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Claims for Patent: 6,150,383

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Claims for Patent: 6,150,383

Title: Pharmaceutical composition
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)
Application Number:09/280,710
Patent Claims: 1. A method for treating lipid metabolism disorders in a mammal in need thereof, which comprises administering to such mammal a therapeutically effective amount of 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; with a proviso that R' does not represent benzopyranyl group when m and n are O, X represents CH, A represents a bond, Q represents sulfur atom, R.sup.1, L and M represent hydrogen atoms and ring E does not have further substituents; or a pharmacologically acceptable salt thereof, in combination with an insulin secretion enhancer.

2. The method according to claim 1, wherein the compound represented by the formula (II) is the compound represented by the formula: ##STR9##

3. The method according to claim 1, wherein the compound represented by the formula (II) is pioglitazone.

4. The method according to claim 1, wherein the insulin secretion enhancer is glibenclamide.

5. The method according to claim 1, wherein the compound represented by the formula (II) is pioglitazone and the insulin secretion enhancer is glibenclamide.

6. The method according to claim 1, wherein the compound is 5-[[4-2-(methyl-2-pyridylamino) ethoxy]phenyl]-methyl]-2,4, -thiazolidinedione or its pharmacologically acceptable salt thereof.

7. The method according to claim 1, wherein the compound represented by the formula (II) is troglitazone.

8. The method according to claim 1, wherein the insulin secretion enhancer is a sulfonylurea.

9. The method according to claim 8, wherein the sulfonylurea is selected from tolbutamide, chlorpropamide, tolazamide, acetohexamide, 4-chloro-N-[(1-pyrolidinylamino)carbonyl]-benzenesulfonamide or its ammonium salt, glibenclamide, gliclazide, 1-butyl-3-metanilylurea, carbutamide, glibonuride, glipizide, gliquidone, glisoxepid, glybuthiazole, glibuzole, glyhexamide, glymidine, glypinamide, phenbutamide and tolcyclamide.

10. A method for treating glycometabolism disorders in a mammal in need thereof, which comprises administering to such mammal a therapeutically effective amount of 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.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; with a proviso that R' does not represent benzopyranyl group when m and n are O, X represents CH, A represents a bond, Q represents sulfur atom, R.sup.1, L and M represent hydrogen atoms and ring E does not have further substituents; or a pharmacologically acceptable salt thereof, in combination with an insulin secretion enhancer.

11. The method according to claim 10, wherein the compound represented by the formula (II) is the compound represented by the formula: ##STR10##

12. The method according to claim 10, wherein the compound represented by the formula (II) is pioglitazone.

13. The method according to claim 10, wherein the insulin secretion enhancer is glibenclamide.

14. The method according to claim 10, wherein the compound represented by the formula (II) is pioglitazone and the insulin secretion enhancer is glibenclamide.

15. The method according to claim 10, wherein the compound is 5-[[4-2-(methyl-2-pyridylamino) ethoxy]phenyl]-methyl]-2,4, -thiazolidinedione or its pharmacologically acceptable salt thereof.

16. The method according to claim 10, wherein the compound represented by the formula (II) is troglitazone.

17. The method according to claim 10, wherein the insulin secretion enhancer is a sulfonylurea.

18. The method according to claim 17, wherein the sulfonylurea is selected from tolbutamide, chlorpropamide, tolazamide, acetohexamide, 4-chloro-N-[(1-pyrolidinylamino)carbonyl]-benzenesulfonamide or its ammonium salt, glibenclamide, gliclazide, 1-butyl-3-metanilylurea, carbutamide, glibonuride, glipizide, gliquidone, glisoxepid, glybuthiazole, glibuzole, glyhexamide, glymidine, glypinamide, phenbutamide and tolcyclamide.
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