Liquid preparation comprising pimobendan

• US 9,107,952 B2
• Filed: 11/05/2007
• Issued: 08/18/2015
• Est. Priority Date: 11/07/2006
• 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: Folger, Martin, Lehner, Stefan
• Primary Examiner(s): Sims, Jason
• Assistant Examiner(s): Bori, Ibrahim D
• Application Number:
  US11/935,129
• Publication Number:
  US 20080207629A1
• Time in Patent Office: 2,843 Days
• Field of Search: 514/252.02
• US Class Current: 1/1
• CPC Class Codes: A61K 31/501 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 47/40 Cyclodextrins; Derivatives thereof
• CPC Class Codes: A61K 47/6951 using cyclodextrin cyclodextrins used as simple excipients A61K47/40
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/08 Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock artificial tears A61P27/04
• 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 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

The invention relates to novel liquid preparation comprising a substituted benzimidazol, preferably pimobendan as pharmaceutically active compound. In particular, the present invention relates to liquid preparation comprising an etherified cyclodextrin derivative, preferably in a concentration of about 20 to 70% (w/v) and said substituted benzimidazol, preferably in a concentration of about 0.005 to 0.15% (w/w).

Claims

1. A liquid preparation comprising:

about 20 to 30% (w/v) of an etherified cyclodextrin derivative selected from the group consisting of alpha-, beta- and gamma-cyclodextrin ethers; and

about 0.075 to 0.1% (w/v) of pimobendan or a pharmaceutically acceptable salt thereof, wherein the molar ratio of pimobendan or the pharmaceutically acceptable salt thereof to the etherified cyclodextrin derivative is about 1;

47 to about 1;

96.

2. The liquid preparation according to claim 1, wherein the etherified cyclodextrin derivative is hydroxypropyl-beta-cyclodextrin.

4. The liquid preparation according to claim 1, wherein the preparation is isotonic.

5. The liquid preparation according to claim 1, wherein the preparation has pH value of about 6.5 to 7.5 and an osmolality of about 280 to 300 mOsm/Kg.

6. The liquid preparation according to claim 1, wherein the preparation contains one or more suitable preservative/s.

7. The liquid preparation according to claim 1,

wherein the etherified cyclodextrin derivative is hydroxypropyl-beta-cyclodextrin;

and wherein the pH of the liquid is adjusted to about 6.5 to 7.5 and the osmolality is about 280 to 300 mOsm/Kg.

8. The liquid preparation according to claim 7, wherein the liquid preparation further comprises 0.025 to 0.075% (w/v) of one or more stabilizers.

9. A process for producing a liquid preparation according to claim 1, comprising the steps:

dissolving the etherified cyclodextrin derivative in a solvent,

adding the pimobendan or pharmaceutically acceptable salt thereof to the solution obtained in step (a) and

admixing the mixture obtained in step (b) to obtain the liquid preparation in the form of an aqueous solution.

10. The process according to claim 9, wherein the solvent is water.

11. A method of treatment of a subject having a congestive heart failure comprising the step:

administering to said subject in need of such treatment a liquid preparation according to claim 1.

12. The method according to claim 11, wherein the subject is a non-human animal.

13. The method according to claim 11, wherein said administration is by injection or infusion.

14. A method of treating a subject comprising:

administering to a subject in need of treatment a liquid preparation according to claim 1, wherein the subject suffers from a condition selected from the group consisting of congestive heart failure (CHF), acute CHF, decompensated endocardiosis (DCE), dilated cardiomyopathy (DCM), asymptomatic (occult) CHF, asymptomatic DCM, maintenance of cardiovascular function and/or renal perfusion during anaesthesia, shock, gastric dilation, volvulus, myocardial and renal ischemia.

15. The method according to claim 14, wherein the subject in need of such treatment is a horse, dog or cat.

16. A kit of parts that comprises:

liquid preparation according to claim 1; and

a package leaflet including the information that the liquid preparation is to be used for the prevention of congestive heart failure in a subject in need of such treatment.

17. The liquid preparation according to claim 1, wherein the etherified cyclodextrin derivative is present in an amount of about 20 to 50% (w/v).

18. The method according to claim 14, wherein said administration is by injection or infusion.

3. The liquid preparation according to claim I, wherein the preparation further comprises pharmaceutical acceptable carriers, excipients, and/or salts.