The present invention relates to an industrial process for the preparation of (5S,10S)-10-benzyl-16-methyl-11,14,18-trioxo-15,17,19-trioxa-2,7,8-trithia-12-azahenicosan-5-aminium (E)-3-carboxyacrylate salt of following formula (I): wherein X is fumarate. This process comprises the following successive key steps: a kinetic resolution, formation of disulfide compound, peptide coupling, and anion exchange reaction to obtain the desired product of formula (I). ##STR00001##

The present invention relates to an industrial process for the preparation of (5S,10S)-10-benzyl-16-methyl-11,14,18-trioxo-15,17,19-trioxa-2,7,8-trithia-12-azahenicosan-5-aminium (E)-3-carboxyacrylate salt of following formula (I): wherein X is fumarate. This process comprises the following successive key steps: a kinetic resolution, formation of disulfide compound, peptide coupling, and anion exchange reaction to obtain the desired product of formula (I). ##STR00001##

A process and apparatus for oxidizing thiol compounds from an alkaline stream. The process includes passing a thiol rich alkaline stream and an oxygen containing gas to a low pressure oxidizing zone to oxidize at least a portion of the thiol compounds to disulfide compounds. A liquid stream comprising the alkali containing the disulfide compounds is passed through a pump to increase the pressure and form a pressurized alkaline stream. The pressurized alkaline stream and a sulfur lean liquid light hydrocarbon stream are introduced to a high pressure disulfide separation vessel to form a sulfur lean alkaline stream and a sulfur rich liquid light hydrocarbon stream.

A process and apparatus for oxidizing thiol compounds from an alkaline stream. The process includes passing a thiol rich alkaline stream and an oxygen containing gas to a low pressure oxidizing zone to oxidize at least a portion of the thiol compounds to disulfide compounds. A liquid stream comprising the alkali containing the disulfide compounds is passed through a pump to increase the pressure and form a pressurized alkaline stream. The pressurized alkaline stream and a sulfur lean liquid light hydrocarbon stream are introduced to a high pressure disulfide separation vessel to form a sulfur lean alkaline stream and a sulfur rich liquid light hydrocarbon stream.

A process and apparatus for oxidizing thiol compounds from an alkaline stream. The process includes passing a thiol rich alkaline stream and an oxygen containing gas to a low pressure oxidizing zone to oxidize at least a portion of the thiol compounds to disulfide compounds. A liquid stream comprising the alkali containing the disulfide compounds is passed through a pump to increase the pressure and form a pressurized alkaline stream. The pressurized alkaline stream and a sulfur lean liquid light hydrocarbon stream are introduced to a high pressure disulfide separation vessel to form a sulfur lean alkaline stream and a sulfur rich liquid light hydrocarbon stream.

The present invention includes pharmaceutical composition comprising deuterated NACA-d3, deuterated di-NACA-d.sub.6, 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 NACA-d.sub.3, di-NACA-d.sub.6, or combinations thereof, 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 rejuvenation, antimicrobial infection, Friedreich's ataxia.

The present invention includes pharmaceutical composition comprising deuterated NACA-d3, deuterated di-NACA-d.sub.6, 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 NACA-d.sub.3, di-NACA-d.sub.6, or combinations thereof, 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 rejuvenation, antimicrobial infection, Friedreich's ataxia.

The present invention includes pharmaceutical composition comprising (2R,2R)-3,3-disulfanediyl bis(2-acetamidopropanamide)(diNACA) or D.sub.3-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.

The present invention includes pharmaceutical composition comprising (2R,2R)-3,3-disulfanediyl bis(2-acetamidopropanamide)(diNACA) or D.sub.3-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.

Divalent salts of S-allylmercapto-N-acetylcysteine and related compositions are disclosed which can be administered in order to provide protection from the formation of aldehyde-protein adducts, protein carbonylation, protein aggregation, and the resulting neuroinflammation. Various neurodegenerative diseases which are suitable for treatment using these compositions include Alzheimer's disease, senile dementia, Parkinson's disease, multiple sclerosis, Lewy body disease, peripheral neuropathy, spinal cord injury, stroke and cerebral ischemia.