VITAMIN-CE, A NOVEL PRODRUG FORM OF VITAMIN-E

Reaction of 5a-bromo-alpha-tocopherol with ascorbic acid produces 5a-t ocopheryl ascorbate which is designated ''vitamin CE.'' This novel toc opherol derivative represents an interesting prodrug form of alpha-toc opherol (vitamin E) that is stable under acidic conditions, but regene rates finely dispersed vitamin E in basic media. The reaction mechanis m of the base-induced decomposition of vitamin CE involves elimination of ascorbate and production of an ortho-quinone methide intermediate that oxidizes ascorbate, and is reduced to vitamin E. Kinetic experime nts showed the reaction to proceed in the pH range of 8 to 11 under ph ysiological conditions. Tissue culture measurements demonstrated that vitamin E generated from the novel derivative is absorbed at much high er rates than conventional preparations and can even be absorbed under simulated conditions of malabsorption where there Is no uptake of con ventional vitamin E medications.