LIQUID PREPARATION COMPRISING PIMOBENDAN

• US 20140235648A1
• Filed: 04/25/2014
• Published: 08/21/2014
• 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
• Granted Patent: US 9,616,134 B2
• Time in Patent Office: Days
• US Class Current: 514/252.06
• 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

A liquid preparation includes an etherified cyclodextrin derivative and a substituted benzimidazol, where the etherified cyclodextrin derivative is one of alpha-, beta, and gamma-cyclodextrin ether.

Claims

1. A liquid preparation comprising an etherified cyclodextrin derivative and pimobendan or a pharmaceutically acceptable salt thereof, wherein the etherified cyclodextrin derivative is selected from the group consisting of alpha-, beta, and gamma-cyclodextrin ether, and wherein the liquid preparation has a pH of 5.5 to 8.5.

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

3. The liquid preparation according to claim 1, wherein the portion of the etherified cyclodextrin derivative contains about 15 to 40% (w/v).

4. The liquid preparation according to claim 3, wherein the portion of the etherified cyclodextrin derivative contains about 20 to 30% (w/v).

5. The liquid preparation according to claim 1, wherein the portion of pimobendan or a pharmaceutical salt thereof contains about 0.005 to 0.15% (w/v).

6. 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.

7. The liquid preparation according to claim 1, wherein the preparation comprises about:

a) 20 to 30% (w/v) of a hydroxypropyl-beta-cyclodextrin;

b) 0.005 to 0.15% (w/v) pimobendan or a pharmaceutical acceptable salt thereof;

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 1, wherein the preparation further comprises pharmaceutical acceptable carriers, excipients, and/or salts.

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

10. The liquid preparation according to claim 1, wherein the preparation contains one or more suitable preservatives.

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

a) dissolving the etherified cyclodextrin derivative in a solvent;

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

c) admixing the mixture obtained in step (b) to obtain the liquid preparation in the form of an aqueous solution at a pH of 5.5 to 8.5.

13. The process according to claim 12, wherein the solvent is water.

14. A method of treatment and/or prevention of diseases in a subject in a need of such treatment, the method comprising:

administering to the subject in need of such treatment a liquid preparation according to claim 1;

wherein the treatment and/or prevention of diseases in the subject is indicated by one 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 ischemia and renal ischemia.

15. The method of claim 14, wherein the subject is a horse, a dog or a cat.

16. The method of claim 14, wherein the liquid preparation is administered by injection or infusion.

17. A kit of parts that comprises:

a) a liquid preparation according to claim 1; and

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

11. The liquid preparation according to claim 11, wherein the liquid preparation further comprises 0.025 to 0.075% (w/v) of one or more stabilizers.