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N-acetylcysteine amide (NAC amide) for the treatment of diseases and conditions associated with oxidative stress

A amide and disease technology, applied in the field of antioxidant treatment of mammals including human diseases, can solve toxic and other problems

Inactive Publication Date: 2008-07-30
格伦·A·戈尔茨坦
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

GSH can be toxic, especially in ascorbate-deficient conditions, as demonstrated when 3.75 mmol / kg (1,152 mg / kg per day) was given in three divided doses to ascorbate-deficient guinea pigs, but not in non-ascorbate-deficient animals In , no toxicity was observed at this dose, but toxicity occurred at double the dose

Method used

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  • N-acetylcysteine amide (NAC amide) for the treatment of diseases and conditions associated with oxidative stress
  • N-acetylcysteine amide (NAC amide) for the treatment of diseases and conditions associated with oxidative stress
  • N-acetylcysteine amide (NAC amide) for the treatment of diseases and conditions associated with oxidative stress

Examples

Experimental program
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Effect test

Embodiment 1

[0218] In this example, the protective effect of NAC amide against glutamate-induced oxidative toxicity in PC12 cells was assessed.

[0219] Materials and methods: N-(1-pyrenyl)-maleimide (NPM) was purchased from Aldrich (Milwaukee, WI, USA). N-acetyl cysteine ​​amide was purchased from Novia Pharmaceuticals, (Israel). High performance liquid chromatography (HPLC) grade solvents were purchased from Fisher Scientific (Fair Lawn, NJ). All other chemicals were purchased from Sigma (St. Louis, MO, USA).

[0220] Cell culture and toxicity studies: stock cultures of PC12 cells purchased from ATCC were grown in 75 cm 2 Grow in RPMI 1640 supplemented with 10% (v / v) heat-inactivated horse serum and 5% (v / v) fetal bovine serum in tissue culture flasks, add 1% (v / v) penicillin and strepto Mycin. Maintain the medium at 37 °C with 5% CO 2 in a humid atmosphere. Cells were passaged twice a week. Unless otherwise stated, all experiments used Dulbecco's modified Eagle's medium (DMEM) a...

Embodiment 2

[0241] This example detects the radioprotective effect of NAC amide. To assess the protective effect of NAC amide against radiation exposure, the radioprotective effect of NAC amide was compared with that of NAC in terms of increasing GSH levels and restoring oxidative stress parameters to their normal control values.

[0242] Animal studies: Rats were irradiated at the Radiation Oncology Department of the Phelps County Regional Medical Center, Rolla, MO, USA, using a 16 MeV beam generated by a Varian linear accelerator, model Clinac 1800, according to standards of humane laboratory animal practice. Use 20×20 or 25×25cm to irradiate the field, and check the output coefficient once a week. 12 animals were divided into 4 groups, each group consisted of 3 animals (control, XRT, NACamide+XRT and NAC+XRT groups). The radiation (XRT) control group received whole-body irradiation of 6Gy 16MeV electrons. The NACamide+XRT group received 500 mg / kg / day of NACamide shortly before irradi...

Embodiment 3

[0320] This example describes a treatment regimen suitable for humans. NACamide was administered between meals (on an empty stomach), 1-3 grams per day, in 2 divided doses. Encapsulated NAC amide is suitable for administration (NAC amide formulation containing 500 mg NAC amide and optionally 250 mg USP grade crystalline ascorbic acid and not more than 0.9 mg magnesium stearate (NF grade) in an OO-type gelatin capsule). Although the human body produces large amounts of glutathione, administration of exogenous NAC amide is also expected to produce a dose-response effect in patients.

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Abstract

Compositions containing N-acetylcysteine ​​amide (NAC amide) and derivatives thereof, and their use in the treatment and therapy of diseases, conditions, disorders and conditions in humans and non-human mammals. Administration of pharmaceutically or physiologically acceptable compositions of NAC amide or derivatives thereof alone or in combination with other suitable drugs to reduce, prevent or antagonize oxidative stress and the formation and excess of free radical oxidants in cells and tissues Produce, and provide a new source of glutathione.

Description

field of invention [0001] The present invention generally relates to the treatment of diseases in mammals, including humans, with antioxidants. More specifically, the present invention relates to the treatment and therapy of various diseases and conditions comprising the administration of N-acetylcysteineamide (NAC amide) or derivatives thereof alone or in combination with another drug Mammals in need. Background of the invention [0002] Oxidative stress plays an important role in the progression of neurodegenerative and age-related diseases, causing protein, DNA and lipid damage. Low molecular weight, hydrophobic antioxidant compounds for the treatment of peripheral tissue diseases such as acute respiratory distress syndrome, amyotrophic lateral sclerosis, atherosclerotic cardiovascular disease, multiple organ dysfunction and central nervous system neurodegeneration , such as Parkinson's disease, Alzheimer's disease and Jacques' disease (Creutzfeldt...

Claims

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Application Information

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IPC IPC(8): A61K31/165C07C321/00
CPCY02A50/30
Inventor 格伦·A·戈尔茨坦
Owner 格伦·A·戈尔茨坦
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