Pharmaceutical composition
View Patent ↗Pharmaceutical composition which comprises an insulin sensitivity enhancer in combination with other antidiabetics differing from the enhancer in the mechanism of action, which shows a potent depressive effect on diabetic hyperglycemia and is useful for prophylaxis and treatment of diabetes.
1. A method for treating circulatory disorders in a mammal in need thereof, which comprises administering to said mammal a therapeutically effective amount of an insulin sensitivity enhancer in combination with a biguanide, wherein the insulin sensitivity enhancer is a compound represented by the formula:
wherein R represents an optionally substituted hydrocarbon or heterocyclic group; Y represents a group represented by —CO—, —CH(OH)— or —NR 3 — wherein R 3 represents an optionally substituted alkyl group; m is 0 or 1; n is 0, 1 or 2; X represents CH or N; A represents a bond or a C 1-7 divalent aliphatic hydrocarbon group; Q represents oxygen atom or sulfur atom; R 1 represents hydrogen atom or an alkyl group; ring E may optionally have 1 to 4 further substituents, and the substituents may optionally be combined with R 1 to form a ring; L and M respectively represent hydrogen atom, or L and M may optionally be combined with each other to form a bond; or a pharmacologically acceptable salt thereof.
2. The method according to claim 1 , wherein R is an optionally substituted heterocyclic group.
3. The method according to claim 1 , wherein m is 0.
4. The method according to claim 1 , wherein X is CH.
5. The method according to claim 1 , wherein R 1 is hydrogen atom.
6. The method according to claim 1 , wherein the partial formula:
wherein R 2 represents hydrogen atom, an alkyl group, an optionally substituted hydroxyl group, a halogen atom, an optionally substituted acyl group, nitro group or an optionally substituted amino group.
7. The method according to claim 1 , wherein L and M are hydrogen atoms.
8. The method according to claim 1 , wherein R is pyridyl, oxazolyl or thiazolyl group optionally having 1 to 3 substituents selected from C 1-3 alkyl, furyl, thienyl, phenyl and naphthyl; m is 0; n is 0 or 1; X is CH; A is a bond or —(CH 2 ) 2 —; R 1 is hydrogen atom, wherein the partial formula:
and wherein R 2 is hydrogen atom or C 1-4 alkoxy group; and L and M are both hydrogen atoms.
9. The method according to claim 1 , wherein the insulin sensitivity enhancer is pioglitazone or its hydrochloride.
10. The method according to claim 1 , wherein the biguanide is selected from the group consisting of phenformin, metformin and buformin.
11. The method according to claim 1 , wherein the biguanide is metformin.
12. The method according to claim 1 , wherein the insulin sensitivity enhancer is pioglitazone or its hydrochloride and the biguanide is metformin.
13. The method according to claim 1 , wherein the insulin sensitivity enhancer is 5-[[4-[2-(methyl-2-pyridylamino)ethoxy]phenyl]-methyl]-2,4-thiazolidinedione or its pharmacologically acceptable salt.
14. The method according to claim 1 , wherein the insulin sensitivity enhancer and biguanide are mixed together to form an admixture and the admixture is administered to the mammal.
15. The method according to claim 1 , wherein the insulin sensitivity enhancer and biguanide are not mixed together but are administered independently to the mammal.