# US 10,117,822 B2 · Cross-linked hyaluronic acid, process for the preparation thereof and use thereof in the aesthetic field

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- Number: US 10,117,822 B2
- Document ID: US10117822B2
- Status: Granted
- Kind: B2
- Application number: 14/905,660
- Filed: 2014-07-16
- Published: 2016-06-09
- Granted: 2018-11-06
- Earliest claimed: 2013-07-16
- Assignees: I.R.A. Istituto Ricerche Applicate S.R.L.
- Applicants: I.R.A. Istituto Ricerche Applicate S.R.L.
- Inventors: Ugo Raffaello Citernesi; Lorenzo Beretta; Lorenzo Citernesi
- Web page: https://patentgrep.com/patent/US10117822B2

## CPC

- A61K 8/735: {Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof}
- A61K 8/42: Amides
- A61L 27/20: Polysaccharides
- 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}
- A61K 2800/74: Biological properties of particular ingredients
- A61K 2800/91: Injection
- A61K 2800/95: Involves in-situ formation or cross-linking of polymers
- A61L 2400/06: Flowable or injectable implant compositions
- A61L 2430/34: for soft tissue reconstruction
- 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)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- 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)

## Abstract

The present invention relates, in one aspect, to the use as dermal filler of a cross-linked biopolymer compatible with the tissues of the human organism based on hyaluronic acid cross-linked with urea. The biopolymer of hyaluronic acid and urea may be applied or injected in a soft tissue of human body for tissue augmentation.

## Claims

### Claim 1

A method for tissue augmentation of an individual, said method comprising:
injecting under the skin of said individual, a biocompatible cross-linked biopolymer wherein said biopolymer consists of hyaluronic acid cross-linked with urea.

### Claim 2 (depends on 1)

A method according to claim 1, wherein the biopolymer has a molecular weight in the range from 100,000 to 20,000,000 Dalton.

### Claim 3 (depends on 1)

A method according to claim 1, wherein the biopolymer is in the form of a hydrogel or particles.

### Claim 4 (depends on 1)

A method according to claim 1, wherein the biopolymer is injected or implanted in the epidermis, dermis, or hypodermis of said individual.

### Claim 5 (depends on 1)

A method according to claim 1, wherein the biopolymer is in the form of an implant or of a subcutaneous filling injection for the treatment of aging.

### Claim 6 (depends on 1)

The method of claim 1 for the cosmetic or aesthetic treatment of lines, wrinkles, folds or furrows associated with face aging of a subject in need of an aesthetic treatment.

### Claim 7 (depends on 1)

The method of claim 1, wherein the tissue augmentation is for the treatment of lines, wrinkles, folds, or furrows.

### Claim 8

A method for the manufacture of a hyaluronic acid biopolymer cross-linked with urea said method comprising:
a) dissolving hyaluronic acid or a salt thereof in a liquid to form a solution of hyaluronic acid;
b) dissolving urea in an aqueous acidic solution with a pH of 3.5 to 4 to form an acidic aqueous solution of urea;
c) combining the solution of hyaluronic acid with the acidic aqueous solution of urea to obtain a mixture, said mixture having a pH in the range of 3.5 to 4, wherein said hyaluronic acid biopolymer crosslinked with urea is formed as a result of said combining.

### Claim 9 (depends on 8)

The method according to claim 8, wherein the acidic aqueous solution of urea contains HCl preferably in a concentration in the range from 20 to 30% by weight.

### Claim 10 (depends on 8)

The method according to claim 8, wherein the hyaluronic acid dissolved in solution is in the form of sodium or calcium salt.