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

A technology of tyrosine kinase and sorafenib, which is applied to the pharmaceutical composition containing sorafenib, cMet inhibitor and EGFR tyrosine kinase inhibitor and its application field, which can solve the problem of reducing drug dosage, interruption , Toxic and side effects and other issues, to achieve the effect of reducing dosage, reducing side effects and improving curative effect

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Example 1 The combination of different ratios of PF-02341066, sorafenib and erlotinib synergistically promotes the death of Hep3B cells, see Table 2.

[0048] Table 2

[0049]

[0050]

[0051] In the experiment investigating the cell death of liver cancer cell line Hep3B caused by related compounds, it was found that when 1.0 μM PF-02341066, 1.5 μM sorafenib, 7.5 μM erlotinib or lower concentrations were used alone, there was almost no cell death, even if the above When any two of the three drugs were combined at lower concentrations, only 1.0 μM PF-02341066+1.0 μM sorafenib and 1.0 μM PF-02341066+5.0 μM erlotinib combined could cause about 20% cell death, while Another combination, namely 1.0 μM sorafenib + 5.0 μM erlotinib, had almost no cell death; but when these three drugs were combined at the lower concentrations mentioned above (1.0 μM +5.0μM erlotinib) produced an obvious synergistic effect, resulting in the death of about 50% of cancer cells; When rafe...

Embodiment 2

[0052]Example 2 The combination of different ratios of PF-02341066, sorafenib and erlotinib synergistically promotes the death of A549 cells, see Table 3.

[0053] table 3

[0054]

[0055]

[0056] In an experiment investigating the death of related compounds in lung cancer cell line A549, it was found that only about 10% of the cells were Even if any two of the above three drugs were combined at a lower concentration, no more than 15% of the cells died; but when the three drugs were combined at the above lower concentration (1.0 μ MPF-02341066 + Sorafenib+5.0μM erlotinib) produced a significant synergistic effect, resulting in the death of about 40% of cancer cells; when the above three drugs were combined in pairs at higher concentrations, there was only 1.5μMPF-02341066 +6.0μM Sorafenib can cause about 27% of cancer cells to die when used in combination, and the other two combinations, namely 1.5μM PF-02341066+7.5μM Erlotinib and 6.0μM Sorafenib+7.5μM Erlotinib only...

Embodiment 3

[0057] Example 3 The combination of different ratios of PF-02341066, sorafenib and erlotinib synergistically promotes the death of HCT116 cells, see Table 4.

[0058] Table 4

[0059]

[0060]

[0061] In an experiment investigating related compounds causing cell death in the colon cancer cell line HCT116, it was found that only about 10% of the cells were Even when any two of the above three drugs were combined at lower concentrations, only about 10% of the cells died; Sorafenib+5.0μM erlotinib) produced a significant synergistic effect, resulting in the death of about 44% of cancer cells; when the above three drugs were combined in pairs at higher concentrations, there was only 1.5μMPF-02341066 +6.0μM Sorafenib can cause about 25% of cancer cells to die when used in combination, and the other two combinations, namely 1.5μM PF-02341066+7.5μM Erlotinib and 6.0μM Sorafenib+7.5μM Erlotinib only Caused no more than 20% cell death, and when the three combined (1.5μMPF-0234...

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Abstract

The invention relates to a medicament composition containing sorafenib, hepatocyte growth factor receptor (cMet) 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 canceror 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, hepatocyte growth factor receptor (cMet) 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 liver cancer, lung cancer, colon 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, primary liver cancer is a cance...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/5377A61K31/44A61K31/517A61K31/519A61K31/4545A61K31/404A61P35/00
Inventor 赵镭
Owner DINKUM INT INVESTMENT HONG KONG
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