Compositions and Methods for Promoting the Healing of Tissue of Multicellular Organisms

Abstract

Compositions are provided for promoting healing of tissue of a vertebrate organism. The compositions can be for internal administration of a therapeutically effective amount of pharmacologically active, protease inhibiting, aqueous media soluble polysulfonated materials in salt form and associated with a secondary material to reduce one or more of inflammation, bacterial proliferation, proteolytic activity, and cancerous cell growth. The compositions may additionally or alternatively be cross-linked so as to alter the solubility of these pharmacologically active salts or slow dissolution by providing biodegradable cross-linkers. Compositions for healing the tissue of a multicellular organism are provided that can include a polysulfonated material in a liquid mixture, as solid particles or constructs that may or may not biodegrade or deliver a pharmacologically relevant value. Some of the compositions are also provided for inclusion into a device for preventing infection, reducing inflammation, and preserving the activity of a protein or protein drug.

1 : A composition for the healing of a multicellular organism, the composition comprising at least one-polysulfonated material, the polysulfonated material being insoluble in deionized water and soluble in ion-comprising aqueous media, wherein the polysulfonated material comprises a arylenevinylsulfonate, a chondroitin sulfonate, and/or a polyvinyl sulfonate. 
     
     
         2 : The composition of  claim 1  wherein the arylenevinylsulfonate comprises one or more of polyalkylstyrene sulfonate, polystyrene arginine sulfonate, polystyrene mafenide sulfonate, silver substituted polystyrene sulfonate, chlorhexidine substituted polystyrene sulfonate, and/or doxycycline substituted polystyrene sulfonate. 
     
     
         3 : The composition of  claim 1  wherein the chondroitin sulfonate comprises one or more of silver chondroitin-6-sulfate, sodium/silver chondroitin-6-sulfate, and/or arginine chondroitin-6-sulfate 
     
     
         4 : The composition of  claim 1  wherein the polyvinyl sulfonate comprises one or more of polyarylene vinyl sulfonate, polyvinyl sulfonate, and, and/or aryl ring-modified polyarylene vinyl sulfonate. 
     
     
         5 : The composition of  claim 1  wherein the polysulfonated material is associated with at least one cation of pharmacologically therapeutic value. 
     
     
         6 : The composition of  claim 1  wherein the polysulfonated material is associated with at least two metal cations. 
     
     
         7 : The composition of  claim 1  wherein the polysulfonated material is associated with at least one organic cation. 
     
     
         8 : The composition of  claim 7  wherein the organic cation is one or more of tetracycline, doxycycline, minocycline, octenidine, chlorhexidine, benzalkonium, cetylpyridinium, quaternary ammonium, arginine, lysine, glutathione, mafenide, albuterol, and lidocaine. 
     
     
         9 : The composition of  claim 1  wherein the polysulfonated material is associated with a mixture of metal and organic cations. 
     
     
         10 : The composition of  claim 1  wherein the polysulfonated material is associated with metallic cations of sodium and silver. 
     
     
         11 : The composition of  claim 1  wherein the polysulfonated material comprises at least two sulfonate groups modified to sulfonamides, the sulfonamides configured to cross-link at least one portion of the polysulfonated material with another portion of the polysulfonated material. 
     
     
         12 : The composition of  claim 1  further comprising a solid matrix material. 
     
     
         13 : The composition of  claim 12  wherein the matrix material comprises biodegradable material. 
     
     
         14 : The composition of  claim 12 , wherein the matrix material is a non-biodegradable biomedical material comprising at least one of a silicone, a polyurethane, a polyalkylene, a hydrogel, or a polyester. 
     
     
         15 : The composition of  claim 1  formulated as a gel, paste, cream, solution, ointment, or lotion. 
     
     
         16 : The composition of  claim 1  further comprising collagen or gelatin. 
     
     
         17 : A composition for the healing of a multicellular organism, the composition comprising a polysulfonated material that is both insoluble in deionized water and soluble in ion-comprising aqueous media. 
     
     
         18 : A composition for the healing of a multicellular organism, the composition comprising a polysulfonated salt that is both insoluble in deionized water and soluble in ion-comprising aqueous media. 
     
     
         19 : The composition of  claim 18  wherein the cation associated with the polysulfonated salt is either organic or inorganic. 
     
     
         20 : The composition of  claim 18  wherein the cation associated with the polysulfonated salt is silver ion.