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Antitumor pharmaceutic preparation composition

A technology of anti-tumor drugs and preparations, applied in the directions of anti-tumor drugs, drug combinations, pharmaceutical formulations, etc., can solve the problems of metastasis, tumor recurrence, and tumor cells are not effectively killed, so as to reduce side effects, eliminate tumor cells, The effect of reducing clinical dosage

Inactive Publication Date: 2016-11-09
THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Due to the unclear understanding of the mechanism of tumor dormancy, the current methods of treating tumors can temporarily cure the tumor clinically, but after several months or years, the tumor will recur because the dormant tumor cells have not been effectively killed. or transfer

Method used

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  • Antitumor pharmaceutic preparation composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1: IFN-β causes B16 melanoma cells to enter dormancy.

[0034] 1. Experimental steps:

[0035] Control group (PBS): 3000 B16 tumor cells were planted in 3D fibrin soft gel on a 24-well plate (the gel volume in a single gel-containing well was 250 μL, and ordinary medium (DMEM) added on the gel Culture medium) is 1 mL), and cultured for 3-5 days with ordinary medium plus PBS (the volume added is very small, only 1 microliter);

[0036]Experimental group (IFN-β): 3000 B16 tumor cells were planted in 3D fibrin soft gel, cultured with ordinary medium for 2 days, and then replaced with ordinary medium + IFN-β medium, The concentration of IFN-β was 1 ng / mL, 5 ng / mL or 10 ng / mL respectively. After stimulating B16 tumor cells for 2-4 days, observe the cell growth, perform cell cycle measurement, collect cell supernatants at different time points to measure glucose concentration, And use the principle of SA-β-gal to judge whether IFN-β causes B16 tumor cell senescence ...

Embodiment 2

[0044] Example 2: Inhibition of IDO signaling pathway reverses tumor dormancy caused by IFN-β (in vitro cell experiment of the combination of anti-tumor drug preparations of the present invention).

[0045] 1. Experimental steps:

[0046] Control group 1 (PBS): 3000 normal B16 tumor cells were planted in a 3D fibrin soft gel on a 24-well plate (the volume of the gel in a single gel-containing well was 250 μL, and the normal medium added on the gel 1 mL), cultured for 2-4 days with ordinary medium+PBS (the volume added is only 1 microliter);

[0047] Control group 2 (IFN-β): 3000 B16 tumor cells were planted in 3D fibrin soft gel, and after being cultured in ordinary medium for 2 days, IFN-β (5ng / mL) was added to ordinary medium to treat 2- 4 days;

[0048] Experimental group: 3000 B16 tumor cells were planted in 3D fibrin soft gel. After culturing in common medium for 2 days, IFN-β (5ng / mL) and 1-MT (0.2mM or 0.5 mM) to treat cells for 2-4 days, or add IFN-β and DMF (20 μM ...

Embodiment 3

[0053] Example 3: Combined application of IFN-β and IDO inhibitors, or combined application of IFN-β and AhR inhibitors can kill tumor cells, especially dormant tumor cells.

[0054] 1. Combined application of IFN-β and IDO inhibitors (see Figure 3A )

[0055] 1) Experimental steps

[0056] Construction of tumor-bearing mice: 40 C57BC / L mice at 4-6 weeks were randomly divided into 4 groups with a weight of 20 g; each mouse was subcutaneously inoculated with 1×10 4 B16 melanoma tumor cells, 15 days later, the tumor grew to 7 mm × 7 mm, and the tumor-bearing mice were given the following different treatments on the 16th day:

[0057] Control group 1 (PBS): only intratumoral injection of PBS to tumor-bearing mice every day;

[0058] Control group 2 (IFN-β): 250ng IFN-β (500U / ng) was injected intratumorally into each tumor-bearing mouse, once every three days, for a total of 3 injections;

[0059] Control group 3 (1-MT): 1-MT was dissolved in the drinking water of tumor-beari...

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Abstract

The invention provides antitumor pharmaceutic preparation composition which is prepared from IRF-beta and an IDO inhibitor or the IFN-beta and a AhR inhibitor. The antitumor pharmaceutic preparation composition can kill differential tumor cells and also can kill dormant tumor cells and has an effect of completely eliminating tumor cells.

Description

technical field [0001] The invention relates to a combination of pharmaceutical preparations, in particular to a combination of antitumor pharmaceutical preparations. Background technique [0002] As a disease that seriously threatens human life and health, malignant tumors have become the top priority of medical research in recent years to find effective and less toxic treatment methods. [0003] Tumor biotherapy is the fourth major tumor treatment technology after surgery, radiotherapy and chemotherapy. It uses biotechnology and biological agents to culture and amplify immune cells or immune factors collected from patients in vitro and then infuse them back into patients. In vivo methods to stimulate and enhance the body's own immune function to achieve the purpose of treating tumors. It has the advantages of high safety, strong tumor killing specificity, and no toxic and side effects, and is known as the "green biological therapy" of oncology. [0004] Tumor dormancy is...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K38/21A61P35/00A61K31/16A61K31/405
CPCA61K45/06A61K31/16A61K31/405A61K38/215A61K2300/00
Inventor 黄波刘玉英梁晓雨尹晓南吕家迪
Owner THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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