Use of pimobendan for the reduction of heart size in mammals suffering from heart failure

• US 9,889,148 B2
• Filed: 02/07/2014
• Issued: 02/13/2018
• Est. Priority Date: 03/25/2004
• Status: Active Grant

• Current Assignee: Boehringer Ingelheim Vetmedica GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim Vetmedica GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Daemmgen, Juergen, Joens, Olaf, Kleemann, Rainer
• Primary Examiner(s): HOWARD, ZACHARY C
• Application Number:
  US14/175,175
• Publication Number:
  US 20140155338A1
• Time in Patent Office: 1,467 Days
• Field of Search: None
• CPC Class Codes: A61K 31/341 not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/4166 having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4412 having oxo groups directly attached to the heterocyclic ring
• CPC Class Codes: A61K 31/4427 containing further heterocyclic ring systems
• CPC Class Codes: A61K 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61K 31/50 Pyridazines; Hydrogenated pyridazines
• CPC Class Codes: A61K 31/501 not condensed and containing further heterocyclic rings
• 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 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 9/08 Vasodilators for multiple indications
• 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

Abstract

A phosphodiesterase type III (PDE III) inhibitor or Ca²⁺-sensitizing agent or a pharmaceutically acceptable derivative thereof is provided for the preparation of a medication for the reduction of the heart size of a patient suffering from heart failure.

Claims

1. A method for reducing heart size in a patient suffering from heart failure comprising:

administering to the patient suffering from heart failure at least one medicament comprising a therapeutically effective amount of pimobendan or a pharmaceutically acceptable salt thereof, wherein the heart failure is accompanied by an increase of heart size and deterioration of cardiac function for the patient, and the patient is a mammal selected from the group consisting of a dog, a cat and a horse; and

reducing the relative mean vertebral heart sum (VHS) of the patient in response to said administration of said at least one medicament to the patient.

2. The method according to claim 1, wherein the administration of the at least one medicament is free from administering pimobendan with a combination of furosemide, enalapril and digoxin.

3. The method according to claim 1, wherein the heart failure is chronic congestive heart failure, heart failure due to myocardial infarction or myocardial ischemia due to worsening angina or cardiac arrest.

4. The method according to claim 2, wherein the heart failure is chronic congestive heart failure, heart failure due to myocardial infarction or myocardial ischemia due to worsening angina or cardiac arrest.

5. The method according to claim 1, wherein the patient is a dog.

6. The method according to claim 1, wherein reducing the relative mean vertebral heart sum (VHS) of the patient in response to said administration of said at least one medicament to the patient comprises reducing the relative mean vertebral heart sum (VHS) of the patient by 0.05 to 0.25 vertebrae within 10 to 100 days of the administration.

7. The method according to claim 2, wherein reducing the relative mean vertebral heart sum (VHS) of the patient in response to said administration of said at least one medicament to the patient comprises reducing the relative mean vertebral heart sum (VHS) of the patient by 0.05 to 0.25 vertebrae within 10 to 100 days of the administration.

8. The method according to claim 1, wherein pimobendan or a pharmaceutically acceptable salt thereof is utilized in oral or parenteral form.

9. The method according to claim 2, wherein pimobendan or a pharmaceutically acceptable salt thereof is utilized in oral or parenteral form.

10. The method according to claim 1, wherein pimobendan or a pharmaceutically acceptable salt thereof is administered in a daily dose from 10 μ

g/kg to 10 mg/kg.

11. The method according to claim 2, wherein pimobendan or a pharmaceutically acceptable salt thereof is administered in a daily dose from 10 μ

g/kg to 10 mg/kg.

12. The method according to claim 1, wherein pimobendan or a pharmaceutically acceptable salt thereof is administered in a single daily dose.

13. The method according to claim 2, wherein pimobendan or a pharmaceutically acceptable salt thereof is administered in a single daily dose.

14. The method according to claim 1, wherein pimobendan or a pharmaceutically acceptable salt thereof is administered together with a medicament selected from the group consisting of a calcium channel blocker, an ACE inhibitor, a diuretic, a platelet inhibitor, aspirin, a beta blocker, an angiotensin II antagonist, an aldosterone antagonist, a digitalis glycoside, an antiarrhythmic agent and combinations thereof.

15. The method according to claim 2, wherein pimobendan or a pharmaceutically acceptable salt thereof is administered together with a medicament selected from the group consisting of a calcium channel blocker, an ACE inhibitor, a diuretic, a platelet inhibitor, aspirin, a beta blocker, an angiotensin II antagonist, an aldosterone antagonist, a digitalis glycoside, an antiarrhythmic agent and combinations thereof.

16. The method according to claim 14, wherein the calcium channel blocker is selected from the group consisting of diltiazem, verapamil and felodipine, and combinations thereof.

17. The method according to claim 14, wherein the ACE inhibitor is selected from the group consisting of omapatrilat, MDL100240, alacepril, benazepril, captopril, cilazapril, delapril, enalapril, enalaprilat, fosinopril, fosinoprilat, imidapril, lisinopril, perindopril, quinapril, ramipril, ramiprilat, saralasin acetate, temocapril, trandoloapril, trandolaprilat, ceranapril, moexipril, quinaprilat and spirapril, and combinations thereof.

18. The method according to claim 14, wherein the beta blocker is selected from the group consisting of bisoprolol, carvediol, metoprolol, propranolol and timolol, and combinations thereof.

19. The method according to claim 14, wherein the angiotensin II antagonist is selected from the group consisting of saralasin acetate, candesartan, cilexetil, valsartan, losartan potassium, eprosartan, irbesartan, tasosartan, pomisartan and telmisartan, and combinations thereof.

20. The method according to claim 14, wherein the aldosterone antagonist is selected from the group consisting of spironolactone, eplerenone, canrenone and potassium canrenone, and combinations thereof.

21. The method according to claim 14, wherein the antiarrhythmic agent is selected from the group consisting of amiodarone, betrylium, disopyramide, dofetilide, flecamide, ibutilide, mexiletine, tocainide, procainamide, propafenone, quinidine and sotalol, and combinations thereof.

22. The method according to claim 14, wherein the diuretic is selected from the group consisting of furosemide, torasemide, bumetanide, etacrynic acid, azosemide, muzolimine, piretanide, tripamide, bendroflumethazide, chlorothiazide, hydrochlorothiazide, hydroflumethiazide, methychlothiazide, polythiazide, trichlormethiazide, chlorthialidone, indapamide, metolazone, quinethazone, etozolin, triamteren and amiloride, and combinations thereof.

23. The method according to claim 14, wherein the digitalis glycoside is selected from the group consisting of digoxin, digitoxin, g-strophantin, beta-methyldigoxin and beta-acetyldigoxin, and combinations thereof.

24. The method according to claim 1, wherein pimobendan or a pharmaceutically acceptable salt thereof is administered together with one or more medicaments selected from the group consisting of one or more ACE inhibitors, one or more diuretics and one or more digitalis glycosides.

25. The method according to claim 2, wherein pimobendan or a pharmaceutically acceptable salt thereof is administered together with one or more medicaments selected from the group consisting of one or more ACE inhibitors, one or more diuretics and one or more digitalis glycosides.

26. The method according to claim 1, further comprising:

measuring the relative mean vertebral heart sum (VHS) of the patient after said administration.

27. A method for reducing heart size in a patient suffering from heart failure comprising:

administering to the patient suffering from heart failure at least one medicament comprising a therapeutically effective amount of pimobendan or a pharmaceutically acceptable salt thereof, wherein the heart failure is accompanied by an increase of heart size and deterioration of cardiac function for the patient, and the patient is a mammal selected from the group consisting of a dog, a cat and a horse; and

measuring the relative mean vertebral heart sum (VHS) of the patient after a period of administration, wherein the VHS of the patient is reduced in response to said administration of said at least one medicament to the patient.