Use of PDE III inhibitors for the treatment of asymptomatic (occult) heart failure

• US 8,980,894 B2
• Filed: 06/11/2009
• Issued: 03/17/2015
• 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, Troetschel, Christian, Vollmar, Andrea
• Primary Examiner(s): HOWARD, ZACHARY C
• Application Number:
  US12/482,481
• Publication Number:
  US 20100035889A1
• Time in Patent Office: 2,105 Days
• Field of Search: None
• US Class Current: 514/247
• 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 31/4412 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 31/501 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• 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: 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

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 prolongation of time until onset of clinical symptoms in patients having an asymptomatic (occult) heart failure or for the reduction of heart size in patients having symptomatic or asymptomatic (occult) heart failure.

Claims

1. A method for the treatment of a patient having International Small Animal Cardiac Health Council (ISACHC) Class I asymptomatic heart failure comprising:

administering to a non-human patient having ISACHC Class I asymptomatic heart failure a therapeutically effective amount of a phosphodiesterase type III (PDE III) inhibitor or a Ca²⁺-sensitizing agent selected from the group consisting of pimobendan, milrinone, levosimendan, amrinone, enoximone, and piroximone,

wherein said therapeutically effective amount is effective to prolong the time until onset of symptoms of ISACHC Class II or Class III heart failure in the patient.

2. The method according to claim 1, wherein the asymptomatic heart failure is asymptomatic dilated cardiomyopathy (DCM).

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

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 said patient is a mammal selected from the group consisting of non-human primates dogs, cats and horses.

7. The method according to claim 1, wherein said administering step has the further effect of causing a reduction in the size of the heart of the patient.

8. A method for prolongation of the time until onset of clinical symptoms in a patient having International Small Animal Cardiac Health Council (ISACHC) Class I asymptomatic heart failure comprising:

administering to a non-human patient having ISACHC Class I asymptomatic heart failure a therapeutically effective amount of pimobendan.

9. The method according to claim 8, wherein the asymptomatic heart failure is asymptomatic dilated cardiomyopathy (DCM).

10. The method according to claim 8, wherein the pimobendan is utilized in oral or parenteral form.

11. The method according to claim 8, wherein the pimobendan is administered in a daily dose from 10 μ

g/kg to 10 mg/kg.

12. The method according to claim 8, wherein the patient is a mammal selected from the group consisting of non-human primates, dogs, cats and horses.

13. The method according to claim 8, wherein said administering step has the further effect of causing a reduction in the size of the heart of the patient.

14. The method according to claim 8, wherein said administering step has the further effect of causing a prolongation of the time until the onset of symptoms in the patient.