Compositions and methods for adhesion to surfaces

Abstract

The present disclosure features adhesive compositions and methods of use thereof related to the medical, veterinary, and dental fields.

We claim: 
     
         1 . A method of increasing bone volume, the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound; and   b) applying the composition into an extraction socket;   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         2 . A method of filling a bone void resulting from the removal of a bone cyst, granuloma, abscess, or similar bone defect, the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound; and   b) applying the composition into said bone void;   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         3 . A method of increasing bone volume, the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound; and   b) applying the composition onto a substantially flat or convex surface of bone to build volume;   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         4 . A method of joining two or more bones, bone fragments, or bone segments with capacity to bear load, the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound; and   b) applying the composition onto the bony surfaces to be joined (e.g., adjacent bones, bone fragments, or bone segments) in a amount sufficient for the bulk of the adhesive composition to be continuous;   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         5 . The method of  claim 4 , wherein the separation between the bones, bone fragments, or bone segments may be caused by a congenital defect (e.g., cleft palate), a trauma (e.g., a jaw or other bone fracture), a disease (e.g, osteosarcoma), or may be the result of a resection of bone (e.g, resulting from removal of a neoplasm or necrotic bone), or may be the result of surgical treatment (e.g., orthognathic procedure or correction of long bone deformity), or may be a result of loss of small fragments that have lost their mechanical integrity. 
     
     
         6 . A method of repairing a defect in a bone, the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound; and   b) applying the composition into or onto said bone defect;   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         7 . A method of repairing a gap or space between articulating bone surfaces (e.g., facet joints) with capacity to bear load and prevent relative motion, the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound; and   b) applying the composition into the gap or space to be joined in an amount sufficient for the bulk of the adhesive composition to be continuous;   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         8 . A method of bridging a gap space between bone surfaces (e.g., between vertebral bodies, between transverse processes, or between spinous processes) with capacity to bear load and/or to prevent relative motion, the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound; and   b) applying the composition to bridge the gap or space to be joined in an amount sufficient for the bulk of the adhesive composition to be continuous;   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         9 . The method of any one of  claims 1 - 8 , wherein the bone comprises cortical bone or cancellous bone. 
     
     
         10 . The method of any one of  claims 1 - 8 , wherein the bone comprises a tooth. 
     
     
         11 . The method of any one of  claims 1 - 8 , wherein the composition the composition hardens and/or cures in less than about 30 minutes with or without applied compressive forces (e.g., clamps, forceps, fingers) or with or without fixation implants (e.g., membranes, mesh, sutures, k-wires, screws, pins). 
     
     
         12 . The method of any one of  claims 1 - 8 , wherein the composition remains substantially attached to bone and does not substantially migrate from the site of application. 
     
     
         13 . The method of any one of  claims 1 - 8 , wherein the composition serves as a barrier to prevent microbial ingress or fibrous tissue ingress. 
     
     
         14 . The method of any one of  claims 1 - 8 , wherein the composition is capable of resorption. 
     
     
         15 . The method of  claim 14 , wherein the resorption comprises replacement of the composition with bone (e.g., natural bone). 
     
     
         16 . The method of  claim 15 , wherein the resorption comprises the substantially maintaining the original volume of the composition. 
     
     
         17 . A method of repairing a defect in a tooth, the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound;   b) applying the composition into or onto said tooth defect; and   c) modifying the repaired tooth upon hardening and/or curing of the composition to attain the desired shape, contour, or surface characteristics of the tooth.   
     
     
         18 . A method of repairing a defect in a tooth, the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound; and   b) applying the composition into or onto said tooth defect in close proximity or in contact with the dental pulp tissue;   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         19 . The method of any one of  claims 1 - 8  and  17 - 18 , further comprising the placement of a structure (e.g., an implant, graft, or device) into the composition prior to the hardening and/or curing of the composition. 
     
     
         20 . The method of any one of  claims 1 - 8  and  17 - 18 , further comprising the placement of a structure (e.g., an implant, graft, or device) into the composition after step b) but prior to the hardening and/or curing of the composition. 
     
     
         21 . The method of any one of  claims 17 - 18 , wherein the defect is present at the root of a tooth. 
     
     
         22 . A method of attaching a dental device to a tooth, the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound;   b) applying the composition into or onto a prepared surface of the said tooth or the dental device to be affixed to the tooth; and   c) orienting the device in a special relationship with the tooth;   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         23 . The method of  claim 22 , wherein the dental device comprises a post, a dental crown restoration, a fixed partial denture, or a similar device. 
     
     
         24 . A method of installing a bone implant or device, the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound;   b) applying the composition into an extraction socket in a bone and/or on the surface of the implant or device; and   c) installing said implant or device into the composition;   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         25 . A method of installing a bone implant or device, the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound;   b) placing said implant or device into an extraction socket in a bone;   c) applying the composition to the installation site (e.g., to secure the implant or device to the bone);   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         26 . A method of closing a wound, the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound; and   b) injecting the composition into, on top of, or adjacent to a wound site;   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         27 . The method of  claim 26 , wherein the method prevents the microbes from entering into the wound. 
     
     
         28 . A method of sealing a site or fistula from the incursion or communication of a fluid or material (e.g., an unwanted fluid or material), the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound; and   b) applying the composition into, on top of, or adjacent to the site;   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         29 . The method of  claim 28 , wherein the fluid or material (e.g., an unwanted fluid or material) comprises one or more microbes. 
     
     
         30 . A method of restoring a bone deformity to a primary palate, the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound; and   b) applying the composition into, on top of, or adjacent to the bone deformity or the bone deficiency;   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         31 . A method of reshaping, molding, or contouring (e.g., additively reshaping, molding, or contouring) the outer surface of a bone (e.g., in the facial region, forehead, mandible, or any articulating bone surface), the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound; and   b) applying the composition to the desired region;   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         32 . A method of reshaping, molding, or contouring bone (e.g., additively reshaping, molding, or contouring) the outer surface of a bone in the facial region of a subject undergoing a cosmetic treatment, the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound; and   b) applying the composition to the desired region;   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         33 . The method of any one of  claims 31 - 32 , wherein the facial region comprises the nose, chin, cheek, mid-face, or forehead. 
     
     
         34 . A method of treating a subject suffering from a disease or condition, the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound; and   b) applying the composition to the desired region;   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         35 . A method of repairing a bone defect in a subject suffering from a disease or condition, the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound; and   b) applying of the composition to the desired region;   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         36 . A method of strengthening a bone in a subject suffering from a disease or condition, the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound; and   b) applying the composition to the desired region;   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         37 . The method of any one of  claims 34 - 36 , wherein the disease or condition comprises cancer (e.g., osteosarcoma), osteoporosis, rickets, osteogenesis imperfecta, fibrous dysplasia, Paget's disease of the bone, hearing loss, renal osteodystrophy, a malignancy of the bone, infection of the bone, osteonecrosis, or other genetic or developmental disease. 
     
     
         38 . The method of any one of  claims 34 - 36 , wherein the subject has decay, fracture, attrition, erosion, abrasion, or abfraction of a bone, or another cause of bone substance loss. 
     
     
         39 . The method of  claim 38 , wherein the bone comprises a tooth. 
     
     
         40 . A method of repairing a bone defect in a subject caused by a trauma, the method comprising:
 a) preparing an adhesive composition comprising a multivalent metal salt and a small organic phosphate compound; and   b) applying of the composition to the desired region;   wherein the composition hardens and/or cures in less than about 30 minutes.   
     
     
         41 . The method of any one of  claims 1 - 8 ,  17 ,  18 ,  22 - 32 ,  34 - 36 , and  40 , wherein the composition hardens and/or cures in less than about 25 minutes (e.g., less than about 20 minutes, about 15 minutes, about 10 minutes, about 8 minutes, or about 5 minutes). 
     
     
         42 . The method of any one of  claims 1 - 8 ,  17 ,  18 ,  22 - 32 ,  34 - 36 , and  40 , wherein the composition comprising a multivalent metal salt and a small organic phosphate compound is prepared in an aqueous solution or suspension. 
     
     
         43 . The method of  claim 42 , wherein the aqueous solution or suspension is supplied exogenously. 
     
     
         44 . The method of  claim 42 , wherein the aqueous solution or suspension is present at the site of application of the adhesive composition. 
     
     
         45 . The method of  claim 42 , wherein the aqueous solution or suspension comprises water, saliva, saline (e.g., phosphate buffered saline), serum, plasma, or blood. 
     
     
         46 . The method of any one of  claims 1 - 8 ,  17 ,  18 ,  22 - 32 ,  34 - 36 , and  40 , wherein the multivalent metal salt comprises a multivalent calcium compound. 
     
     
         47 . The method of  claim 46 , wherein the multivalent calcium compound comprises tetracalcium phosphate. 
     
     
         48 . The method of  claim 46 , wherein the composition comprises a plurality of multivalent calcium compounds. 
     
     
         49 . The method of  claim 48 , wherein the plurality comprises tetracalcium phosphate and at least one other multivalent calcium compound. 
     
     
         50 . The method of  claim 46 , wherein the multivalent calcium compound does not comprise tetracalcium phosphate. 
     
     
         51 . An adhesive composition comprising a mixture of at least two multivalent metal salts and a compound of Formula (I) or a salt thereof in an aqueous solution or suspension: 
       
         
           
           
               
               
           
         
       
       wherein
 L is O, S, NH, or CH 2 ; 
 each of R 1a  and R 1b  is independently H, optionally substituted alkyl, or optionally substituted aryl; 
 R 2  is H, NR 4a R 4b , C(O)R 5 , or C(O)OR 5 ; 
 R 3  is H, optionally substituted alkyl, or optionally substituted aryl; 
 each of R 4a  and R 4a  is independently H, C(O)R 6 , or optionally substituted alkyl; 
 R 5  is H, optionally substituted alkyl, or optionally substituted aryl; 
 R 6  is optionally substituted alkyl or optionally substituted aryl; and 
 each of x and y is independently 0, 1, 2, or 3. 
 
     
     
         52 . The method of  claim 51 , wherein L is O or S. 
     
     
         53 . The method of  claim 52 , wherein L is O. 
     
     
         54 . The method of  claim 51 , wherein each of R 1a  and R 1b  is independently H. 
     
     
         55 . The method of  claim 51 , wherein L is O and each of R 1a  and R 1b  is H. 
     
     
         56 . The method of  claim 51 , wherein R 2  is H, NR 4a R 4b , or C(O)R 5 . 
     
     
         57 . The method of  claim 56 , wherein R 2  is NR 4a R 4b    
     
     
         58 . The method of  claim 51 , wherein R 2  is NR 4a R 4b  and each of R 4a  and R 4b  is independently H. 
     
     
         59 . The method of  claim 51 , wherein L is O, each of R 1a  and R 1b  is independently H, R 2  is NR 4a R 4b , and each of R 4a  and R 4b  is independently H. 
     
     
         60 . The method of  claim 51 , wherein R 3  is H. 
     
     
         61 . The method of  claim 51 , wherein L is O, each of R 1a  and R 1b  is independently H, R 2  is NR 4a R 4b , each of R 4a  and R 4b  is independently H, and R 3  is H. 
     
     
         62 . The method of  claim 51 , wherein each of x and y is independently 0 or 1. 
     
     
         63 . The method of  claim 51 , wherein each of x and y is independently 1. 
     
     
         64 . The method of  claim 51 , wherein L is O, each of R 1a  and R 1b  is independently H, R 2  is NR 4a R 4b , each of R 4a  and R 4b  is independently H, R 3  is H, and each of x and y is 1. 
     
     
         65 . The method of  claim 51 , wherein the compound of Formula (I) is phosphoserine. 
     
     
         66 . The method of  claim 51 , wherein mixture of at least two multivalent metal salts comprises calcium. 
     
     
         67 . The method of  claim 51 , wherein at least one of the multivalent metal salts comprises calcium and phosphate. 
     
     
         68 . The method of  claim 67 , wherein at least one of the multivalent metal salts comprises tricalcium phosphate. 
     
     
         69 . The method of  claim 68 , wherein the tricalcium phosphate comprises either alpha tricalcium phosphate or beta tricalcium phosphate. 
     
     
         70 . The method of  claim 68 , wherein the tricalcium phosphate is present in an amount from about 15% to about 85% weight by weight (w/w). 
     
     
         71 . The method of  claim 51 , wherein at least one of the multivalent metal salts comprises hydroxyapatite. 
     
     
         72 . The method of  claim 71 , wherein the hydroxyapatite is present in the composition in an amount from about 10% to about 90% weight by weight (w/w). 
     
     
         73 . The method of  claim 51 , wherein at least one of the multivalent metal salts comprises an oxide. 
     
     
         74 . The method of  claim 51 , wherein at least one of the multivalent metal salts is calcium oxide. 
     
     
         75 . The method of  claim 51 , wherein the composition comprises tricalcium phosphate and calcium oxide. 
     
     
         76 . The method of  claim 51 , wherein the composition does not contain tetracalcium phosphate. 
     
     
         77 . The method of  claim 51 , wherein the aqueous solution or suspension comprises water, saliva, saline (e.g., phosphate buffered saline), serum, plasma, or blood. 
     
     
         78 . The method of  claim 77 , wherein the aqueous solution or suspension comprises saliva, serum or blood. 
     
     
         79 . The method of  claim 51 , wherein the multivalent metal salt is initially provided as granules or a powder. 
     
     
         80 . The method of  claim 51 , wherein the composition further comprises an additive. 
     
     
         81 . A method for fixation of a structure to a bone, the method comprising use of an adhesive composition comprising at least two multivalent metal salts and a compound of Formula (I) or a salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein
 L is O, S, NH, or CH 2 ; 
 each of R 1a  and R 1b  is independently H, optionally substituted alkyl, or optionally substituted aryl; 
 R 2  is H, NR 4a R 4b , C(O)R 5 , or C(O)OR 5 ; 
 R 3  is H, optionally substituted alkyl, or optionally substituted aryl; 
 each of R 4a  and R 4a  is independently H, C(O)R 6 , or optionally substituted alkyl; 
 R 5  is H, optionally substituted alkyl, or optionally substituted aryl; 
 R 6  is optionally substituted alkyl or optionally substituted aryl; and 
 each of x and y is independently 0, 1, 2, or 3; 
 
       in an aqueous solution or suspension to thereby fix the structure to the bone. 
     
     
         82 . A method of filling a void or gap in a bone, the method comprising use of an adhesive composition comprising at least two multivalent metal salts and a compound of Formula (I) or a salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein
 L is O, S, NH, or CH 2 ; 
 each of R 1a  and R 1b  is independently H, optionally substituted alkyl, or optionally substituted aryl; 
 R 2  is H, NR 4a R 4b , C(O)R 5 , or C(O)OR 5 ; 
 R 3  is H, optionally substituted alkyl, or optionally substituted aryl; 
 each of R 4a  and R 4a  is independently H, C(O)R 6 , or optionally substituted alkyl; 
 R 5  is H, optionally substituted alkyl, or optionally substituted aryl; 
 R 6  is optionally substituted alkyl or optionally substituted aryl; and 
 each of x and y is independently 0, 1, 2, or 3; 
 
       in an aqueous solution or suspension to thereby fill the void or gap in the bone. 
     
     
         83 . The method of any one of  claim 82  or  83 , further comprising preparation of the adhesive composition prior to use thereof. 
     
     
         84 . A kit for fixation of a structure to a bone comprising:
 a) a first container containing a composition comprising at least two multivalent metal salts and a compound of Formula (I) or a salt thereof:   
       
         
           
           
               
               
           
         
         wherein
 L is O, S, NH, or CH 2 ; 
 each of R 1a  and R 1b  is independently H, optionally substituted alkyl, or optionally substituted aryl; 
 R 2  is H, NR 4a R 4b , C(O)R 5 , or C(O)OR 5 ; 
 R 3  is H, optionally substituted alkyl, or optionally substituted aryl; 
 each of R 4a  and R 4a  is independently H, C(O)R 6 , or optionally substituted alkyl; R 5  is H, optionally substituted alkyl, or optionally substituted aryl; 
 R 6  is optionally substituted alkyl or optionally substituted aryl; and 
 each of x and y is independently 0, 1, 2, or 3; and 
 
         b) a second container containing an aqueous medium. 
       
     
     
         85 . A kit for filling a void or gap in a bone comprising:
 a) a first container containing a composition comprising at least two multivalent metal salts and a compound of Formula (I) or a salt thereof:   
       
         
           
           
               
               
           
         
         wherein
 L is O, S, NH, or CH 2 ; 
 each of R 1a  and R 1b  is independently H, optionally substituted alkyl, or optionally substituted aryl; 
 R 2  is H, NR 4a R 4b , C(O)R 5 , or C(O)OR 5 ; 
 R 3  is H, optionally substituted alkyl, or optionally substituted aryl; 
 each of R 4a  and R 4a  is independently H, C(O)R 6 , or optionally substituted alkyl; R 5  is H, optionally substituted alkyl, or optionally substituted aryl; 
 R 6  is optionally substituted alkyl or optionally substituted aryl; and 
 each of x and y is independently 0, 1, 2, or 3; and 
 
         b) a second container containing an aqueous medium. 
       
     
     
         86 . A kit for increasing the volume of a bone comprising:
 a) a first container containing a composition comprising a multivalent metal salt and a compound of Formula (I) or a salt thereof:   
       
         
           
           
               
               
           
         
         wherein
 L is O, S, NH, or CH 2 ; 
 each of R 1a  and R 1b  is independently H, optionally substituted alkyl, or optionally substituted aryl; 
 R 2  is H, NR 4a R 4b , C(O)R 5 , or C(O)OR 5 ; 
 R 3  is H, optionally substituted alkyl, or optionally substituted aryl; 
 each of R 4a  and R 4a  is independently H, C(O)R 6 , or optionally substituted alkyl; R 5  is H, optionally substituted alkyl, or optionally substituted aryl; 
 R 6  is optionally substituted alkyl or optionally substituted aryl; and 
 each of x and y is independently 0, 1, 2, or 3; and 
 
         b) a second container containing an aqueous medium. 
       
     
     
         87 . The kit of any one of  claims 84 - 86 , wherein the multivalent salt comprises tetracalcium phosphate. 
     
     
         88 . The kit of any one of  claims 84 - 86 , wherein the multivalent salt does not comprise tetracalcium phosphate. 
     
     
         89 . The kit of any one of  claims 84 - 86 , wherein the compound of Formula (I) is phosphoserine. 
     
     
         90 . The kit of any one of  claims 84 - 86 , wherein the aqueous medium comprises water or saline (e.g., phosphate buffered saline). 
     
     
         91 . The kit of any one of  claims 84 - 86 , wherein the first container further comprises an additive. 
     
     
         92 . The kit of any one of  claims 84 - 86 , wherein upon mixing the contents of the first container with the contents of the second container, the resulting composition comprises an adhesive strength greater than about 1 MPa (e.g, greater than about 1.5 MPa, about 2.0 MPa, about 2.5 MPa, or about 3 MPa) upon hardening or curing. 
     
     
         93 . The kit of  claim 92 , wherein the hardening or curing occurs within at least about 30 minutes (e.g., within at least about 25 minutes, about 20 minutes, about 15 minutes, about 12 minutes, about 10 minutes, about 8 minutes, or about 5 minutes) after mixing the contents of the first container with the contents of the second container.