Use of Quaternary Ammonium Compounds to Inhibit Endogenous MMPs in Tooth Dentin
Disclosed are compositions and methods of using such compositions for inhibiting matrix metalloproteinase activity in dental tissue. The compositions, methods and uses may prevent degradation of the bonding between restorative materials and dental tissues, thereby increasing durability and longevity of the restorative material-dental tissue bonds. For example, the compositions, methods, and uses of the present invention may be used for treating carious dental tissue such as by the creation of dental fillings, crowns, bridges, among other techniques, as well as the creation of esthetic laminate restorations.
1 . A composition comprising polymerizable quaternary ammonium monomers capable of inhibiting matrix metalloproteinase activity in dental tissue.
2 . The composition of claim 1 , wherein the composition is a dental adhesive.
3 . The composition of claim 1 , wherein the polymerizable quaternary ammonium monomers are compounds of Formula I
wherein X is selected from the group consisting of —R 4 —O—C(O)C(R 5 )═CH 2 , —CH 2 —CH═CH 2 , and
wherein Y is selected from the group consisting of hydrogen, methyl, and —CH 2 —CH═CH 2 ;
or X and Y together with the nitrogen atom to which they are attached form a five membered ring with X and Y having the structure —CH 2 —C(R 6 )H—C(R 7 )H—CH 2 —;
wherein Z is a counterion sufficient to balance the charge of the monomer;
wherein R 1 is selected from the group consisting of hydrogen and C 1-2 alkyl;
wherein R 2 is selected from the group consisting of hydrogen and C 1-2 alkyl;
wherein R 4 is C 2-3 alkylene;
wherein R 5 is selected from the group consisting of hydrogen and methyl;
wherein R 6 is an ethylene, acrylate or methacrylate group; and
wherein R 7 is an ethylene, acrylate or methacrylate group.
4 . The composition of claim 3 , wherein the polymerizable quaternary ammonium monomers are compounds of Formula Ia
wherein R 4 is ethylene and wherein R 5 is a methyl group.
5 . The composition of claim 3 , wherein the compounds are selected from the group consisting of [2-(methyl-acryloyloxy)ethyl-N-trimethyl ammonium chloride (METMAC), 2-(methacryloyloxy)ethyltrimethylammonium methyl sulfate (MCMS), 2-Acryloxyethyltrimethylammonium chloride (ATA), diayllyldimethyl ammonium chloride (DDAC), 3-[3,4-dimethyl-9-oxo-9H-trioxanthen-2-yloxy]-2-hydroxypropyl] trimethyl ammonium chloride (QTX), [3-(methacryloylamino) propyl]trimethylammonium chloride (MERQUAT 106), and N—N-dimethylaminomethacrylate methyl chloride.
6 . The composition of claim 5 further comprising chlorhexidine (CHX).
7 . The composition of claim 3 further comprising diphenyl (2,4,6-trimethylbenzoyl)-phosphine oxide (TPO) and/or benzoyl peroxide.
8 . The composition of claim 3 , wherein
wherein Y is selected from the group consisting of methyl, and —CH 2 —CH═CH 2 ;
wherein Z is a counterion selected from the group consisting of a halo group, a methyl sulfate group, or an acetate group;
wherein R 1 is methyl;
wherein R 2 is methyl;
wherein R 4 is ethylene; and
wherein R 5 is selected from the group consisting of hydrogen and methyl.
9 . The composition of claim 1 , wherein the polymerizable quaternary ammonium monomers are present in the composition in concentrations from about 0.2 to 40% by weight.
10 . A method of inhibiting matrix metalloproteinase activity in dental tissue in a subject comprising administering to the subject a dental composition comprising polymerizable quaternary ammonium monomers of Formula I
wherein X is selected from the group consisting of —R 4 —O—C(O)C(R 5 )═CH 2 , —CH 2 —CH═CH 2 , and
wherein Y is selected from the group consisting of hydrogen, methyl, and —CH 2 —CH═CH 2 ;
or X and Y together with the nitrogen atom to which they are attached form a five membered ring with X and Y having the structure —CH 2 —C(R 6 )H—C(R 7 )H—CH 2 —;
wherein Z is a counterion sufficient to balance the charge of the monomer;
wherein R 1 is selected from the group consisting of hydrogen and C 1-2 alkyl;
wherein R 2 is selected from the group consisting of hydrogen and C 1-2 alkyl;
wherein R 4 is C 2-3 alkylene;
wherein R 5 is selected from the group consisting of hydrogen and methyl;
wherein R 6 is an ethylene, acrylate or methacrylate group; and
wherein R 7 is an ethylene, acrylate or methacrylate group.
11 . The method of claim 10 , wherein the dental composition comprises an acid-etching solution, a primer, an adhesive or a cement, or mixtures thereof.
12 . The method of claim 10 , wherein the polymerizable quaternary ammonium monomers is a compound of Formula Ia:
wherein R 4 is ethylene and wherein R 5 is a methyl group.
13 . The method of claim 10 , wherein
Y is selected from the group consisting of methyl, and —CH 2 —CH═CH 2 ;
wherein Z is a counterion selected from the group consisting of a halo group, a methyl sulfate group, or an acetate group;
wherein R 1 is methyl;
wherein R 2 is methyl;
wherein R 4 is ethylene; and
wherein R 5 is selected from the group consisting of hydrogen and methyl.
14 . The method of claim 10 , wherein the polymerizable quaternary ammonium monomers are present in the composition in concentrations from about 0.2 to 40% by weight.
15 . The method of claim 11 , wherein the dental composition further comprises a photopolymerizable initiator and one or more of the following: (i) a polymerizable monomer containing an acid group, (ii) a polymerizable monomer selected from the group consisting of pyridinium bases and phosphonium bases, (iii) a hydrophilic polymerizable monomer, (iv) a hydrophobic polymerizable monomer, and (v) a polymerizable dimethacrylate monomer.
16 . The method of claim 15 , wherein the photopolymerizable initiator is TPO.
17 . The method of claim 16 , wherein the dental composition comprises a member from each of (i) a polymerizable monomer containing an acid group, (ii) a polymerizable monomer selected from the group consisting of pyridinium bases and phosphonium bases, (iii) a hydrophilic polymerizable monomer, and (iv) a polymerizable dimethacrylate monomer.
18 . The method of claim 15 , wherein the dental composition further comprises a photopolymerization inhibitor.
19 . A method of repairing dental caries in a tooth comprising the steps:
a) drilling the tooth;
b) acid-etching the tooth;
c) administering a dental adhesive wherein the dental adhesive comprises a compound of Formula I
wherein X is selected from the group consisting of —R 4 —O—C(O)C(R 5 )═CH 2 , —CH 2 —CH═CH 2 , and
wherein Y is selected from the group consisting of hydrogen, methyl, and —CH 2 —CH═CH 2 ;
or X and Y together with the nitrogen atom to which they are attached form a five membered ring with X and Y having the structure —CH 2 —C(R 6 )H—C(R 7 )H—CH 2 —;
wherein Z is a counterion sufficient to balance the charge of the monomer;
wherein R 1 is selected from the group consisting of hydrogen and C 1-2 alkyl;
wherein R 2 is selected from the group consisting of hydrogen and C 1-2 alkyl;
wherein R 4 is C 2-3 alkylene;
wherein R 5 is selected from the group consisting of hydrogen and methyl;
wherein R 6 is an ethylene, acrylate or methacrylate group; and
wherein R 7 is an ethylene, acrylate or methacrylate group.
20 . A use of a compound of Formula I for preparation of a medicament for treatment of tooth decay
wherein X is selected from the group consisting of —R 4 —O—C(O)C(R 5 )═CH 2 , —CH 2 —CH═CH 2 , and
wherein Y is selected from the group consisting of hydrogen, methyl, and —CH 2 —CH═CH 2 ;
or X and Y together with the nitrogen atom to which they are attached form a five membered ring with X and Y having the structure —CH 2 —C(R 6 )H—C(R 7 )H—CH 2 —;
wherein Z is a counterion sufficient to balance the charge of the monomer;
wherein R 1 is selected from the group consisting of hydrogen and C 1-2 alkyl;
wherein R 2 is selected from the group consisting of hydrogen and C 1-2 alkyl;
wherein R 4 is C 2-3 alkylene;
wherein R 5 is selected from the group consisting of hydrogen and methyl;
wherein R 6 is an ethylene, acrylate or methacrylate group; and
wherein R 7 is an ethylene, acrylate or methacrylate group.
21 . The use of claim 20 , wherein the medicament comprises an acid-etching solution, a primer, an adhesive or a cement mixture, or mixtures thereof.
22 . A use of a compound of Formula I for treatment of tooth decay
wherein X is selected from the group consisting of —R 4 —O—C(O)C(R 5 )═CH 2 , —CH 2 —CH═CH 2 , and
wherein Y is selected from the group consisting of hydrogen, methyl, and —CH 2 —CH═CH 2 ;
or X and Y together with the nitrogen atom to which they are attached form a five membered ring with X and Y having the structure —CH 2 —C(R 6 )H—C(R 7 )H—CH 2 —;
wherein Z is a counterion sufficient to balance the charge of the monomer;
wherein R 1 is selected from the group consisting of hydrogen and C 1-2 alkyl;
wherein R 2 is selected from the group consisting of hydrogen and C 1-2 alkyl;
wherein R 4 is C 2-3 alkylene;
wherein R 5 is selected from the group consisting of hydrogen and methyl;
wherein R 6 is an ethylene, acrylate or methacrylate group; and
wherein R 7 is an ethylene, acrylate or methacrylate group;
wherein the compound of Formula I is incorporated into a dental adhesive.