Composition and methods for regulating chondrocyte proliferation and increasing of cartilage matrix production

Patent metadata

Field	Value
Publication number	US-2021401944-A1
Application number	US-201917294079-A
Country	US
Kind code	A1
Filing date	Nov 18, 2019
Priority date	Nov 19, 2018
Publication date	Dec 30, 2021
Grant date	—

Abstract

A pharmaceutical compositions includes GLP-1 and GLP-1 analogues inducing an anabolic stimulation of chondrocytes and a decreasing in chondrocyte catabolic including a decrease in cartilage matrix loss and cartilage degeneration for use in the treatment of cartilage disease. The composition induces cartilage regeneration and anabolic stimulation of chondrocytes, including chondrocyte proliferation and/or stem cell differentiation into chondrocytes.

First claim

1 . A pharmaceutical composition which induces anabolic stimulation of chondrocytes, including chondrocyte proliferation, and/or decreasing catabolic activity, including a decrease in cartilage matrix loss for use in the treatment of cartilage disease comprising Glucagon Like Peptide-1 analogue as the active ingredient therein.

2 . The pharmaceutical composition for use according to claim 1 , wherein the Glucagon Like Peptide-1 (GLP-1) analogue is liraglutide.

3 . The pharmaceutical composition for use according to claim 2 , wherein the concentration of liraglutide is between 1 ng/ml and 10 mg/ml.

4 . The pharmaceutical composition for use according to claim 3 , wherein the formulation provides a therapeutically effective amount of GLP-1 analogue and an excipient comprising a polymer selected from the group consisting of non-ionic surfactant, cellulose, polyether, glucan, glycerophospholipids, polysaccharides, proteins, and combinations thereof.

5 . The pharmaceutical composition for use according to claim 4 , wherein the GLP-1 analogue is liraglutide, and comprises albumin.

6 . The pharmaceutical composition for use according to claim 5 , wherein the albumin concentration is about 0.1% to about 10% (wt/wt), preferably 5% (wt/wt), of the formulation.

7 . The pharmaceutical composition for use according to claim 1 wherein the cartilage disease is selected from the group consisting of cartilage defect caused by external injuries or surgical treatment, osteochondritis dissecans, osteoarthritis, congenital cartilage disease, and cartilage injury.

8 . A method of increasing anabolic cytokine secretion or production in chondrocytes in a patient, said method comprising administering to the patient a composition according to claim 1 .

9 . The method according to claim 8 wherein said anabolic cytokine is GMCSF and/or CXCL10/IP10.

10 . A method of decreasing catabolic cytokine secretion or production in chondrocytes in a patient, said method comprising administering to the patient the composition according to claim 1 .

11 . The method according to claim 10 wherein said catabolic cytokine is selected from the group consisting MMP3, MMP13, PGE2, IL7, MCP1.

12 . The method according to claim 8 wherein the composition is administered to the subject via intra-articular injection.

13 . A method comprising the step of using liraglutide in the manufacture of a medicament for treating a cartilage disease by increasing anabolic cytokine secretion or production and lowering cartilage loss and/or repair through stimulation of chondrocyte proliferation.

14 . The method of claim 13 , wherein the cartilage disease is selected from the group consisting of cartilage defect caused by external injuries or surgical treatment, osteochondritis dissecans, osteoarthritis, congenital cartilage disease, and cartilage injury.

15 . A composition for use in cartilage regeneration which comprises Glucagon Like Peptide-1 analogue.

16 . The composition for use in cartilage regeneration according to claim 15 , wherein Glucagon Like Peptide-1 analogue is selected from the group consisting of xenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, semaglutide or liraglutide.

17 . The composition for use in cartilage regeneration according to claim 16 , wherein, Glucagon Like Peptide-1 analogue is liraglutide.

18 . The composition for use in cartilage regeneration according to claim 17 , wherein, the concentration of said Glucagon Like Peptide-1 is of about 0.1 nM to 625 μM.

19 . The composition for use in cartilage regeneration according to claim 18 , which further comprises at least 5% of more weight of a pharmaceutically acceptable formulation vehicle to be used in combination.

20 . The composition for use in cartilage regeneration according to claim 19 , wherein the pharmaceutically acceptable formulation vehicle is selected from the group consisting of albumin or alpha1-acid glycoprotein.

21 . The composition for use in cartilage regeneration according to claim 20 , wherein the pharmaceutically acceptable formulation vehicle concentration is about 0.1% to about 10% (wt/wt), preferably 5% (wt/wt), of the formulation.

22 . The composition for use in cartilage regeneration according to claim 21 , wherein the pharmaceutically acceptable formulation vehicle concentration is 5% (wt/wt) of the formulation.

23 . The composition for use in cartilage regeneration according to claim 22 , wherein the pharmaceutically acceptable formulation vehicle is albumin.

24 . The composition for use in cartilage regeneration according to claim 23 , wherein the pharmaceutically acceptable formulation vehicle is alpha1-acid glycoprotein.

25 . The composition for use in cartilage regeneration according to claim 1 , wherein the composition is administered by intra-articular injection to cartilage injury lesion.

26 . The composition for use in cartilage regeneration according to claim 1 , wherein the composition induces anabolic stimulation of chondrocytes, including chondrocyte proliferation and/or stem cell differentiation into chondrocytes.

Assignees

• 4Moving Biotech
• Univ Sorbonne

Inventors

• Berenbaum Francis
• Rattenbach Revital

Classifications

• A61K47/42

  Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34) · CPC title

• A61K9/0019

  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 title

• A61P19/02 Primary

  for joint disorders, e.g. arthritis, arthrosis · CPC title

• A61K38/26 Primary

  Glucagons · CPC title

• A61K38/38

  Albumins · CPC title