Control of radiation injury

a radiation injury and treatment technology, applied in the direction of antinoxious agents, peptide/protein ingredients, extracellular fluid disorders, etc., can solve the problems of no effective drug to ameliorate radiation injury and no effective prophylactic drug to prevent, so as to reduce the lymphocyte count, prevent the absorption of swallowed materials, and improve the effect of radiation exposur

Inactive Publication Date: 2009-11-12
BIOTEMPT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

To date, there is no effective drug to ameliorate radiation injury after accidental exposure to ionizing irradiation, or after damage to healthy tissues during therapeutic radiation or radio-mimetic agents; nor is there an effective prophylactic drug to prevent or minimize such injuries when administered before the event (for example, to first responders).

Method used

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  • Control of radiation injury
  • Control of radiation injury
  • Control of radiation injury

Examples

Experimental program
Comparison scheme
Effect test

example 1 and example 2

[0113]In the first experiment, 12-week-old female BALB / c mice were treated intraperitoneally with a single injection of either PBS (n=9) or with a peptide (LQGV (SEQ ID NO:117), VLPALP (SEQ ID NO:140), LPGCPRGVNPVVS (SEQ ID NO:114), MTRVLQGVLPALPQVVC (SEQ ID NO:113); n=8, 10 mg / kg). One and a half hours after the treatment, mice were exposed whole body to a single dose of 10 Gy 137Cs-γ-irradiation. In the second experiment, 12-week-old female BALB / c mice were first exposed whole body to a single dose of 10 Gy 137Cs-γ-irradiation and then 1.5 hours after the irradiation treated intraperitoneally with a single injection of either PBS (n=9) or with a peptide (n=8 or 9, 10 mg / kg). During the experiment, mortality and clinical signs (e.g., watery eyes indicating conjunctivitis and weight loss) were observed at different time points. As can be seen from Table 2, all peptides tested had good effect on reducing conjunctivitis in the treated mice, however, no effects were seen on mortality, ...

example 3

[0114]Six oligopeptides (i.e., A: LAGV (SEQ ID NO:121); B: AQGV (SEQ ID NO:120); C: LAG; D: AQG; E: MTR; and F: MTRV (SEQ ID NO:119)) were tested and compared with PBS (control) in a double blind animal study for each peptide's relative ability to aid recovery in a mouse renal ischemia reperfusion test. In this test, the mice were anesthetized, and one kidney from each mouse was removed. The other kidney was tied off for 25 minutes, and the serum urea levels were allowed to increase. Both before and after tying off, each of the separate peptides was administered to thirty (30) different mice (5 mg oligopeptide / kg body mass intravenously), after which, the mortality of the mice was determined for each oligopeptide as well as was the BUN concentration at two hours, 24 hours and 72 hours. The results are shown in Table 3 below (excluding the results of peptide A (LAGV (SEQ ID NO:121)) obtained in Example 3).

[0115]Under inhalation anesthesia, the left kidney with its artery and vein was...

example 4

[0118]One oligopeptide (A) (SEQ ID NO:121) was retested for its capacity to reduce BUN levels in the mice test for the reasons as described above. The results are shown in Table 4 below. As can be seen, mice administered the oligopeptide LAGV (SEQ ID NO:121) now did much better in terms of both survival (a significant reduction in mortality versus the PBS control group) and reduced BUN concentration than the control group (PBS).

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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 LD50 / 30 of the peptide-treated animals by the LD50 / 30 of the vehicle-treated animals.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a divisional of U.S. patent application Ser. No. 11 / 715,314, filed Mar. 7, 2007, pending, which application claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Patent Application Ser. No. 60 / 811,878, filed Jun. 7, 2006, and U.S. Provisional Patent Application Ser. No. 60 / 779,896, filed Mar. 7, 2006, and claims priority to European Patent Application Serial No. EP 06076181.4, filed Jun. 7, 2006, the contents of the entirety of each of which are hereby incorporated herein by this reference.TECHNICAL FIELD[0002]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.BACKGROUND[0003]Radiation injury is damage to tissues caused by expo...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/16A61K38/10A61K38/08A61K38/07A61K38/06A61K38/05A61P43/00
CPCA61K38/08A61K9/0019A61P1/00A61P39/00A61P43/00A61K38/06A61K38/07
Inventor BENNER, ROBBERTKHAN, NISAR AHMEDCARLTON, RICHARD MICHAEL
Owner BIOTEMPT
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