Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2001-09-26
2004-01-13
Weddington, Kevin E. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S003100
Reexamination Certificate
active
06677363
ABSTRACT:
TECHNICAL FIELD
The present invention relates to an agent for improving (ameliorating or treating) ketosis which comprises an insulin sensitizer (insulin resistance-improving agent).
Also, the present invention relates to an agent for improving (ameliorating or treating) acidosis which comprises an insulin sensitizer.
Further, the present invention relates to an agent for preventing or treating hyperosmolar nonketonic coma, infectious disease, diabetic osteoporosis, diabetic gangrene, xerostomia, lowered sense of hearing, angina pectoris, cerebrovascular disease or peripheral circulatory disturbance, which comprises an insulin sensitizer.
BACKGROUND ART
Ketosis is a condition in which a large amount of ketone bodies are accumulated in tissue and body fluids because of enhanced production of ketone bodies exceeding the body's ability to utilize them. An increase in the concentration of hydrogen ions released by the ketone bodies is known to cause acidosis.
Acidosis is a condition in which the acid-base balance of body fluids, especially blood is skewed to the acid side. Serious acidosis is known to cause disturbance of consciousness or coma.
An insulin sensitizer is also called an insulin sensitivity enhancer, and is employed as an anti-diabetic agent, if necessary in combination with other anti-diabetic agents.
JP-A H9(1997)-67271 describes “a pharmaceutical composition which comprises an insulin sensitivity enhancer in combination with at least one member selected from the group consisting of &agr;-glucosidase inhibitor, an aldose reductase inhibitor, a biguanide, a statin compound, a squalene synthesis inhibitor, a fibrate compound, a LDL catabolism enhancer and an angiotensin converting enzyme inhibitor”.
WO 98/57634 describes “a method for the treatment of diabetes mellitus and conditions associated with diabetes mellitus in a mammal, which method comprises administering an effective non-toxic and pharmaceutically acceptable amount of an insulin sensitiser and a biguanide antihyperglycaemic agent, to a mammal in need thereof”.
An insulin sensitizer is also known to be useful as an agent for the prophylaxis and treatment of cachexia (WO 97/37656).
However, there has been no report that an insulin sensitizer is useful as an agent for improving ketosis or an agent for improving acidosis.
Development of an agent for improving ketosis with excellent action and low toxicity is desired.
Further, an agent for improving acidosis with excellent action and low toxicity is also desired.
DISCLOSURE OF INVENTION
The present invention relates to
(1) an agent for improving ketosis which comprises an insulin sensitizer;
(2) an agent according to the above (1), wherein the insulin sensitizer is a compound of the formula:
wherein R represents a hydrocarbon group that may be substituted or a heterocyclic group that may be substituted; Y represents a group of the formula —CO—, —CH(OH)—, or —NR
3
— where R
3
represents an alkyl group that may be substituted; m is 0 or 1; n is 0, 1 or 2; X represents CH or N; A represents a chemical bond or a bivalent aliphatic hydrocarbon group having 1 to 7 carbon atoms; Q represents oxygen or sulfur; R
1
represents hydrogen or an alkyl group; ring E may have further 1 to 4 substituents, which may form a ring in combination with R
1
; L and M respectively represent hydrogen or may be combined with each other to form a chemical bond; or a salt thereof;
(3) an agent according to the above (1), wherein the insulin sensitizer is pioglitazone hydrochloride, troglitazone, rosiglitazone, 4-[4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]benzyl]isoxazolidin-3,5-dione or 5-[[6-(2-fluorobenzyloxy)-2-naphthyl]methyl]-2,4-thiazolidinedione;
(4) an agent according to the above (1), wherein the ketosis is diabetic ketosis;
(5) an agent according to the above (1), wherein the ketosis is ketosis caused by a biguanide;
(6) an agent according to the above (1), which is an agent for preventing or treating hepatic glycogenosis, endocrine diseases, congenital metabolic disorders of carbohydrates or organic acids, acetonemia vomiting or gastrointestinal diseases;
(7) an agent for improving acidosis which comprises an insulin sensitizer;
(8) an agent according to the above (7), wherein the insulin sensitizer is a compound of the formula:
wherein R represents a hydrocarbon group that may be substituted or a heterocyclic group that may be substituted; Y represents a group of the formula —CO—, —CH(OH)—, or —NR
3
— where R
3
represents an alkyl group that may be substituted; m is 0 or 1; n is 0, 1 or 2; X represents CH or N; A represents a chemical bond or a bivalent aliphatic hydrocarbon group having 1 to 7 carbon atoms; Q represents oxygen or sulfur; R
1
represents hydrogen or an alkyl group; ring E may have further 1 to 4 substituents, which may form a ring in combination with R
1
; L and M respectively represent hydrogen or may be combined with each other to form a chemical bond; or a salt thereof;
(9) an agent according to the above (7), wherein the insulin sensitizer is pioglitazone hydrochloride, troglitazone, rosiglitazone, 4-[4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]benzyl]isoxazolidin-3,5-dione or 5-[[6-(2-fluorobenzyloxy)-2-naphthyl]methyl]-2,4-thiazolidinedione;
(10) an agent according to the above (7), wherein the acidosis is diabetic acidosis;
(11) an agent according to the above (7), wherein the acidosis is acidosis caused by a biguanide;
(12) an agent according to the above (7), which is an agent for preventing or treating disturbance of consciousness, coma or respiratory diseases;
(13) an agent for preventing or treating hyperosmolar nonketonic coma, infectious disease, diabetic osteoporosis, diabetic gangrene, xerostomia, lowered sense of hearing, angina pectoris, cerebrovascular disease or peripheral circulatory disturbance, which comprises an insulin sensitizer;
(14) an agent according to the above (13), wherein the insulin sensitizer is pioglitazone hydrochloride, troglitazone, rosiglitazone, 4-[4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]benzyl]isoxazolidin-3,5-dione or 5-[[6-(2-fluorobenzyloxy)-2-naphthyl]methyl]-2,4-thiazolidinedione;
(15) an agent for improving ketosis which comprises an insulin sensitizer in combination with insulin;
(16) an agent for improving acidosis which comprises an insulin sensitizer in combination with insulin;
(17) method for improving or treating ketosis in a mammal in need thereof, which comprises administering to said mammal an effective amount of an insulin sensitizer;
(18) method for improving or treating acidosis in a mammal in need thereof, which comprises administering to said mammal an effective amount of an insulin sensitizer;
(19) method for preventing or treating hyperosmolar nonketoniccoma, infectious disease, diabetic osteoporosis, diabetic gangrene, xerostomia, lowered sense of hearing, angina pectoris, cerebrovascular disease or peripheral circulatory disturbance in a mammal in need thereof, which comprises administering to said mammal an effective amount of an insulin sensitizer;
(20) use of an insulin sensitizer for the manufacture of a pharmaceutical preparation for improving or treating ketosis;
(21) use of an insulin sensitizer for the manufacture of a pharmaceutical preparation for improving or treating acidosis; and
(22) use of an insulin sensitizer for the manufacture of a pharmaceutical preparation for treating hyperosmolar nonketonic coma, infectious disease, diabetic osteoporosis, diabetic gangrene, xerostomia, lowered sense of hearing, angina pectoris, cerebrovascular disease or peripheral circulatory disturbance.
The insulin sensitizer used in the present invention means any and all drugs that restore the impaired insulin receptor function and improve insulin resistance. Specific examples of the insulin sensitizer include the above-mentioned compound represented by the formula (I) or a salt thereof.
Referring to the formula (I), examples of the hydrocarbon group in the hydrocarbon gr
Odaka Hiroyuki
Suzuki Masami
Chao Mark
Ramesh Elaine M.
Takeda Chemical Industries Ltd.
Weddington Kevin E.
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