Anti-tumor combination medicament

An anti-tumor and drug-based technology, applied in the field of medicine, can solve the problems that there are no reports on the combined use of disulfiram and copper in the treatment of tumors

Inactive Publication Date: 2012-02-22
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] After searching the literature, there is no report on the combined use of disulfiram and copper in the treatment of tumors

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Cytotoxicity of combined disulfiram and copper in breast cancer:

[0041] The cytotoxicity of disulfiram against different breast cancer cell lines - MCF7, MDA-MB-231 and T47D was examined.

[0042] 1. Materials and methods

[0043] 1.1 Tumor cell lines and cell culture

[0044] Breast cancer cell lines, MCF7, MDA-MB-231 and T47D were purchased from LGC Standard (ATCC), UK. Copper (Cu)-rich cells were passaged with at least 5 μM CuCl per day 2 Cells were cultured and obtained for 3 consecutive days. These cell lines were cultured in DMEM medium supplemented with 10% fetal bovine serum, 1% (v / v) penicillin-streptomycin (10000U / mL) and 1% (v / v) L-glutamic acid (200mM) .

[0045] 1.2 Monocyte Direct Cytotoxicity Test (MTT) Procedure

[0046] The cells that need to be cultured in the serum-containing culture medium for the experiment are laid at a density of 5000 cells / well in a 96-well plate. After overnight incubation, the medium was replaced with disulfiram and / or...

Embodiment 2

[0054] Effect of Disulfiram and Copper on the Cytotoxicity of Other Antineoplastic Drugs:

[0055] Disulfiram is extremely cytotoxic to common types of tumors, including glioblastoma multiforme (GBM). Disulfiram also enhances the cytotoxicity of drugs to tumor cells and protects normal cells in the kidney, gastrointestinal tract, and bone marrow, thereby improving the anticancer therapeutic index, such as gemcitabine (dFdC), cyclophosphamide, cisplatin, and ionizing radiation .

[0056] Table 2 Cytotoxicity test results of different drug combinations on GBM cell lines

[0057] U251MG U87MG IC50s of DS DS alone ＞10000 ＞10000 DS + Cu 1μΜ 143.3(0.8) 202.3(6.1) IC50s of dFdC dFdC alone 100.4(22.3) ＞400 dFdC : DS / Cu1μΜ 17.5(5.1) 17.1(3.0) CI IC50 0.39 0.47 IC75 0.33 0.46 IC90 0.31 0.45

[0058] It can be seen from the table that disulfiram alone is less toxic to tumor cells, an...

Embodiment 3

[0060] Tumor inhibition experiment of low-dose disulfiram:

[0061] 1. Materials and methods:

[0062] Tumor inoculation: BALB / c-nu male nude mice were used for experiments. Three nude mice bearing human hepatocellular carcinoma HepG2 tumors were routinely disinfected in the chest and abdomen of nude mice in each group; the tumor mass was stripped under aseptic conditions, the necrotic tissue in the center of the tumor mass and the fibrous and fat tissue around the tumor mass were removed, and the tumor tissue was cut into 1.5 ×1.5×1.5mm3 tumor tissue block. A small skin incision was made in the axilla of the right forelimb of the nude mice, and the tumor tissue was implanted subcutaneously in the axilla of the right forelimb of the nude mice.

[0063] Experimental procedure: Weigh the tumor-bearing nude mice on the 8th to 10th day after transplantation of the human liver cancer HepG2 cancer strain, and measure the long diameter (a) and short diameter (b) of the tumor with ...

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Abstract

The invention relates to a medicament in combination of a disulfiram preparation and copper, having an anti-tumor function. The combination of disulfiram and copper in the invention plays a role in treating tumor cells, belonging to the technical field of medicaments. The anti-tumor combination medicament comprises disulfiram or derivatives thereof and copper and any one or more optional medicinal vectors, which are used simultaneously, respectively or sequentially; the dosage of the disulfiram in each single medicament ranges from 2 to 200 mg/kg or equals to the equivalent dosage of disulfiram derivatives; and the copper comprises micro copper ions contained in the human body and other absorbable forms of copper irons, wherein the dosage of the copper in each single medicament is 0.1-5 mg per day. The combination medicament disclosed by the invention has remarkable effect in treating tumors and reduced toxic and side effects.

Description

technical field [0001] The invention relates to a combination drug of disulfiram preparation and copper with antitumor effect. The combined use of disulfiram and copper has therapeutic effect on tumor cells and belongs to the technical field of medicine. Background technique [0002] Disulfiram (disulfiram, DS), also known as disulfide tetraethylthiuram, disulfiram, the structure is as figure 1 , was synthesized for the first time in 1881, and was initially used as a catalyst for rubber vulcanization in the rubber industry; in the 1930s, DS was first used as a drug for the treatment of scabies; subsequently, it was found that DS has a strong chelation effect with copper ions It can reduce the activity of copper-containing respiratory enzymes, and intestinal worms are extremely sensitive to DS, so DS is used as an insect repellent; in 1948, two doctors in Copenhagen, Hald and Jacobsen, accidentally discovered that taking the insect repellent disulfiram After drinking a small...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K33/34A61K31/30A61P35/00A61K31/145
Inventor 唐星何海冰张宇吴春福杨静玉
Owner SHENYANG PHARMA UNIVERSITY
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