Application of SIRT1 inhibitor in prevention and treatment of radiation-induced intestinal diseases

A 1. SIRT1, inhibitor technology, applied in the field of biomedicine, can solve the problem of lack of ideal drugs and effective treatment methods for intestinal damage, and achieve the effect of reducing epithelial cell death, promoting regeneration ability, and broad market application prospects.

Active Publication Date: 2017-11-21
D1 MEDICAL TECH (SHANGHAI) CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, the present invention can effectively solve the problem that radiation-induced intestinal damage lacks ideal medicines and effective treatment methods

Method used

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  • Application of SIRT1 inhibitor in prevention and treatment of radiation-induced intestinal diseases
  • Application of SIRT1 inhibitor in prevention and treatment of radiation-induced intestinal diseases
  • Application of SIRT1 inhibitor in prevention and treatment of radiation-induced intestinal diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] (1) To study the protective effect of nicotinamide administered at different times on intestinal damage caused by X-ray 6Gy irradiation:

[0062] Small intestinal crypts were isolated from 8-12 week-old C57BL mice, planted in Matrigel with conditioned medium, and inoculated for 24 hours, and five groups of small intestinal organoids were taken, and they were set as blank control group (no irradiation) and model control group , the administration group 24 hours before the irradiation, the administration group 1 hour after the irradiation, and the administration group 24 hours after the irradiation. X-ray 6Gy was used to irradiate the small intestinal organoids in the model control group, the 24 hours before irradiation group, the 1 hour after irradiation group, and the 24 hours after irradiation group. The first 24 hours administration group was administered nicotinamide 10 mM before irradiation, and the administration group 1 hour after irradiation and the administratio...

Embodiment 2

[0071] To study the protective effect of EX527 on radiation-induced intestinal injury:

[0072] Small intestinal crypts were isolated from 8-12 week-old C57BL mice, planted in Matrigel with conditioned medium, and three groups of small intestinal organoids were taken 24 hours after inoculation, and were set as the model control group and the nicotinamide group 24 hours after irradiation. 24 hours after exposure to the EX527 group. X-ray (RAD-320 X-ray machine (PXI, USA)) 8Gy was used to irradiate small intestinal organoids in the model control group, the nicotinamide group 24 hours after irradiation, and the EX527 group 24 hours after irradiation. Among them, the model control group No administration, nicotinamide 10mM 24 hours after irradiation, nicotinamide 10mM for 24 hours after irradiation, EX527 (100μM) for EX527 group 24 hours after irradiation. The above three groups were cultured for 5 days and observed There were differences in organ survival rate and size between t...

Embodiment 3

[0077] To study the protective effect of Sirtinol against radiation-induced intestinal damage:

[0078] Small intestinal crypts were isolated from 8-12-week-old C57BL mice, planted in Matrigel with conditioned medium, and inoculated for 24 hours. Five groups of small intestinal organoids were taken, and they were set as model control groups, and Sirtinol ( 10 μM) group, Sirtinol (50 μM) group 24 hours after irradiation, Sirtinol (100 μM) group 24 hours after irradiation, nicotinamide (10 mM) 24 hours after irradiation. Then 8Gy was irradiated with x-ray (RAD-320 X-ray machine (PXI, USA), and different concentrations of SIRT1 inhibitor Sirtinol (10 μM, 50 μM, 100 μM) were added 24 hours after irradiation, and DMSO control and nicotinamide control were set. Culture 5 Days later, the difference in organoid survival rate between the treatment group and the control group was observed.

[0079] result: Figure 10 It shows the model control group, the Sirtinol (10μM) group given 24...

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Abstract

The invention discloses an application of an SIRT1 inhibitor in the prevention and treatment of radiation-induced enteric diseases, and concretely discloses a use of the SIRT1 inhibitor in the preparation of medicines, a medicinal composition for preventing or treating radiation-induced intestinal injury, and a method for treating or preventing the radiation-induced intestinal injury. Radiation-induced intestinal epithelial injury can effectively be prevented or treated, and the survival rate of animals is significantly improved, so the problem of lack of ideal therapeutic medicines and effective treatment methods for the radiation-induced intestinal injury is effectively solved.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to the application of SIRT1 inhibitors in the prevention and treatment of intestinal diseases caused by radiation. Background technique [0002] Intestinal mucosa is a highly radiation-sensitive tissue. Radiation damage to normal intestinal tissue is the biggest limiting factor in clinical abdominal tumor radiotherapy. About 50% of patients receiving abdominal tumor radiotherapy will develop secondary radiation enteritis, which will aggravate the condition and affect the quality of life of patients. In addition, in other extreme cases, such as nuclear leaks, nuclear terrorist attacks and space exploration by astronauts, the human body is exposed to high doses of radiation, which can cause fatal intestinal necrosis. High doses of radiation inhibit the proliferation of small intestinal stem cells and cause a large number of stem cells to die, leading to the destruction...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61P1/00
CPCA61K45/00
Inventor 华国强富国祥
Owner D1 MEDICAL TECH (SHANGHAI) CO LTD
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