Method of reducing toxicity of retinoids
AssigneeWisconsin Alumni Research Foundation
InventorsHector F. DeLuca, Margaret Clagett-Dame, Margaret A. Highland
Life of this patent
Estimating the term…
Abstract
A method of minimizing or reducing the toxicity of a retinoid having a free carboxyl group is described. The method comprises the step of esterifying the carboxyl group of the retinoid with a highly sterically hindered compound, which is preferably an alcohol. The resulting retinoid esters are rendered much less toxic than the starting or parent retinoid. This process provides a retinoid ester analog of reduced toxicity so that it may be administered orally with minimal side effects and with a much greater therapeutic window.
Claims19
A method of minimizing toxicity of a retinoid having a carboxyl group, comprising the step of esterifying the carboxyl group with a highly sterically hindered alcohol, wherein the sterically hindered alcohol comprises a tertiary alcohol having the formula
- where R3, R4 and R5 which may be the same or different are each independently selected from the group consisting of a straight chain or branched alkyl group in all isomeric forms having 1 to 10 carbon atoms, and an aryl group;
- and
- formulating said ester derivative for oral or topical administration.
A method of reducing the toxicity of a retinoid which comprises:
- selecting a retinoid having a carboxyl group and having a desirable in vivo therapeutic activity;
- selecting a highly sterically hindered alcohol which when reacted with the carboxyl group of the retinoid will provide an ester derivative that will modify the in vivo activity profile of said retinoid by reducing its in vivo toxicity wherein the sterically hindered alcohol comprises a tertiary alcohol having the formula
- where R3, R4 and R5 which may be the same or different are each independently selected from the group consisting of a straight chain or branched alkyl group in all isomeric forms having 1 to 10 carbon atoms, and an aryl group;
- modifying the retinoid by derivatizing the carboxyl group with said highly sterically hindered alcohol to obtain said ester deserivated;
- and
- formulating said ester derivative for oral or topical administration.
A method of modulating the activity profile of a retinoid, comprising the steps of:
- selecting a retinoid having a carboxyl group and having an in vivo therapeutic activity profile;
- and
- prolonging the activity profile of said retinoid by:
- (a) selecting a highly sterically hindered alcohol which is hydrolyzable in vivo to the carboxyl group at a desired rate wherein the sterically hindered alcohol comprises a tertiary alcohol having the formula
- where R3, R4 and R5 which may be the same or different are each independently selected from the group consisting of a straight chain or branched alkyl group in all isomeric forms having 1 to 10 carbon atoms, and an aryl group;
- and
- (b) providing an esterified form of said retinoid by derivatizing the carboxyl group with said hindered alcohol, to obtain an ester derivative;
- and
- formulating said ester derivative for oral or topical administration.
Dependencies are inferred from the claim text.