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Treatment of metabolic disorders in equine animals

a metabolic disorder and equine technology, applied in the field of veterinary medicine, can solve the problems that insulin-related disorders have a severe and life-threatening impact on the health of equine animals, and no satisfactory treatment is currently available for metabolic disorders, so as to achieve optimal dosing and compliance, attenuate, delay or prevent the progression of metabolic disorders

Inactive Publication Date: 2014-10-09
BOEHRINGER LNGELHEIM VETMEDICA GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention relates to the use of SGLT2 inhibitors for the treatment and prevention of metabolic disorders in equine animals. The advantages of using an SGLT2 inhibitor include its ability to improve insulin resistance, plasma insulin levels, and glucose tolerance, among others. Additionally, it can be administered orally and once per day, making it convenient for optimal dosing and compliance. The invention also provides methods for treatment and prevention of metabolic disorders in equine animals by administering an effective dose of an SGLT2 inhibitor.

Problems solved by technology

Insulin-related disorders thus have a severe and life-threatening impact on the health of equine animals.
No satisfactory treatment is currently available for metabolic disorders such as insulin resistance, hyperinsulinaemia and associated disorders in equine animals.
When insulin-resistant target tissues, e.g. skeletal muscle, have a reduced capacity for glucose uptake, the pancreas is stimulated to release more insulin, leading to hyperinsulinaemia.

Method used

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  • Treatment of metabolic disorders in equine animals
  • Treatment of metabolic disorders in equine animals
  • Treatment of metabolic disorders in equine animals

Examples

Experimental program
Comparison scheme
Effect test

example 1

Pharmacokinetics (PK) / Pharmacodynamics (PD) of Compound A Single Oral Dosing in Horses

[0212]Compound A was administered to overnight fasted horses. The groups (n=3 per group) received a single oral or intravenous (i.v.) administration of either vehicle alone (purified water, macrogol 15, hydroxystearate) or vehicle containing the SGLT2 inhibitor at a dose of 0.3 mg / kg bodyweight and 3 mg / kg bodyweight orally and 1 mg / kg bodyweight i.v. PK / PD measurements were taken until day 3 after a single administration of compound A or its vehicle.

TABLE 2Pharmacokinetic data, single doseParameter1 mg / kg i.v.0.3 mg / kg p.o.3.0 mg / kg p.o.tmax [hour]mean21Cmax [nmol / L]mean3533867AUC0→∞, mean41251286929752[nmol · h / l]T1 / 2 [hour]mean7.98.58.2

[0213]Pharmacodynamic Data:[0214]A prominent increase of urinary glucose concentration was evident at all doses already 1 h after administration (mean group values: controls 0.6 mmol / L; 1 mg / kg iv-253 mmol / L; 0.3 mg / kgpo-103 mmol / L; 3 mg / kg po-217 mmol / L) and was ...

example 2

The Effect of Compound A on Urinary and Blood Glucose as Well as Glucose Tolerance after Repeated Dosing in Horses

[0218]Compound A was administered to freely fed normoglycemic, hyperinsulinemic, insulin resistant, obese horses, which exhibit an impaired glucose tolerance. The groups (n=4 per group) received a once daily oral administration of either vehicle alone (purified water, macrogol 15, hydroxystearate—0.2 mL / 100 kg and approximately 35 mL of apple sauce) or vehicle containing the SGLT2 inhibitor in increasing doses up to 1 mg / kg for 4 weeks. The treated horses received a daily dose of compound A at 0.1 mg / kg bodyweight for the first 7 days, followed by 0.2 mg / kg bodyweight, from day 20 the dose was increased to 1 mg / kg bodyweight. Urinary glucose and blood glucose were measured. Additionally, to evaluate the glucose tolerance, blood glucose was measured during an oral sugar test (OST, corn syrup 0.15 mL / kg) was performed. Blood was collected via jugular vein catheters. Blood ...

example 3

The Effect of Compound A on Postprandial Blood Glucose in Horses

[0224]The following example shows the effect of compound A on postprandial blood glucose in horses. Compound A was administered to overnight fasted horses. The groups (n=3 per group) received a single oral or i.v. administration of either vehicle alone (purified water, macrogol 15, hydroxystearate) or vehicle containing the SGLT2 inhibitor at a dose of 0.3 mg / kg and 3 mg / kg orally and 1 mg / kg i.v. Two hours after compound administration horses were fed a test meal. The postprandial glycaemia is quantified 2 hours thereafter and significantly blunted by all doses of compound A, as shown in 0. Compound A is thus clearly capable of effectively reducing postprandial glucose levels in horses.

[0225]The efficacy of SGLT2 inhibition in accordance with the invention in the treatment of pathological fasting glucose and / or insulin and / or impaired glucose tolerance can be tested using clinical studies. In studies over a shorter or ...

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Abstract

The present invention relates to SGLT2 inhibitor or a pharmaceutically acceptable form thereof for use in the treatment and / or prevention of a metabolic disorder of an equine animal. In particular, the present invention relates the SGLT2 inhibitor or a pharmaceutically acceptable form thereof for use in the treatment and / or prevention of insulin resistance, hyperinsulinemia, impaired glucose tolerance, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low grade systemic inflammation, obesity, and / or regional adiposity in an equine animal.

Description

FIELD OF THE INVENTION[0001]The present invention relates to veterinary medicine, in particular to the treatment and / or prevention of metabolic disorders in equine animals.BACKGROUND OF THE INVENTION[0002]Equine animals, e.g. horses, are affected by various metabolic disorders, including insulin resistance and hyperinsulinaemia. Such insulin-related disorders in equine animals, for example, are only rarely associated with diabetes mellitus and hyperglycaemia as it is in humans or various other mammals. However, in equine animals, insulin also regulates vital metabolic functions; e.g. insulin drives glucose into tissues such as liver, adipose, and skeletal muscle; induces vasoconstrictive and vasodilatory pathways; and regulates protein and fat metabolism. Insulin-related disorders thus have a severe and life-threatening impact on the health of equine animals. They are correlated or may be associated with a number of further equine disorders, conditions or syndromes, including impair...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07H15/207
CPCC07H15/207A61K9/02A61K9/2018A61K9/4866A61K31/70A61K31/7042A61K31/7048A61K31/7056A61K9/0019A61K9/0031A61K31/7034A61P3/00A61P3/04A61P3/10A61K47/545A61K31/351C07D309/10A61K31/357A61P3/08A61K31/381A61K9/0053A61K9/20A61K9/48
Inventor REICHE, DANIA BIRTEJOHNSTON, LAURAMOHREN, NICOLE
Owner BOEHRINGER LNGELHEIM VETMEDICA GMBH
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