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Application of anti-malarial drug-phosphate primaquine in preparation of drugs for treating leukemia

A technology of primaquine phosphate and leukemia, applied in the field of leukemia treatment, can solve the problems of prolonged APL patients, achieve obvious growth inhibition effect and inhibit the colony formation ability of primary cells

Active Publication Date: 2020-04-28
WENZHOU MEDICAL UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although the all-trans retinoic acid (ATRA)-induced differentiation regimen greatly prolongs the survival of APL patients, relapse and primary drug resistance are the main reasons for the failure of APL treatment. 6

Method used

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  • Application of anti-malarial drug-phosphate primaquine in preparation of drugs for treating leukemia
  • Application of anti-malarial drug-phosphate primaquine in preparation of drugs for treating leukemia
  • Application of anti-malarial drug-phosphate primaquine in preparation of drugs for treating leukemia

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Embodiment Construction

[0021] In order to better understand the essence of the present invention, the use of primaquine phosphate on leukemia at the cell level, patient sample level and animal level and the inhibitory effect and mechanism experiment results will be described below.

[0022] experimental method:

[0023] Cell proliferation experiment: First, count the cells, take an appropriate volume of cells as needed, and centrifuge at 1000 rpm for 5 minutes at room temperature. Add an appropriate volume of complete medium to resuspend, and adjust the density of each cell to 2×10 5 / mL, PBMC (adding IL-2 with a final concentration of 100U / mL) and neutrophils were adjusted to 1×10 7 / mL. Cell suspensions with gradient PRQ (0, 5, 10, 20, 40 μM) concentrations were prepared by doubling dilution. Mix the cells of each treatment group thoroughly in turn, take 100 μL and put it into a 96-well plate, set up 3 duplicate holes, put the 96-well plate into CO 2 Routine culture in the incubator for 48h. ...

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Abstract

The invention discloses an application of an anti-malarial drug-phosphate primaquine in preparation of drugs for treating leukemia. Through the system screening on multiple drugs approved by the FDA,an anti-malarial drug-phosphate primaquine is found that the phosphate primaquine has significant anti-leukemia effects. At the cellular level, the phosphate primaquine can significantly inhibit the growth of multiple myeloid leukemia cell lines but has no significant growth inhibiting effects on normal human peripheral blood mononuclear cells and neutrophil, and the phosphate primaquine has moreobvious growth inhibiting effects on acute promyelocytic leukemia cells; at the patient level, the phosphate primaquine can inhibit the primary cell colony forming ability of patients with acute myeloid leukemia; and at the animal level, the phosphate primaquine has obvious inhibition effects on all-trans retinoic acid-resistant acute promyelocytic leukemia. The potential clinical transformation and application of the phosphate primaquine in the treating of the leukemia, especially the acute promyelocytic leukemia, can provide important scientific theoretical bases.

Description

technical field [0001] The invention specifically relates to the technical field of leukemia treatment, in particular to the application of an antimalarial drug primaquine phosphate in the preparation of a drug for treating leukemia. Background technique [0002] Acute myeloid leukemia (AML) is a clonal malignant proliferative disease of myeloid stem and progenitor cells in the hematopoietic system. Acute promyelocytic leukemia (APL) is an M3 type of AML, most of which have a characteristic chromosome t(15; 17) (q22-23; q12-21) translocation, resulting in PML-RARa Fusion gene plays a key role in the pathogenesis of APL 3 . Although the all-trans retinoic acid (ATRA)-induced differentiation regimen greatly prolongs the survival of APL patients, relapse and primary drug resistance are the main reasons for the failure of APL treatment. 6 . Therefore, there is an urgent need to find new drugs with low toxicity and side effects that have anti-ATRA drug-resistant acute promyel...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4706A61P35/02A61P35/00
CPCA61K31/4706A61P35/00A61P35/02
Inventor 贺立彩顾海华马兰吕建新
Owner WENZHOU MEDICAL UNIV
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