# US 10,307,362 B2 · Dermal injectable sterile composition

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- Number: US 10,307,362 B2
- Document ID: US10307362B2
- Status: Granted
- Kind: B2
- Application number: 15/874,144
- Filed: 2018-01-18
- Published: 2018-05-24
- Granted: 2019-06-04
- Earliest claimed: 2012-10-24
- Assignees: Teoxane
- Applicants: Teoxane
- Inventors: François Bourdon; Stéphane Meunier
- Web page: https://patentgrep.com/patent/US10307362B2

## CPC

- A61K 8/735: {Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof}
- A61K 8/042: {Gels}
- A61K 31/728: Hyaluronic acid
- A61P 17/00: Drugs for dermatological disorders
- A61Q 19/08: Anti-ageing preparations
- C08B 37/0072: {Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates}
- C08L 5/08: Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
- A61K 2800/91: Injection
- A61Q 19/00: Preparations for care of the skin
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- C08B: POLYSACCHARIDES; DERIVATIVES THEREOF (polysaccharides containing less than six saccharide radicals attached to each other by glycosidic linkages C07H; fermentation or enzyme-using processes C12P19/00; sugar industry C13; production of cellulose D21)
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)

## Abstract

The present invention relates to a crosslinked hyaluronic acid gel which derives from the crosslinking of hyaluronic acid or of a salt thereof in the presence of at least an effective amount of at least one endogenous polyamine as a crosslinking agent, said crosslinking being carried out under conditions favorable to the coupling of said hyaluronic acid and of said endogenous polyamine(s).

## Claims

### Claim 1

A process for preparing a crosslinked gel of hyaluronic acid or a salt thereof, comprising the steps:
a) providing an aqueous gel of hyaluronic acid or of a salt thereof, in the noncrosslinked state,
b) bringing the gel obtained in step a) into contact with an effective amount of at least one endogenous polyamine to form a mixture, wherein said at least one endogenous polyamine is used in a content between 0.1% and 3% by number of moles of the at least one endogenous polyamine relative to the number of moles of hyaluronic acid,
c) crosslinking said mixture formed in step b), said crosslinking being carried out under conditions favourable to the covalent coupling of said hyaluronic acid and of said at least one endogenous polyamine to form a crosslinked hydrogel, and
d) recovering said crosslinked hydrogel, wherein said crosslinked hydrogel has a degree of modification of less than or equal to 1%, the degree of modification being the ratio between the number of moles of endogenous polyamine attached to the hyaluronic acid and the number of moles of hyaluronic acid forming said crosslinked hydrogel.

### Claim 2 (depends on 1)

The process according to claim 1, wherein said process also comprises a step e) of stopping the crosslinking, consisting of exposing the crosslinked hydrogel to conditions capable of stopping the crosslinking thereof, wherein the stopping step is carried out before, jointly with or after the recovering step d).

### Claim 3 (depends on 1)

The process according to claim 1, wherein the at least one endogenous polyamine is selected from the group consisting of spermidine, spermine, and a mixture thereof.

### Claim 4 (depends on 1)

The process according to claim 1, wherein the hyaluronic acid or a salt thereof is used in a content of between 0.5% and 12% by weight relative to the total weight of the mixture obtained at the end of step b).

### Claim 5 (depends on 1)

The process according to claim 1, wherein the crosslinking is carried out in the presence of a supplementary crosslinking agent.

### Claim 6 (depends on 1)

The process according to claim 1, wherein the coupling is carried out in the presence of at least one activator and, optionally combined with at least one other agent as auxiliary coupling agent.

### Claim 7 (depends on 1)

The process according to claim 1, wherein the process uses (i) sodium hyaluronate, (ii) spermine, as crosslinking agent, and (iii) 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) in combination with N-hydroxybenzotriazole (HOBt), as, respectively, activator and auxiliary coupling agent.