Organophosphorous, multivalent metal compounds, & polymer adhesive interpenetrating network compositions & methods

Abstract

Certain small molecule amino acid phosphate compounds such as phosphoserine and certain multivalent metal compounds such as calcium phosphate containing cements have been found to have improved properties and form an interpenetrating network in the presence of a polymer that contains either an electronegative carbonyl oxygen atom of the ester group or an electronegative nitrogen atom of the amine group as the bonding sites of the polymer surfaces to the available multivalent metal ions.

1 . A non-covalently bonded interpenetrating network comprising a reactive mixture of a small amino acid phosphate species, a multivalent metal compound, and a polymeric material that contains functional groups that contains electronegative atoms as the bonding sites of the polymer surfaces to the available metal ions, in an aqueous environment. 
     
     
         2 . The network as described in  claim 1  wherein the metal compound is divalent. 
     
     
         3 . The network as described in  claim 2  wherein the divalent metal compound is calcium based compound. 
     
     
         4 . The network as described in  claim 3  wherein the calcium based compound is calcium phosphate. 
     
     
         5 . The network of  claim 1  wherein;
 (i) the multivalent metal compound is a calcium phosphate, 
 (ii) the polymeric material contains esters, carbonyl, carbonate, carboxylic acids, amides, amine groups and mixtures thereof, 
 (iii) the small amino acid phosphate species is a compound of the formula; 
 
       
         
           
           
               
               
           
         
         where A is O, CH 2 , or S; R is H, NH 2 , NHCO(CH 2 ) t CH 3  where t is 0 to 2, NH(CH 2 ) x CH 3  where x is 0 to 3, NR1R2 where R1 is (CH 2 ) y CH 3  and R2 is (CH 2 ) y CH 3  where y is 0 to 2, (CH 2 ) z CH 3  where z is 0 to 3, where m is 0 to 1, and where n is 0 to 3 and wherein the compound is present in an amount greater than about 10% by weight based on the combined weight of the calcium phosphate and the compound, and 
         (iv) the aqueous environment is an aqueous medium. 
       
     
     
         6 . The network as described in  claim 5  wherein the polymeric material is selected from the group consisting of poly(L-lactide), poly(D,L-lactide), polyglycolide, poly(ε-caprolactone), polycarbonate, poly(teramethylglycolic-acid), poly(dioxanone), poly(hydroxybutyrate), poly(hydroxyvalerate), poly(L-lactide-co-glycolide), poly(glycolide-co-trimethylene-carbonate), poly(glycolide-co-caprolactone), poly(glycolide-co-dioxanone-co-trimethylene-carbonate), poly(tetramethylglycolic-acid-co-dioxanone-co-trimethylene-carbonate), poly(glycolide-co-caprolactone-co-L-lactide-co-trimethylene-carbonate), poly(hydroxybutyrate-co-hydroxyvalerate), poly(methyl-methacrylate), poly(acrylate), polyamines, polyamines, polyimidazoles, poly(vinyl-pyrrolidone), collagen, silk, chitosan, hyaluronic acid, gelatin, a copolymer thereof and mixtures thereof. 
     
     
         7 . The network as described in  claim 7  wherein the polymeric material is a linear homopolymer, a linear copolymer, a cross linked polymer, a block polymer, a branched polymer, a hyper branched polymers, star shaped polymers and mixtures thereof. 
     
     
         8 . The network as described in  claim 1  wherein the polymeric material is added in the form of a solution, powder, fiber, resin, liquid crystal, hydrogel, chip, flake, a foam, a film and mixtures thereof. 
     
     
         9 . The network as described in  claim 4  wherein the calcium phosphate is tetracalcium phosphate. 
     
     
         10 . The network as described in  claim 5  wherein the small amino acid phosphate species is phosphoserine. 
     
     
         11 . The network as described in  claim 1  wherein:
 (i) the multivalent metal compound is present in an amount from about 10 to about 89.9 weight percent based on the weight of the combination of the multivalent metal compound, the polymeric material, and the small amino acid phosphate species; 
 (ii) the polymeric material is present in an amount from about 0.1 to about 75 weight percent based on the weight of the combination of the multivalent metal compound, the polymeric material, and the small amino acid phosphate species; and 
 (iii) the small amino acid phosphate species is present in an amount from about 10 to about 89.9 weight percent based on the weight of the combination of the multivalent metal compound, the polymeric material, and the small amino acid phosphate species. 
 
     
     
         12 . A bone restorative composition comprising;
 (i) a multivalent metal phosphate compound,   (ii) a polymer that contain esters, carbonyl, carbonate, carboxylic acids, amides, amine groups and mixtures thereof as the bonding sites of the polymer surfaces to the available metal ions,   (iii) a compound of the formula;   
       
         
           
           
               
               
           
         
         where A is O, CH 2 , or S; R is H, NH 2 , NHCO(CH 2 ) t CH 3  where t is 0 to 2, NH(CH 2 ) x CH 3  where x is 0 to 3, NR1R2 where R1 is (CH 2 ) y CH 3  and R2 is (CH 2 ) y CH 3  where y is 0 to 2, (CH 2 ) z CH 3  where z is 0 to 3, where m is 0 to 1, and where n is 0 to 3 and wherein the compound is present in an amount greater than about 10% by weight based on the combined weight of the multivalent metal phosphate salt and the compound, and 
         (iv) an aqueous medium. 
       
     
     
         13 . The bone restorative composition as described in  claim 12  wherein the polymeric material is selected from the group consisting of poly(L-lactide), poly(D,L-lactide), polyglycolide, poly(ε-caprolactone), poly(teramethylglycolic-acid), poly(dioxanone), poly(hydroxybutyrate), poly(hydroxyvalerate), poly(L-lactide-co-glycolide), poly(glycolide-co-trimethylene-carbonate), poly(glycolide-co-caprolactone), poly(glycolide-co-dioxanone-co-trimethylene-carbonate), poly(tetramethylglycolic-acid-co-dioxanone-co-trimethylene-carbonate), poly(glycolide-co-caprolactone-co-L-lactide-co-trimethylene-carbonate), poly(hydroxybutyrate-co-hydroxyvalerate), poly(methyl-methacrylate), poly(acrylate), polyamines, polyamines, polyimidazoles, poly(vinyl-pyrrolidone), collagen, silk, chitosan, hyaluronic acid, gelatin and mixtures thereof. 
     
     
         14 . The bone restorative composition as described in  claim 12  wherein the polymeric material is a linear homopolymers, a linear copolymer, a cross linked polymer, a block polymer, a branched polymer, a hyper branched polymers, star shaped polymers and mixtures thereof. 
     
     
         15 . The bone restorative composition as described in  claim 12  wherein the polymeric material is added in the form of a solution, powder, fiber, resin, liquid crystal, hydrogel, chip, flake, a foam, a film and mixtures thereof. 
     
     
         16 . The bone restorative composition as described in  claim 12  wherein the multivalent metal calcium compound is tetracalcium phosphate. 
     
     
         17 . The bone restorative composition as described in  claim 12  wherein the small amino acid phosphate species is phosphoserine. 
     
     
         18 . The bone restorative composition as described in  claim 12  wherein:
 (i) the multivalent metal phosphate compound is present in an amount from about 10 to about 89.9 weight percent based on the weight of the combination of the multivalent metal compound, the polymeric material, and the small amino acid phosphate species; 
 (ii) the polymeric material is present in an amount from about 0.1 to about 75 weight percent based on the weight of the combination of the multivalent metal compound, the polymeric material, and the small amino acid phosphate species; and 
 (iii) the small amino acid phosphate species is present in an amount from about 10 to about 89.9 weight percent based on the weight of the combination of the multivalent metal compound, the polymeric material, and the small amino acid phosphate species. 
 
     
     
         19 . A kit for restoring bone comprising;
 A) A first container containing a composition comprising:   (i) a multivalent metal phosphate compound,   (ii) a polymer that contain esters, carbonyl, carbonate, carboxylic acids, amides, amine groups and mixtures thereof as the bonding sites of the polymer surfaces to the available metal ions, and   (iii) a compound of the formula;   
       
         
           
           
               
               
           
         
         where A is O, CH 2 , or S; R is H, NH 2 , NHCO(CH 2 ) t CH 3  where t is 0 to 2, NH(CH 2 ) x CH 3  where x is 0 to 3, NR1R2 where R1 is (CH 2 ) y CH 3  and R2 is (CH 2 ) y CH 3  where y is 0 to 2, (CH 2 ) z CH 3  where z is 0 to 3, where m is 0 to 1, and where n is 0 to 3 and wherein the compound is present in an amount greater than about 10% by weight based on the combined weight of the multivalent metal phosphate compound and the compound, and 
         B) a second container containing an aqueous medium. 
       
     
     
         20 . The kit as described in  claim 19  wherein the polymeric material is selected from the group consisting of poly(L-lactide), poly(D,L-lactide), polyglycolide, poly(ε-caprolactone), poly(teramethylglycolic-acid), poly(dioxanone), poly(hydroxybutyrate), poly(hydroxyvalerate), poly(L-lactide-co-glycolide), poly(glycolide-co-trimethylene-carbonate), poly(glycolide-co-caprolactone), poly(glycolide-co-dioxanone-co-trimethylene-carbonate), poly(tetramethylglycolic-acid-co-dioxanone-co-trimethylene-carbonate), poly(glycolide-co-caprolactone-co-L-lactide-co-trimethylene-carbonate), poly(hydroxybutyrate-co-hydroxyvalerate), poly(methyl-methacrylate), poly(acrylate), polyamines, polyamines, polyimidazoles, poly(vinyl-pyrrolidone), collagen, silk, chitosan, hyaluronic acid, gelatin and mixtures thereof. 
     
     
         21 . The kit as described in  claim 19  wherein the polymeric material is a linear homopolymers, a linear copolymer, a cross linked polymer, a block polymer, a branched polymer, a hyper branched polymers, star shaped polymers and mixtures thereof. 
     
     
         22 . The kit as described in  claim 19  wherein the polymeric material is added in the form of a solution, powder, fiber, resin, liquid crystal, hydrogel, chip, flake, a foam, a film and mixtures thereof. 
     
     
         23 . The kit as described in  claim 19  wherein the multivalent metal phosphate compound is tetracalcium phosphate. 
     
     
         24 . The kit as described in  claim 19  wherein the small amino acid phosphate species is phosphoserine. 
     
     
         25 . The kit as described in  claim 19  wherein:
 (i) the multivalent metal phosphate compound is present in an amount from about 10 to about 89.9 weight percent based on the weight of the combination of the multivalent metal phosphate compound, the polymeric material, and the small amino acid phosphate species; 
 (ii) the polymeric material is present in an amount from about 0.1 to about 75 weight percent based on the weight of the combination of multivalent metal phosphate compound, the polymeric material, and the small amino acid phosphate species; and 
 (iii) the small amino acid phosphate species is present in an amount from about 10 to about 89.9 weight percent based on the weight of the combination of the multivalent metal phosphate compound, the polymeric material, and the small amino acid phosphate species. 
 
     
     
         26 . A method of adhering a material to a polymer comprising the steps of:
 placing a composition between the material and the polymer wherein the composition comprises:   (i) a multivalent metal phosphate compound,   (ii) a compound of the formula;   
       
         
           
           
               
               
           
         
         where A is O, CH 2 , or S; R is H, NH 2 , NHCO(CH 2 ) t CH 3  where t is 0 to 2, NH(CH 2 ) x CH 3  where x is 0 to 3, NR1R2 where R1 is (CH 2 ) y CH 3  and R2 is (CH 2 ) y CH 3  where y is 0 to 2, (CH 2 ) z CH 3  where z is 0 to 3, where m is 0 to 1, and where n is 0 to 3 and wherein the compound is present in an amount greater than about 10% by weight based on the combined weight of the multivalent metal phosphate salt and the compound, and 
         an aqueous medium 
         and 
         allowing the composition to cure to form an interpenetrating network at the interface between the composition and the polymer, 
         wherein the polymer contain esters, carbonyl, carbonate, carboxylic acids, amides, amine groups and mixtures thereof as the bonding sites of the polymer surfaces to the available metal ions, and wherein the composition adheres to the material. 
       
     
     
         27 . The method of  claim 26  wherein the polymeric material is selected from the group consisting of poly(L-lactide), poly(D,L-lactide), polyglycolide, poly(ε-caprolactone), poly(teramethylglycolic-acid), poly(dioxanone), poly(hydroxybutyrate), poly(hydroxyvalerate), poly(L-lactide-co-glycolide), poly(glycolide-co-trimethylene-carbonate), poly(glycolide-co-caprolactone), poly(glycolide-co-dioxanone-co-trimethylene-carbonate), poly(tetramethylglycolic-acid-co-dioxanone-co-trimethylene-carbonate), poly(glycolide-co-caprolactone-co-L-lactide-co-trimethylene-carbonate), poly(hydroxybutyrate-co-hydroxyvalerate), poly(methyl-methacrylate), poly(acrylate), polyamines, polyamines, polyimidazoles, poly(vinyl-pyrrolidone), collagen, silk, chitosan, hyaluronic acid, gelatin and mixtures thereof. 
     
     
         28 . The method of  claim 26  wherein the polymeric material is a linear homopolymers, a linear copolymer, a cross linked polymer, a block polymer, a branched polymer, a hyper branched polymers, star shaped polymers and mixtures thereof. 
     
     
         29 . The method of  claim 26  wherein the multivalent metal phosphate compound is tetracalcium phosphate. 
     
     
         30 . The method of  claim 26  wherein the small amino acid phosphate species is phosphoserine. 
     
     
         31 . The method of  claim 26  wherein:
 (i) the multivalent metal phosphate compound is present in an amount from about 10 to about 90.0 weight percent based on the weight of the combination of the multivalent metal phosphate compound, the polymeric material, and the small amino acid phosphate species; 
 (ii) (iii) the small amino acid phosphate species is present in an amount from about 10 to about 90.0 weight percent based on the weight of the combination of the multivalent metal phosphate compound, the polymeric material, and the small amino acid phosphate species.