Kent State University

University of Chester

Nicola E Brasch

John Henry Howatson Williams

Ling Xia

Catherine Stephanie Birch

Edward Suarez-Moreira

Therapeutic applications, such as prevention, treatment and supplementation, for the use of novel and other thiolatocobalamins to protect human cells against the effects of oxidative stress. In particular, this invention relates to the use of a novel synthetic thiolatocobalamin, N-acetyl-L-cysteinylcobalamin (NACCbl) to protect animal cells against oxidative stress damage. This invention also relates to the use of thiolatocobalamins, such as NACCbl, in lieu of current, commercially available forms of vitamin Bfor the treatment and prevention of conditions associated with oxidative stress damage and for dietary supplementation.

[object Object]

The invention provides a method for preparing the sodium salt of the novel thiol derivative of vitamin B, N-acetyl-L-cysteinylcobalamin (Na[NACCbl]). The method involves carrying out the reaction in aqueous solvent with a relatively small excess of ligand reactant, specifically from one to less than four molar equivalents. The cobalamin derivative formed is precipitated from the aqueous solvent, preferably by the addition of a precipitate inducing solvent. This provides a product in acceptable purity without the need for an additional chromatographic purification step.

Method of synthesis of a salt of N-acetyl-L-cysteinylcobalamin

The invention provides a method for preparing glutathionylcobalamin (GluSCbl) which involves running the reaction in an aqueous solvent with a relatively small excess of glutathione, i.e. GluSH, specifically from one to less than four molar equivalents of GluSH. The formed GluSCbl is precipitated from the aqueous solvent, preferably by the addition of a precipitate inducing solvent. This provides GluSCbl in acceptable purity without the need for an additional chromatographic purification step. Additionally, it has been found that the reaction can be run to an acceptable level of purity by using very high concentrations of the reactants, i.e. around saturation concentrations for aquocobalamin. This has the advantage of eliminating the need for air-free conditions.

Growing community of inventors

Kent, OH, United States of America

Nicola E Brasch