Hyaluronic acid composition

Abstract

An injectable hyaluronic acid composition including a hyaluronic acid; a local anesthetic selected from the group of amide and ester type local anesthetics or a combination thereof; and an ascorbic acid derivative in an amount which prevents or reduces the effect on the viscosity and/or elastic modulus G′ of the composition caused by the local anesthetic upon sterilization by heat. Further, the medical and non-medical, such as cosmetic, use of such a composition, and to a method of manufacturing such a composition.

1 - 40 . (canceled) 
     
     
         41 . A sterilized injectable hyaluronic acid composition for use in a dermatological treatment of a subject in need thereof, wherein the sterilized injectable hyaluronic acid composition comprises:
 (a) modified hyaluronic acid in a concentration from about 1 to about 100 mg/ml,   (b) a local anesthetic in a concentration from about 0.1 to about 30 mg/ml, and   (c) an ascorbic acid derivative in a concentration from about 0.01 mg/ml to about 5 mg/ml,   
       wherein the composition is subjected to sterilization by autoclaving at a F0-value≥4, and wherein no or mild local or systemic effects occur after the subject is treated with the hyaluronic acid composition. 
     
     
         42 . The composition of  claim 41 , wherein the dermatological treatment is selected from the group consisting of wound healing, treatment of dry skin conditions and sun-damaged skin, treatment of hyper pigmentation disorders, treatment and prevention of hair loss, and treatment of conditions that have inflammation as a component of the disease process. 
     
     
         43 . The composition of  claim 41 , wherein the composition is used to treat psoriasis or asteototic eczema. 
     
     
         44 . The composition of  claim 41 , wherein the dermatological treatment is cosmetic or medical. 
     
     
         45 . The composition of  claim 41 , wherein the modified hyaluronic acid is crosslinked with a chemical crosslinking agent to form a crosslinked hyaluronic acid, wherein a degree of modification of the hyaluronic acid gel is less than 2 mol %. 
     
     
         46 . The composition of  claim 45 , wherein the crosslinked hyaluronic acid is biocompatible. 
     
     
         47 . The composition of  claim 45 , wherein the crosslinked hyaluronic acid is a gel or a hydrogel. 
     
     
         48 . The composition of  claim 47 , wherein the crosslinked hyaluronic acid is a gel and wherein the hyaluronic acid concentration and extent of crosslinking affect mechanical properties of the gel. 
     
     
         49 . The composition of  claim 46 , wherein no, or mild immune response occurs in the subject after treatment. 
     
     
         50 . The composition of  claim 47 , wherein the crosslinked hyaluronic acid is a gel and wherein the hyaluronic acid gel comprises a portion of hyaluronic acid which is not crosslinked. 
     
     
         51 . A cosmetic use of a sterilized injectable hyaluronic acid composition in a subject in need thereof, wherein the sterilized injectable hyaluronic acid composition comprises:
 (a) modified hyaluronic acid in a concentration from about 1 to about 100 mg/ml,   (b) a local anesthetic in a concentration from about 0.1 to about 30 mg/ml, and   (c) an ascorbic acid derivative in a concentration from about 0.01 mg/ml to about 5 mg/ml, wherein:   
       the cosmetic use is to improve the appearance of skin, prevent hair loss, treat hair loss, fill wrinkles or contour the face or body of the subject. 
     
     
         52 . The sterilized injectable hyaluronic acid composition of  claim 41 , wherein the composition is subjected to sterilization by autoclaving at a F0-value≥4, and wherein no or mild local or systemic effects occur after the subject is treated with the hyaluronic acid composition. 
     
     
         53 . The composition of  claim 52 , wherein the modified hyaluronic acid is crosslinked with a chemical crosslinking agent to form a crosslinked hyaluronic acid, wherein a degree of modification of the hyaluronic acid gel is less than 2 mol %. 
     
     
         54 . The composition of  claim 53 , wherein the crosslinked hyaluronic acid is biocompatible. 
     
     
         55 . The composition of  claim 54 , wherein the crosslinked hyaluronic acid is a gel or a hydrogel. 
     
     
         56 . The composition of  claim 55 , wherein the crosslinked hyaluronic acid is a gel and wherein the hyaluronic acid concentration and extent of crosslinking affect mechanical properties of the gel. 
     
     
         57 . The composition of  claim 55 , wherein the crosslinked hyaluronic acid is a gel and wherein the hyaluronic acid gel comprises a portion of hyaluronic acid which is not crosslinked. 
     
     
         58 . A cosmetic method of improving the appearance of skin, preventing hair loss, treating hair loss, filling wrinkles or contouring the face or body of a subject, comprising:
 a) providing the sterilized injectable hyaluronic acid composition of  claim 51 , and   b) injecting said sterilized injectable hyaluronic acid composition into the skin of the subject.   
     
     
         59 . The method of  claim 57 , wherein the sterilized injectable hyaluronic acid composition is injected into the cutis and/or subcutis. 
     
     
         60 . A sterilized injectable hyaluronic acid composition for use in the treatment of a joint disorder by intraarticular injection, wherein the sterilized injectable hyaluronic acid composition comprises:
 (a) a hyaluronic acid gel,   (b) a therapeutically relevant concentration of lidocaine, and   
       (c) an ascorbic acid derivative selected from the group consisting of ascorbyl phosphates, ascorbyl sulfates, and ascorbyl glycosides, in an amount which prevents or reduces the effect on the viscosity and/or elastic modulus G′ of the composition caused by the lidocaine upon sterilization by heat, wherein the concentration of the ascorbic acid derivative in the composition is in the range of 0.01 to 5 mg/ml, and the composition has been subjected to sterilization by autoclaving at a F0-value≥4, wherein the hyaluronic acid gel is crosslinked by modification with a chemical crosslinking agent, wherein a degree of modification of the hyaluronic acid gel is less than 2 mol %, and wherein the hyaluronic acid composition does not exhibit increased stability compared to the same composition without an ascorbic acid derivative.