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Composition and application and medicine thereof

A composition and drug technology, applied in the field of medicine, can solve the problems of acquired drug resistance and little effect

Pending Publication Date: 2022-06-03
NEWISH TECH (BEIJING) CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At present, even the third-generation inhibitors have acquired drug resistance, and radiotherapy and chemotherapy have little effect

Method used

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  • Composition and application and medicine thereof
  • Composition and application and medicine thereof
  • Composition and application and medicine thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Example 1: SY-009 (Yabao Pharmaceutical) / Licogliflozin (Novartis Pharmaceuticals) combined with apatinib

[0054] 1. Inhibitory effect of combined drug on tumor cells (determination of IC50 value of combined drug)

[0055] VEGFR inhibitors are anti-angiogenesis inhibitors. If the anti-vascular effect theory is used, drug resistance should not occur. However, consistent with the vast majority of targeted drugs, VEGFR-targeting inhibitors will also develop drug resistance. A possible The reason is that the anti-tumor effect of VEGFR inhibitors is not only by inhibiting the formation of new blood vessels, but also by targeting the VEGFR overexpressed by the tumor itself. Therefore, the present invention first uses a type of VEGFR-targeting TKI drug apatinib to verify, According to the tissue distribution characteristics of apatinib and SY-009 (Yabao Pharmaceuticals) / Licogliflozin (Novartis Pharmaceuticals) drug targets VEGFR and SGLT1 / 2, the present invention takes the cer...

Embodiment 2

[0070] Example 2: Validation of other TKI drugs

[0071] In this example, the liver cancer cell line HepG2 was selected for experimental verification. The method is as follows: when the cells grow to 80% density, trypsinize the cells, subculture and spread them in a 96-well plate with 5000 cells per well, and replace them with the corresponding concentration of tyrosine kinase activity inhibitor, SY-009 after 24 hours. (Yabao Pharmaceutical), Licogliflozin (Novartis Pharmaceuticals), and the culture medium of tyrosine kinase activity inhibitor and SY-009 / Licogliflozin combination drug, the absorbance value at each concentration was detected by MTT method at 48 hours.

[0072] The experimental method was the same as the previous example, and the incubation time was 1 h. A blank control group was set in the experiment, that is, normal cultured HepG2 cells, in which the concentration of SY-009, Licogliflozin or TKI was 0. The survival rate of cells in the blank control group was...

Embodiment 3

[0074] Example 3: Anti-drug resistance assay

[0075] The long-term culture of QGY-7703 cells in a medium containing gradually increasing concentrations of apatinib can enable the cells to acquire resistance to apatinib. Long-term survival of QGY-7703 apatinib-resistant cell line in Nigeria.

[0076] Adding 35 μM apatinib and 40 μM soxagliflozin (S) composition to the apatinib-resistant cell line obtained by the present invention can still effectively kill the cell line. However, apatinib and solagliflozin alone had no effect on the drug-resistant cell line. It shows that the combination of sodagliflozin and apatinib reverses the resistance of tumor cells to apatinib, and the results are as follows Figure 25 shown.

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Abstract

The invention relates to the technical field of medicines, and particularly discloses a composition, application thereof and a medicine. The composition comprises an SGLT inhibitor and a tyrosine kinase activity inhibitor. The present invention provides a composition containing an SGLT inhibitor and a tyrosine kinase activity inhibitor. Based on the inhibition effect of TKI on tyrosine kinase of receptors such as VEGFR (vascular endothelial growth factor receptor), EGFR (epidermal growth factor receptor), HER2 (human epidermal growth factor receptor 2) and the like, an in-vitro anti-tumor test shows that SGLT inhibitors such as sofogliflozin, SY-009, Licogliflozin and the like can generate a synergistic inhibition effect on tumors when being combined with a tyrosine kinase activity inhibitor; in addition, the curative effect of TKI drugs can be remarkably enhanced, the drug resistance can be reversed, and the compound can be used for cancer treatment and preparation of anti-cancer drugs.

Description

technical field [0001] The present invention relates to the technical field of medicine, more particularly to a composition for treating cancer and its application and medicine. Background technique [0002] 1. Cancer Epidemiology [0003] Non-communicable diseases are the main cause of death globally, and cancer is the disease with the highest fatality rate among non-communicable diseases, which imposes a heavy burden on social health care systems. Traditional cancer treatment is based on surgery, radiotherapy and chemotherapy, and for advanced cancer, chemotherapy is the mainstay. Classic chemotherapy has serious side effects due to poor targeting. The emergence of targeted chemotherapy drugs represented by Gleevec has greatly reduced the pain caused by chemotherapy to patients. Targeted drugs are designed for molecules with different growth characteristics and expression of cancer cells than normal cells. For example, Gleevec specifically targets the constitutively act...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K31/455A61K31/7048A61P35/00
CPCA61K45/06A61K31/455A61K31/7048A61P35/00A61K2300/00
Inventor 齐海龙陈立功王晓芳孙忠杰李伟伟
Owner NEWISH TECH (BEIJING) CO LTD
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