Granted Patent B2

US 12,667,534 · App. 18/348,736 · Granted Jun 30, 2026

Inventors: Johan Olsson (Bromma, SE); Morgan Karlsson (Almunge, SE)

Assignee: Galderma Holding SA

A61K8/735A61K8/042A61Q19/00

Abstract

Claims (31)

1 . A hydrogel product comprising a hyaluronic acid hydrogel crosslinked by amide bonds, obtained by a method comprising:

crosslinking a hyaluronic acid (HA) having a molecular weight of 2.1 to 10 MDa with a crosslinker, to obtain the hyaluronic acid hydrogel crosslinked by amide bonds, wherein:

the crosslinker is a di- or multinucleophile functional crosslinker comprising a spacer group selected from the group consisting of di-, tri-, tetra-, and oligosaccharides;

a concentration of the HA is between 2% to 10% (w/w); and

a molar ratio of the crosslinker to the HA is less than or equal to 2 mol % per HA disaccharide.

2 . The hydrogel product according to claim 1 , wherein the spacer group is trehalose.

3 . The hydrogel product according to claim 1 , wherein the di- or multinucleophile functional crosslinker is diaminotrehalose (DATH).

4 . The hydrogel product according to claim 1 , wherein the HA has a molecular weight of 2.1-3.5 MDa.

5 . The hydrogel product according to claim 1 , wherein:

the HA has a molecular weight of 2.1-3.5 MDa;

the crosslinker is diaminotrehalose (DATH); and

during the crosslinking, the concentration of HA is between 3-5% (w/w) and the molar ratio of DATH to HA is between 0.9-1.1 mol % per HA disaccharide.

6 . The hydrogel product according to claim 1 , wherein the hydrogel product is essentially free of synthetic non-carbohydrate structures or linkers.

7 . The hydrogel product according to claim 1 , wherein the crosslinked HA molecules have an apparent molecular weight (Mwapp) above 1.0 MDa.

8 . The hydrogel product according to claim 1 , wherein the crosslinked HA molecules have an apparent molecular weight (Mwapp) of 2.1 MDa or above.

9 . The hydrogel product according to claim 1 , wherein the hydrogel product has a HA concentration of 10-45 mg/mL.

10 . The hydrogel product according to claim 1 , wherein the crosslinking comprises:

(1) providing a solution of the HA molecules;

(2) activating carboxyl groups on the HA molecules with a coupling agent to form activated HA molecules;

(3) crosslinking the activated HA molecules via their activated carboxyl groups using a di- or multinucleophile functional crosslinker to obtain a HA hydrogel crosslinked by amide bonds.

11 . The hydrogel product according to claim 1 , wherein the concentration of the HA is between 3-5% (w/w) during the crosslinking.

12 . The hydrogel product according to claim 1 , wherein the molar ratio of crosslinker to HA is between 0.9-1.1 mol % per HA disaccharide during the crosslinking.

13 . The hydrogel product according to claim 1 , further comprising a local anesthetic.

14 . The hydrogel product according to claim 13 , wherein the local anesthetic comprises lidocaine.

15 . A syringe comprising the hydrogel product according to claim 1 .

16 . A method of performing a reparative or esthetic dermatologic treatment, the method comprising:

injecting a subject with the hydrogel product of claim 1 .

17 . The method of claim 16 , wherein the injecting is performed as a subdermal, intradermal, subcutaneous, intramuscular, submuscular, or intragingival injection.

18 . The method of claim 16 , wherein the reparative or esthetic dermatologic treatment comprises dermal filling.

19 . The method of claim 18 , wherein the injection is administered to fill lines, fine lines, wrinkles, or skin cracks.

20 . The method of claim 19 , wherein the lines, fine lines, wrinkles, or skin cracks are located on the face, neck, hands, feet, knees, or elbows.

Assignments (3)

Continuity (3)

References Cited (142)