Compositions and method comprising aminoalcohol derivatives as membrane penetration enhancers for physiological active agents

A method of enhancing the rate of dermal or mucosal membrane absorption of a topically administrable composition for local or systemic application, said method comprising the step of applying to a mucosal or dermal tissue of a patient a therapeutically effective dosage amount of a physiologically active agent in admixture with a non-toxic, effective amount of a membrane penetration enhancing agent having the structure shown in formula I, ##STR6## wherein R is selected from H, and an aliphatic hydrocarbon group with from about 1 to about 20 carbon atoms, optionally containing a heteroatom in the hydrocarbon chain;

• R1 is selected from H, OH or O-CO-R5, where R5 is an aliphatic hydrocarbon group with from about 1 to about 18 carbon atoms;
• R2 is selected from H, a lower aliphatic hydrocarbon group, acyl, hydroxyacyl or alkoxyoxyacyl group with up to about 40 carbon atoms;
• R3 is selected from H, an aliphatic hydrocarbon group with up to about 16 carbon atoms unsubstituted or substituted with hydroxy, acyloxy or alkytthio, or an aryl or aralkyl group;
• and
• R4 is H or an acyl group with from 2 to about 18 carbon atoms;
• or
• R, R2 and R3 are as defined above, and R1 and R4 together form a compound having a 1,3-dioxane ring, of the structure ##STR7## wherein, R6 and R7 are selected from H, an aliphatic hydrocarbon group unsubstituted or substituted with hydroxy, acyloxy, or carbalkoxy, or an aryl group, or they may combine to form a carbonyl group.

A method of treating a physiological dissorder in a human or other animal in need thereof comprising applying to the skin or mucosal membrane of the human or other animal a composition comprising a physiological active agent and a non-toxic amount sufficient to assure penetration through the skin or mucous membrane of an agent of Formula I:

• ##STR8## wherein:
• R is selected from H, and an aliphatic hydrocarbon group with from about 1 to about 20 carbon atoms, optionally containing a heteroatom in the hydrocarbon chain;
• R1 is selected from H, OH or O-CO-RS, where R5 is an aliphatic hydrocarbon group with from about 1 to about 18 carbon atoms;
• R2 is selected from H, a lower aliphatic hydrocarbon group, acyl, hydroxyacyl or alkoyloxyacyl group with up to about 40 carbon atoms;
• R3 is selected from H, an aliphatic hydrocarbon group with up to about 16 carbon atoms, unsubstituted or substituted with hydroxy, acyloxy or alkylthio or an aryl or aralkyl group;
• and
• R4 is H or an acyl group with from about 1 to about 18 carbon atoms;
• or
• R1 OH and R4 are combined to form a 1,3-dioxane ring, ##STR9## wherein, R6 and R7 are selected from H, an aliphatic hydrocarbon group unsubstituted or substituted with hydroxy, acyloxy, or carboalkoxy, or an aryl group, or they may combine to form a carbonyl group,
• or a physiologically acceptable salt thereof.