Methods of Making Deuterium-Enriched N-acetylcysteine Amide (D-NACA) and (2R, 2R')-3,3'-Disulfanediyl BIS(2-Acetamidopropanamide) (DINACA) and Using D-NACA and DINACA to Treat Diseases Involving Oxidative Stress

Abstract

The present invention includes pharmaceutical composition comprising (2R,2R′)-3,3′-disulfanediyl bis(2-acetamidopropanamide)(diNACA) or D₃-N-acetyl cysteine amide, or a physiologically acceptable salt thereof, having a deuterium enrichment above the natural abundance of deuterium, and derivatives or solids thereof, and methods of using diNACA to treat eye diseases and other diseases associated with oxidative damage including, e.g., antivenom, beta-thallassemia, cataract, chronic obstructive pulmonary disease, macular degeneration, contrast-induced nephropathy, asthma, lung contusion, methamphetamine-induced oxidative stress, multiple sclerosis, Parkinson's disease, platelet apoptosis, Tardive dyskinesia, Alzheimer disease, HIV-1-associated dementia, mitochondrial diseases, myocardial myopathy, neurodegenerative diseases, pulmonary fibrosis, skin pigmentation, skin in need of rejuventation, antimicrobial infection, Friedreich's ataxia.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Application Ser. No. 62 / 583,984, filed Nov. 9, 2017 and U.S. Provisional Application Ser. No. 62 / 587,246, filed Nov. 16, 2018, the entire contents of which are incorporated herein by reference.STATEMENT OF FEDERALLY FUNDED RESEARCH[0002]None.TECHNICAL FIELD OF THE INVENTION[0003]The present invention relates in general to the field of making (2R,2R′)-3,3′-disulfanediyl bis(2-acetamidopropanamide) (diNACA), pharmaceutical compositions, and methods of making and using NACA-d3 to treat diseases associated with oxidative damage including, but not limited to, antivenom, beta-thallassemia, cataract, chronic obstructive pulmonary disease, macular degeneration, contrast-induced nephropathy, asthma, lung contusion, methamphetamine-induced oxidative stress, multiple sclerosis, Parkinson's disease, platelet apoptosis, Tardive dyskinesia, Alzheimer disease, HIV-1-associated dementia, mitochondrial ...

AI Technical Summary

Problems solved by technology

These modifications can impair the function of macromolecules and while there are endogenous repair processes, they are overwhelmed by severe oxidative stress resulting in reduced cellular function and eventually apoptosis.

The posterior spread of cone death results in constriction of the visual field and eventually a central island of vision and its elimination causes blindness.

Currently, there is no approved therapy that stops the evolution of the disease or restores vision.

The therapeutic approach is restricted to slowing down the degenerative process by sunlight protection and vitamin A supplementation, treating complications (cataract and macular edema), and helping patients to cope with the social and psychological impact of blindness.

Although the Argis II Retinal Prosthesis System was approved by FDA in 2013 as an implanted Humanitarian device (HUD) to treat adults with several RP, it only produces the sensation of light, thereby helping patients identify the location or movement of objects and people; the device is not disease modifying.

Images