Treatment of metabolic disorders in canine animals

Patent metadata

Field	Value
Publication number	US-10603300-B2
Application number	US-201515113127-A
Country	US
Kind code	B2
Filing date	Jan 20, 2015
Priority date	Jan 23, 2014
Publication date	Mar 31, 2020
Grant date	Mar 31, 2020

Abstract

The present invention relates to one or more SGLT2 inhibitors or pharmaceutically acceptable forms thereof for use in the treatment and/or prevention of a metabolic disorder in a canine animal, preferably wherein the metabolic disorder is one or more selected from the group consisting of: ketoacidosis, pre-diabetes, insulin dependent diabetes mellitus, insulin resistance diabetes, insulin resistance, obesity, hyperglycemia, hyperglycemia induced cataract formation, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low grade systemic inflammation, hepatic lipidosis, inflammation of the pancreas, metabolic disorder consequences, such as hypertension, renal dysfunction and/or muscoskeletal disorders, and/or Syndrome X (metabolic syndrome), wherein preferably the development of hyperglycemia induced cataract formation is prevented or remission is achieved and/or wherein preferably the development of metabolic disorder consequences, such as hypertension, renal dysfunction and/or muscoskeletal disorders, is prevented or progression is slowed or remission is achieved.

First claim

The invention claimed is:

1. A method for treating a metabolic disorder in a canine animal, the method comprising administering to the canine animal one or more active ingredients, the one or more active ingredients consisting of:
a single SGLT2 inhibitor or pharmaceutical acceptable form thereof, wherein the single SGLT2 inhibitor is a 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranos-1-yl)-benzene represented by the following formula:

or
a combination of the SGLT2 inhibitor or pharmaceutical acceptable form thereof and insulin;
wherein:
the metabolic disorder is selected from the group consisting of: ketoacidosis, pre-diabetes, insulin dependent diabetes mellitus, insulin resistance diabetes, insulin resistance, obesity, hyperglycemia, hyperglycemia induced cataract formation, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low grade systemic inflammation, hepatic lipidosis, inflammation of the pancreas, metabolic disorder consequences, Syndrome X (metabolic syndrome), and combinations thereof; and
the SGLT2 inhibitor or pharmaceutically acceptable form thereof is administered at a dose of 0.01 to 1.0 mg/kg body weight per day.

2. A method for treating a metabolic disorder in a canine animal, the method comprising administering to the canine animal one or more active ingredients, the one or more active ingredients consisting of:
a single SGLT2 inhibitor or pharmaceutical acceptable form thereof, wherein the single SGLT2 inhibitor is a 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranos-1-yl)-benzene represented by the following formula:

or
a combination of the SGLT2 inhibitor or pharmaceutical acceptable form thereof and insulin;
wherein:
the metabolic disorder is selected from the group consisting of: ketoacidosis, pre-diabetes, insulin dependent diabetes mellitus, insulin resistance diabetes, insulin resistance, obesity, hyperglycemia, hyperglycemia induced cataract formation, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low grade systemic inflammation, hepatic lipidosis, inflammation of the pancreas, metabolic disorder consequences, Syndrome X (metabolic syndrome), and combinations thereof;
wherein the treatment includes prevention or remission of hyperglycemia induced cataract formation.

3. The method of claim 1 , wherein the treatment includes slowed progression or remission of the metabolic disorder consequences, and the metabolic disorder consequences are selected from the group consisting of hypertension, renal dysfunction or musculoskeletal disorders and combinations thereof.

4. The method of claim 1 , wherein the metabolic disorder is selected from clinical conditions associated with pre-diabetes, insulin dependent diabetes mellitus, insulin resistance, or combinations thereof.

5. The method of claim 4 , wherein said clinical conditions are selected from the group consisting of ketoacidosis, insulin resistance, obesity, hyperglycemia, hyperglycemia induced cataract formation, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low grade systemic inflammation, hepatic lipidosis, inflammation of the pancreas, metabolic disorder consequences, such as hypertension, renal dysfunction and/or musculoskeletal disorders, Syndrome X (metabolic syndrome) and combinations thereof.

6. The method of claim 1 , wherein said metabolic disorder is a metabolic disorder consequence selected from the group consisting of hypertension, renal dysfunction a musculoskeletal disorder, and combinations thereof.

7. The method of claim 1 , wherein the canine animal is suffering from diabetes, pre-diabetes or insulin dependent diabetes.

8. The method of claim 7 , wherein the canine animal is a dog.

9. The method of claim 1 , wherein the pharmaceutically acceptable form thereof is a crystalline complex between the SGLT2 inhibitor or pharmaceutically acceptable form thereof and an amino acid.

10. The method of claim 9 , wherein said amino acid is proline.

11. The method of claim 10 , wherein said amino acid is L-proline.

12. The method of claim 1 , wherein the SGLT2 inhibitor or pharmaceutically acceptable form thereof is administered orally or parenterally.

13. The method of claim 1 , wherein the SGLT2 inhibitor or pharmaceutically acceptable form thereof is administered orally.

14. The method of claim 1 , wherein the SGLT2 inhibitor or pharmaceutically acceptable form thereof is administered once per day.

15. The method of claim 1 , wherein the SGLT2 inhibitor or pharmaceutically acceptable form thereof is administered in combination with insulin.

16. The method of claim 15 , wherein administration of the combination is a simultaneous, a sequential, or a chronologically staggered co-administration.

17. The method of claim 15 , wherein administration of the combination is a chronologically staggered combination with a long acting insulin.

18. The method according to claim 1 , wherein the composition comprises a 1:1 crystalline complex of the SGLT2 inhibitor or pharmaceutically acceptable form thereof and an amino acid, and the crystalline complex is a crystalline hydrate.

19. The method according to claim 1 , wherein the composition comprises a 1:1:1 crystalline complex of the SGLT2 inhibitor or pharmaceutically acceptable form thereof, L-proline and water in a crystalline form.

20. The method of claim 1 , wherein
the SGLT2 inhibitor or pharmaceutically acceptable form thereof is administered at a dose of 0.03 to 0.3 mg/kg body weight per day.

21. The method according to claim 1 , wherein the SGLT2 inhibitor or pharmaceutically acceptable form thereof is administered at a dose of 0.01 to 0.5 mg/kg body weight per day.

22. A method of treatment of a metabolic disorder in a canine animal comprising administering to the canine animal a composition comprising a 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranos-1-yl)-benzene represented by the following formula:

wherein:
the metabolic disorder is selected from the group consisting of: ketoacidosis, pre-diabetes, insulin dependent diabetes mellitus, insulin resistance diabetes, insulin resistance, obesity, hyperglycemia, hyperglycemia induced cataract formation, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low grade systemic inflammation, hepatic lipidosis, inflammation of the pancreas, metabolic disorder consequences, Syndrome X (metabolic syndrome), and combinations thereof; and
the composition comprises a 1:1 crystalline complex of the SGLT2 inhibitor or pharmaceutically acceptable form thereof and an amino acid, and the crystalline complex is a crystalline hydrate.

Assignees

• Boehringer Ingelheim Vetmedica Gmbh

Inventors

• Kley Saskia
• Reiche Dania Birte

Classifications

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/401

  Proline; Derivatives thereof, e.g. captopril · CPC title

• A61K9/4858

  Organic compounds · CPC title

• A61K9/2018

  Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates · CPC title

• A61K31/00

  Medicinal preparations containing organic active ingredients · CPC title