Solid glp-1 derivative compositions for oral administration

Patent metadata

Field	Value
Publication number	US-11167014-B2
Application number	US-201816620363-A
Country	US
Kind code	B2
Filing date	Jun 11, 2018
Priority date	Jun 9, 2017
Publication date	Nov 9, 2021
Grant date	Nov 9, 2021

Abstract

The present invention relates to solid compositions for oral administration comprising (i) a GLP-1 derivative and the SGLT2 inhibitor dapagliflozin or (ii) a GLP-1 derivative and a salt of NAC in combination with an SGLT2 inhibitor.

First claim

The invention claimed is:

1. A solid pharmaceutical composition for oral administration comprising a GLP-1 derivative and dapagliflozin, wherein the GLP-1 derivative is selected from the group consisting of:
(a) N ε26 {2-[2-(2-{2-[2-(2-{(S)-4-Carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butyrylamino}ethoxy) ethoxy]acetylamino}ethoxy)ethoxy]acetyl}, N ε37 -{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butyrylamino}ethoxy)ethoxy] acetylamino}ethoxy)ethoxy] acetyl}-[Aib 8 ,Arg 34 ,Lys 37 ] GLP-1(7-37)-peptide

(b) N ε37 -[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butanoyl]amino]ethoxy] ethoxy]acetyl] amino]ethoxy]ethoxy]acetyl], N ε36 -[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[10-(4-carboxy-phenoxy) decanoylamino] butanoyl] amino]ethoxy]ethoxy]acetyl] amino]ethoxy] ethoxy]acetyl]-[Aib8,Glu22,Arg26,Lys27,Glu30,Arg34,Lys36]-GLP-1-(7-37)-peptidyl-Glu-Gly

(c) N {Epsilon-36}-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[11-(4-carboxyphenoxy)undecanoylamino]butanoyl] amino] ethoxy] ethoxy] acetyl]amino]ethoxy] ethoxy]acetyl],N {Epsilon-371-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[11-(4-carboxyphenoxy)undecanoylamino]butanoyl]amino]ethoxy] ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl]-[Aib8,Glu22,Arg26,Arg34,Lys36,Lys37]-GLP-1-(7-37)-peptide

(d) N{Epsilon-36}-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[11-(4-carboxyphenoxy)undecanoylamino]butanoyl] amino]ethoxy]ethoxy] acetyl]amino]ethoxy]ethoxy]acetyl],N{Epsilon-37}-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[11-(4-carboxyphenoxy)undecanoylamino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl]-[Aib8,Arg26,Arg34,Lys36,Lys37]-GLP-1-(7-37)-peptide

(e) N{Epsilon-36}-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[10-(3-carboxyphenoxy)decanoylamino]butanoyl]amino] ethoxy]ethoxy]acetyl] amino]ethoxy]ethoxy]acetyl],N {Epsilon-37}-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[10-(3-carboxyphenoxy)decanoylamino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl]-[Aib8,Glu22,Arg26,Arg34,Lys36,Lys37]-GLP-1-(7-37)-peptide

wherein the oral bioavailability of the GLP-1 derivative is increased in the presence of dapagliflozin.

2. The solid pharmaceutical composition according to claim 1 , wherein the GLP-1 derivative is Compound B.

3. The pharmaceutical composition according to claim 1 , wherein the composition further comprises an absorption enhancer.

4. The composition according to claim 3 , wherein the absorption enhancer is N-(8-(2-hydroxybenzoyl)amino)caprylate (NAC).

5. The pharmaceutical composition according to claim 4 , wherein the absorption enhancer is a salt of NAC.

6. The pharmaceutical composition according to claim 5 , wherein the salt of NAC is monosodium N-[8-(2-hydroxybenxoyl) amino] caprylate (SNAC) or polymorphs thereof.

7. The pharmaceutical composition according to claim 1 , wherein one or both of the GLP-1 derivative and the dapagliflozin is in the form of a pharmaceutically acceptable salt, ester, or solvate.

8. The pharmaceutical composition according to claim 1 , wherein the dosage of the dapagliflozin is 0.5-50 mg per day and the dosage of the GLP-1 derivative is 0.1-100 mg per day.

9. The pharmaceutical composition according to claim 1 , wherein the composition comprises one or more additional pharmaceutically acceptable excipients.

10. The pharmaceutical composition according to claim 1 , wherein the dosage of the composition administered is in the range of 200-1000 mg.

11. The pharmaceutical composition according to claim 1 , wherein the composition is administered once daily.

12. The pharmaceutical composition according to claim 1 , wherein the composition comprises 5-300 mg dapagliflozin and 20-800 mg of a salt of NAC.

13. The pharmaceutical composition according to claim 12 , wherein the salt of NAC is SNAC or polymorphs thereof.

14. The pharmaceutical composition according to claim 1 , wherein the composition is in a form selected from the group consisting of a tablet, a capsule, and a sachet.

15. A method of treating type 2 diabetes in a subject in need of such method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition according to claim 1 and one or more pharmaceutically acceptable excipients.

Assignees

• Novo Nordisk As

Inventors

• Vegge Andreas
• Scheele Susanne
• Bjerregaard Simon

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61K31/7034

  attached to a carbocyclic compound, e.g. phloridzin · CPC title

• A61K38/26 Primary

  Glucagons · CPC title

• A61K45/06

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

• A61K31/70 Primary

  Carbohydrates; Sugars; Derivatives thereof (sorbitol A61K31/047) · CPC title