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Application of FG-4592 to preparation of drug for preventing acute radiation bone marrow injury

A FG-4592, 1. The technology of FG-4592 is applied in the field of pharmaceutical compositions containing FG-4592 or its derivatives to achieve the effect of reducing bone marrow hemorrhage, reducing anemia and improving survival rate

Inactive Publication Date: 2018-03-30
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no literature report that FG-4592 plays a protective role in acute radiation-induced bone marrow injury by up-regulating hypoxia-inducible factors and down-regulating key apoptosis molecules

Method used

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  • Application of FG-4592 to preparation of drug for preventing acute radiation bone marrow injury
  • Application of FG-4592 to preparation of drug for preventing acute radiation bone marrow injury
  • Application of FG-4592 to preparation of drug for preventing acute radiation bone marrow injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1: FG-4592 can improve the survival rate of mice after irradiation, and reduce bone marrow damage in mice after irradiation.

[0035] 1. Experimental method

[0036] C57 / BL male mice aged 6-8 weeks were selected for the experiment, and the mice were divided into two groups: FG-4592 group and control group. FG-4592 was purchased from MCE (MedChem Express, Cat. No.: HY-13426 / CS-1094, 200 mg) company. 24 hours before irradiation and 2 hours before irradiation, the mice were intraperitoneally injected with FG-4592 (25 mg / kg / time). Because FG-4592 was dissolved in sterile saline, the mice in the control group were given the same dose of sterile physiological brine.

[0037]The mice in the FG-4592 group and the control group were irradiated by a single whole body irradiation, the dose was 7.5Gy, the dose rate was 1Gy / min, and the irradiation source was 60 Co gamma rays.

[0038] After irradiation, the survival period of the mice was recorded, and the femurs of the...

Embodiment 2

[0045] Example 2: FG-4592 reduces apoptosis after HIEC irradiation.

[0046] 1. Experimental method:

[0047] In order to verify the effect of FG-4592 on apoptosis after irradiation, apoptosis detection was performed on HIEC after irradiation.

[0048] Apoptosis detection adopts Annexin V / PI double staining (purchased from Invitrogen) flow cytometry method, the principle is: apoptosis is a process of programmed initiation, which can be divided into two processes: early apoptosis and late apoptosis . During early apoptosis, phosphatidylserine (PS) can change from the original state inside the cell phospholipid membrane to outward. At this time, Annexin V can combine with the everted PS as a detection mark of early apoptosis. In the late stage of apoptosis, the permeability of the cell membrane increases. At this time, propidium iodide (PI), as a nucleic acid dye, can enter the interior of the cell and bind to the nucleic acid, and the nucleus is stained red. Annexin V is lab...

Embodiment 3

[0052] Example 3: FG-4592 reduces the DNA damage effect of irradiation on HIEC.

[0053] 1. Experimental method:

[0054] γH2AX foci immunofluorescence detection is detected by laser confocal microscope. The principle is: DNA double-strand breaks can be caused after irradiation, and phosphorylated γH2AX forms a focus at the DNA double-strand break site, and γH2AX foci is detected by immunofluorescence. Formation, and then indirectly reflect the situation of DNA damage.

[0055] The specific operation steps are: 24 hours before irradiation, inoculate HIEC cells in a 6-well plate with a cover glass in each well, after the cells adhere to the wall, add drugs 12 hours and 2 hours before irradiation, Give FG-4592 (40ug / ml) and NS. The irradiation dose was 6.0Gy, and the dose rate was 1Gy / min. After irradiation, the medium was replaced to continue culturing. After 24 hours of irradiation, 4% paraformaldehyde was fixed for 15 minutes. After washing with phosphate buffer, Triton X w...

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Abstract

The invention relates to the field of biological medicines, in particular to application of FG-4592 or a derivative thereof to preparation of drug for preventing acute radiation bone marrow injury. Proved by in vivo experiments, the FG-4592 can obviously increases the survival rate, relieves the degree of damages on a bone marrow hematopoietic system caused by ionizing radiation, reduces the apoptosis rate of bone marrow nucleated cells and spleen cells after radiation, promotes recovery of the hematopoietic system and the like. Proved by in vitro experiments, the FG-4592 can reduce the apoptosis rate of cells after radiation and the damage condition of cell DNA after radiation. Verified by a Western blot method, the FG-4592 can upregulate expression of hypoxia-inducible factors and downregulate expression of apoptosis proteins. Illustrated that the survival rate can be increased by applying the FG-4592 before radiation, the acute radiation bone marrow injury is relieved, the bone marrow nucleated cells are protected, and a new basis is provided for preventing the acute radiation bone marrow injury by the FG-4592.

Description

technical field [0001] The present invention relates to the field of biomedicine, specifically, the application of FG-4592 or its derivatives in the preparation of medicines for protecting acute radiation-induced bone marrow injury, and the pharmaceutical composition containing FG-4592 or its derivatives. Background technique [0002] At present, the nuclear industry, nuclear energy and nuclear radiation technology have been widely used in the national economy, military and medical fields. The wide application of nuclear and radiation has greatly increased the chances of radiation workers and the public being injured by nuclear radiation. Nuclear radiation damage and protection It has also attracted more and more attention from academia and the public. After receiving large doses of ionizing radiation, exposed personnel may develop acute radiation sickness, among which acute radiation-induced bone marrow injury (also known as bone marrow-type acute radiation sickness) has at...

Claims

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Application Information

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IPC IPC(8): A61K31/472A61P7/00A61P7/06
Inventor 杜继聪蔡建明高福刘聪张沛刘虎程赢杨彦勇赵海男东肃河韩家琦
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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