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|Abstract:||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.|
|Inventor(s):||Ikeda; Hitoshi (Higashiosaka, JP), Sohda; Takashi (Takatsuki, JP), Odaka; Hiroyuki (Kobe, JP)|
|Assignee:||Takeda Chemical Industries, Ltd. (Osaka, JP)|
|Filing Date:||Jun 17, 2003|
|Claims:||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: ##STR8## |
wherein R represents an optionally substituted hydrocarbon or heterocyclic group; Y represents a group represented by --CO--, --CH(OH)-- or --NR.sup.3 -- wherein R.sup.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.sub.1-7 divalent aliphatic hydrocarbon group; Q represents oxygen atom or sulfur atom; R.sup.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.sup.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.sup.1 is hydrogen atom.
6. The method according to claim 1, wherein the partial formula: ##STR9##
wherein R.sup.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.sub.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.sub.2).sub.2 --; R.sup.1 is hydrogen atom, wherein the partial formula: ##STR10##
and wherein R.sup.2 is hydrogen atom or C.sub.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-thiazolidinedio ne 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.
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