Biodegradable single-phase cohesive hydrogels

Abstract

Biodegradable single-phase cohesive hydrogels useful, e.g., for the formulation of viscosupplementation compositions or compositions for filling wrinkles, contain a homogeneous blend of x polymers, which may be identical or different, crosslinked prior to the interpenetration thereof by mixing in the form of a single-phase hydrogel, wherein such crosslinked polymers are insoluble in water and miscible with one another, and x ranges from 2 to 5; in one embodiment, the hydrogels are such that the x polymers have identical or different degrees of crosslinking, at least one of the x polymers having a degree of crosslinking x1 and at least one of the x polymers having a degree of crosslinking x2, with x1 being greater than or equal to x2.

1 .- 24 . (canceled) 
     
     
         25 . A biodegradable single-phase cohesive hydrogel, comprising a homogeneous mixture of  x  identical or different polymers, crosslinked prior to their interpenetration by mixing, in the single-phase hydrogel form, said crosslinked polymers being insoluble in water and miscible with one another, and wherein  x  ranges from 2 to 5. 
     
     
         26 . The biodegradable single-phase cohesive hydrogel as defined by  claim 25 , wherein the  x  polymers exhibit different degrees of crosslinking, at least one of the x polymers exhibiting a degree of crosslinking x1 and at least one of the  x  polymers exhibiting a degree of crosslinking x2, with x1 being greater than or equal to x2. 
     
     
         27 . The biodegradable single-phase cohesive hydrogel as defined by  claim 25 , wherein the  x  polymers exhibit identical degrees of crosslinking. 
     
     
         28 . The biodegradable single-phase cohesive hydrogel as defined by  claim 25 , wherein the polymers comprise polysaccharides. 
     
     
         29 . The biodegradable single-phase cohesive hydrogel as defined by  claim 28 , wherein the polysaccharides are selected from the group consisting of hyaluronic acid, keratan, heparin, cellulose and derivatives thereof, alginic acid, xanthan, carrageenan, chitosan and chondroitin and the biologically acceptable salts thereof. 
     
     
         30 . The biodegradable single-phase cohesive hydrogel as defined by  claim 28 , wherein the  x  polysaccharides are selected from the group consisting of hyaluronic acid and the biologically acceptable salts thereof. 
     
     
         31 . The biodegradable single-phase cohesive hydrogel as defined by  claim 28 , wherein at least one of the  x  polysaccharides is selected from the group consisting of cellulose derivatives and the biologically acceptable salts thereof. 
     
     
         32 . The biodegradable single-phase cohesive hydrogel as defined by  claim 28 , wherein at least one of the  x  polysaccharides is selected from the group consisting of chondroitin and the biologically acceptable salts thereof. 
     
     
         33 . The biodegradable single-phase cohesive hydrogel as defined by  claim 28 , wherein at least one of the  x  polysaccharides is selected from the group consisting of chitosan and the biologically acceptable salts thereof. 
     
     
         34 . The biodegradable single-phase cohesive hydrogel as defined by  claim 25 , wherein  x  is equal to 2. 
     
     
         35 . The biodegradable single-phase cohesive hydrogel as defined by  claim 34 , wherein the first of the  x  polymers is hyaluronic acid and the second is selected from the group consisting of chondroitin sulfate and salts thereof, chitosan and salts and derivatives thereof, cellulose derivatives and salts thereof and alginic acids. 
     
     
         36 . The biodegradable single-phase cohesive hydrogel as defined by  claim 34 , wherein the first of the  x  polysaccharides is selected from the group consisting of hyaluronic acid and salts thereof, cellulose derivatives and salts thereof and xanthan and the second is selected from the group consisting of chondroitin sulfate and salts thereof, chitosan and salts and derivatives thereof, cellulose derivatives and salts thereof and alginic acids. 
     
     
         37 . The biodegradable single-phase cohesive hydrogel as defined by  claim 25 , further comprising one or more active principle(s) selected from among antioxidants, antiseptics, anti-inflammatories and local anesthetics, and mixtures thereof. 
     
     
         38 . The biodegradable single-phase cohesive hydrogel as defined by  claim 37 , comprising antioxidants selected from among mannitol and/or sorbitol. 
     
     
         39 . The biodegradable single-phase cohesive hydrogel as defined by  claim 37 , comprising the local anesthetic lidocaine. 
     
     
         40 . A process for the preparation of a biodegradable single-phase cohesive hydrogel as defined by  claim 25 , comprising the stages of:
 crosslinking a first polymer to a degree of crosslinking x1;   crosslinking a second polymer to a degree of crosslinking x2;   interpenetration by intimate mixing of the two polymers;   hydration; and   final interpenetration by final mixing after hydration.   
     
     
         41 . The process as defined by  claim 40 , comprising  x  stages of crosslinking the  x  polymers before mixing the  x  crosslinked polymers. 
     
     
         42 . The process as defined by  claim 40 , wherein the crosslinkings are carried out by the action of a polyfunctional crosslinking agent selected from the group consisting of bi- or polyfunctional epoxy compounds, divinyl sulfone, carbodiimides and formaldehyde. 
     
     
         43 . The process as defined by  claim 40 , wherein the crosslinking agents employed in the crosslinking stages are identical or different. 
     
     
         44 . The process as defined by  claim 40 , wherein the degree of crosslinking x1 is greater than or equal to the degree of crosslinking x2. 
     
     
         45 . The process as defined by  claim 40 , wherein the degrees of crosslinking range from 0.02 to 0.4. 
     
     
         46 . The biodegradable single-phase cohesive hydrogel as defined by  claim 25 , formulated as a viscosupplementation composition. 
     
     
         47 . The biodegradable single-phase cohesive hydrogel as defined by  claim 25 , formulated as a composition for filling in wrinkles. 
     
     
         48 . A kit comprising a biodegradable single-phase cohesive hydrogel as defined by  claim 25 , packaged in a sterile syringe.