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Application of chloroquine compound or salt thereof in preparation of medicament for treating acute leukemia

An acute leukemia and compound technology, applied in the field of biomedicine, can solve problems such as poor curative effect, high cost, and large toxicity of chemotherapy

Inactive Publication Date: 2010-09-15
RENJI HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The effect of bone marrow transplantation is better, but it is necessary to find a suitable donor and grasp the timing of transplantation, which is costly; the combination of traditional Chinese and Western medicine, biological regulators, etc. are not effective, and can only be used as adjuvant treatment
Chemotherapy is currently the main method for the treatment of leukemia. However, chemotherapy in the traditional sense has high toxicity and side effects, common drug resistance, and poor overall efficacy. Therefore, it is necessary to find new drugs
However, the development cycle of new drugs is long and requires a lot of manpower and financial resources. According to my country's national conditions, blood disease researchers in China have made important contributions to the new use of old drugs: the application of all-trans retinoic acid and traditional The traditional Chinese medicine arsenic trioxide combined with acute promyelocytic leukemia has achieved good results with a five-year survival rate of about 95%, making acute promyelocytic leukemia the first leukemia that can be considered to have been conquered

Method used

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  • Application of chloroquine compound or salt thereof in preparation of medicament for treating acute leukemia
  • Application of chloroquine compound or salt thereof in preparation of medicament for treating acute leukemia
  • Application of chloroquine compound or salt thereof in preparation of medicament for treating acute leukemia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1: Cell Culture

[0023] The leukemia cell line U937 was provided by Shanghai Institute of Blood. In the RPMI 1640 medium containing 10% fetal bovine serum and 100 u / ml of penicillin and streptomycin, the cells were cultured at 37°C in a cell incubator containing 5% CO2, and subcultured once every 2 days. All experiments were carried out in the logarithmic growth phase of cells.

Embodiment 2

[0024] Embodiment 2: MTT experiment

[0025] Chloroquine phosphate was purchased from Sigma Company, dissolved in normal saline, filtered and sterilized with a 0.22 μm sterile filter, prepared into various concentrations, and stored in the dark. The dry powder of methyl thiazolyl tetrazolium (MTT) was purchased from Sigma Company.

[0026] The cells were adjusted to 2×105 cells / ml, and the control group and the treatment group were divided into two groups. The final concentrations of chloroquine phosphate were 0, 2, 10, 50, 250, and 1000 μg / ml respectively; each group was set with 3 replicate wells. After culturing for 24 hours, add 20 μl of 5% MTT solution to each well, and incubate for 4 hours in a 37-degree incubator. After centrifuging and discarding the supernatant, add 200 μl of dimethyl sulfoxide (DMSO) to each well, shake well to dissolve, and detect 570nm on a microplate reader. Optical density value (D), the average value of 3 replicate wells, the experiment was rep...

Embodiment 3

[0029] Embodiment 3: the study of chloroquine phosphate to the apoptosis effect of leukemia cells

[0030] Annexin V-Alexa Fluor488 / PI apoptosis detection kit was purchased from Invitrogen. U937 cells were cultured for 24 hours after adding 50 μg / ml chloroquine phosphate, and 2×10 5 Cells were washed once with 1×PBS, and resuspended in 200 μl of 1×binding buffer. Add Annexin V-Alexa Fluor4885μl, PI 2μl and incubate in the dark for 15min, and then detect cell apoptosis by flow cytometry and laser confocal microscopy. Repeat the experiment three times.

[0031] After U937 cells were added with 50 μg / ml chloroquine phosphate and cultivated for 24 hours, flow cytometry detected that the percentage of apoptosis in the control group was (2.71±1.35)%, and the percentage of apoptosis in the drug-dosed group was (39.86±13.59)%, P figure 2 ). Visible on the laser confocal microscope image ( image 3 ), quadrant I is the image obtained from the detection of PI, red is the positive cell...

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Abstract

The invention provides an application of a chloroquine compound or a salt thereof in the preparation of a medicament for treating acute leukemia. The chloroquine compound or the salt thereof can be any one of chloroquine, chloroquine phosphate, hydroxychloroquine, chloroquine hydrochloride, nivaquin, chloroquine silicate or aminochloroquine. By using the chloroquine medicament having stabilizing effect on the cell membrane and the intra-cellular membrane structure to treat the leukemia cell strain and the primary cell, the growth of the leukemia cell can be retarded and the apoptosis rate of the leukemia cell can be obviously increased after the treatment, thereby indicating that the chloroquine compound and the salt thereof can be used for treating leukemia.

Description

Technical field: [0001] The invention relates to the field of biomedicine, in particular to medicines for treating acute leukemia, in particular to the application of a chloroquine compound or its salts in the preparation of medicines for treating acute leukemia. Background technique: [0002] The applicant described in the patent application document "An Apoptosis-Related Gene and a Drug Targeting It for the Treatment of Leukemia" with the publication number CN101333530A that "because CHMP5 / PNAS-2 participates in the multivesicular body (MVB) , and MVB is limited to the cytoplasm, so it can be seen that the PNAS-2 protein should be more limited to the cytoplasm rather than diffusely distributed in the cytoplasm. Therefore, the PNAS-2 protein in U937 cells Abnormal subcellular localization of PNAS-2 protein is likely to be abnormal. The abnormal subcellular localization of PNAS-2 protein in acute leukemia cell lines is involved in the occurrence of leukemia." The applicant c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4706A61P35/02
Inventor 王海嵘陈芳源刘佳
Owner RENJI HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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