Stabilisation and controlled-release systems for medicaments unstable on sterilisation

Patent metadata

Field	Value
Publication number	US-12465596-B2
Application number	US-202017440396-A
Country	US
Kind code	B2
Filing date	Jan 28, 2020
Priority date	Mar 18, 2019
Publication date	Nov 11, 2025
Grant date	Nov 11, 2025

Abstract

Disclosed are alkenylamides of sulfated hyaluronic acid and their use for the stabilisation and release of medicaments in the form of micellar suspensions which can be administered locally and/or locoregionally, in particular intra-articularly.

First claim

The invention claimed is:

1 . Sulfated hyaluronic acid amides (HAS) with C4-C20 alkenylamines, wherein a molar degree of derivatization of the alkenylamine in the sulfated hyaluronic acid amide ranges from 2 to 20%.

2 . Amides according to claim 1 wherein the sulfated hyaluronic acid has a number of sulfate groups per disaccharide unit ranging from 0.5 to 3.5.

3 . Amides according to claim 2 wherein the sulfated hyaluronic acid has a number of sulfate groups per disaccharide unit ranging from 0.5 to 1.5.

4 . Amides according to claim 2 wherein the sulfated hyaluronic acid has a number of sulfate groups per disaccharide unit ranging from 1.5 to 2.5.

5 . Amides according to claim 2 wherein the sulfated hyaluronic acid has a number of sulfate groups per disaccharide unit ranging from 2.5 to 3.5.

6 . Amides according to claim 1 wherein the alkenylamine is selected from oleylamine, (2E)-hex-2-en-1-amine and pent-2-en-1-amine.

7 . Amides according to claim 6 wherein the alkenylamine is oleylamine.

8 . Amides according to claim 1 wherein the molecular weight of the starting hyaluronic acid used for the sulfation ranges from 100,000 to 250,000 Da.

9 . Amides according to claim 1 wherein the molecular weight of the starting hyaluronic acid used for the sulfation ranges from 500,000 to 730,000 Da.

10 . Micellar suspensions comprising an aqueous micellar suspension of an amide and a hydrophobic or hydrophilic medicament, wherein the amide is the oleylamide of claim 7 .

11 . Micellar suspensions according to claim 10 wherein the oleylamide concentration is 13 mg/mL.

12 . A process for the preparation of the micellar suspensions of claim 10 , which comprises:
reacting a C4-C20 alkenylamine with a benzalkonium or tetrabutylammonium salt of sulfated hyaluronic acid in an aprotic apolar solvent in the presence of condensing agents; mixing the sulfated hyaluronic acid amide obtained in the previous step with an aqueous solution or suspension of the medicament; sonication of the mixture and sterile filtration.

13 . A method of stabilizing and controlling the release of a medicament, which comprises combining a medicament with the sulfated hyaluronic acid amides according to claim 1 .

Assignees

• Fidia Farm Spa

Inventors

• Guarise Cristian
• Pizzocaro Carlo

Classifications

• A61K47/36

  Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin · CPC title

• A61K47/18

  Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids · CPC title

• A61K38/23

  Calcitonins · CPC title

• A61K31/573

  substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone · CPC title

• A61K31/495

  having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) · CPC title