Heat stable hyaluronic acid compositions for dermatological use

Abstract

The disclosure provides hyaluronic acid (HA) gel formulations and methods for treating the appearance of the skin. The formulations hyaluronic acid and at least one additional ingredient. Methods for treating lines, wrinkles, fibroblast depletions, and scars with the disclosed composition are provided as well.

1 . A stable dermal filler formulation comprising a hyaluronic acid (HA) and at least one additional ingredient selected from the group consisting of a wrinkle reduction, antioxidant, haemostatic, vasoconstriction, anti-itching, anti-inflammatory and anti-irritant ingredient 
     
     
         2 . The dermal filler formulation of  claim 1 , wherein stability of the dermal filler formulation is determined by subjecting the dermal filler formulation to a heat treatment selected from the group consisting of (a) steam sterilization at between about 120° C. and about 135° C., and (b) about 32 days at about 45° C., with substantial retention after the heat treatment of one or more of the dermal filler characteristics of being clear, homogenous, and cohesive, and without substantial degradation of the dermal filler formulation after the heat treatment. 
     
     
         3 . The dermal filler formulation of  claim 1 , wherein the HA is cross-linked. 
     
     
         4 . The dermal filler formulation of  claim 1 , wherein the HA is present in an amount of about 1 to about 40 mg/mL. 
     
     
         5 . The formulation of  claim 1 , wherein the additional ingredient is a vitamin C. 
     
     
         6 . The formulation of  claim 1 , wherein the additional ingredient is a vitamin E. 
     
     
         7 . The formulation of  claim 1 , wherein the formulation is stable, as determined by substantial retention at room temperature of one or more of the dermal filler characteristics of being clear, homogenous, and cohesive, and without substantial degradation of the dermal filler formulation, for a period of at least 2 years. 
     
     
         8 . The formulation of  claim 7 , wherein the formulation is stable for at least 3 years. 
     
     
         9 . The formulation of  claim 1 , wherein the additional ingredient is present in an amount of about 0.001% to about 10% w/w. 
     
     
         10 . The formulation of  claim 1 , wherein the additional ingredient provides the formulation with improved rheological properties resulting in less extrusion force required for administration compared to an HA gel formulation without the additional constituent. 
     
     
         11 . A method of treating fine lines, wrinkles, fibroblast depletions, or scars of a patient, the method comprising the step of administering to the patient an effective amount of a steam sterilization stable dermal filler formulation comprising a hyaluronic acid (HA) and at least one additional ingredient selected from the group consisting of wrinkle reduction, antioxidant, haemostatic, vasoconstriction, anti-itching, anti-inflammatory and anti-irritant ingredients, wherein the formulation is clear, homogenous, monophasic, cohesive, stable and not degraded after steam sterilization and wherein the appearance of the fine lines, wrinkles, fibroblast depletions, or scars is diminished. 
     
     
         12 . The method of  claim 11  wherein the formulation is sub dermal injected into the facial skin of the subject. 
     
     
         13 . The method of  claim 11 , wherein the additional ingredient is present in an amount of about 0.1% to about 3% w/w. 
     
     
         14 . The method of  claim 11 , wherein the HA is cross-linked. 
     
     
         15 . The method of  claim 14 , wherein the HA is present in an amount of about 1 to about 40 mg/mL. 
     
     
         16 . A method of treating fine lines, wrinkles, fibroblast depletions, or scars of a patient, the method comprising the step of local injection to the patient of a steam sterilization stable dermal filler formulation comprising about 1 to about 40 mg/mL of a cross-linked hyaluronic acid (HA) and at least one additional ingredient selected from the group consisting of wrinkle reduction, antioxidant, haemostatic, vasoconstriction, anti-itching, anti-inflammatory and anti-irritant ingredients, wherein the formulation is clear, homogenous, cohesive, stable and not degraded after steam sterilization and wherein the appearance of the fine lines, wrinkles, fibroblast depletions, or scars is diminished by the injection. 
     
     
         17 . A steam sterilization stable dermal filler formulation comprising a hyaluronic acid and at least one additional ingredient selected from the group consisting of AA2G and dexpanthenol, wherein the stability of the dermal filler formulation is significantly increased by the addition of the additional ingredient.