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Medicament composition containing sorafenib, MEK inhibitors and EGFR tyrosine kinase inhibitors and application thereof

A tyrosine kinase and kinase inhibitor technology, which is applied to a pharmaceutical composition containing sorafenib, a MEK inhibitor and an EGFR tyrosine kinase inhibitor and its application field, can solve the toxic and side effects and reduce the dosage of the drug , interruption and other issues, to achieve the effect of improving efficacy, reducing dosage, and reducing side effects

Inactive Publication Date: 2010-09-22
DINKUM INT INVESTMENT HONG KONG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, Sorafenib has more adverse reactions, such as "Toxic and Side Effects of Sorafenib and Its Treatment", recorded in the 370-373 pages of "Journal of Cancer Progress", Volume 5, No. 4, July 2007 , adverse reactions include hand-foot syndrome, fatigue, diarrhea, skin toxicity and gastrointestinal reactions, etc., and often lead to interruption of drug administration or reduction of drug dosage

Method used

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  • Medicament composition containing sorafenib, MEK inhibitors and EGFR tyrosine kinase inhibitors and application thereof
  • Medicament composition containing sorafenib, MEK inhibitors and EGFR tyrosine kinase inhibitors and application thereof
  • Medicament composition containing sorafenib, MEK inhibitors and EGFR tyrosine kinase inhibitors and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Example 1 The combination of different ratios of ARRY-142886, sorafenib and erlotinib synergistically promotes the death of A549 cells, see Table 2.

[0051] Table 2

[0052]

[0053]

[0054] In the experiment investigating the death of lung cancer cell line A549 caused by related compounds, it was found that when 0.6μM ARRY-142886, 3.0μM sorafenib, 5.0μM erlotinib or lower concentrations were used alone, there was almost no cell death, even if the above When any two of the three drugs are combined at lower concentrations, only 0.4μM ARRY-142886+3.0μM Sorafenib can cause about 20% cell death, while the other two combinations are 0.4μM ARRY-142886+5.0μM Erlotinib and 3.0 μM sorafenib + 5.0 μM erlotinib also had only a small amount of cell death; but when these three drugs were combined at the lower concentrations mentioned above (0.4 μM ARRY-142886 + 3.0 μM Sorafenib+5.0μM Erlotinib) produced a significant synergistic effect, resulting in the death of about 50% o...

Embodiment 2

[0055]Example 2 The combination of different ratios of U0126, sorafenib and erlotinib synergistically promotes the death of A549 cells, see Table 3.

[0056] table 3

[0057]

[0058]

[0059] In the experiment investigating the death of lung cancer cell line A549 caused by related compounds, it was found that when 25.0 μM U0126, 3.0 μM sorafenib, 5.0 μM erlotinib or lower concentrations were used alone, there was almost no cell death, even if the above three When any two drugs were combined at lower concentrations, only 15.0 μM U0126+3.0 μM sorafenib could cause 15% cell death, while the other two combinations were 15.0 μM U0126+5.0 μM erlotinib and 3.0 μM Sorafenib+5.0μM erlotinib also had only a small amount of cell death; but when these three drugs were combined at the lower concentrations mentioned above (15.0μM U0126+3.0μM sorafenib+5.0μM erlotinib Tini) produced an obvious synergistic effect, leading to the death of 43% of cancer cells; when the above three drugs...

Embodiment 3

[0060] Example 3 The combination of different ratios of ARRY-142886, sorafenib and erlotinib synergistically promotes the death of HCT116 cells, see Table 4.

[0061] Table 4

[0062]

[0063]

[0064] In the experiment investigating the cell death of colon cancer cell line HCT116 caused by related compounds, it was found that when 0.5 μM ARRY-142886, 3.0 μM sorafenib, 5.0 μM erlotinib or lower concentrations were used alone, there was almost no cell death, Even when any two of the above three drugs were combined at lower concentrations, only 0.3μM ARRY-142886+3.0μM Sorafenib could cause 20% cell death, while the other two combinations, 0.3μM ARRY-142886+ 5.0 μM erlotinib and 3.0 μM sorafenib+5.0 μM erlotinib also had only a small amount of cell death; μM sorafenib+5.0μM erlotinib) produced a significant synergistic effect, leading to the death of 47% of cancer cells; when the above three drugs were combined in pairs at higher concentrations, only 0.5μM +5.0μM Sorafeni...

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Abstract

The invention relates to a medicament composition containing sorafenib, mitogen extracellular kinase (MEK) inhibitors and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and application thereof in preparing medicaments for treating lung cancer, colon cancer, liver cancer, kidney cancer, stomach cancer, encephaloma, sarcoma, pancreatic cancer, ovarian cancer, breast cancer or prostatic cancer. The medicament composition has remarkable synergistic effect, improves the curative effect of the medicament, decreases the administration dosage and reduces the occurrence of side effects.

Description

technical field [0001] The present invention relates to a kind of pharmaceutical composition and its application in preparing the medicine for treating cancer, be specifically related to containing sorafenib, mitogenic extracellular kinase (MEK) inhibitor and epidermal growth factor receptor (EGFR) tyrosine A pharmaceutical composition of an acid kinase inhibitor and its application in the preparation of medicines for treating lung cancer, colon cancer, liver cancer, kidney cancer, gastric cancer, brain tumor, sarcoma, pancreatic cancer, ovarian cancer, breast cancer or prostate cancer. Background technique [0002] The survey report of the World Health Organization shows that the global cancer situation is getting worse. In the next 20 years, the number of new patients will increase from the current 10 million to 15 million per year, and the number of deaths from cancer will also increase from 6 million to 10 million per year. Among them, lung cancer is one of the common ma...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K31/44A61P35/00
Inventor 赵镭
Owner DINKUM INT INVESTMENT HONG KONG
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