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Application of β-methoxyacrylate compound in preparing medicine for preventing and/or treating radiation damage

A technology of radiation damage and pyrimidate, applied in the field of medicine, can solve the problems of limiting the practical application of radiation therapy, normal cell damage, and high mortality in acute radiation sickness

Active Publication Date: 2020-03-20
ACADEMY OF MILITARY MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Acute radiation sickness has a high mortality rate and is difficult to cure. Currently, there is no precedent for resuscitating patients with radiation doses greater than 8Gy
In addition, when cancer patients receive radiation therapy, radiation kills tumor cells and damages normal cells, which often limits the practical application of radiation therapy.

Method used

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  • Application of β-methoxyacrylate compound in preparing medicine for preventing and/or treating radiation damage
  • Application of β-methoxyacrylate compound in preparing medicine for preventing and/or treating radiation damage
  • Application of β-methoxyacrylate compound in preparing medicine for preventing and/or treating radiation damage

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Example 1, β-methoxyacrylate compounds inhibit radiation-induced hematopoietic cell apoptosis

[0059] (1) In vitro incubation of β-methoxyacrylate compounds can significantly reduce the apoptosis of bone marrow nucleated cells in mice induced by γ-ray irradiation.

[0060] In order to study the effect of β-methoxyacrylate compounds on the apoptosis of mouse bone marrow hematopoietic cells caused by radiation, the inventors selected β-methoxyacrylate compounds Fluacrypyrim (FAPM) and Azoxystrobin (AZO) to carry out experiments . will male C 57 Femur bone marrow cells were collected from BL / 6J mice after cervical dislocation, and bone marrow nucleated cells (BMNCs) were isolated for experiments. BMNCs are divided into normal control (Con), normal + drug administration group (Con+X), irradiation control (IR) and irradiation control + drug administration group (IR+X), where X represents the drugs used, here are FAPM and AZO. The cells in the IR group and IR+X group wer...

Embodiment 2

[0068] Example 2. The effect of prophylactic administration of β-methoxyacrylate compounds on the survival of mice with acute radiation injury.

[0069] The β-methoxyacrylate compound FAPM significantly improved the survival rate of mice with acute radiation injury.

[0070] In order to study whether β-methoxyacrylate compounds have anti-radiation damage effects, the 60 Coγ-ray whole-body irradiated mice were used as a model (n=10). The study found that 50 mg / kg was injected intraperitoneally once a day two days before FAPM irradiation, and administered continuously for 3 times (-2d, -1d, -3h). Gy whole-body irradiation increases mouse survival by 50% (100% vs. 50%), and 8.5Gy whole-body irradiation improves mouse survival by 60% (60% vs. 0), see Figure 4 . This indicates that FAPM has a significant radioprotective effect on mice with acute radiation sickness.

Embodiment 3

[0071] Example 3, Effects of Prophylactic Administration of β-Methoxyacrylate Compounds on Peripheral Blood of Acute Radiation Injured Mice

[0072] Prophylactic administration of FAPM significantly promoted the recovery of multilineage hematopoietic cells in peripheral blood of irradiated mice.

[0073] In order to study the effect of FAPM on the hematopoietic function of mice with acute radiation injury, 16 male C 57 BL / 6J mice were divided into irradiated control (IR) group and FAPM group, with 8 mice in each group. All mice were irradiated with 6.5Gy γ-ray whole body. The mice in the FAPM group were administered once a day for three consecutive times (-2d, -1d, -3h) from 2 days before irradiation, and 50 mg / kg was injected intraperitoneally each time, and the irradiation control group was injected with solvent. Peripheral blood images were detected at different times before and after irradiation. The results are shown in the figure, after 6.5Gy γ-ray whole-body irradiati...

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Abstract

The present invention relates to compounds represented by general formula I with anti-radiation damage effects, their isomers, and pharmaceutical compositions containing them for the preparation of prevention or treatment of acute radiation sickness, nuclear and radiation damage, and radiation damage caused by tumor radiotherapy The medical use of the drug, or the application as a tool drug for the study of resistance to radiation damage.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to the application of β-methoxyacrylate compounds in the preparation of medicines for preventing and / or treating radiation damage. Background technique [0002] Nuclear energy and nuclear technology are increasingly widely used in various fields such as industrial and agricultural production, medical and health care, scientific research, and national defense. While they bring huge benefits to mankind, they also pose potential threats. Nuclear wars, nuclear-related terrorist attacks, earthquakes or tsunamis, etc. cause nuclear leakage in nuclear power plants, as well as civilian radioactive sources, medical exposure, etc., due to poor management or operational errors, etc., which can cause personnel to be exposed to radiation. Acute Radiation Sickness (ARS), collectively known as Acute Radiation Syndrome disease (ARS), occurs when the body is exposed to large doses (>...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/505A61P39/00A61P7/00
CPCA61P7/00A61P39/00A61K31/505
Inventor 余祖胤邢爽申星熊国林从玉文王芳敏
Owner ACADEMY OF MILITARY MEDICAL SCI
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