MX2008008639A - Dermatological viscoelastic gel - Google Patents

Abstract

The invention relates to a natural dermatological polysaccharide gel comprising a polysaccharide aqueous solution whose weight/volume ratio ranges from 0.1 to 5%, for, example a hyaluronic acid, and a biocompatible viscous highly-hydrophilic alcohol whose weight/volume ratio ranges from 0.5 to 5%, for example a glycerol, and, possibly, adjuvants used in dermatology. The inventive gel is prepared by mixing the polysaccharide solution and the viscous highly-hydrophilic alcohol prior to sterilising the totality for example by wet heat.

Description

VISCOELASTIC GEL FOR DERMATOLOGICAL USE DESCRIPTION OF THE INVENTION The invention is concerned with a viscoelastic gel for dermatological use. Several polymers of natural origin such as collagen, hyaluronic acid or cellulose derivatives are frequently used in aesthetic medicine and in dermatology to fill wrinkles, reshape the face, increase the volume of lips and rejuvenate the skin of the face; This last type of treatment is directly derived from mesotherapy. To rejuvenate the skin, doctors often use hyaluronic acid, sometimes combined with a complex of vitamins, amino acids, mineral salts and nucleic acids. The object of this invention consists of the combination of a polysaccharide of natural origin, more particularly hyaluronan and a viscous alcohol to propose a composition prepared for injectable use that optimizes the treatment of skin rejuvenation, in particular involving a polysaccharide gel of natural origin that is used as an injection in dermatology, comprising an aqueous solution of polysaccharide at 0.1 - 5% w / v and a viscous and strongly hydrophilic biocompatible alcohol at 0.5 - 5% w / v, obtained by preparation of an aqueous solution of the polysaccharide and alcohol, then sterilization of this solution and optionally the adjuvants which are commonly used in dermatology, sterilization after the mixing of the components which has the effect of considerably increasing the viscosity of the resulting gel. The combination of a polysaccharide or its salts, in particular hyaluronan or sodium hyaluronate, has now been found and a small amount of a biocompatible viscous alcohol provides a composition whose viscosity increases extensively, and which when the biocompatible viscous alcohol is also hydrophilic, considerably increases the water retention properties when the composition is injected under the skin to be treated. A hydrophilic compound is defined as any compound that has a strong affinity for water. In an alcohol, the higher the density of OH groups, the more hydrophilic it is. For example, glycerol, low molecular weight alcohol (92.09 g.mol) and containing three OH groups, is extremely hydrophilic. It has been found that the addition of a small amount, of the order of 0.5 to 5% w / v, of a viscous biocompatible alcohol effects a significant increase in the viscosity of a polysaccharide solution of natural origin at 0.1-5% by weight / volume, stabilizes this solution during sterilization and maintains particularly advantageous viscous properties for skin tissue rejuvenation. The viscous alcohol can participate in the restructuring of the skin and the maturation of cells of this tissue and ensures the isotonicity of the mixture. A biocompatible alcohol having antiseptic properties, which reduces this risk of skin infections, is preferably used. Actually, this risk is significant during a rejuvenation treatment, taking into account the large number of injections performed on the face. Examples of such alcohols are in particular glycerol and polyethylene glycol lauryl sulfate. Commercial hyaluronic acids have different molecular weights (MW) and different concentrations according to the manufacturer. By way of illustration, it is possible to use a concentration of 1.8% weight / volume for hyaluronic acid of low to medium weight (0.5 to 1.8 MDa) and a concentration of 1.5% weight / volume for high weight hyaluronic acid (2.0 to 3.0 MDa). The invention also provides a process for the preparation of a polysaccharide gel of natural origin for dermatological use, comprising the steps consisting of: (a) Preparing an aqueous solution of polysaccharide and viscous and strongly hydrophilic alcohol in the desired proportions, (b) Sterilize the resulting solution, in particular by moist heat, and (c) Optionally put the gel in a ready-for-use form. Figures 1 to 3 are graphs showing the viscosities of the compositions of Examples 1 and 2 according to the invention and Example 3 (by comparison). Example 1: Influence of the concentration of hyaluronic acid and the presence of glycerol on the viscosity of solutions for the rejuvenation of the face. Three solutions based on the same hyaluronic acid which is characterized by an average molecular weight of 1.6 MDa were prepared. The first solution is a 1% hyaluronic acid solution. The second solution is a solution of the same hyaluronic acid, but concentrated at 2%. The third solution contains only 1.8% of this same hyaluronic acid to which 2% w / v glycerol is added. The three preparations were sterilized by moist heat, then their rheological properties were analyzed using a rheometer to measure the viscosity based on the shear rate disposed on the product. It is clearly seen that, according to the graph of Figure 1, for the low shear rates (corresponding to those to which the preparation is exposed for skin tissue rejuvenation after injection), the addition of glycerol to a solution of hyaluronic acid has more influence to obtain a preparation of high viscosity than the increase in the concentration of hyaluronic acid. Example 2: Influence of glycerol on the viscosity of solutions of hyaluronic acid with high molecular weight. Two solutions based on hyaluronic acid, characterized by a very high average molecular weight (2.6 MDa) were prepared. The first preparation is a 1.5% hyaluronic acid solution. The second preparation also contains 1.5% hyaluronic acid with high molecular weight to which 2% w / v glycerol is added. The two preparations were sterilized by moist heat, then their rheological properties were analyzed using a rheometer to measure the viscosity based on the shear rate imposed on the product. The graph of Figure 2 demonstrates that, although the preparation consists of a high molecular weight hyaluronic acid - hence characterized initially by a high viscosity - the glycerol itself tends to increase the viscous properties of the product. Example 3: Stabilization of the preparation by glycerol during sterilization (by comparison). A solution was prepared with 1.5% hyaluronic acid, characterized by a very high average molecular weight (2.6 MDa). This solution was then sterilized by moist heat (preparation 1). Glycerol was added to several milliliters of this sterilized solution (preparation 2). No rheological difference was observed between these two preparations; The graph of Figure 3 and the examples presented above demonstrate the stabilizing effect of glycerol during sterilization. Therefore, it is essential that the viscous alcohol be mixed with the hyaluronic acid solution before sterilization to obtain the increase in viscosity. After sterilization, the composition can be put into a form ready for use, for example in an ampoule or vial containing the dose to be injected by means of a syringe. The composition may comprise adjuvants that are commonly used in dermatology, added to the mixture before sterilization. Such adjuvants are vitamins, mineral acids, mineral salts and nucleic acids.

Claims (6)

1. CLAIMS 1. A polysaccharide gel of natural origin that is used for injection in dermatology, characterized in that it comprises an aqueous solution of polysaccharide at 0.1 - 5% w / v, and a viscous and strongly hydrophilic biocompatible alcohol at 0.5 - 5% in weight / volume, obtained by preparing an aqueous solution of the polysaccharide and alcohol, then sterilizing this solution, and optionally the adjuvants that are commonly used in dermatology, whereby sterilization after mixing of the components has the effect of increase appreciably the viscosity of the resulting gel.
2. 2. The gel according to claim 1, characterized in that the polysaccharide is hyaluronic acid.
3. 3. The gel according to claim 1 or 2, characterized in that the biocompatible alcohol is glycerol. The one according to any of claims 1 to 3, characterized in that the aqueous solution contains 1.8% w / v hyaluronic acid of average MW (0.5 to 1.8 MDa) and 2% w / v glycerol. The gel according to any of claims 1 to 3, characterized in that the aqueous solution contains 1.5% w / v of high PM hyaluronic acid (2.0 to 3.0 MDa) and 2% w / v glycerol.

   6. A process for the preparation of a polysaccharide gel of natural origin for dermatological use according to any of claims 1 to 3, characterized in that the steps consisting of: (a) Prepare an aqueous solution of polysaccharide and viscous biocompatible alcohol and strongly hydrophilic in the desired proportions, (b) Sterilize the resulting solution, in particular by moist heat, and (c) Optionally put the gel in a ready-to-use form.