INJECTABLE HYDROGEL FOR THE LONG-TERM SUPPLEMENTATION OF GLYCEROL IN THE SKIN

• US 20120108674A1
• Filed: 05/14/2010
• Published: 05/03/2012
• Est. Priority Date: 05/26/2009
• Status: Active Grant

• Current Assignee: ANTEIS S.A. (Merz Pharma GmbH & Company Kgaa)
• Original Assignee: ANTEIS S.A. (Merz Pharma GmbH & Company Kgaa)
• Inventors: Gavard Molliard, Samuel, Vinchon, Cyrille
• Granted Patent: US 9,623,150 B2
• Time in Patent Office: Days
• US Class Current: 514/738
• CPC Class Codes: A61K 2800/91 Injection
• CPC Class Codes: A61K 8/042 Gels
• 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 27/20 Polysaccharides
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61Q 19/08 Anti-ageing preparations
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

An injectable hydrogel, includes, in weight, in a physiologically acceptable carrier fluid: 0.01 to 5% of glycerol and 0.1 to 5% of cross-linked hyaluronic acid, or one of the salts thereof; characterized in that the hyaluronic acid or one of the salts thereof is cross-linked by the formation of covalent bonds using bifunctional or polyfunctional molecules, the injectable hydrogel being sterilized in moist heat and having viscoelastic properties such that Tanδ at a frequency of 1 Hz is less than or equal to 1.10. A method for producing the hydrogel, to a kit containing the hydrogel, as well as to the use thereof in dermatology are also described.

Claims

1. An injectable hydrogel comprising, by weight, in a physiologically acceptable carrier fluid:

0.01% to 5% of glycerol and 0.1% to 5% of a crosslinked biopolymer of hyaluronic acid or one of the salts thereof relative to the total weight of the hydrogel, characterized in that the hyaluronic acid or one of the salts thereof is crosslinked by formation of covalent bonds between the chains of said biopolymer by means of bifunctional or polyfunctional molecules, said injectable hydrogel being sterilized in moist heat and having a Tanδ

at a frequency of 1 Hz less than or equal to 1.10.

2. The injectable hydrogel as claimed in claim 1, in which glycerol is present at a concentration by weight in the range from 0.5% to 2.5% relative to the total weight of the hydrogel.

3. The injectable hydrogel as claimed in claim 1, in which hyaluronic acid or one of the salts thereof is present at a concentration by weight in the range from 0.5% to 3% relative to the total weight of the hydrogel.

4. The injectable hydrogel as claimed in claim 1, for which the parameter Tanδ

at a frequency of 1 Hz is less than or equal to 0.80.

5. The injectable hydrogel as claimed in claim 1, in which the molecular weight of the hyaluronic acid or of one of the salts thereof is between 1000 Da and 10×

10⁶ Da, preferably between 500,000 and 4×

10⁶ Da.

6. The injectable hydrogel as claimed in claim 1, in which crosslinking is effected by bifunctional or polyfunctional molecules selected from epoxides, epihalohydrins and divinylsulfone, on noncrosslinked or already crosslinked hyaluronic acid with or without one or more other polysaccharides of natural origin. For example, the crosslinking agent used can be butanediol diglycidyl ether (BDDE) or divinylsulfone (DVS).

7. The injectable hydrogel as claimed in claim 1, characterized in that it comprises at least one other biocompatible polymer and/or at least one pharmacologically active substance and/or at least one nonpharmacologically active substance having positive effects on the organism or on the hydrogel.

13. A kit in the form of a syringe and containing the injectable hydrogel as claimed in claim 1.

14. A kit in the form of a vial or bottle and containing the injectable hydrogel as claimed in claim 1 and suitable to be taken up in an injecting syringe.

15. The injectable hydrogel as claimed in claim 1 applied for improving the chemical, physical and mechanical characteristics of the skin of mammals.

16. The injectable hydrogel as claimed in claim 1 applied for filling wrinkles and lines and/or creating volume and/or for skin moisturization and/or for reviving epidermal cellular activity and/or maintaining the mechanical properties of firmness and elasticity of the skin and/or maintaining epidermal and dermal stimulation and/or for stimulating the antioxidant activity of the dermis and/or for preventing skin aging and/or accelerating the process of wound healing.

8. A process for manufacturing an injectable hydrogel, comprising the steps consisting of:

a) preparing a first mixture comprising at least 0.1% to 5 wt. % of a crosslinked biopolymer of hyaluronic acid or of one of the salts thereof by formation of covalent bonds between the chains of said biopolymer by means of bifunctional or polyfunctional molecules,

b) adding 0.01% to 5 wt. % of glycerol before, during or after the crosslinking of the biopolymer of hyaluronic acid or of one of the salts thereof during step a), so as to form a homogeneous mixture,

c) transforming the gel thus obtained into a form that is ready to use,

d) sterilizing the product in moist heat.

9. The process for manufacturing an injectable hydrogel as claimed in claim 8, in which the sterilization temperature is above 100°

C.

10. The process for manufacturing an injectable hydrogel as claimed in claim 8, in which sterilization is carried out at a temperature above or equal to 121°

C.

11. The process for manufacturing an injectable hydrogel as claimed in claim 8, in which sterilization is carried out according to one of the following cycles:

131°

C. for 1 min/130°

C. for 3 min/125°

C. for 7 min/121°

C. for 20 min or 121°

C. for 10 min.

12. The process for manufacturing an injectable hydrogel as claimed in claim 8, for which the gel obtained possesses a Tanδ

at a frequency of 1 Hz less than or equal to 1.10, preferably less than or equal to 0.80.