Liquid preparation comprising pimobendan

• US 10,639,305 B2
• Filed: 02/27/2017
• Issued: 05/05/2020
• 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): Bredefeld, Rachael E
• Assistant Examiner(s): Bori, Ibrahim D
• Application Number:
  US15/443,029
• Publication Number:
  US 20170165260A1
• Time in Patent Office: 1,163 Days
• 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 method of treatment of a disease or a condition in a subject in a need of such treatment, wherein the subject is a mammal, the method comprising:

administering to the subject in need of such treatment 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;

wherein;

the disease or the condition to be treated is selected from the group consisting of;

congestive heart failure (CHF), acute CHF, decompensated endocardiosis (DCE), dilated cardiomyopathy (DCM), asymptomatic (occult) CHF, asymptomatic DCM, shock, gastric dilation, volvulus, myocardial ischemia, and renal ischemia; and

the liquid preparation has a pH of 5.5 to 8.5.

2. The method of claim 1, wherein the subject is a horse, a dog or a cat.

3. The method of claim 1, wherein the liquid preparation is administered by injection or infusion.

4. The method of claim 1, wherein the etherified cyclodextrin derivative comprises hydroxypropyl-beta-cyclodextrin.

5. The method of claim 1, wherein the etherified cyclodextrin derivative is present in the liquid preparation in an amount of about 15 to 70% (w/v).

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

7. The method of claim 1, wherein the etherified cyclodextrin derivative is present in the liquid preparation in an amount of about 20 to 40% (w/v).

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

9. The method of 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.

10. The method of claim 1, wherein the liquid preparation is administered to the subject in a daily dosage amount that provides about 0.05 to 0.5 mg pimobendan per kg body weight of the subject.

11. The method of claim 1, wherein the liquid preparation is administered to the subject in a daily dosage amount that provides about 0.1 to 0.3 mg pimobendan per kg body weight of the subject.

12. The method of claim 1, wherein the liquid preparation is administered to the subject in a daily dosage amount that provides about 0.15 mg pimobendan per kg body weight of the subject.

13. The method of claim 1, wherein pimobendan is provided in the liquid formulation in a concentration of about 0.75 mg/ml.