinib, nilotinib, dasatinib, bosutinib, ponatinib.

[0033] Cell lines: chronic myelogenous leukemia cell line K562, human normal hematopoietic stem cell HSPC-1

[0034] 1.2 Test method

[0035] Inoculate 100 μl of cells in a 96-well culture plate under sterile conditions, and the number of inoculated cells is 5×l0 3 / hole. cells at 37°C, 5% CO 2 Incubate in the incubator separately, and the cells are divided into: blank control group, negative control group, single drug group, chlorogenic acid group and combined drug group, and the blank control group is not inoculated with cells. The total amount of culture solution and drug in each well was 200 μl, and three replicate wells were set up for each concentration, and an equal volume of culture solution was used instead of drug as a blank control. Continue to set 5% CO 2 ...

Embodiment 2

[0053] Example 2 Chlorogenic acid reverses the drug resistance of human leukemia cells to dasatinib in vitro

[0054] 2.1 Materials

[0055] Drugs under test: chlorogenic acid, dasatinib

[0056] Cell line: The chronic myeloid leukemia cell line K562 is a routinely cultured cell in the laboratory. It is passaged before use, and the cells in good growth state and in the logarithmic phase of growth are used for future use.

[0057] 2.2 Test method

[0058] 2.2.1 Cultivation of drug-resistant cell lines

[0059] K562 cell lines were exposed to Dasatinib 100nmol / L for 3 months, centrifuged, and Dasatinib-resistant K562 / NY cells were cultured, and the cells were observed every day, and the cells were passed 1 pass 3 passages in about 3 days to ensure cell viability .

[0060] 2.2.2 Detect the IC50 of dasatinib on cell lines and drug-resistant strains, and calculate the multiple of drug resistance

[0061] Take K562 cells in the logarithmic growth phase and drug-resistant cell ...

Embodiment 3

[0078] Example 3 Synergism and attenuation of anti-tumor effect of drug combination of chlorogenic acid and BCR-ABL small molecule inhibitor in vivo

[0079] 3.1 Materials and Instruments

[0080] Drugs under test: chlorogenic acid; imatinib, nilotinib, dasatinib, bosutinib, ponatinib

[0081] Tested cell line: chronic myelogenous leukemia cell line K562

[0082] Test animals: BABL / c-nu mice, 18-22g, female

[0083] 3.2 Test method

[0084] 3.2.1 Establishment of experimental animal tumor models

[0085] Collect the cells in the logarithmic growth phase, centrifuge at 1000rpm for 5min, wash the cell sediment twice with PBS, and adjust the cell concentration to 1x10 with serum-free medium after counting 7 / m1, sent to the animal room under sterile conditions. Under sterile experimental conditions, mice were subcutaneously injected with 1×10 7 / m1 cells, 0.1ml each, obvious skin mounds appeared in the injection site, and rice grain nodules appeared in the left armpit of th...

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Abstract

The invention discloses an anti-tumor combined drug and its application in the preparation of anti-cancer drugs. The combined drug includes a first preparation and a second preparation, and the anti-tumor combined drug is the first preparation in parts by weight. 10-40 parts of the preparation, 0.1-10 parts of the second preparation. The invention also discloses the use of chlorogenic acid in the preparation of inhibitors of toxic and side effects of anticancer drugs, and the anticancer drugs are BCR‑ABL small molecule inhibitors. The technical scheme of the present invention can improve the targeting of BCR-ABL small molecule inhibitors in chronic myeloid leukemia, reduce its toxic and side effects, and reverse the drug resistance of BCR-ABL small molecule inhibitors.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to an anti-tumor combined drug and its use in preparing anti-cancer drugs. Background technique [0002] Chlorogenic acid is a phenylpropanoid synthesized by the intermediate product of the pentose phosphate pathway during the process of plant aerobic respiration. Its extraction and synthesis technology is mature, and chlorogenic acid has been developed and applied in many fields such as food, health care products, cosmetics and pharmaceuticals. Current research results show that chlorogenic acid has cardiovascular protection, anti-oxidation, anti-ultraviolet and anti-radiation, anti-cancer, antibacterial, anti-viral and immune regulation effects. [0003] Leukemia is a common hematopoietic malignancy that seriously threatens human health. In my country, the annual incidence of leukemia is 300,000-400,000, ranking seventh among malignant tumors in adults and first among malignant tumors...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/06A61K31/216A61K31/506A61K31/5025A61K31/496A61P35/00A61P35/02
CPCA61K31/216A61K31/496A61K31/5025A61K31/506A61K45/06A61K2300/00
Inventor 张洁黄望杨华蓉张梦甜
Owner SICHUAN JIUZHANG BIO TECH CO LTD
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