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Prevention of nuclear, solar, and other radiation-induced tissue damage

A technology of ionizing radiation and ionizing radiation exposure, applied in the directions of X-ray/γ-ray/particle irradiation therapy, drug combination, active ingredients of phosphorus compounds, etc.

Inactive Publication Date: 2009-11-11
IP 6 RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

With the exception of a compound called WR2727, none of these compounds have proven useful in military or industrial situations or in cancer radiation therapy

Method used

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  • Prevention of nuclear, solar, and other radiation-induced tissue damage
  • Prevention of nuclear, solar, and other radiation-induced tissue damage
  • Prevention of nuclear, solar, and other radiation-induced tissue damage

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0121] Enhanced cell viability by administering myo-inositol / IP-6 compound following standard procedures of irradiation:

[0122] Human keratinocytes (HaCaT) were cultured in Dulbecco's solution containing 7 mg / L inositol (38.8 μM) supplemented with 10% heat-inactivated fetal bovine serum, 1% L-glutamine, and 1% antibiotics (penicillin, streptomycin). Grow in modified Eagle's medium. Keep cells at 37 °C and 5% CO 2 . Na-IP-6 was diluted from a 100 mM stock solution to the desired concentration (0.05-2.0 mM) using cell culture medium as a diluent. Use 15, 30, 60 and 120mJ / cm 2 The UVB intensity obtained by varying the exposure time of the cells to UVB light (80% of the light output is in the 290-320 nm UVB range).

[0123] HaCaT cells were grown to approximately 80-90% confluency. 100 μL of 1 x 10 4 cells / mL HaCaT cells were seeded in each well of four 96-well plates. Treat cells with IP-6 (0-2.0 mM) and add 100 μL of 1 mg / mL aqueous MTT dissolved in DMEM medium to each ...

Embodiment 2

[0128] Effects of IP-6 and UVB radiation on attached cells

[0129] will be 5×10 4 HaCaT cells were seeded into each well of four 6-well tissue culture plates and incubated at 37 °C and 5% CO 2 Incubate for 24 hours. One hour before UVB irradiation, two plates were treated with IP-6 (0 and 0.1 mM), one for IP-6 pretreatment and the other for IP-6 pretreatment and posttreatment. All four plates were then washed twice with PBS 1X, and a small amount of PBS 1X was added to the wells at 30 mJ / cm 2 irradiated. After UVB exposure, PBS was removed from the wells, and DMEM medium was added to each well. IP-6 (0.05 and 0.1 mM) was then added to non-UVB exposed, IP-6 post-treated, and pre- and post-treated labeled plates. The cells were then incubated (37°C and 5% CO 2) for 18 hours. After incubation, cells were washed 4 times with PBS 1X (pH 7.4), then fixed with 4.0% formaldehyde for 15 minutes, and stained with 0.5% aqueous crystal violet for at least 5 minutes. Excess crysta...

Embodiment 3

[0133] Effects of IP-6 and UVB radiation on the apoptosis of HaCaT cells

[0134] HaCaT cells were plated onto 60mm tissue culture dishes for 24 hours. Cells were then left unexposed or exposed to 30mJ / cm 2 UVB irradiation and immediate treatment with 0, 0.5 mM or 1.0 mM IP-6. Cells were harvested 6 and 18 hours after UVB exposure. Add 5 μL RNase (DNase-free) to 10 6 cells / mL. The cell suspension was incubated at 37°C for 30 minutes. The suspension was then frozen on ice (2-8°C). 100 μL of PI was added to the cell suspension (Cellular DNA Flow Cytometry Analysis Kit, Roche Diagnostics, Indianapolis, IN). DNA quantification was performed on the same day by flow cytometry using FACS.

[0135] Compared with the non-UVB exposure control group, at 30mJ / cm 2 Six hours after UVB irradiation, the G1 phase was significantly increased while the S phase was significantly decreased, p<0.001. However, G2M phase was not significantly different between exposed and non-exposed groups...

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Abstract

Inositol hexaphosphate (IP-6) is a polyphosphorylated carbohydrate with potent antioxidant activity to prevent active oxygen species-mediated mutagenesis, cell injury and carcinogenesis. IP-6 also activates DNA repair mechanisms. Sublethal radiation causes DNA damage through the formation of free radicals, reactive oxygen species, and pyrimidine crosslinks leading to cellular proliferation, cell cycle arrest and apoptosis. In the skin it results in the induction of skin cancer, premature skin aging, immuno-suppression, inflammation, and cell death. Likewise sublethal exposure to ionizing radiation as in nuclear blasts (war-time, accidental, terrorist-induced etc), cosmic radiation, etc. also causes the same spectrum of damage to the cells and the organisms with acute symptoms and eventual high risk of many cancers. IP-6 and / or inositol and their pharmaceutically acceptable salts and derivatives, including pyrophosphates and citrate derivatives, significantly counteract the harmful effects of radiation, affecting cell cycle progression in a protective manner (more cells in the protective GI phase) as well as decreasing apoptosis and caspase-3 activation. Various salts of IP-6 are used with comparable efficacy and the combination of IP-6+inositol affords the best protection against radiation-induced cell injury. Thus IP-6 and inositol are effective agents for protection against nuclear, solar and other radiation injuries.

Description

field of invention [0001] The present invention relates to the field of protecting mammalian cells and tissues from the adverse effects of intended, planned or unintentional exposure to radiation, in particular exposure to ionizing radiation. In particular, the present invention relates to inositol hexaphosphate (IP-6) and its derivatives (including pyrophosphate and citrate derivatives) with or without inositol before, during or after radiation exposure. Administration to mammalian individuals or mammalian cells for the prophylaxis or treatment of exposure to solar radiation, nuclear radiation, cosmic radiation and other forms of electromagnetic or particulate radiation (including such radiation exposure as occurs during anticancer radiotherapy) Use for damage to mammals and their tissues and cells. Background of the invention [0002] Radiation is energy distributed across the electromagnetic spectrum that interacts with matter in a manner described by reference to waves ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A01N57/00A61K31/66
CPCA61K31/66A61N2005/1094A61P17/18A61P39/06A61P43/00
Inventor A·M·沙姆斯丁I·武塞尼克
Owner IP 6 RES
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