Abstract: The present invention relates in general to compositions and methods for treating an animal or human patient in need of treatment for ophthalmic diseases or conditions involving oxidative stress and treatment with an ophthalmic implant containing (2R,2R?)-3,3?-disulfanediyl bis(2-cetamidopropanamide) (diNACA), wherein such ophthalmic diseases or conditions include but not limited to cataracts, cataracts in a subject that does not have diabetes, corneal endothelial cell loss, age-related macular degeneration, presbyopia, retinitis pigmentosa (RP), Usher syndrome, Stargardt syndrome, glaucoma, diabetic retinopathy, and/or retinal disease.

Abstract: The present invention includes a method for the treatment of age-related macular degeneration, glaucoma, or diabetic retinopathy in a human that comprises administering to the human a therapeutically effective amount of N-acetylcysteine amide (NACA) or (2R,2R?)-3,3?-disulfanediyl bis(2-acetamidopropanamide) (diNACA) sufficient to treat or reduce the symptoms of the age-related macular degeneration, glaucoma, or diabetic retinopathy.

Abstract: The present invention includes pharmaceutical composition comprising (2R,2R?)-3,3?-disulfanediyl bis(2-acetamidopropanamide) (diNACA), deuterated NACA-d3, deuterated di-NACA-d6, combinations thereof, 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, NACA-d3, di-NACA-d6, or combinations thereof, to treat eye diseases and other diseases associated with oxidative damage including, e.g.

Abstract: The present invention includes a method for the treatment of age-related macular degeneration, glaucoma, or diabetic retinopathy in a human that comprises administering to the human a therapeutically effective amount of N-acetylcysteine amide (NACA) or (2R,2R?)-3,3?-disulfanediyl bis(2-acetamidopropanamide) (diNACA) sufficient to treat or reduce the symptoms of the age-related macular degeneration, glaucoma, or diabetic retinopathy.

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.

Abstract: Presented herein are methods for making, isolating, and purifying N-acetylcysteine amide, (2R,2R?)-3,3?-disulfanediyl bis(2-acetamidopropanamide, diNACA), intermediates and derivatives thereof comprising: alternatively contacting cystine with methanol and a chlorinating reagent to form an organic solution containing L-cystine dimethylester dihydrochloride; combining dried or undried L-cystine dimethylester dihydrochloride with a triethylamine, an acetic anhydride, and an acetonitrile to form a di-N-acetylcystine dimethylester; mixing dried di-N-acetylcystine dimethylester with ammonium hydroxide to form a di-N-acetylcystine amide (diNACA); and separating dried di-N-acetylcystine dimethylester into N-acetylcysteine amide with dithiothreitol, triethylamine, and an alcohol.

Abstract: The present invention includes methods for making and isolating N-acetylcysteine amide, (2R,2R?)-3,3?-disulfanediyl bis(2-acetamidopropanamide, diNACA), intermediates and derivatives thereof comprising: contacting cystine with an alcohol and a chlorinating reagent to form an organic solution containing L-cystine dimethylester dihydrochloride; combining dried or undried L-cystine dimethylester dihydrochloride with a triethylamine, an acetic anhydride, and an acetonitrile to form a di-N-acetylcystine dimethylester; mixing dried di-N-acetylcystine dimethylester with ammonium hydroxide to form a di-N-acetylcystine amide (diNACA); and separating dried di-N-acetylcystine dimethylester into N-acetylcysteine amide with dithiothreitol, triethylamine and an alcohol.

Abstract: The present invention relates in general to the field of compositions and methods for using N-acetylcysteine amide (NACA) or (2R,2R?)-3,3?-disulfanediyl bis(2-acetamidopropanamide) (diNACA) for treating or alleviating a disorder or condition associated with ferroptosis, which can cause or contribute to diseases, disorders and conditions including aging associated with declining cognition, cognitive impairment, declining physical function, physical decline, elevated inflammation, endothelial dysfunction, insulin resistance, central obesity, loss of muscle mass (sarcopenia), neurological diseases and disorders, including neurodegeneration, stroke, including ischemic stroke and post-hemorrhagic stroke damage, and neurotrauma, including traumatic brain injury, Alzheimers disease, Huntington's disease, Niemann-Pick disease, Parkinson's disease, motor neuron disease, Amyotrophic Lateral Sclerosis, Sedaghatian-type spondylo-metaphyseal dysplasia, cancer, including breast cancer, kidney injuries including ischemia-re

Abstract: The present invention includes a method for the use of N-acetylcysteine (NAC), N-acetylcysteine amide (NAC A) or (2R,2R?)-3,3?-disulfanediylbis(2-acetamidopropanamide) (diNACA) for the prevention and treatment of radiation dermatitis, radiation damage to the skin, xeroderma pigmentosa or protect patients with xeroderma pigmentosa from skin damage caused by exposure to the sun or other radiation, bioweapons, chemical burns, heat burns, contact damage caused by friction, contact dermatitis, hypersensitivity reactions and skin wrinkles and dehydration, skin lightening, skin whitening, and/or skin improvement in a human that comprises administering to the human a therapeutically effective amount of NAC, NACA or diNACA.

Abstract: The present invention includes a method for the use of N-acetylcysteine amide (NACA) or (2R,2R?)-3,3?-disulfanediyl bis(2-acetamidopropanamide) (diNACA) for prevention and treatment of radiation pneumonitis and treatment of pulmonary function in Cystic Fibrosis (CF), chronic obstructive pulmonary disease (COPD), or bronchitis in a human that comprises administering to the human a therapeutically effective amount of NACA or diNACA sufficient to treat, reduce the symptoms, or prevent radiation pneumonitis and treatment of pulmonary function in Cystic Fibrosis (CF), chronic obstructive pulmonary disease (COPD), bronchitis, or respiratory disorder due to oxidative stress, and diNACA for the reduction of mucus viscosity and/or elasticity.

Abstract: The present invention includes methods for making and isolating N-acetylcysteine amide, (2R,2R?)-3,3?-disulfanediyl bis(2-acetamidopropanamide, diNACA), intermediates and derivatives thereof comprising: contacting cystine with an alcohol and a chlorinating reagent to form an organic solution containing L-cystine dimethylester dihydrochloride; combining dried or undried L-cystine dimethylester dihydrochloride with a triethylamine, an acetic anhydride, and an acetonitrile to form a di-N-acetylcystine dimethylester; mixing dried di-N-acetylcystine dimethylester with ammonium hydroxide to form a di-N-acetylcystine amide (diNACA); and separating dried di-N-acetylcystine dimethylester into N-acetylcysteine amide with dithiothreitol, triethylamine and an alcohol.

Abstract: The present invention relates in general to the field of compositions and methods for using N-acetylcysteine amide (NACA) or (2R,2R?)-3,3?-disulfanediyl bis(2-acetamidopropanamide) (diNACA) for treating cystinosis. This present invention also relates to the general field of using NAC, NACA or diNACA to treat ophthalmic, ocular or corneal effects of cystinosis. This present invention also relates to the general field of using NAC, NACA, diNACA, cysteamine (or cysteamine salts, e.g., the hydrochloride salt or other salts) or any other cystine-depleting agent for treating ophthalmic, ocular or corneal effects of cystinosis by administration in an ophthalmic or ocular insert.

Abstract: The present invention includes methods for making and isolating N-acetylcysteine amide, (2R,2R?)-3,3?-disulfanediyl bis(2-acetamidopropanamide, diNACA), intermediates and derivatives thereof comprising: contacting cystine with an alcohol and a chlorinating reagent to form an organic solution containing L-cystine dimethylester dihydrochloride; combining dried or undried L-cystine dimethylester dihydrochloride with a triethylamine, an acetic anhydride, and an acetonitrile to form a di-N-acetylcystine dimethylester; mixing dried di-N-acetylcystine dimethylester with ammonium hydroxide to form a di-N-acetylcystine amide (diNACA); and separating dried di-N-acetylcystine dimethylester into N-acetylcysteine amide with dithiothreitol, triethylamine and an alcohol.

Abstract: The present invention includes a method for using diNACA as a prodrug to deliver diNACA, NACA and NAC to a mammal for therapeutic purposes to prevent or treat diseases or disorders involving oxidative stress. The method includes any disease that involves the therapeutic use of NACA or NAC as a therapeutic agent. Also, compositions and methods for the prevention, reduction or treatment of corneal endothelial cell loss in a patient that comprise providing the patient with an amount of at least one, alone or in combination, of N-acetylcysteine amide (NACA) or (2R,2R?)-3,3?-disulfanediyl bis(2-acetamidopropanamide) (diNACA) (diNACA) to prevent or reduce the corneal endothelial cell loss or to prevent or treat presbyopia. DiNACA can be used to prevent or treat cataracts.

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.

Abstract: The present invention includes methods for making and isolating N-acetylcysteine amide, (2R,2R?)-3,3?-disulfanediyl bis(2-acetamidopropanamide, diNACA), intermediates and derivatives thereof comprising: contacting cystine with an alcohol and a chlorinating reagent to form an organic solution containing L-cystine dimethylester dihydrochloride; combining dried or undried L-cystine dimethylester dihydrochloride with a triethylamine, an acetic anhydride, and an acetonitrile to form a di-N-acetylcystine dimethylester; mixing dried di-N-acetylcystine dimethylester with ammonium hydroxide to form a di-N-acetylcystine amide (diNACA); and separating dried di-N-acetylcystine dimethylester into N-acetylcysteine amide with dithiothreitol, triethylamine and an alcohol.

Abstract: The present invention includes a method for the treatment of age-related macular degeneration, glaucoma, or diabetic retinopathy in a human that comprises administering to the human a therapeutically effective amount of N-acetylcysteine amide (NACA) or (2R,2R?)-3,3?-disulfanediyl bis(2-acetamidopropanamide) (diNACA) sufficient to treat or reduce the symptoms of the age-related macular degeneration, glaucoma, or diabetic retinopathy.

Abstract: The present invention includes a method of detecting free and total NAC, NACA, or both in a biological sample and/or the effectiveness of a treatment with NAC, NACA, or diNACA comprising: adding 2-chloro-1-methylpyridinium iodide (CMPI) to a biological sample suspected of having NAC or NACA to convert free thiols into stable thioethers; precipitating the protein in the sample; extracting the stable thioethers and separating into a first and a second extract; detecting the thioether derivatives from the first extract with LC-MS/MS; reducing from the second extract free thiols by adding tris(2-carboxyethyl)phosphine (TCEP) followed by converting to stable thioethers with CMPI; detecting the disulfides reduced to free thioether derivatives from the second extract with LC-MS/MS; and calculating from the LC-MS/MS and TCEP of the first and second extracts a free and a total sample NAC or NACA.

Abstract: The present invention includes methods for making and isolating N-acetylcysteine amide, intermediates and derivatives thereof comprising: contacting cystine with an alcohol and a chlorinating reagent to form an organic solution containing L-cystine dimethylester dihydrochloride; combining dried or undried L-cystine dimethylester dihydrochloride with a triethylamine, an acetic anhydride, and an acetonitrile to form a di-N-acetylcystine dimethylester; mixing dried di-N-acetylcystine dimethylester with ammonium hydroxide to form a di-N-acetylcystine amide; and separating dried di-N-acetylcystine dimethylester into N-acetylcysteine amide with dithiothreitol, triethylamine and an alcohol.

Abstract: The present invention includes compositions and methods for treating an eye disease caused by oxidative damage in a subject in need thereof, the method comprising: identifying or causing the subject to have a compromised blood-retinal barrier; and providing an effective amount of an N-acetylcysteine amide (NACA) sufficient to afford or reach a concentration of NACA in a retina that is greater than the concentration in plasma over the same time period.