Hybrid cooperative complexes of hyaluronic acid

Abstract

Describes cooperative hybrid complexes of hyaluronic acid, a simple and economical method for production thereof and use thereof in the area of medicine, cosmetics and food.

1 . Stable, hybrid cooperative L/H-HA complexes prepared by submitting to thermal treatment, at temperature comprised between 80° and 160°, solutions containing simultaneously L-HA hyaluronic acid or hyaluronans and H-HA hyaluronic acid or hyaluronans wherein the molecular weight of L-HA is comprised between 1×10 4  to 1×10 6  Da and that of H-HA is given by the formula MW H-HA ≧ MWL-HA /0.9. 
     
     
         2 . Stable complexes according to  claim 1  wherein said temperature is comprised between 100° and 120° C. 
     
     
         3 . Hybrid cooperative complexes according to  claim 1 , wherein H-HA and L-HA are present in relative quantities comprised between 0.1 and 10. 
     
     
         4 . L/H-HA complexes according to  claim 1  having a viscosity from 1.1 to 200-fold less than that of a solution containing the H-HA hyaluronic acid alone used for forming the complex. 
     
     
         5 . L/H-HA complexes according to  claim 4 , wherein other chemical species in addition to solvent and hyaluronic acid are also present in the solution. 
     
     
         6 . L/H-HA complexes according to  claim 1 , wherein the solvent used is water. 
     
     
         7 . L/H-HA complexes according to  claim 1 , wherein the thermal treatment is carried out in autoclave. 
     
     
         8 . L/H-HA complexes according to  claim 1 , wherein the thermal treatment includes keeping the sample at the maximal temperature for times which are from 10 seconds to 2 hrs. 
     
     
         9 . L/H-HA complexes according to  claim 8 , wherein the thermal treatment includes reaching the maximal temperature over times from 1 min to 1 h. 
     
     
         10 . L/H-HA complexes according to  claim 8  wherein the thermal treatment includes cooling the solution, after exposure at the maximal temperature, over times from 1 min to 1 h. 
     
     
         11 . L/H-HA complexes according to  claim 1 , prepared in the solid state by precipitation of the solutions containing them. 
     
     
         12 . L/H-HA complexes according to  claim 11 , wherein the precipitation is obtained by adding a compound miscible with the solution and acting as a non-solvent for the complex. 
     
     
         13 . L/H-HA complexes according to  claim 12 , wherein the non-solvent compound for the complex is a water-miscible organic solvent, selected from the group consisting of acetone, methanol, ethanol, propanol, isopropanol and butanol. 
     
     
         14 . L/H-HA complexes according to  claim 1 , prepared by removing the solvent by means of vacuum evaporation, spray-drying or freeze-drying in the dry state. 
     
     
         15 . Hybrid cooperative complexes according to  claim 1 , wherein the low molecular weight hyaluronic acid is replaced by other low molecular weight polysaccharides, such as chondroitin, chondroitin sulphate, dextrins, cyclodextrins, dextrans. 
     
     
         16 . Hybrid cooperative complexes according to  claim 15  wherein by low molecular weight of polysaccharides is meant less than one million of Da. 
     
     
         17 . Method of treating patients in need thereof with hybrid cooperative complexes of  claim 1  comprising:
 administering to said patients said hybrid cooperative complexes as a replacement for high molecular weight hyaluronic acid in all clinical treatments based on said high weight hyaluronic acid and 
 treating said patients in need. 
 
     
     
         18 . Method for intradermal bio-revitalizing treatment with hybrid cooperative complexes according to  claim 1  comprising:
 administering said hybrid cooperative complexes to patients in need thereof and 
 treating said patients. 
 
     
     
         19 . Method for intra-articular viscosupplementation with hybrid cooperative complexes according to  claim 1  comprising
 administering said hybrid cooperative complexes to patients in need thereof and 
 treating said patients. 
 
     
     
         20 . Method for intra-bladder treatments of cystitis with hybrid cooperative complexes according to  claim 1  comprising:
 administering said hybrid cooperative complexes to patients in need thereof and 
 treating said patients. 
 
     
     
         21 . Method of treating vaginal inflammatory diseases with hybrid cooperative complexes according to  claim 1  comprising
 administering said hybrid cooperative complexes to patients in need thereof and 
 treating said patients. 
 
     
     
         22 . Method of treating alveolar diseases with hybrid cooperative complexes according to  claim 1  comprising
 administering said hybrid cooperative complexes to patients in need thereof and 
 treating said patients. 
 
     
     
         23 . Method of treating oral disease with hybrid cooperative complexes according to  claim 1  comprising
 administering said hybrid cooperative complexes to patients in need thereof and 
 treating said patients.