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Combined pharmaceutical preparation for treating melanoma, lung cancers or colorectal cancers

A pharmaceutical preparation and technology for colorectal cancer, applied in the field of tumor treatment, can solve the problems of insufficient efficacy of PD-L1 inhibitor single drug, narrow application range of cilengitide, low objective tumor remission rate, etc., and achieve enhanced anti-tumor efficacy , low risk of action, reduced tumor growth effect

Pending Publication Date: 2019-08-30
TONGJI HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Aiming at the defects of narrow application range of cilengitide, low objective tumor response rate and insufficient curative effect of PD-L1 inhibitor alone, the present invention provides a combined pharmaceutical preparation for treating melanoma, lung cancer or colorectal cancer. The drug preparation improves the effective indication range and tumor killing effect of the drug by intervening in the tumor and tumor microenvironment; the combination of the programmed death receptor 1 ligand 1 (PD-L1) antibody and cilengitide can play a role Synergistic effect delays individual tumor growth and enhances inhibition of tumor growth

Method used

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  • Combined pharmaceutical preparation for treating melanoma, lung cancers or colorectal cancers
  • Combined pharmaceutical preparation for treating melanoma, lung cancers or colorectal cancers
  • Combined pharmaceutical preparation for treating melanoma, lung cancers or colorectal cancers

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Forty-four 6-week-old female C57BL / 6 wild-type mice were selected, and each mouse was inoculated with 5×10 5 melanoma B16F10 cells, observed tumor formation 8 days later, and then divided them into control group (11), cilengitide group (11), PD-L1 antibody group (11) and cilengitide+ Anti-PDL-1 antibody combination group (11 rats). After grouping, the mice in the control group were given isotype control IgG, and the mice in the experimental group were given cilengitide (dissolved in PBS), 25 mg / Kg, once a day, intraperitoneally injected; or given anti-PDL-1 antibody, 200 μg each time (about 10mg / Kg), once every other day, a total of 4 administrations, intraperitoneal injection; or a combination of the two. After administration, the subcutaneous tumor size of each group of mice was measured every day, and the tumor volume was calculated (tumor volume=long diameter of tumor×short diameter of tumor) 2 / 2). On the ninth day after the administration, the mice in each grou...

Embodiment 2

[0031] At the end of the observation (the ninth day), one C57 was selected from the four groups in Example 1, and the peeled tumor tissue was fixed with 4% paraformaldehyde for 12 hours, and the fixed tissue was gradually treated with ethanol from low to high concentrations. Grade dehydration (50%, 75%, 85%, 95%, 100%), followed by three replacements of ethanol with xylene. Infiltrate the tissue quickly with paraffin wax with a melting point of 60 degrees. First trim the excess paraffin around the tissue block with a blade, and then place the sliced ​​slices in a 42-degree oven for 2 hours. Next, the paraffin sections were dewaxed to water, soaked in environmental transparent agent (three cylinders 10min, 10min, 10min), gradient alcohol (anhydrous, 95%, 75%), 5min in each cylinder, then rinsed once with distilled water and soaked in in distilled water. After repairing with high temperature and high pressure, use 3% H2O2 to block endogenous peroxidase at room temperature for 2...

Embodiment 3

[0035] At the end point of observation (the ninth day), one C57 was selected from the four groups in Example 1, and the tumor tissue and spleen were peeled off to make a single cell suspension, and the lymphocytes in the tumor tissue were extracted with percoll, and the recommended dosage was used according to the instructions. Add fluorescently labeled antibodies, mix well, place at 4°C, and incubate in the dark for 30 minutes, add PBS containing 0.1% BSA to resuspend cells, and use flow cytometry for detection and analysis.

[0036] Such as Figure 8 As shown, the results of flow cytometry of the tumor tissues of the four groups of mice showed that CD3 in the tumor tissues of the mice in the combination group + CD8 + T cell infiltration was significantly increased. Such as Figure 9 As shown, CD3 in spleen tissue of four groups of mice + CD8 + There was no significant difference in T cell infiltration.

[0037] The above experiments confirmed that simultaneous administ...

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Abstract

The present invention discloses a combined pharmaceutical preparation for treating melanoma, lung cancers or colorectal cancers. The pharmaceutical preparation comprises an effective amount of an antibody of a programmed death receptor ligand 1 (PD-L1) and cilengitide. The combined pharmaceutical preparation combines the integrin inhibitor cilengitide and the PD-L1 inhibitor to inhibit tumor cellproliferation while inhibiting formation of new blood vessels in a tumor microenvironment and enhancing infiltration and activation of T cells to improve an immune microenvironment. Compared with single drug use, the inhibition effects of the cilengitide and PD-L1 inhibitors are relatively clear, side effects are relatively low, and risks are relatively low. After the combined use, an objective remission rate of the tumors is higher than that of the single drug use, total survival time is increased and no lethal side effects are observed.

Description

technical field [0001] The invention relates to the field of treating tumors, in particular to a combined pharmaceutical preparation for treating melanoma, lung cancer or colorectal cancer. Background technique [0002] PD-L1 antibody is a second-generation immune checkpoint inhibitor, which has good efficacy in melanoma, non-small cell lung cancer and urothelial cancer, and was approved by the FDA in 2016. It not only changes the treatment mode of malignant tumors, but also prolongs the overall survival time of patients. As a key target of tumor immune escape, the high expression of PD-L1 in the tumor microenvironment indicates a poor prognosis. PD-L1 inhibitors can target and compete for the combination of PD-L1 and PD-1, relieve the inhibition of T cell activation, enable antigen-presenting cells to present antigens to T cells more efficiently, and activate T cell differentiation. [0003] Cilengitide is an inhibitor that selectively inhibits integrins αvβ3 and αvβ5. It ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K38/12A61P35/00
CPCA61K39/39558A61K38/12A61P35/00A61K2039/876A61K2039/86A61K2039/82A61K2039/836A61K2300/00
Inventor 袁响林王璐潘欣
Owner TONGJI HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI TECH
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