Use of metallofluorocomplexes for dental compositions

Drug – bio-affecting and body treating compositions – Dentifrices – Ammonia – amine – or derivative thereof

Reexamination Certificate

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C424S049000, C424S053000, C523S115000, C523S116000, C106S035000

Reexamination Certificate

active

06391286

ABSTRACT:

FIELD OF THE INVENTION
This invention relates to the use of metallofluorocomplexes in dental compositions.
BACKGROUND
The discovery of the effect of fluoride ion in the prevention and inhibition of caries was a major breakthrough in the preservation of dental health. Subsequent research has demonstrated that the caries resistance was due to the incorporation of fluoride into dental enamel during matrix formation, calcification and pre-eruptive maturation. After the formation and eruption of the tooth crown the surface layers of enamel continue to acquire additional fluoride. This discovery has lead to the development of many dentrifices and dental restorative materials that release fluoride into the surrounding oral environment. Most of these compositions incorporate simple inorganic fluoride salts as the fluoride source. The most common of these is sodium fluoride or sodium fluorophosphate, although compositions containing tin fluorides are becoming increasingly popular.
U.S. Pat. No. 4,629,746 calls for adding simple fluoride salts of rare earth elements (elements 57-71 of the periodic table) into dental compositions, particularly dental restoratives. U.S. Pat. No. 4,515,910 discloses a fluoride releasing interpolymer which is the reaction product of a monomer bearing an anion-exchange site carrying fluoride ions e.g. a quaternary ammonium fluoride. Organic fluoride sources such as those from alkylonium tetrafluoborate sources have been described in U.S. Pat. No. 4,871,786.
A very popular way of releasing fluoride in the oral environment has been the use of glass ionomer cements. In these cases, an ion-leachable fluoride glass is utilized along with an aqueous acidic solution. The decomposition of the glass results in the slow release of fluoride ions. See generally,
Glass Ionomer Cement
. A. D. Wilson and J. W. McLean, Quintessence Publishing Co., Inc. 1988. Many modifications of these cements exist.
SUMMARY OF THE INVENTION
In the present invention, a curable dental composition is provided with a fluoride releasing material that is a metal complex described by formula
M(G)
g
(F)
n
or M(G)
g
(ZF
m
)
n
where
M represents an element capable of forming a cationic species and having a valency of 2 or more,
G is an organic chelating moiety capable of complexing with the element M
Z is hydrogen, boron, nitrogen, phosphorus, sulfur, antimony, arsenic
is F is a fluoride atom
g, m and n are at least 1.
DETAILED DESCRIPTION OF THE INVENTION
This invention provides novel compositions which release fluoride into a surrounding aqueous environment.
Examples of preferred M elements are the metals of groups IIA, IIIA, IVA, and transition and inner transition metal elements of the periodic table. Specific examples include Ca
+2
, Mg
+2
, Sr
+2
, Zn
+2
, Al
+3
, Zr
+4
, Sn
+2
,Yb
+3
, Y
+3
, Sn
+4
. Most preferably, M is Zn
+2
.
The G group, as noted above, is an organic chelating moiety. This chelating moiety may or may not contain a polymerizable group. Although not absolutely essential, in some instances it may be advantageous for the chelating moiety to contain a polymerizable functionality that matches the reactivity of the polymerizable matrix into which it is incorporated:
A wide range of chelating moieties may be used in the present invention. Chelates in which the metal ion is bound in a ring structure of 4-8 members are preferred, with the 5-7 membered ring chelates being particularly preferred. The chelates useful in the present invention are multidentate, and are preferably bi-, tri- or quadra-dentate. Chelates containing hydroxyl or carboxy groups or both are more particularly preferred. Examples of such chelating agents are tartaric acid, citric acid, ethylenediamine tetraacetic acid, salicylic acid, hydroxybenzoic acids, hydroxytartaric acids, nitrilotriacetic acid, salicylic acid, melletic acids, and polyglycols. Chelates containing one or more acid groups derived from phosphorus, boron or sulfur can also be used, with the proviso that the molecular weight of the chelating agent is less than about 1000. Examples of especially suitable metal chelates include complexes of &bgr;-diketones and &bgr;-ketoesters.
The polymerizable metal-fluoride chelates preferably contain one or more polymerizable groups that match the reactivity of the polymerizable matrix into which it is incorporated. In addition to the chelating functionalities outlined above, these complexes can contain ethylenically unsaturated groups, epoxy groups, ethyleneimine groups and the like.
Preferred G groups include the polyphosphates, such as sodium tripolyphosphate and hexametaphosphoric acid; arninocarboxylic acids, such as ethylenediaminetetraacetic acid, hydroxyethylethylenediaminetriacetic acid, nitrilotriacetic acid, N-dihydroxyethylglycine and ethylenebis(hydroxyphenylglycine); 1,3-diketones, such as acetylacetone, trifluoroacetylacetone and thenoyltrifluoroacetone; hydroxycarboxylic acids, such as tartaric acid, citric acid, gluconic acid, and 5-sulfosalicylic acid; polyamines, such as malic acid, ethylenediamine, triethylenetetramine and triaminotriethylamine; aminoalcohols, such as triethanolamine and N-hydroxyethylethylenediamine; aromatic heterocyclic bases, such as dipyridyl and o-phenanthroline; phenols, such as salicyladehyde, disulfopyrocatechol and chromotropic acid; aminophenols, such as oxime, 8-hydroxyquinoline and oxinesulfonic acid; oximes, such as dimethylglyoxime and salicyladoxime hydroxamic acid and its derivatives; Schiff bases, such as disalicyladehyde 1,2-propylenedimine; tetrapyrroles, such as tetraphenylporphin and phthalocyanine; sulfur compounds, such as toluenedithiol(Dithiol), dimercaptopropanol, thioglycolic acid, potassium ethylxanthate, sodium diethyldithiocarbamate, dithizone, diethyl dithiophosphoric acid and thiourea; synthetic macrocyclic compounds, such as dibenzo[18]crown-6(5), (CH
3
)
6
[14]4,11-dieneN
4
(6) and (2.2.2-cryptate) (7); polymeric compounds such as polyethylenimine, polymetharyloylacetone, and poly(p-vinylbenzyliminodiacetic acid); and phosphonic acids, such as nitrilotrimethylenephosphonic acid, ethylenediaminetetra(methylenephosphonic acid) and hydroxyethylidenediphosphonic acid.
Particularly preferred G groups are compounds of the following formulas:
Fluoride is associated with the complexed metal as either a counterion or as a ligand. Thus, the designation (ZF) above indicates that the fluoride is associated with the Z group as a complex, which in turn is associated with the metal as a counterion or as a ligand.
The fluorocomplex materials of the invention can be incorporated into dental compositions that undergo setting reactions by virtue of a complexation reaction other than polymerization. Thus they can form components of zinc phosphate cements, polycarboxylate cements, glass ionomer cements and dental amalgams in order to release or enhance the release of fluoride ions. Additionally, these fluorocomplex materials can be incorporated into compositions that have both a complexation reaction as described above and a polymerization reaction.
Finally, the fluorocomplex materials of the invention can be incorporated into dental compositions that undergo only polymerization reactions as a cure mechanism. Useful polymerizable monomers are described in U.S. Pat. No. 4,871,786. Suitable initiators and fillers can be added to these compositions. In general, the more hydrophilic the resin matrix is the greater the initial fluoride release rate provided all other factors are maintained equal. In some instances, it may be advantageous to increase the water-absorbing property of the polymerizing matrix by incorporating hydrophilic monomers, oligomers, polymers or prepolymers with polymerizing groups. The water absorbing capacity is thereby increased by the incorporation of suitable hydrophilic moieties. Organic moieties suitable for this are pyrrolidone, alkylamides of lower alkyl groups, polyethers, polysulfones, derivatives of sulphonic and carboxylic acids and the like. This type

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