Uses of DPP IV inhibitors

• US 9,173,859 B2
• Filed: 01/22/2014
• Issued: 11/03/2015
• Est. Priority Date: 05/04/2006
• Status: Active Grant

• Current Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Dugi, Klaus, Himmelsbach, Frank, Mark, Michael
• Primary Examiner(s): Weddington, Kevin E
• Application Number:
  US14/161,007
• Publication Number:
  US 20140135348A1
• Time in Patent Office: 650 Days
• Field of Search: 514/263.21, 514/635, 514/868
• US Class Current: 1/1
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• CPC Class Codes: A61K 31/4184 condensed with carbocyclic rings, e.g. benzimidazoles
• CPC Class Codes: A61K 31/4985 Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/5025 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/38 : of the suprarenal hormones
• CPC Class Codes: A61P 5/48 : of the pancreatic hormones
• CPC Class Codes: A61P 5/50 : for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 : Antiarrhythmics
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Abstract

The specification describes the use of selected DPP IV inhibitors for the treatment of physiological functional disorders and for reducing the risk of the occurrence of such functional disorders in at-risk patient groups. In addition, the use of the above-mentioned DPP IV inhibitors in conjunction with other active substances is described, by means of which improved treatment outcomes can be achieved. These applications may be used to prepare corresponding medicaments.

Claims

1. A method of treating type 2 diabetes comprising

administering to a patient in need thereof (a) 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine, or a therapeutically active salt thereof, in an oral dosage of 2.5 mg or 5 mg, and (b) metformin

wherein the dose of metformin is 100 mg to 500 mg or 200 mg to 850 mg (1-3 times a day), or 300 mg to 1000 mg once or twice a day, or as delayed-release metformin in a dose of 500 mg to 1000 mg once or twice a day, or 500 mg to 2000 mg once a day, or

wherein the dose of metformin is 500 mg, 850 mg or 1000 mg as a single dose with a total daily dose of metformin of 500-2850 mg, or 500 mg, 1000 mg, 1500 mg or 2000 mg metformin in delayed release form, or

wherein the dose of metformin is 500 mg to 1000 mg.

2. The method according to claim 1, wherein 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-l-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine and metformin are administered orally in the form of a fixed combination.

3. The method according to claim 2, wherein the fixed combination is a tablet or capsule.

4. The method according to claim 2, wherein the fixed combination is a tablet.

5. The method according to claim 2, wherein the dosage of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine is 2.5 mg.

6. The method according to claim 2, wherein the dosage of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine is 5 mg.

7. The method according to claim 2, wherein metformin is provided in a dose of 100 mg to 500 mg or 200 mg to 850 mg (1-3 times a day), or 300 mg to 1000 mg once or twice a day, or as delayed-release metformin in a dose of 500 mg to 1000 mg once or twice a day, or 500 mg to 2000 mg once a day.

8. The method according to claim 1, wherein the dose of metformin is 500 mg, 850 mg or 1000 mg as a single dose with a total daily dose of metformin of 500 mg to 2850 mg, or 500 mg, 1000 mg, 1500 mg or 2000 mg metformin in delayed release form.

9. The method according to claim 2, wherein the amount of metformin is 500 mg to 1000 mg.

10. The method according to claim 2, wherein the amount of metformin is 500 mg.

11. The method according to claim 2, wherein the amount of metformin is 850 mg.

12. The method according to claim 2, wherein the amount of metformin is 1000 mg.

19. The method according to claim 1, wherein 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine is administered in a daily oral amount of 5 mg.

21. The method according to claim 5, wherein 1-[(4-methyl-quinazolin-2-yl)methyl]-3 -methyl-7-(2-butyn-1-y1)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in a dosage of 2.5 mg is administered twice daily.

22. The method according to claim 6, wherein 1[(4-methyl-quinazolin-2 -yl)methyl]-3-methyl-7-(2-butyn-1-y1)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in a dosage of 5mg is administered once daily.

13. A method of treating type 2 diabetes comprising administering twice daily to a patient in need thereof 1-[(4-methyl-quinazolin-2-yl)methyl]-3 -methyl-7-(2-butyn-1-y1)-8-(3-(R)-amino-piperidin-1 -yl)- xanthine in an oral dosage of 2.5 mg in fixed combination with metformin in an amount of 500 mg to 1000 mg.

14. An oral tablet formulation comprising 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in an amount of 2.5 mg or 5 mg optionally in combination with metformin, and a pharmaceutically acceptable carrier or diluent.

15. The oral tablet according to claim 14, containing 500 mg to 1000 mg metformin.

20. A method of treating type 2 diabetes comprising administering to a patient in need thereof the oral tablet of claim 14, wherein the daily oral amount of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine administered to said patient is 5 mg.

16. A method of treating type 2 diabetes comprising administering to a patient in need thereof (a) 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in a daily oral amount of 5 mg and (b) metformin, in the form of a fixed combination, wherein metformin is administered in a dose of 100 mg to 500 mg or 200 mg to 850 mg (1-3 times a day), or 300 mg to 1000 mg once or twice a day, or as delayed-release metformin in a dose of 500 mg to 1000 mg once or twice a day, or 500 mg to 2000 mg once a day.

17. A method of treating type 2 diabetes comprising administering to a patient in need thereof (a) 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in a daily oral amount of 5 mg and (b) metformin, in the form of a fixed combination, wherein the dose of metformin is 500 mg, 850 mg or 1000 mg as a single dose with a total daily dose of metformin of 500-2850 mg, or 500 mg, 1000 mg, 1500 mg or 2000 mg metformin in delayed release form.

18. A method of treating type 2 diabetes comprising administering to a patient in need thereof (a) 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in a daily oral amount of 5 mg and (b) metformin, in the form of a fixed combination, wherein the amount of metformin is 500 mg to 1000 mg.