Combined pharmaceutical composition for treating acute myelogenous leukemia and application thereof

An acute myeloid and composition technology, applied in the field of biomedicine, can solve the problem of less acute myeloid leukemia, and achieve the effects of prolonging survival time, significantly inducing apoptosis of AML cells, and inhibiting proliferation of AML cells

Active Publication Date: 2021-11-02
THE FIRST AFFILIATED HOSPITAL OF XIAMEN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, there are still relatively few effective drug combination strategies disclosed in the prior art for the treatment of acute myeloid leukemia, and it is very meaningful to develop more new therapeutic strategies for acute myeloid leukemia

Method used

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  • Combined pharmaceutical composition for treating acute myelogenous leukemia and application thereof
  • Combined pharmaceutical composition for treating acute myelogenous leukemia and application thereof
  • Combined pharmaceutical composition for treating acute myelogenous leukemia and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Inhibitory effect of combined pharmaceutical composition on proliferation of AML cell line

[0048] The operation method is: take the quantity as 2×10 4 AML cell lines in the logarithmic growth phase (including KG1α and Kasumi cell lines) were inoculated in 96-well plates, and Apatinib group, Chidamide group, and mixed groups of different concentrations of Apatinib and different concentrations of Chidamide were set up respectively. After each group was treated for 48 hours, CCK8 was applied. The kit detects the proliferation of different groups of AML cells.

[0049] The result is as figure 1 and figure 2 as shown, figure 1 It is the result of KG1α cell line acting for 48h, figure 2 It is the result of Kasumi cell line acting for 72 hours. Depend on figure 1 It can be seen from the above that: the combined use of Apatinib and Chidamide has the effect of significantly inhibiting the proliferation of various AML cell lines, which is more significant than that of s...

Embodiment 2

[0054] Evaluation of the Apoptosis Inducing Effect of Combined Pharmaceutical Composition on AML Cell Lines

[0055] The operation method is: take the quantity as 2×10 5 The AML cell line (KG1α cell line) in the logarithmic growth phase was seeded in a 24-well plate, and the Apatinib group, the Chidamide group, and the mixed group of different concentrations of Apatinib and different concentrations of Chidamide were respectively set up. After each group was treated for 48 hours, Annexin V / PI was applied. The kit detects the apoptosis of different groups of AML cells (the specific operation steps are carried out according to the instructions of the kit).

[0056] The result is as image 3 shown by image 3 It can be seen from the above that: the combination of Apatinib and Chidamide has the effect of significantly inducing the apoptosis of AML cell lines, which is more significant than that of Apatinib or Chidamide alone; Apoptosis induction was significantly concentration d...

Embodiment 3

[0058] Evaluating the effect of combined pharmaceutical composition on AML cells from primary cell level

[0059] The operation method is as follows: collect bone marrow samples from 20 AML patients (specific information is shown in Table 2), and extract mononuclear cells with lymphocyte separation medium. Primary AML cells were treated with Apatinib, Chidamide, different concentrations of Apatinib and different concentrations of Chidamide mixed for 48 hours, and the apoptosis ratio of primary AML cells was detected by Annexin V / PI double staining flow cytometry.

[0060] Table 2

[0061]

[0062]

[0063] The result is as Figure 4 shown by Figure 4 It can be seen that the combination of Apatinib and Chidamide can significantly induce the apoptosis of AML primary cells, which is more significant than that of Apatinib or Chidamide alone; The apoptosis-inducing effect of the strain was significantly concentration-dependent.

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Abstract

The invention provides a combined pharmaceutical composition for treating acute myelogenous leukemia and application of the combined pharmaceutical composition. The combined pharmaceutical composition for treating acute myelogenous leukemia comprises chidamide and apatinib. According to the combined medicine composition, the medicine chidamide and the medicine apatinib are creatively combined to serve as a medicine for treating acute myelogenous leukemia, and the research shows that the combined chidamide and apatinib have the effect of more remarkably inhibiting AML cell proliferation compared with single chidamide or apatinib; has the effect of more remarkably inducing AML cell apoptos compared with single chidamide or apatinib, and has the effect of more remarkably prolonging the survival time of an AML mouse model compared with single chidamide or apatinib. The combined pharmaceutical composition provides a new strategy and thought for the treatment of acute myelogenous leukemia, and has very significant significance.

Description

technical field [0001] The invention belongs to the technical field of biomedicine and relates to a new treatment method for acute myeloid leukemia, in particular to a combined pharmaceutical composition for treating acute myeloid leukemia and its application in treating acute myeloid leukemia. Background technique [0002] Acute myeloid leukemia (AML) is a malignant clonal disease originating from AML stem cells. Currently, the treatment of AML is at the bottleneck stage, and refractory recurrence is the most important factor leading to its treatment failure. Leukemia stem cells (LSCs) play an important role in the occurrence and development of leukemia. Research by Wang, W. et al. in Reduced hematopoietic stem cell frequency predicts outcome in acutemyeloid leukemia. Haematologica, 2017.102(9): p.1567-1577 showed that the number of LCSs after diagnosis and treatment was negatively correlated with the prognosis of AML patients. LSCs become the key to cure AML. Pollyea, D....

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/444A61K31/4406A61P35/02
CPCA61K31/4406A61K31/444A61P35/02A61K2300/00
Inventor 徐兵赵海军鲁先平李志峰查洁付鑫
Owner THE FIRST AFFILIATED HOSPITAL OF XIAMEN UNIV
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