Use of PDE III inhibitors for the reduction of heart size in mammals suffering from heart failure

• US 20090082282A1
• Filed: 03/23/2005
• Published: 03/26/2009
• 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: Joens, Olaf, Daemmgen, Juergen, Kleemann, Rainer
• Granted Patent: US 9,463,199 B2
• Time in Patent Office: Days
• US Class Current: 514/1.100
• 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

The invention relates to the use of a phosphodiesterase type III (PDE III) inhibitor or Ca²⁺-sensitizing agent or a pharmaceutically acceptable derivative thereof 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 treating an animal suffering from heart failure to reduce the size of such animal'"'"'s heart which comprises administering to such animal a therapeutically effective amount of a phosphodiesterase type III (PDE III) inhibitor or a Ca²⁺-sensitizing agent or a pharmaceutically acceptable derivative of either or a combination of the inhibitor and sensitizing agent, or a combination of derivatives of the inhibitor and sensitizing agent.

2. The method according to claim 1, wherein the PDE III inhibitor exhibits additionally calcium sensitising effects.

3. The method according to claim 1, wherein the PDE III inhibitor or Ca²⁺-sensitizing agent is selected from the group consisting of pimobendan, milrinone, levosimendan, amrinone, enoximone, piroximone, a pharmaceutically acceptable derivative thereof and combinations thereof.

4. The method according to claim 1, wherein the PDE III inhibitor or Ca²⁺-sensitizing agent is utilized in oral or parenteral form.

5. The method according to claim 1, wherein the PDE III inhibitor or Ca²⁺-sensitizing agent is administered in a daily dose from 10 μ

g/kg to 10 mg/kg.

6. The method according to claim 1, wherein the PDE III inhibitor or Ca²⁺-sensitizing agent is administered together with a medicament selected from the group consisting of calcium channel blockers, ACE inhibitors, diuretics, aspirin, beta blockers, angiotensin II antagonists, and combinations thereof.

7. The method according to claim 6, wherein the ACE inhibitor is selected from the group consisting of omapatrilat, MDL100240, alacepril, benazepril, captopril, trandolaprilat, ceranapril, moexipril, quinaprilat and spirapril, a pharmaceutically acceptable derivative thereof, and combinations thereof.

8. The method according to claim 6, wherein the angiotensin II antagonist is selected from the group consisting of saralasin acetate, candesartan cilexetil, valsartan, candesartan, losartan potassium, eprosartan, irbesartan, tasosartan and telmisartan, a pharmaceutically acceptable derivative thereof, and combinations thereof.

9. The method according to claim 1, wherein the PDE III inhibitor or Ca²⁺-sensitizing agent is administered together with one or more medicaments selected from one or more of the following groups:

the ACE-inhibitors, diuretics and digitalis glycosides.

10. The method according to claim 1, wherein the relative mean vertebral heart sum (VHS) of said patient is reduced by 0.05 to 0.25 within 10 to 100 days of treatment with the PDE III inhibitor or Ca²⁺-sensitizing agent.

11. 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 of angina, or cardiac arrest.

12. The method according to claim 1, wherein said patient is a mammal selected from the group consisting of primates including humans, dogs, cats and horses.