Methods and reagents for the treatment of metabolic disorders
The invention features compositions, methods, and kits for the treatment of metabolic disorders such as diabetes and obesity.
1. A composition consisting of active and inert ingredients, wherein the sole active ingredients are:
(a) a fibrate selected from the group consisting of bezafibrate, binifibrate, ciprofibrate, clinofibrate, clofibrate, etofibrate, fenofibrate, and gemfibrozil; and
(b) diflunisal, a diflunisal analog, cinnamic acid, or a cinnamic acid analog, wherein said diflunisal analog has the structure of formula (III):
wherein each X is, independently, a halogen atom; R 1 is hydroxy, phenoxy, di(C 1 -C 4 )alkylamino, di(C 1 -C 4 )alkylamino, or (C 1 -C 4 )alkoxy; R 2 is hydrogen or (C 1 -C 4 )alkanoyl; and R 3 is hydrogen or methyl;
wherein said cinammic acid analog has the structure of formula (II):
wherein R 1 and R 2 are each, independently, a hydrogen atom or a C 1-4 alkyl group; R 3 and R 4 each represent a hydrogen atom or may be combined together to form an additional chemical bond; n is zero or an integer from 1 to 3; each X is, independently, a hydroxyl group, a halogen atom, a straight or branched chain saturated or unsaturated C 1-4 alkyl group, a straight or branched chain saturated or unsaturated C 1-4 alkoxy group, a C 1-4 acyloxy group, or a C 3-6 cycloalkyl group; when n is 2 or 3 and two X's are commonly C 1-4 alkyl or C 1-4 alkoxy, both X's may be combined together to form a ring.
2. A composition consisting of active and inactive ingredients, wherein the sole active ingredients are bezafibrate and diflunisal.
3. A composition consisting of active and inactive ingredients, wherein the sole active ingredients are bezafibrate and cinnamic acid.
4. A composition consisting of active and inactive ingredients, wherein the sole active ingredients are:
(a) bezafibrate or a bezafibrate analog having a structure of formula (I):
wherein R 1 and R 2 are each, independently, hydrogen, halogen, C 1-4 alkyl, or C 1-4 alkoxy; R 3 and R 4 are each, independently, hydrogen or C 1-4 alkyl; n is 1, 2, or 3; and Z is hydroxyl or C 1-4 alkyl; and
(b) diflunisal, a diflunisal analog, cinnamic acid, or a cinnamic acid analog; wherein said diflunisal analog has the structure of formula (III):
wherein each X is, independently, a halogen atom; R 1 is hydroxy, phenoxy, di(C 1 -C 4 )alkylamino, di(C 1 -C 4 )alkylamino, or (C 1 -C 4 )alkoxy; R 2 is hydrogen or (C 1 -C 4 )alkanoyl; and R 3 is hydrogen or methyl;
wherein said cinnamic acid analog has the structure of formula (II):
wherein R 1 and R 2 are each, independently, a hydrogen atom or a C 1-4 alkyl group; R 3 and R 4 each represent a hydrogen atom or may be combined together to form an additional chemical bond; n is zero or an integer from 1 to 3; each X is, independently, a hydroxyl group, a halogen atom, a straight or branched chain saturated or unsaturated C 1-4 alkyl group, a straight or branched chain saturated or unsaturated C 1-4 alkoxy group, a C 1-4 acyloxy group, or a C 3-6 cycloalkyl group; when n is 2 or 3 and two X's are commonly C 1-4 alkyl or C 1-4 alkoxy, both X's may be combined together to form a ring.
5. The composition of claim 4 , wherein said bezafibrate analog is selected from the group consisting of alpha-[4-(2-methoxy-5-chlorobenzoylaminoethyl)-phenoxy]-isobutyric acid, alpha-[4-(4-methylbenzoylaminomethyl)-phenoxy]-isobutyric acid, alpha-[4-(2-methylbenzoylaminoethyl)-phenoxy]isobutyric acid, and alpha-[4-(4-chlorobenzoylaminoethyl)-phenoxy]-proprionic acid.
6. The composition of claim 4 , wherein said bezafibrate or bezafibrate analog and said diflunisal, diflunisal analog, cinnamic acid, or cinnamic acid analog are present in amounts that, when administered to a patient, are sufficient to treat or reduce type II diabetes.