Inhibitors for treating and preventing heart failure in felines

a technology of inhibitors and heart failure, applied in the field of veterinary medicine, can solve the problems of heart failure, undesired side effects, and complicating the interpretation of the effect of heart rate, so as to improve the quality of life and reduce the risk of death

Inactive Publication Date: 2013-02-14
BOEHRINGER LNGELHEIM VETMEDICA GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0013]The present invention provides methods and uses for the treatment of heart failure in feline patients, in particular cats. Further, the invention provides a means of improving the quality of life while reducing the risk of death in feline patients, such as cats, especially in those suffering from heart failure of any etiology.

Problems solved by technology

Typically cats with underlying cardiomyopathies remain clinically asymptomatic in the early stages of the disease until they are presented to the veterinarian because the disease has progressed and ventricular diastolic and / or systolic function is severely impaired resulting in heart failure.
Drugs that reduce heart rate should be of benefit; however, known heart rate-reducing drugs are nonspecific and have a range of actions on the cardiovascular and other systems, which both complicate the interpretation of the effects on heart rate and lead to undesired side effects.
However, the use of these drugs remains controversial since a beneficial effect on disease progression or survival has not been demonstrated with either drug.
However, all of these therapeutic regimens are only supportive in character and therefore limited.

Method used

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  • Inhibitors for treating and preventing heart failure in felines

Examples

Experimental program
Comparison scheme
Effect test

example 1

Formulation of a Compound for the Treatment of a Heart Disease

[0079]This example provides the formulation of compound (+)-3-[(N-(2-(3,4-dimethoxy-phenyl)ethyl)-piperidin-3-(S)-yl)-methyl]-(7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on hydrochloride in liquid form. For the production of multi-layered particles for incorporation into a liquid dosage form, a three-step process was applied that is summarized in Table 1.

TABLE 1Flow chart for the production of multi-layered particles according to theinvention, comprising (+)-3-[(N-(2-(3,4-dimethoxy-phenyl)ethyl)-piperidin-3-(S)-yl)-methyl]-(7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on hydrochloride as active ingredient.startingstepmaterialCoatingresult1inert coredrug layering withIR pelletsparticlespharmaceutically activeingredient and HPMC / magnesium stearate2IR pelletsseal coating with PVPSC (seal coated)K 30 / Talc / colloidalsiliciumdioxidepellets3SC pelletstaste masking coating withfinal multi-EC / HPMC / magnesiumlayered par...

example 2

Preparation of a Liquid Pharmaceutical Composition

[0087]In order to prepare a liquid pharmaceutical composition, the final multi-layered particles comprising the active ingredient ciloradine prepared in the way explained above were incorporated into an oily liquid. This liquid consisted of a mixture of Medium chain triglycerides (Miglyol® 821, bought from Sasol, Hamburg, Germany), a hydrophilic colloidal silicium dioxide (Aerosil® 200, Evonik), a hydrophobic colloidal silicium dioxide (Aerosil ® R972, Evonik) and meat flavor, at the weight ratios listed in Table 7 below.

TABLE 7Liquid pharmaceutical composition comprising multi-layeredparticles comprising (+)-3-[(N-(2-(3,4-dimethoxy-phenyl)ethyl)-piperidin-3-(S)-yl)-methyl]-(7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on hydrochloride.AmountComponent[% (w / w)]medium chain triglycerides (Miglyol ® 821)93.23hydrophilic colloidal silicium dioxide (Aerosil ® 200)4.44hydrophobic colloidal silicium dioxide (Aerosil ® R972)1.82meat fl...

example 3

Treatment of Cats Suffering from HF Due to HCM

[0090]A blinded, controlled, randomised, efficacy field study was conducted with HCM cats receiving cilobradine (initial dose: 0.2 mg / kg po. twice daily) or a placebo (dose: 0.0 mg / kg po. twice daily) for 85 days. The dose of cilobradine could be adjusted during the study (dose range 0.1-0.5 mg / kg per-oral twice daily). The administration of furosemide was allowed in both groups. All cats were hospitalised in the first week of the study (study days 1-6), and they were allowed to go home afterwards (study days 7-85).

[0091]Cats with a diagnosis of HCM were included in the study. The diagnosis of HCM was established by using echocardiography showing global, regional or segmental thickness of the interventricular septum and / or left ventricular free-wall in diastole greater than 6 mm. Further inclusion criteria were: systolic blood pressure less than 170 mmHg; serum thyroxine (T4) was normal; and body weight was higher than 2 kg.

[0092]The own...

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Abstract

The present invention relates to an If blocker or a pharmaceutically acceptable salt thereof and methods of using the If blocker or a pharmaceutically acceptable salt thereof to treat and/or prevent heart failure (HF) in a feline patient. The invention also relates to improving the quality of life, improving the general health condition, as well as, prolonging the life expectancy in feline patients suffering from heart failure, specifically heart failure due to one or more of the following etiologies hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), unclassified cardiomyopathy (UCM), dilated cardiomyopathy (DCM) and/or arrhythmogenic right ventricular cardiomyopathy (ARVC).

Description

BACKGROUND OF THE INVENTION[0001]A. Field of the Invention[0002]The invention relates to veterinary medicine. In particular, the invention relates to inhibitors, or a pharmaceutically acceptable salt thereof, for the treatment of heart diseases, preferably heart failure (HF), in feline patients. It further relates to improving the quality of life, life expectency, and general health of felines suffering from heart failure, especially failure due to one or more of the following etiologies of hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), unclassified cardiomyopathy (UCM), dilated cardiomyopathy (DCM) and / or arrhythmogenic right ventricular cardiomyopathy (ARVC).[0003]B. Description of the Related Art[0004]Feline heart failure is predominantly caused by different cardiomyopathies. The most common feline cardiomyopathy (CMP) is hypertrophic cardiomyopathy (HCM), followed by restrictive cardiomyopathy (RCM), unclassified cardiomyopathy (UCM), dilated cardiomyopathy...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/55A61P9/00A61P9/04
CPCA61K9/2072A61K9/2893A61K9/5089A61K31/501A61K31/522A61K31/5415A61K31/55A61K9/0056A61K9/0095A61K9/5026A61K9/5047A61K31/00A61K31/4168A61K9/1635A61K9/1652A61K9/1676A61K9/5078A61P25/00A61P29/00A61P3/00A61P43/00A61P7/10A61P9/00A61P9/04A61K8/73A61K38/005
Inventor ALBRECHT, BALAZSFOLGER, MARTINKLEY, SASKIALANG, INGOSEIDLER, RANDOLPH
Owner BOEHRINGER LNGELHEIM VETMEDICA GMBH
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