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 - 31 . (canceled) 
     
     
         32 . An adhesive composition comprising a mixture of an amino phosphate species, multivalent metal compound, and a polymeric material comprising an ester, carbonyl, carbonate, carboxylic acid, amide, amine, or a mixture thereof, in an aqueous environment, wherein the amino phosphate species is present at a concentration greater than about 100 mM. 
     
     
         33 . The composition of  claim 32 , wherein the amino acid phosphate species is a compound of the formula: 
       
         
           
           
               
               
           
         
       
       wherein A is O, CH 2 , or S; R is H, NH 2 , NHCO(CH 2 ) t CH 3 , NH(CH 2 ) x CH 3 , NR 1 R 2 ; R 1  is (CH 2 ) y CH 3 ; R 2  is (CH 2 ) y CH 3 (CH 2 ) z CH 3 ; m is 0 to 1; n is 0 to 3; t is 0 to 2; x is 0 to 3; y is 0 to 2; and z is 0 to 3. 
     
     
         34 . The composition of  claim 32 , wherein the amino acid phosphate species is present at a concentration greater than about 1 M. 
     
     
         35 . The composition of  claim 32 , wherein the amino acid phosphate species is phosphoserine. 
     
     
         36 . The composition of  claim 32 , wherein the multivalent metal compound is tetracalcium phosphate. 
     
     
         37 . The composition of  claim 32 , wherein the polymeric material is a linear homopolymer, a linear copolymer, a cross linked polymer, a block polymer, a branched polymer, a hyper branched polymer, a star shaped polymer, or a mixture thereof. 
     
     
         38 . The composition of  claim 32 , wherein the polymeric material is added to the composition in the form of a solution, powder, fiber, resin, liquid crystal, hydrogel, chip, flake, foam, film, or a mixture thereof. 
     
     
         39 . The composition of  claim 32 , wherein the polymeric material comprises 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), a polyamine, a polyamide, a polyimidazole, poly(vinyl-pyrrolidone), collagen, silk, chitosan, hyaluronic acid, gelatin, or a copolymer or mixture thereof. 
     
     
         40 . The composition of  claim 32 , wherein the polymeric material comprises 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-caprolactone), or a copolymer or mixture thereof. 
     
     
         41 . The composition of  claim 32 , 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 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 amino acid phosphate species; and   (iii) the 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 amino acid phosphate species.   
     
     
         42 . The composition of  claim 32 , wherein the aqueous environment comprises an aqueous medium selected from water, blood, and saline. 
     
     
         43 . The method of  claim 32 , wherein the adhesive strength of the composition upon curing is greater than about 100 kPa. 
     
     
         44 . A method of adhering bone fragments together within the body, the method comprising the steps of mixing:
 (i) a multivalent metal compound;   (ii) an amino acid compound of the formula:   
       
         
           
           
               
               
           
         
         where A is O, CH 2  or S; R is H, NH 2 , or NHCO(CH 2 ) t CH 3  where t is 0 to 2, NH(CH 2 ) x CH 3  where x is 0 to 3, NR 1 R 2  where R 1  is (CH 2 ) y CH 3  and R 2  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 compound and the compound of the formula as shown; 
         (iii) a polymeric material comprising an ester, carbonyl, carbonate, carboxylic acid, amide, amine, or a mixture thereof; and 
         (iv) an aqueous medium to form a composition; 
         applying the composition to the bone fragments; and 
         allowing the composition to cure to adhere said bone fragments together. 
       
     
     
         45 . The method of  claim 44 , wherein the amino acid phosphate species is present at a concentration greater than about 1 M. 
     
     
         46 . The method of  claim 44 , wherein the amino acid phosphate species is phosphoserine. 
     
     
         47 . The method of  claim 44 , wherein the multivalent metal compound is tetracalcium phosphate. 
     
     
         48 . The method of  claim 44 , wherein the polymeric material is added to the composition in the form of a solution, powder, fiber, resin, liquid crystal, hydrogel, chip, flake, foam, film, or a mixture thereof. 
     
     
         49 . The method of  claim 44 , wherein the polymeric material comprises 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), a polyamine, a polyamide, a polyimidazole, poly(vinyl-pyrrolidone), collagen, silk, chitosan, hyaluronic acid, gelatin, or a copolymer or mixture thereof. 
     
     
         50 . The method of  claim 44 , 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 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 amino acid phosphate species; and   (iii) the 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 amino acid phosphate species.   
     
     
         51 . The method of  claim 44 , wherein the aqueous environment comprises an aqueous medium selected from water, blood, or saline. 
     
     
         52 . The method of  claim 44 , wherein the adhesive strength of the composition upon curing is greater than about 100 kPa. 
     
     
         53 . A method of adhering an implant device to bone, the method comprising the steps of mixing:
 (i) a multivalent metal compound;   (ii) an amino acid compound of the formula:   
       
         
           
           
               
               
           
         
         where A is O, CH 2  or S; R is H, NH 2 , or NHCO(CH 2 ) t CH 3  where t is 0 to 2, NH(CH 2 ) x CH 3  where x is 0 to 3, NR 2 R 2  where R 1  is (CH 2 ) y CH 3  and R 2  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 compound and the compound of the formula as shown; 
         (iii) a polymeric material comprising an ester, carbonyl, carbonate, carboxylic acid, amide, amine, or a mixture thereof; and 
         (iv) an aqueous medium to form a composition; 
         applying the composition to the implant device and/or bone; and 
         allowing the composition to cure to adhere said implant device to the bone. 
       
     
     
         54 . The method of  claim 53 , wherein the amino acid phosphate species is present at a concentration greater than about 1 M. 
     
     
         55 . The method of  claim 53 , wherein the amino acid phosphate species is phosphoserine. 
     
     
         56 . The method of  claim 53 , wherein the multivalent metal compound is tetracalcium phosphate. 
     
     
         57 . The method of  claim 53 , wherein the polymeric material is added to the composition in the form of a solution, powder, fiber, resin, liquid crystal, hydrogel, chip, flake, foam, film, or a mixture thereof. 
     
     
         58 . The method of  claim 53 , wherein the polymeric material comprises 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), a polyamine, a polyamide, a polyimidazole, poly(vinyl-pyrrolidone), collagen, silk, chitosan, hyaluronic acid, gelatin, or a copolymer or mixture thereof. 
     
     
         59 . The method of  claim 53 , 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 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 amino acid phosphate species; and   (iii) the 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 amino acid phosphate species.   
     
     
         60 . The method of  claim 53 , wherein the aqueous medium comprises water, blood, or saline. 
     
     
         61 . The method of  claim 53 , wherein the adhesive strength of the composition upon curing is greater than about 100 kPa. 
     
     
         62 . The method of  claim 53 , wherein the implant device comprises a joint replacement prosthesis, a dental implant, a plate, an anchor, a pin, or a screw. 
     
     
         63 . A kit for repairing a hard surface comprising;
 A) a first container containing a composition comprising:   (i) a multivalent metal compound,   (ii) a polymeric material comprising an ester, carbonyl, carbonate, carboxylic acid, amide, amine, or a mixture thereof, and   (iii) an amino acid 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, NR 1 R 2  where R 1  is (CH 2 ) y CH 3  and R 2  is (CH 2 ) y CH 3  where y is 0 to 2, (CH 2 ) z CH 3  where z is 0 to 3; m is 0 to 1; n is 0 to 3; and 
         B) a second container containing an aqueous medium; 
         wherein upon mixing the contents of the first container with the contents of the second container, the resulting composition comprises a compound of component (iii) at a concentration greater than about 100 mM. 
       
     
     
         64 . The kit of  claim 63 , wherein the amino acid phosphate species is present at a concentration greater than about 1 M. 
     
     
         65 . The kit of  claim 63 , wherein the amino acid phosphate species is phosphoserine. 
     
     
         66 . The kit of  claim 63 , wherein the multivalent metal compound is tetracalcium phosphate. 
     
     
         67 . The kit of  claim 63 , wherein the polymeric material is added to the composition in the form of a solution, powder, fiber, resin, liquid crystal, hydrogel, chip, flake, foam, film, or a mixture thereof. 
     
     
         68 . The kit of  claim 63 , wherein the polymeric material comprises 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), a polyamine, a polyamide, a polyimidazole, poly(vinyl-pyrrolidone), collagen, silk, chitosan, hyaluronic acid, gelatin, or a copolymer or mixture thereof. 
     
     
         69 . The kit of  claim 63 , 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 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 amino acid phosphate species; and   (iii) the 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 amino acid phosphate species.   
     
     
         70 . The kit of  claim 63 , wherein the aqueous medium comprises water or saline. 
     
     
         71 . The kit of  claim 63 , wherein the adhesive strength of the composition upon curing is greater than about 100 kPa. 
     
     
         72 . The method of  claim 63 , wherein the hard surface comprises a bone.