US 5,498,729 A · Prodrug compositions

Abstract

Compositions degrading by hydrolysis to release a bioactive compound having carboxylic acid moieties, which are organic acid anhydrides having the following formula: ##STR1## wherein R' is a residue of a therapeutic bioactive compound, for example, a non-steroidal anti-inflammatory agent; a penicillin or cephalosporin antibiotic; or bioactive compounds for non-therapeutic use, for example, herbicides, insecticides, fungicides, antimicrobials, pesticides, pheromones, and fertilizers; m is an integer of between 1 and 3; and R is a carrier. The resulting mixed anhydrides are characterized by having between one and three drug molecules attached to a single carrier molecule. The prodrugs are highly susceptibility to hydrolytic degradation in a predictable and controlled fashion, have variable solubilities in water and lipids, with increased biomembrane transport, elicit a bio-affecting/pharmacological response, and are less irritating to topical and gastric or intestinal mucosal membranes.

Claims11

Dependent claims

A mixed anhydride having the formula ##STR4## wherein R is selected from the group consisting of C.sub.2-24 alkenyl;

C.sub.5-6 cycloalkyl;
C.sub.2-8 cycloalkenyl;
aryl C.sub.1-6 alkyl;
C.sub.1-6 alkyl-aryl;
CH.sub.3 (CH.sub.2 --CH.sub.2 --O)n, where n is between 1 and 50;
CH.sub.3 (CH.sub.2 CHCH.sub.3 O)n, where n is between 1 and 50;
lactic and glycolic oligomers of Mn<3,000;
caprolactone oligomers of Mn<3,000;
amino acids;
peptides;
saccharides;
and heterocyclic compounds, selected from the group consisting of nicotinic acid, and hydroxy, carboxy and halogen substituted nicotinic acids;
R' is derived from a compound selected from the group consisting of acetylsalicylic acid;
salicylic acid;
indomethacin;
sulindac;
naproxen;
fenoprofen;
ibuprofen, ketoprofen;
diflunisal;
tolmetin;
flurbiprofen;
mefenamic acid;
suprofen;
and tolfenamic acid;
m is an integer of between 1 and 3;
and
wherein R and R' are different.

25 more elements

Dependencies are inferred from the claim text.

Prodrug compositions

Life of this patent

Prodrug compositions

Life of this patent

Abstract

Claims11