Dental products comprising bone growth enhancing peptide

Abstract

Dental products such as toothpastes, mouthwash and dental floss are disclosed which products are enhanced by having dissolved, dispersed or coated thereon a compound which promotes bone growth. Preferred compounds are peptide sequences comprising 10 to 50 amino acids are disclosed. The sequences are characterized by containing an integrin binding motif such as RGD sequence and the remainder of amino acids contiguous with the RGD sequence in matrix extracellular phosphoglycoprotein. The sequences may be formulated for dispersed in toothpaste or a mouthwash and administered to enhance bone/tooth growth. When the dental products are used repeatedly over time they enhance good dental health.

1 - 15 . (canceled) 
     
     
         16 . A method of treating bone tissue of a patient, comprising:
 administering to the patient a therapeutically effective amount of a formulation comprising:   a pharmaceutically acceptable carrier and a peptide consisting of ten to fifty amino acids, wherein the peptide is comprised of an RGD integrin binding motif and further wherein the peptide is characterized by biological activity which enhances bone growth; and   allowing the formulation to enhance both growth in the patient.   
     
     
         17 . The method of  claim 16 , wherein the peptide is contiguous with an RGD sequence of naturally occurring protein matrix extracellular phosphoglycoprotein. 
     
     
         18 . The method of  claim 16 , wherein the peptide consists of 15 to 35 amino acids. 
     
     
         19 . The method of  claim 16 , wherein the amino acids are in an L-conformation. 
     
     
         20 . The method of  claim 16 , wherein the peptide is chosen from: 
       
         
           
                 
                 
                 
                 
               
                     
                   DFEGSGYTDLQERGD 
                   (SEQ ID NO:42) 
                     
                 
                     
                     
                 
                     
                   YTDLQERGDNDISPF 
                   (SEQ ID NO:43) 
                 
                     
                     
                 
                     
                   ERGDNDISPFSGDGQ 
                   (SEQ ID NO:44) 
                 
                     
                     
                 
                     
                   TDLQERGDNDISPFSGDGQPFKD. 
                   (SEQ ID NO:46) 
                 
             
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         21 . A method of  claim 16 , wherein the peptide is TDLQERGDNDISPFSGDGQPFKD (SEQ ID NO:46). 
     
     
         22 . The method of  claim 16 , wherein the administering is by injection. 
     
     
         23 . The method as claimed in  claim 16 , wherein the peptide is selected from the group consisting of: 
       
         
           
                 
                 
               
                   (SEQ ID NO:2) 
                     
                 
                 
                 
               
                   AQKSPVKSKSTHRIQHNIDYLKHLSKVKKIPSDFEGSGYTDLQE RGD   
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:3) 
                     
                 
                 
                 
               
                     RGD AQKSPVKSKSTHRIQHNIDYLKHLSKVKKIPSDFEGSGYTDLQE 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:4) 
                     
                 
                 
                 
               
                   DSQAQKSPVKSKSTHRIQHNIDYLKHLSKVKKIPSDFEGSGYTD RGD   
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:5) 
                     
                 
                 
                 
               
                     RGD SPVKSKSTHRIQHNIDYLKHLSKVKKIPSDFEGSGYTDLQE 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:6) 
                     
                 
                 
                 
               
                   DSQAQKSPVKSKSTHRIQHNIDYLKHLSKVKKIPSDFEGSG RGD   
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:7) 
                     
                 
                 
                 
               
                     RGD THRIQHNIDYLKHLSKVKKIPSDFEGSGYTDLQE 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:8) 
                     
                 
                 
                 
               
                   DSQAQKSPVKSKSTHRIQHNIDYLKHLSKVKKIPSDFE RGD   
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:9) 
                     
                 
                 
                 
               
                     RGD LKHLSKVKKIPSDFEGSGYTDLQE 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:10) 
                     
                 
                 
                 
               
                   DSQAQKSPVKSKSTHRIQHNIDYLKHLSKVKKIPS RGD   
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:11) 
                     
                 
                 
                 
               
                     RGD LSKVKKIPSDFEGSGYTDLQE 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:12) 
                     
                 
                 
                 
               
                   DSQAQKSPVKSKSTHRIQHNIDYLKHLSK RGD   
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:13) 
                     
                 
                 
                 
               
                     RGD VKKIPSDFEGSGYTDLQE 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:14) 
                     
                 
                 
                 
               
                   DSAQKSPVKSKSTHRIQHNIDYLK RGD   
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:15) 
                     
                 
                 
                 
               
                     RGD IPSDFEGSGYTDLQE 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:16) 
                     
                 
                 
                 
               
                   DSQAQKSPVKSKSTHRIQHNID RGD   
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:17) 
                     
                 
                 
                 
               
                     RGD DFEGSGYTDLQE 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:18) 
                     
                 
                 
                 
               
                   DSQAQKSPVKSKSTHR RGD   
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:19) 
                     
                 
                 
                 
               
                     RGD GSGYTDLQE 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:20) 
                     
                 
                 
                 
               
                   DSQAQKSPVK RGD   
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:21) 
                     
                 
                 
                 
               
                     RGD GYTDLQE 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:22) 
                     
                 
                 
                 
               
                   DSQAQKS RGD   
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:23) 
                     
                 
                 
                 
               
                     RGD NDISPFSGDGQPFKDIPGKGEATGPDLEGKDIQTGFA 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:24) 
                     
                 
                 
                 
               
                   NDI  RGD SPFSGDGQPFKDIPGKGEATGPDLEGKDIQTGFA 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:25) 
                     
                 
                 
                 
               
                   NDISPF  RGD SGDGQPFKDIPGKGEATGPDLEGKDI 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:26) 
                     
                 
                 
                 
               
                   NDISPFSGD  RGD GQPFKDIPGKGEATGPDL 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:27) 
                     
                 
                 
                 
               
                   FSGDGQPFKDIPGKGEATGPDLEGKDIQTGFAGPSEAES  RGD THL 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:28) 
                     
                 
                 
                 
               
                   IPGKGEATGPDLEGKDIQTGFAGPSE  RGD AESTHL 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:29) 
                     
                 
                 
                 
               
                   EATGPDLEGKDIQTGFAG  RGD PSEAESTHL 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:30) 
                     
                 
                 
                 
               
                   NDISPFSGDGQPFKD  RGD IPGKGEATGPDLEGK 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:31) 
                     
                 
                 
                 
               
                   GKGEATGPDLEGKDI  RGD QTGFAGPSEAESTHL 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:32) 
                     
                 
                 
                 
               
                   FSGDGQPFKDIPGKGEATG  RGD PDLEGKDIQTGFAGPSEA 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:33) 
                     
                 
                 
                 
               
                   DGQPFKDIPGKGEATG  RGD PDLEGKDIQTGF 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:34) 
                     
                 
                 
                 
               
                   PFKDIPGKGEATG  RGD PDLEGKDIQ 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:35) 
                     
                 
                 
                 
               
                   DIPGKGEATG  RGD PDLEGKDIQTGFAGP 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:36) 
                     
                 
                 
                 
               
                   DGQPFKDIPGKGEATG  RGD PDLEGKDIQTGF 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:37) 
                     
                 
                 
                 
               
                   GKGEATG  RGD PDLEGKDIQTGFAGPSEA 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:38) 
                     
                 
                 
                 
               
                   EATG  RGD PDLEGKDIQTGF 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:39) 
                     
                 
                 
                 
               
                   EATG  RGD PDLEGK 
                     
                 
                     
                 
                 
                 
               
                   (SEQ ID NO:40) 
                     
                 
                 
                 
               
                     EATG  RGD PDL.   
                     
                 
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
               
            
           
         
       
     
     
         24 . A method of treating bone tissue of a patient, comprising:
 administering to the patient a therapeutically effective amount of a formulation comprising:   a pharmaceutically acceptable carrier and a peptide consisting of 15 to 35 amino acids in an L-conformation, wherein the peptide is comprised of an RGD integrin binding motif and further wherein the peptide is characterized by biological activity which enhances bone growth; and   allowing the formulation to enhance both growth in the patient.   
     
     
         25 . The method of  claim 24 , wherein the peptide is contiguous with an RGD sequence of naturally occurring protein matrix extracellular phosphoglycoprotein.