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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:||Jul 06, 2000|
|Claims:||1. A method for reducing the side effects of active components administered to a diabetic patient, which comprises administering to said patient a therapeutically effective amount of insulin sensitivity enhancer in combination with an aldose reductase inhibitor as said active components. |
2. The method according to claim 1, 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 an oxygen atom or sulfur atom; R.sup.1 represents a hydrogen atom or an alkyl group; ring E may optionally have further 1 to 4 substituents, and the substituents may optionally be combined with R.sup.1 to form a ring; L and M respectively represent hydrogen atoms, or L and M may optionally be combined with each other to form a bond; or a pharmacologically acceptable salt thereof.
3. The method according to claim 2, wherein R is an optionally substituted heterocyclic group.
4. The method according to claim 2, wherein m is 0.
5. The method according to claim 2, wherein X is CH.
6. The method according to claim 2, wherein R.sup.1 is hydrogen atom.
7. The method according to claim 2, 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.
8. The method according to claim 2, wherein L and M are hydrogen atoms.
9. The method according to claim 2, 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; the partial formula: ##STR10##
and R.sup.2 is hydrogen atom or C.sub.1-4 alkoxy group; and L and M are both hydrogen atoms.
10. The method according to claim 2, wherein the compound represented by the formula (I) is pioglitazone.
11. The method according to claim 1, wherein the insulin sensitivity enhancer is pioglitazone or its pharmacologically acceptable salts.
12. The method according to claim 1, wherein the insulin sensitivity enhancer is troglitazone or its pharmacologically acceptable salts.
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 salts.
14. The method according to claim 1, wherein the aldose red uctase inhibitor is selected from the group consisting of tolurestat; epalrestat; 3,4-dihydro-2,8-diisopropyl-3-thioxo-2H-1,4-benzoxazine-4-acetic acid; imirestat; zenarestat; 6-fluoro-2,3-dihydro-2',5'-dioxo(spiro-4H-1-benzopyran-4,4'-imidazolidine) -2-carboxamide; zopolrestat; sorbinil; and 1-((3-bromo-2-benzofuranyl)sulfonyl)-2,4-imidazolidinedione.
15. The method according to claim 1, wherein the insulin sensitivity enhancer and aldose reductase inhibitor are mixed together to form an admixture and the admixture is administered to the mammal.
16. The method according to claim 1, wherein the insulin sensitivity enhancer and aldose reductase inhibitor are not mixed together but are administered independently to the mammal.
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