Oral Care Compositions Containing Deoxy Sugar Antimetabolites

Abstract

Described herein are oral care compositions comprising a deoxy sugar antimetabolite and methods of inhibiting microbial biofilm formation and/or degrading a microbial biofilm in a subject.

1 . A method of inhibiting microbial biofilm formation and/or degrading a microbial biofilm in the oral cavity of a subject comprising administering to the subject an oral care composition comprising a deoxy sugar antimetabolite with no additional antibacterial agent and an orally acceptable carrier. 
     
     
         2 . The method according to  claim 1 , wherein the deoxy sugar antimetabolite is a compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is H, OH, CH 3 , NH 2  or halogen; 
         R 2  is H, OH, CH 3 , NH 2  or halogen; 
         R 3  is H, OH, CH 3 , NH 2  or halogen; 
         R 4  is H, OH, NH 2  or halogen; and 
         at least three of R 1 , R 2 , R 3  and R 4  is OH. 
       
     
     
         3 . The method of  claim 2 , wherein the deoxy sugar antimetabolite is the compound of formula (I) wherein:
 R 1  is H, OH, CH 3 , NH 2 , F or Cl;   R 2  is H, OH, CH 3 , NH 2 , F or Cl;   R 3  is H, OH, CH 3 , NH 2 , F or Cl;   R 4  is H, OH, NH 2 , F or Cl; and   at least three of R 1 , R 2 , R 3  and R 4  is OH.   
     
     
         4 . The method of  claim 3  wherein, the deoxy sugar antimetabolite is the compound of formula (I) wherein:
 R 1  is H, OH, or F; 
 R 2  is H, OH, or F; 
 R 3  is H, OH, or F; 
 R 4  is H, OH, or F; and 
 at least three of R 1 , R 2 , R 3  and R 4  is OH. 
 
     
     
         5 . The method of  claim 1  wherein, the deoxy sugar antimetabolite comprises a compound of formula (II)-(V). 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is H, OH, CH 3 , NH 2  or halogen; 
         R 2  is H, OH, CH 3 , NH 2  or halogen; 
         R 3  is H, OH, CH 3 , NH 2  or halogen; 
         R 4  is H, OH, NH 2  or halogen; and 
         at least three of R 1 , R 2 , R 3  and R 4  is OH. 
       
     
     
         6 . The method of  claim 1  wherein, the deoxy sugar antimetabolite comprises a compound of formula (II) 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is H, OH, CH 3 , NH 2  or halogen; 
         R 2  is H, OH, CH 3 , NH 2  or halogen; 
         R 3  is H, OH, CH 3 , NH 2  or halogen; 
         R 4  is H, OH, NH 2  or halogen; and 
         at least three of R 1 , R 2 , R 3  and R 4  is OH. 
       
     
     
         7 . The compound of  claim 6  wherein, the deoxy sugar antimetabolite is the compound of formula (II) wherein:
 R 1  is H, OH, CH 3 , NH 2 , F or Cl; 
 R 2  is H, OH, CH 3 , NH 2 , F or Cl; 
 R 3  is H, OH, CH 3 , NH 2 , F or Cl; 
 R 4  is H, OH, NH 2 , F or Cl; and 
 at least three of R 1 , R 2 , R 3  and R 4  is OH. 
 
     
     
         8 . The compound of  claim 7  wherein, the deoxy sugar antimetabolite is the compound of formula (II) wherein:
 R 1  is H, OH, CH 3 , NH 2 , F or Cl; 
 R 2  is H, OH, CH 3 , NH 2 , F or Cl; 
 R 3  is H, OH, CH 3 , NH 2 , F or Cl; 
 R 4  is H, OH, NH 2 , F or Cl; and 
 at least three of R 1 , R 2 , R 3  and R 4  is OH, with the proviso that the deoxy sugar antimetabolite is not 2-deoxy-D-glucose or 2-amino-2-deoxy-D-glucose. 
 
     
     
         9 . The compound of  claim 8  wherein, the deoxy sugar antimetabolite is the compound of formula (II) wherein:
 R 1  is H, OH, or F; 
 R 2  is H, OH, or F; 
 R 3  is H, OH, or F; 
 R 4  is H, OH, or F; and 
 at least three of R 1 , R 2 , R 3  and R 4  is OH, with the proviso that the deoxy sugar antimetabolite is not 2-deoxy-D-glucose. 
 
     
     
         10 . The method of  claim 9 , wherein the deoxy sugar antimetabolite is selected from the group consisting of 6-deoxy-D-glucose, 2-fluoro-2-deoxy-D-glucose, and mixtures thereof. 
     
     
         11 . The method of  claim 8 , wherein the deoxy sugar antimetabolite is 2-amino-2-deoxy-D-mannosamine. 
     
     
         12 . The method of  claim 1 , wherein bacteria is decreased by less than 5% and biofilm is inhibited by at least 25%. 
     
     
         13 . The method of  claim 1 , wherein the biofilm efficiency is at least 1000%. 
     
     
         14 . The method according to  claim 1 , wherein the method comprises prevents or treats a disease condition of the oral cavity by inhibiting microbial biofilm formation and/or degrading a microbial biofilm in the oral cavity which is selected from the group consisting of dental plaque, tooth decay, periodontal disease and gingivitis. 
     
     
         15 . The method according to  claim 1 , wherein the biofilm is formed from one or more species of bacteria selected from  Actinomyces viscosus, Actinomyces naeslundii, Lactobacillus casei, Streptococcus oralis, Fusobacterium nucleatum  and  Veillonella parvula , and  Porphyromonas gingivalis.    
     
     
         16 . An oral care composition for inhibiting microbial biofilm formation and/or degrading a microbial biofilm in the oral cavity of a subject comprising a deoxy sugar antimetabolite wherein the deoxy sugar antimetabolite is present in the composition at a concentration of less than about 1 wt. % based on the total weight of the composition;
 an orally acceptable carrier for a toothpaste, a dental cream, a mouthwash, a chewing gum or a denture adhesive;   one or more of agents selected from the group consisting of an anti-plaque agent, a whitening agent, cleaning agent, a flavoring agent, a sweetening agent, adhesion agents, surfactants, foam modulators, abrasives, pH modifying agents, humectants, mouth feel agents, colorants, abrasive, tartar control (anticalculus) agent, fluoride ion source, saliva stimulating agents, an antisensitivity agent, an antioxidant agent, nutrients, viscosity modifiers, diluents, opacifiers, breath freshening agents and zinc salts and combinations thereof; and   does not contain an additional antibacterial agent.   
     
     
         17 . The oral care composition according to  claim 16 , wherein the deoxy sugar antimetabolite is a compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is H, OH, CH 3 , NH 2  or halogen; 
         R 2  is H, OH, CH 3 , NH 2  or halogen; 
         R 3  is H, OH, CH 3 , NH 2  or halogen; 
         R 4  is H, OH, NH 2  or halogen; and 
         at least three of R 1 , R 2 , R 3  and R 4  is OH. 
       
     
     
         18 . The oral care composition of  claim 17 , wherein the deoxy sugar antimetabolite is the compound of formula (I) wherein:
 R 1  is H, OH, CH 3 , NH 2 , F or Cl;   R 2  is H, OH, CH 3 , NH 2 , F or Cl;   R 3  is H, OH, CH 3 , NH 2 , F or Cl;   R 4  is H, OH, NH 2 , F or Cl; and   at least three of R 1 , R 2 , R 3  and R 4  is OH.   
     
     
         19 . The oral care composition of  claim 18  wherein, the deoxy sugar antimetabolite is the compound of formula (I) wherein:
 R 1  is H, OH, or F; 
 R 2  is H, OH, or F; 
 R 3  is H, OH, or F; 
 R 4  is H, OH, or F; and 
 at least three of R 1 , R 2 , R 3  and R 4  is OH. 
 
     
     
         20 . The oral care composition of  claim 16  wherein, the deoxy sugar antimetabolite comprises a compound of formula (II)-(V). 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is H, OH, CH 3 , NH 2  or halogen; 
         R 2  is H, OH, CH 3 , NH 2  or halogen; 
         R 3  is H, OH, CH 3 , NH 2  or halogen; 
         R 3  is H, OH, NH 2  or halogen; and 
         at least three of R 1 , R 2 , R 3  and R 4  is OH. 
       
     
     
         21 . The oral care composition of  claim 20  wherein, the deoxy sugar antimetabolite comprises a compound of formula (II) 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is H, OH, CH 3 , NH 2  or halogen; 
         R 2  is H, OH, CH 3 , NH 2  or halogen; 
         R 3  is H, OH, CH 3 , NH 2  or halogen; 
         R 4  is H, OH, NH 2  or halogen; and 
         at least three of R 1 , R 2 , R 3  and R 4  is OH. 
       
     
     
         22 . The oral care composition of  claim 21  wherein, the deoxy sugar antimetabolite is the compound of formula (II) wherein:
 R 1  is H, OH, CH 3 , NH 2 , F or Cl; 
 R 2  is H, OH, CH 3 , NH 2 , F or Cl; 
 R 3  is H, OH, CH 3 , NH 2 , F or Cl; 
 R 4  is H, OH, NH 2 , F or Cl; and 
 at least three of R 1 , R 2 , R 3  and R 4  is OH. 
 
     
     
         23 . The oral care composition of  claim 22  wherein, the deoxy sugar antimetabolite is the compound of formula (II) wherein:
 R 1  is H, OH, CH 3 , NH 2 , F or Cl; 
 R 2  is H, OH, CH 3 , NH 2 , F or Cl; 
 R 3  is H, OH, CH 3 , NH 2 , F or Cl; 
 R 4  is H, OH, NH 2 , F or Cl; and 
 at least three of R 1 , R 2 , R 3  and R 4  is OH, with the proviso that the deoxy sugar antimetabolite is not 2-deoxy-D-glucose or 2-amino-2-deoxy-D-glucose. 
 
     
     
         24 . The oral care composition of  claim 23  wherein, the deoxy sugar antimetabolite is the compound of formula (II) wherein:
 R 1  is H, OH, or F; 
 R 2  is H, OH, or F; 
 R 3  is H, OH, or F; 
 R 4  is H, OH, or F; and 
 at least three of R 1 , R 2 , R 3  and R 4  is OH, with the proviso that the deoxy sugar antimetabolite is not 2-deoxy-D-glucose. 
 
     
     
         25 . The oral care composition of  claim 24 , wherein the deoxy sugar antimetabolite is selected from the group consisting of 6-deoxy-D-glucose, 2-fluoro-2-deoxy-D-glucose and mixtures thereof. 
     
     
         26 . The method of  claim 23 , wherein the deoxy sugar antimetabolite is 2-amino-2-deoxy-D-mannosamine. 
     
     
         27 . The oral care composition of  claim 16 , wherein the bacteria is decreased by less than 5% and biofilm formation is inhibited by at least 25%. 
     
     
         28 . The oral care composition of  claim 16 , wherein the biofilm efficiency is at least 1000%.