Cross-linked hyaluronic acid, process for the preparation thereof and use thereof in the aesthetic field

• US 10,117,822 B2
• Filed: 07/16/2014
• Issued: 11/06/2018
• Est. Priority Date: 07/16/2013
• Status: Active Grant

• Current Assignee: I.R.A. Istituto Ricerche Applicate S.r.l
• Original Assignee: I.R.A. Istituto Ricerche Applicate S.r.l
• Inventors: Citernesi, Ugo Raffaello, Beretta, Lorenzo, Citernesi, Lorenzo
• Primary Examiner(s): Berry, Layla D
• Assistant Examiner(s): Miller, Dale R
• Application Number:
  US14/905,660
• Publication Number:
  US 20160158140A1
• Time in Patent Office: 1,574 Days
• CPC Class Codes: A61K 2800/74 Biological properties of particular ingredients
• CPC Class Codes: A61K 2800/91 Injection
• CPC Class Codes: A61K 2800/95 Involves in-situ formation or cross-linking of polymers
• CPC Class Codes: A61K 8/42 Amides
• CPC Class Codes: A61K 8/735 Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 2430/34 for soft tissue reconstruction
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61Q 19/08 Anti-ageing preparations
• CPC Class Codes: C08B 37/0072 Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

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

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.

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

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

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

5. 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.

6. 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.

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

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.

9. 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.

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