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Use of peptides for the control of radiation injury

A radiation injury and application technology, applied in the field of drug research and development of acute radiation injury, can solve problems such as cell cycle mitosis delay

Active Publication Date: 2009-05-27
BIOTEMPT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Furthermore, radiation causes mitotic delay of the cell cycle

Method used

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  • Use of peptides for the control of radiation injury
  • Use of peptides for the control of radiation injury
  • Use of peptides for the control of radiation injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1 and Embodiment 2

[0109] In the first experiment, 12-week-old female BALB / c mice were given a single intraperitoneal injection of PBS (n=9) or peptides (LGQV, VLPALP, LPGCPRGVNPVVS, MTRVLQGVLPALPQVVC; n=8, 10 mg / kg). Mice were systemically exposed to a single dose of 10 Gy 1.5 hours after treatment 137 Cs-γ-irradiation. In the second experiment, 12-week-old female BALB / c mice were first systemically exposed to a single dose of 10 Gy 137 Cs-γ-irradiation followed by a single intraperitoneal injection of PBS (n=9) or peptide (n=8 or 9, 10 mg / kg) 1.5 hours after irradiation. Mortality and clinical signs (eg, watery eyes indicating conjunctivitis, and weight loss) were observed at various time points during the experiment. It can be seen from Table 2 that all the tested peptides have a good effect on reducing conjunctivitis in the treated mice, but has no effect on the mortality rate, which prompted us to choose a peptide that is most suitable for fighting acute inflammation, so that in the later...

Embodiment 3

[0113] Six oligopeptides (i.e. A: LAGV, B: AQGV, C: LAG, D: AQG, E: MTR, and F: MTRV) were tested in double-blind animal experiments and compared with PBS (control), each peptide was tested Relative ability to promote recovery in the mouse kidney ischemia-reperfusion assay. In the experiment, mice were anesthetized and one kidney was removed. The other kidney was ligated for 25 minutes, and the serum urea level increased. Each of the different peptides (5 mg oligopeptide / kg body weight) was intravenously administered to 30 different mice before and after ligation, and then the mortality and BUN concentration of each peptide-treated mice were determined at 2 hours, 24 hours and 72 hours. The results are shown in Table 3 (excluding the results of peptide A (LAGV (SEQ ID NO: 4)) obtained in Example 3).

[0114] Under inhalational anesthesia, the left kidney was isolated with its arteries and veins and blocked with microvascular clamps for 25 minutes. Animals were placed on a h...

Embodiment 4

[0121] For the reasons mentioned previously, one oligopeptide (A) was retested for its ability to reduce BUN levels in mice. The results are shown in Table 4. It can be seen that the mice receiving the oligopeptide LAGV were much better than the control group (PBS) in terms of survival (significantly lower mortality compared to the PBS control group) and lower BUN concentration.

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Abstract

The invention relates to the field of drug development against acute radiation injury caused by exposure to high-energy electromagnetic waves (X-rays, gamma rays) or particles (alpha particles, beta particles, neutrons). To date, there is no effective drug to ameliorate radiation injury after accidental exposure to ionizing irradiation. The invention provides a method of treating radiation injury of a subject in need thereof comprising administering to the subject a peptide, or functional analogue or derivative thereof, of smaller than 30 amino acids. Furthermore, the invention provides use of a peptide, or functional analogue or derivative thereof, of smaller than 30 amino acids for the production of a pharmaceutical composition for the treatment of a subject suffering from or believed to be suffering from radiation injury. In particular, the invention provides anti-radiation peptides having a dose reduction factor (DRF) against acute gamma irradiation of at least 1.10, said DRF determinable by testing which dose of radiation results in 50% mortality at 30 days (LD50 / 30) after whole body radiation (WBI) in a test group of mice treated with said peptide at 72 hours after WBI and, testing which dose of radiation results in 50% mortality at 30 days (LD50 / 30) after whole body radiation (WBI) in a control group of mice treated only with the vehicle of said peptide at 72 hours after WBI and wherein the DRF is calculated by dividing the LD5O / 3O of the peptide-treated animals by the LD50 / 30 of the vehicle-treated animals.

Description

technical field [0001] The present invention relates to the field of drug development against acute radiation damage caused by exposure to high energy electromagnetic waves (X-rays, gamma rays) or particles (alpha particles, beta particles, neutrons). To date there are no effective drugs to reduce radiation damage following accidental exposure to ionizing radiation. Background technique [0002] Radiation injury is tissue damage caused by exposure to radiation. Here, radiation refers to ionizing radiation produced by high-energy electromagnetic waves (X-rays, gamma rays) or particles (alpha particles, beta particles, neutrons). Such radiation is emitted by radioactive substances (radioisotopes) such as uranium, radon, and plutonium. Such radiation can also be produced by man-made radiation sources, such as X-rays and radiotherapy machines. Radiation dose is measured using a number of different units, but they all refer to the amount of energy deposited. These units inclu...

Claims

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Application Information

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IPC IPC(8): A61P39/00A61M31/00A61K38/08
Inventor R·贝内N·A·卡恩R·M·卡尔顿
Owner BIOTEMPT
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