CA2235580A1 - Fluoride-releasing compositions - Google Patents

Abstract

Dental compositions are provided comprising a) a polymerizable component, b) a fluoride-releasing material, c) a hydrophilic component, d) a polymerization initiator, and e) an acidic component. This dental composition is substantially free of added water, and has a Water Uptake Value of at least about 1.5 g of water per 100 g composition in 2 weeks.

Description

CA 0223~80 1998-04-22

2 PCTIUS96/16299 FLUOR.lDE-RELEASlNG COMPOSITIONS

Field of the Invention s This invention relates to a novel dental composition or article that is hydrophilic and is compatible in the humid oral environn~el-t. In another aspect, the composition and article allow f'or the release of fluoride ions at a high level and in a sustained manner. The compositions of the invention are generally intended for placement followed by in-situ curing, although these compositions are also quite0 suitable for the fabrication of pre-polymerized articles intended for oral applications Back~round Many types of materials have been developed to restore tooth. Although the use o:f amalgam has been common in dentistry, over tl-e Iast few decades the tooth-5 colored restorative materials have become more popular. These compositionsgenerally comprise polymerizable ethylenically unsaturated monomers and an inert filler. The resin systems generally consist of mixtures of Bis-GMA, TEGDMA, Urethane dimethacrylates etc. The resultant restorative compositions are generally quite hydrophobic and immiscible with water, and hence require the elimination of 2() water from the surface of the tooth structure to be restored. The clinical procedure calls for stringent moisture control through the use of rubber dam or other suitable procedure. However, since moisture is constantly replenished in the mouth through saliva flow and/or exudation oi' dentinal fluid, its control makes the restorative procedure quite challenging for the practitioner. Hydrophilic compositions, on the 2s other hand, can imbibe water from the surrounding environment. Water-based cement compositions, particularly the glass ionomer cements, are tolerant of extraneous moisture. Thus the cements described by Wilson et al. have been used advantageously. These are two part powder:liquid systems consisting of a solution of a polyalkenoic acid in water and an acid-reactive glass powder. Modifications of 30 these cements by incorporation of curable moieties to obtain in situ polymerizable cements have been described. A particularly attractive benefit of these cements is CA 0223~80 1998-04-22 W(~ 97/18792 PCT/US96tl6299 the prolonged release of high amounts of fluoride from the set cements in the oral environment. It is believed that this leads to a protection from secondary caries attack. The disadvantage of these cements, however, is that they are generally two-part powder~ uid systems and require mixing prior to use. Furthermore, the glassiono~l~er cemel~ materials in general have much lower mechanical properties compared to the resin-based composites. Hence their usc is confined to non-stress bearing applications. ln order to overcome this disadvantage, other systems havebeen devised, such as described in U.S. Patent No. ~,15 l,453. The fluoride release levels from these materials, however, is quite low compared to the glass ionomercements.

Sllmmarv of the Invention In the present invention, a dental composition is provided comprising a) a polymerizable component, b) a fluoride-releasing material, c) a hydrophilic IS component, d) a polymerization initiator, and e) an acidic component. This dental composition is substantially free of added water, and has a "Water Uptake Value"of at least about l .S g of water per l()0 g composition in 2 weeks.

Det~iled Description of the ~nvention The invention overcomes the disadvantages of low fluoride release of non-agueous-based dental materials and yet provides cured systems of high mechanicalstrength.

For purposes of the present invention, the term "substantially free of added water" means that the composition does not contain water that is intentionally 2~ added as a non-complexed or coordinated entity. lt is understood that many materials, such as metals or glasses, contain water that is taken up from the atmosphere or is present as a coordination complex in its normal state. Water taken up by hygroscopic materials or present as a hydrate is permissibly present in the compositions described herein. Any u7ater that is present in the composition, regardless of source, should not be present in amounts such that the water will have a deleterious effect of the long term properties of the composition. For example, CA 0223~80 1998-04-22 water should not be present in an amount- that would facilitate reaction of the fluoride-releasing material with the acidic component so that lumpiness or graininess ofthe material develops during commercially required storage time.
The polymerizable component of the present compositions are compounds, 5 which may be monomers, oligomers, or polymers, containing a polymerizable group. These polymerizable groups may be selected from free radically polymerizable groups, cationically polymerizable groups, or mixtures thereof.
Preferably, the polymerizable compound has a molecular weight of between about 100 to ~000, and more preferably, has a molecular weight between about 200 and o 1000. Mixtures of both higher and lower molecular weight polymerizable materials are also contemplated as providing special benefits in handling properties and ultimate cure material physical properties. In a preferred aspect of the presentinvention, at least some of the polymerizable material is relatively lower in viscosity than other ingredients of the composition so that it serves a viscosity lowering5 function in the overall uncured material. Preferably, at least some of the polymerizable material has a viscosity of less than 2000 cp, more preferably less than S00 cp, and most preferably less than 300 cp.

Preferred materials that provide the polymerizable component are the esters of aclylic or methacrylic acid. Examples of these compounds are methyl acrylate,20 methvl methacrylate, ethyl acrylate, ethyl methacrylate, propyl acrylate, propyl methacrylate, isopropyl acrylate, isopropyl methacrylate, 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate ("HEMA"), hydroxypropyl acrylate, hydroxypropyl methacrylate, tetrahydrofurfuryl acrylate, tetrahydrofurfuryl methacrylate, glycidyl acrylate, glycidyl methacrylate, the diglycidyl methacrylate of bis-phenol A ("Bis-25 GMA"), glycerol mono- and di- acrylate, glycerol mono- and di- methacrylate, ethyleneglycol diacrylate, ethyleneglycol dimethacrylate, polyethyleneglycol diacrylate (where the number of repeating ethylene oxide units vary from 2 to 30), polyethyleneglycol dimethacrylate [where the number of repeating ethylene oxide units vary from 2 to 30, especially triethylene glycol dimethacrylate ~"TEGDMA")], 30 neopentyl glycol diacrylate, neopentylglycol dimethacrylate, trimethylolpropane triacrylate, trimethylol propane trimethacrylate, mono-, di-, tri-, and tetra- acrylates CA 0223~80 1998-04-22 wo 97/18792 PCT/US96/16299 and methacrylates of pentaerythritol and-dipentaerythritol, 1,3-butanediol diacrylate, 1,3-butanediol dimeth.~;rylate 1,4-bul.medioldiacrylate, 1, 4-butanediol dimethacrylate, 1,6-hexane diol diacrylate, 1,6-hexanediol dimethacrylate di-2-methacryloyloxethyl hexamethylene dicarbamate, di-2-methacryloyloxyethyl s trimethylhexanethylene dicarbamate, di-2-methacryloyl oxyethyl dimethylbenzene dicarbamate, methylene-bis-2-methacryloxyethyl-4-cyclohexyl carbamate, di-2-methacryloxyethyl-dimethylcyclohexane dicarbamate, methylene-bis-2-methacryloxyethyl-4-cyclohexyl carbamate, di- I -meth~ 1-2-methacryloxyethyl-trimethyl-hexamethylene dicarbamate, di-l-methyl-2-methacryloxyethyl-lo dimethylbenzene dicarbamate, di-l-methyl-2-methacryloxyethyl-dimethylcyclohexane dicarbamate, methylene-bis-l-methyl-2-methacryloxyethyl-4-cyclohexyl carbamate, di-l-chloromethyl-2-methacryloxyethyl-hexamethylene dicarbamate, di-l-chloromethyl-2-methacryloxyethyl-trimethylhexamethylene dicarbamate, di-l-chloromethyl-2-methacryloxyethyl-dimethylbenzene dicarbamate, di-1-chloromethyl-2-methacryloxyethyl-dimethylcyclohexane dicarbamate, methylene-bis-2-methacryloxyethyl-4-cyclohexyl carbamate, di-1-methyl-2-methacryloxyethyl-hexamethylene dicarbamate, di-l-methyl-2-methacryloxyethyl-trimethylhexamethylene dicarbamate, di-l-methyl-2-methacryloxyethyl-dimethylbenzene dicarbamate, di- 1 -methyl-2-metha-cryloxyethyl-dimethylcyclohexanedicarbamate, methylene-bis-1-methyl-2-methacryloxyethyl-4-cyclohexyl carbamate, di-b l-chloromethyl-2-methacryloxyethyl-hexamethylene dicarbamate, di-l-chloromethyl-2-methacryloxyethyl-trimethylhexamethylene dicarbamate, di-l-chloromethyl-2-methacryloxyethyl-dimethylbenzene dicarbamate, di- I -chloromethyl-2-methacryloxyethyl-dimethylcyclohexane dica- ban~ale~
2~ methylene-bis-1-chloromethyl-2-methacryloxyethyl-4-cyclohexyl carbamate, 2,2'-bis(4-methacryloxyphenyl)propane, 2,2'bis(4-acryloxyphenyl)propane, 2,2'-bis[4(2-hydroxy-3-methacryloxy-phenyl)]propane, 2,2'-bis[4(2-hydroxy-3-acryloxy-phenyl)propane, 2,2'-bis(4-methacryloxyethoxyphenyl)propane, 2,2'-bis(4-acryloxyethoxyphenyl)propane, 2,2'-bis(4-methacryloxypropoxyphenyl)propane, 2,2'-bis(4-acryloxypropoxyphenyl)propane, 2,2'-bis(4-methacryloxydiethoxyphenyl)propane, 2~2'-bis(4-acryloxydiethoxyphenyl)propane, CA 0223~80 1998-04-22 2,2'-bis[3(4-phenoxy)-2-hydroxypropane-1-methacrylate]propane, 2,2'-bis[3(4-phenoxy)-2-h~ ~roxypropane- 1 -~Icryalte]propane, and the like.
Other preferred polymerizable components can be substituted acryl amides and rnethacrylall~ides. F~xample~i are acrylamide, methylene bis-acrylamide, 5 methylene bis-methacrylamide, diacetone!acryl~mide diacetone methacylamide, N-alkyl acrylamides and N-alkyl methacrylamides where alkyl is a lower hydrocarbylunit of 1-6 carbon atoms. Other suitable examples of polymerizable components are isopropenyl oxazoline, vinyl azalactone, vinyl pyrrolidone, styrene, divinylbenzene, urethane acrylates or methacrylates, epoxy acrylates or 0 methacrylates and polyol acrylates or methacrylates Alternatively, the polymerizable component may be a cationically cured material, such as epoxy materials, oxetanes, oxolanes, cyclic acetals, l~ct~m~
lactones, and vinyl ethers or spirocyclic compounds containing O atoms in the rings.
The cationically polymerizable epoxy resins useful in the compositions of the 15 invention comprise organic compounds having an oxirane ring, i.e., polymerizable by ring opening. Such materials, broadly called epoxides, include monomeric epoxy compounds and epoxides of the polymeric type and can be 20 aliphatic, cycloaliphatic, aromatic or heterocyclic These materials generally have, on the average, at least 1 polymerizable epoxy group per molecule, and preferably at least about 1 ~ polymerizable epoxy groups per molecule The polymeric epoxides include linear polymers having terminal epoxy groups te.g., a diglycidyl ether of a polyoxyalkylene glycol), polymers having skeletal oxirane units (e.g., 2~ polybutadiene polyepoxide), and polymers having pendent epoxy groups (e.g., a glycidyl methacrylate polymer or copolymer). The epoxides may be pure compounds or may be mixtures containing one, two, or more epoxy groups per molecule. The "average" number of epoxy groups per molecule is determined by dividing the total number of epoxy groups in epoxy-containing material by the total 30 number of epoxy molecules present.

CA 0223~80 1998-04-22 WO 9~118792 PCT/US96J16299 These epoxy-containing materials may vary from low molecular weight monomeric materials to high molecular weight polymers and may vary greatly in the nature of their backbone and substituent groups. For example, the backbone may be of any type and substituent groups thereon can be any group that does not substAnti~lly interfere with cationic cure at room temperature. Illustrative of permissible substituent groups include halogens, ester groups, ethers, sulfonategroups, siloxane groups, nitro groups, phosphate groups, and the like. The molecular weight ofthe epoxy-containing materials may vary from about 58 to about 100,000 or more.
o Useful epoxy-containing materials include those which contain cyclohexene oxide groups such as the epoxycyclohexanecarboxylates, typified by 3,4-epoxycyclohexylmethyl-3,4-epoxycyclohexanecarboxylate, 3,4-epoxy-2-methylcyclohexylmethyl-3,4-epoxy-2-methylcyclohexane carboxylate, and bis(3,4-epoxy-6-methylcyclohexylmethyl) adipate. For a more detailed list of useful epoxides ofthis nature, reference is made to the U.S. Patent No. 3,1171099, incorporated herein by reference.
Further epoxy-containing materials which are particularly usefill in the practice of this invention include glycidyl ether monomers of the formula R'(OCH2--CH--CH2)n o where R' is alkyl or aryl and n is an integer of I to 6. Examples are glycidyl ethers of polyhydric phenols obtained by reacting a polyhydric phenol with an excess ofchlorohydrin such as epichlorohydrin (e.g., the diglycidyl ether of 2,2-bis-(2,3-epoxypropoxyphenol)-propane). Further examples of epoxides of this type which can be used in the practice of this invention are described in U. S. Patent No.

3,018,262, incorporated herein by reference, and in "Handbook of Epoxy Resins"
by Lee and Neville, McGraw-Hill Book Co., New York ( 1967).
There are a host of commercially available epoxy resins which can be used in this invention. In particular~ epoxides which are readily available include octadecylene oxide, epichlorohydrin, styrene oxide, vinyl cyclohexene oxide, CA 0223~80 1998-04-22 glycidol, glycidylmethacrylate, diglycidyl ether of Bisphenol A (e.g., those available under the trade designations "Epon 828", "Epon 825", "Epon ] 004" and "Epon 1010'~ from Shell Chemical Co., "DER-331", "DER-332", and "DER-334", from Dow Chemical Co.), vinylcyclohexene dioxide (e.g., "ERL-4206" from Union Carbide Corp.), 3,4-epoxycyclohexylmethyl-3,4-epoxycyclohexene carboxylate (e.g., "ERL-4221 " or "UVR 6110" or "UVR 6105" from Union Carbide Corp.), 3,4-epoxy-6-methylcyclohexylmethyl-3,4-epoxy-6-methyl-cyclohexene carboxylate (e.g., "ERL-4201" from Union Carbide Corp.), bis(3,4-epoxy-6-methylcyclohexylmethyl) adipate (e.g., "ERL-4289" from Union Carbide Corp.), 0 bis(2,3-epoxycyclopentyl) ether (e.g., "ERL-0400" from Union Carbide Corp.),aliphatic epoxy modified with polypropylene glycol (e.g., "ERL-4050" and "ERL-4052" from Union Carbide Corp.), dipentene dioxide (e.g., "ERL-4269" from Union Carbide Corp.), epoxidized polybutadiene (e.g., "Oxiron 2001" from FMC
Corp.), silicone resin containing epoxy fi~nctionality, flame retardant epoxy resins (e.g., "DER-580", a brominated bisphenol type epoxy resin available from Dow Chemical Co.), 1,4-butanedio] diglycidyl ether of phenolformaldehyde novola~
(e.g., "DEN-431" and "DEN-438" from Dow Chemical Co.), and resorcinol diglyc:idyl ether (e.g., "Kopoxite" from Koppers Company, Tnc.). bis(3,4-epoxycyclohexyl)adipate (e.g., "ERL-4299" or "UVR-6128", from Union Carbide Corp.), 2-(3,4-epoxycyclohexyl-5, 5-spiro-3,4-epoxy) cyclohexane-meta-dioxane (e.g., "ERL-4234" from Union Carbide Corp.), vinylcyclohexene monoxide (from Union Carbide Corp.), 1,2-epoxyhexadecane (e.g., "UVR-6216" from Union Carbide Corp.), allcyl glycidyl ethers such as alkyl C8-C~o glycidyl ether (e.g., "HEL,OXY Modifier 7" from Shell Chemical Co.), alkyl C~2-CI~ glycidyl ether (e.g., "HELOXY Modifier 8" from Shell Chemical Co.), butyl glycidyl ether (e.g.,"HELOXY Modifier 61 " from Shell Chemical Co.), cresyl glycidyl ether (e.g., "HELOXY Modifier 62" from Shell Chemical Co.), p-tert butylphenyl glycidyl ether(e.g., "HELOXY Modifier 65" from Shell Chemical Co.), polyfunctional glycidyl ethers such as diglycidyl ether of 1,4-butanediol (e.g., "HELOXY Modifier 67"
from Shell Chemical Co.), diglycidyl ether of neopentyl glycol (e.g., "HELOXY
Modifier 68" from Shell Chemical Co.), diglycidyl ether of cyclohexanedimethanol CA 0223~80 1998-04-22 (e.g., "HELOXY Modifier 107" from Shell Chemical Co.), trimethylol ethane triglycidyl ether (e.g., "HELOXY Modifier 44" from Shell Chemical Co.), trimethylol propane triglycidyl ether (e.g., "HELOXY Modifier 48" from Shell Chemical Co.), polyglycidyl ether of an aliphatic polyol (e.g., "HELOXY Modifiers 84" from Shell Chemical Co.), polyglycol diepoxide (e.g., "HELOXY Modifier 32"
from Shell Chemical Co.), bisphenol F epoxides (e.g., "EPN-I 138" or "GY-281"
from Ciba-Geigy Corp.), 9,9-bis[4-(2,3-epoxypropoxy)-phenyl]fluorenone (e.g., "Epon 1079" from Shell Chemical Co.).
Still other epoxy resins contain copolymers of acrylic acid esters or glycidol 0 such as glycidylacrylate and glycidylmethacrylate with one or more copolymerizable vinyl compounds. Examples of' such copolymers are 1 :1 styrene-glycidylmethacrylate, 1:1 methylmethacrylate-glycidylacrylate and a 62.5:24:13.5methylmethacrylate-ethyl acrylate-glycidylmethacrylate.
Other useful epoxy resins are well known and contain such epoxides as epichlorohydrins, e.g., epichlorohydrin; alkylene oxides, e.g., propylene oxide,styrene oxide; alkenyl oxides, e.g., butadiene oxide; glycidyl esters, e.g., ethyl glycidate.
The polymers of the epoxy resin may optionally contain other functionalities that do not substantially interfere with cationic cure at room temperature.
Blends of various epoxy-containing materials are particularly contemplated in this invention. Examples of such blends include two or more molecular weight distributions of epoxy-containing compounds, such as low molecular weight (below200), intermediate molecular weight (about 200 to 10,000) and higher molecular weight ( above about 10,000). Alternatively or additionally, the epoxy resin maycontain a blend of epoxy-containing materials having different chemical nature, such as aliphatic and aromatic, or functionality, such as polar and non-polar. Other cationically polymerizable polymers may additionally be incorporated. Particularly p~ ed epoxy containing compositions also contain materials having hydroxyl functionality.

CA 0223~80 1998-04-22 WO 97/1879;', PCT/US96/16299 Mixtures of polymerizable materials, including hybrid systems containing both ~ree-radically polymerized components and cationically polymerized components, are also contemplated.
The fluoride-releasing material of the present invention may be naturally occuring or synthetic fluoride minerals, fluoride glass such as fluoroaluminosilicate glass, simple and complex inorganic fluoride salts, simple and complex organic fluoride salts or combinations thereof Optionally these fluoride sources can be treated with surface treatment agents.
Examples of the fluoride-releasing material are fluoroaluminosilicate glasses o described in U.S. Pat. No 4,3814,717, which may be optionally treated as described in U.,S. Pat. No. 5,332,429, the disclosures of which are both incorporated by reference herein.
The fluoride releasing material may optionally be a metal complex described by formula M(G)g(F)n or M(G)g(ZFm)n where M represents an element capable of forming a cationic species and having avalency 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 F is a fluoride atom g, m and n are at least I .

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 examplesinclude Ca 2, Mg+2, Sr+2, Zn+2 Al+3 Zr+~ Sn+2 Yb+3 Y+3 S +4 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 CA 0223~80 1998-04-22 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. Thechelates 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, o hydroxytartaric acids, nitrilotriacetic acid, salicylic acid, melletic acids, and polyglycols. Chelates containing one or more acid ~roups 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 ~-diketones and ,~-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 chelatin~ functionalities outlined above, these complexes can contain ethylenically unsaturated ~roups, epoxy groups, ethyleneimine groups and the like.
Preferred G groups include the polyphosphates, such as sodium tripolyphosphate and hexametaphosphoric acid; aminocarboxylic 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 malic acid, tartaric acid, citric acid, gluconic acid, and S-sulfosalicylic acid;
polyamines, such as 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 oxine, 8-hydroxyquinoline and oxinesulfonic acid; oximes, such as dimethylglyoxime and salicyladoxime hydroxamic acid and its derivative; 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, diethyldithiophosphoric acid and thiourea; synthetic macrocyclic compounds, such as dibenzo~l8]crown-6(5), (CHJ)G[14]4,1 I-dieneN4 (6) and (2.2.2-cryptate) (7), polymeric compounds such as polyethylenimine, polymetharyloylacetone, and poly(p-vinylbenzyliminodiacetic acid); and phosphonic acids, such as 0 nitrilotrimethylenephosphonic acid, ethylenediaminetetra(methylenephosphonic acid) and hydroxyethylidenediphosphonic acid.
Particularly preferred G groups are compounds of the following formulas:

~2C C\

1~

HO,C\ CH~CO~H H,C 1~l ,CO~H
rH ~C--NH--CH--CH
/ CH, H~C CO~H
NH--CO--C~
CH., HlC~ CO~H H C~C ~ ~COo~,H

~CO2H
HCI--OH
HC--OH O
CO--NH--ICl--CH2--CH2-O--C~

H~C 1~l 1~l CO~H
~C--NH--CH~CH~--C--NH--CH--C
H3C CH~CO~H

H~C~C--O CH~CH~ O--C--CH~--C--CH~

HO~C~ ,CH~--CO~H
CH7--N--CH~CH~--N~ 1~
CO~H--CH~/CH~--CO--NHCH~CH~--O--C~

HO2C~ ~CO2HHO2C~ ~CO2H

\\C Cl~lC ciC--C ~ CO2H
H3C o ~ CH2 H C' Fluoride is associated with the complexed metal as either a counterion or as a ligand. Thus, the desi~n~tion (YF) above indicates that the fluoride is associated CA 0223~80 1998-04-22 Wo 97/187g2 PCT/USg6/16299 with the Y group as a complex, which in turn is associated with the metal as a counl:erion or as a ligand.
Particularly pre~el-ed compositions ofthe present invention comprise at least two sources of fluoride. The first source is the fluoride-containing metal5 complex as described above. The second source is a fluoride-releasing fluoroaluminosilicate glass. With the use of both materials, excellent fluoride release is provided both in the initial period and over the long term use of the composltion.

0 The hydrophilic component can be provided as a monomer1 oligomer or polymer. Preferably, it is provided as either a linear homopolymer or copolymer,either of which may optionally be lightly crosslinked. The hydrophilic component is preferably miscible in water at concentrations of about 3% by weight or can absorb at least 2g of water per hundred g of polymer. Optionally, the hydrophilic component can be a hydrophilic monomer which undergoes polymerization in situ leading to a hydrophilic, water-absorbing polymer.
~n many cases, compounds containing acidic functionality are hydrophilic in nature. Such compounds may be useful in the present invention if they satisfy the above hydrophilicity characteristics. It has been found, however, that preferredhydrophilic components for use in the present invention have at least a portion of their hydrophilic properties provided by non-acidic functionalities. Thus, preferred hydrophilic compounds for use in the present invention contain acidic functionality and non-acidic hydrophilic functionality, and most preferred hydrophilic compounds for use in the present invention contain no acidic functionalities.
Examples of hydrophilic components include monomers or polymers such as pyrrolidone, a moiety containing hydroxy groups and polyether groups, a moiety containing a sulfonate group (SO~), a moiety containing a sulfonic group (SO2), N-oxysl1ccinimide, N-vinylacetamide and acrylamide.
More specific examples of preferred hydrophilic components are non-ionic polymers or copolymers, e.g. polyalkylene oxides (polyoxymethylene, polyethyleneoxide, polypropylene oxide) polyethers (polyvinylmethyl ether), CA 0223~80 1998-04-22 polyethyleneimine copolymers, polyacrylamides and polymethacrylamides, polyvinylalcohol, saponified polyvinylacetate, polyvinylpyrrolidone, polyvinyloxazolidone, polymers containin;, N-oxysuccinimdo groups, ionic or ionizable polymers and copolymers containing polyacrylic acid, polymethacrylic 5 acid in unionized, partially neutralized or fully neutralized form, polyethyleneimine and its salts, polyethylene sulfonic acid and polyaryl sulfonic acids in unionized, partially neutralized or fully neutralized form, polyphoshoric and phosphonic acids in unionized, partially neutralized or fi~lly neutralized form.
Generally, any compound having a polar group may provide a hydrophilic 0 aspect to a composition. Preferred hydrophilic compounds may be prepared by reaction of vinylic monomers such as acrylates, methacrylates, crotonates, itaconates and the like that contain polar groups that are acidic, basic or provided as a salt. These groups can also be ionic or neutral.
Examples of polar or polarizable groups include neutral groups such as s hydroxy, thio, substituted and unsubstituted amido, cyclic ethers (such as oxanes, oxetanes, furans and pyrans), basic groups (such as phosphines and amines, including primary, secondary, tertiary amines), acidic groups (such as oxy acids, and thiooxyacids of C, S, P, B) and ionic groups (such as quarternary ammonium, carboxylate salt, sulfonic acid salt and the like) and the precursors and protected 20 forms of these groups. More specific examples of such groups follow.
The hydrophilic component may be derived from mono- or multifunctional carboxyl group containing molecules represented by the general formula:

CH2=CR2G-(COOH)d 2s where R2=H, methyl, ethyl, cyano, carboxy or carboxymethyl, d=1-5 and G is a bond or a hydrocarbyl radical linking group containing from 1-12 carbon atoms ofvalence d+l and optionally substituted with and/or interrupted with a substituted or unsubstituted heteroatom (such as O, S, N and P). Optionally, this unit may be 30 provided in its salt form. The preferred monomers in this class are acrylic acid, methacrylic acid, itaconic acid and N-acryloyl glycine.

CA 0223~80 1998-04-22 W(~ 97/18792 PCT/US96116299 Tlle hydrophilic component may, for example, be derived from mono- or multifunctional hydroxy ~roup containing molecules represented by the general formula:

CH2=CR2-Co-L-R3-(oH)~, where R2=H, methyl, ethyl, cyano, carboxy or carboxyalkyl, L=O, NH, d=1-5 and R3is a hydrocarbyl radical of valence d+l containing from 1-12 carbon atoms. Thepreferred monomers in this class are hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, hydroxybutyl (meth)acrylate, glycerol mono(meth)acrylate, o tris(hydroxymethyl)ethane monoacrylate, pentaerythritol mono(meth)acrylate, N-hydroxymethyl (meth)acrylamide, hydroxyethyl (meth)acrylamide and hydroxypropyl (meth)acrylamide.
The hydrophilic component may alternatively be derived from mono- or multi.functional amino group containin~ molecules of the general formula:
s CH2=CR2-Co-L-R3-(NR~Rs)~
where R2, L, R~, and d are as defined above and RJ and Rs are H or alkyl groups of 1-12 carbon atoms or together they constitute a carbocyclic or heterocyclic group.
Preferred monomers of this class are aminoethyl (meth)acrylate, aminopropyl (meth)acrylate, N,N-dimethylaminoethyl (meth)acrylate, N,N-diethylaminoethyl (meth)acrylate, N,N-dimethylaminopropyl (meth)acrylamide, N-isopropylaminopropyl (meth)acrylamide and 4-methyl-1-acryloyl-piperazine.
The hydrophilic component may also be derived from alkoxy substituted (meth)acrylates or (meth)acrylamides such as methoxyethyl (meth)acrylate, 2(2-etho~yethoxy)ethyl (meth)acrylate, polyethylene glycol mono(meth)acrylate or polypropylene glycol mono(meth)acrylate.
Hydrophilic components may be derived from substituted or unsubstituted ammonium monomers of the general formula:
~33 CH2=CR2_co_L_R3_(NR4R5R~)dQ -CA 0223~80 1998-04-22 where R2, R-', R~, R5, L and d are as defined above, and where R6 is H or alkyl of 1-12 carbon atoms and Q- is an organic or inorganic anion. Preferred examples of such monomers are 2-N,N,N-trimethylammonium ethyl (meth)acrylate, 2-N,N,N-triethylammonium ethyl (meth)acrylate, 3-N,N,N-trimethylammonium propyl (meth)acrylate, N(2-N',N',N'-trimethylammonium) ethyl (meth)acrylamide, N-(dimethyl hydroxyethyl ammonium) propyl (meth)acrylamide etc. where the counterion may be fluoride, chloride, bromide, acetate, propionate, laurate, palmitate, stearate etc. The monomer can also be N,N-dimethyl diallyl ammonium salt of an organic or inorganic counterion.
o Arnmonium group containing polymers can also be prepared by using as the hydrophilic component any of the amino group containing monomer described above, and acidifying the resultant polymers with organic or inorganic acid to a pH
where the pendant amino groups are substantially protonated. Totally substitutedammonium group containing polymers may be prepared by alkylating the above described amino polymers with alkylating groups, the method being commonly known in the art as the Menschutkin reaction.
The hydrophilic component of the invention can also be derived from sulfonic acid group containing monomers, such as vinyl sulfonic acid, styrene sulfonic acid, 2-acrylamido-2-methyl propane sulfonic acid, allyloxybenzene sulfonic acid, and the like. Alternatively, the hydrophilic component may be derived fromphosphorous acid or boron acid group-containing monomers. These monomers may be used in the protonated acid form as monomers and the corresponding polymers obtained may be neutralized with an organic or inorganic base to give the salt form of the polymers.
2s Compositions of the invention contain one or more suitable polymerization initiators, so that the composition may be polymerized in use The initiator is selected such that it is capable of initiating the polymerization of the polymerizable material. That is, if the polymerizable material is a free radical polymerizablematerial, the initiator is a free-radical polymerization initiator. Likewise, if the CA 0223~80 1998-04-22 WO 97/18792 PCI'/US96/16299 polymerizable material is a cationically polymerizable material, the initiator is a cationic polymerization initiator.
Compositions of the invention that are free-radically polymerized preferably contain one or more suitable photopolymerization initiators that act as a source of free radicals when activated. Such initiators can be used alone or in combination with one or more accelerators and/or sensitizers.
The photoinitator should be capable of promoting free radical crosslinking of the ethylenically unsaturated moiety on exposure to light of a suitable wavelength and intensity. It also preferably is suf~lciently shelf stable and free of undesirable o coloration to permit its storage and use under typical dental conditions. Visible light photoinitiators are preferred. The photoinitiator frequently can be used alone, but typically it is used in combination with a suitable donor compound or a suitable accelerator (for example, amines, peroxides, phosphorus compounds, ketones and alpha-diketone compounds).
Preferred visible light-induced initiators include camphorquinone (which typically is combined with a suitable hydrogen donor such as an amine), diaryliodonium simple or metal complex salts, chromophore-substituted halomethyl-s-triazines and halomethyl oxadiazoles. Particularly preferred visible light-induced photoinitiators include combinations of an alpha-diketone, e.g., camphorquinone,and a diaryliodonium salt, e.g., diphenyliodonium chloride, bromide, iodide or hexafluorophosphate, with or without additional hydrogen donors (such as sodium benzene sulfinate, amines and amine alcohols).
Preferred ultraviolet light-induced polymerization initiators include ketones such as benzyl and benzoin~ and acyloins and acyloin ethers. Preferred commercially available ultraviolet light-induced polymerization initiators include 2,2-dimethoxy-2-phenylacetophenone ("IRGACURE 6~1 ") and benzoin methyl ether (2-methoxy-2-phenylacetophenone), both from Ciba-Geigy Corp.
The photoinitiator should be present in an amount sufficient to provide the desired rate of photopolymerization. This amount will be dependent in part on the light source, the thickness of the layer to be exposed to radiant energy, and the extinction coefficient of the photoinitiator. Typically, the photoinitiator CA 0223~80 1998-04-22 components will be present at a total weight of about 0.01 to about 5%, more preferably from about 0.1 to about 5%, based on the total weight of the composition.
The compositions of the present invention may alternatively incorporate a mode of initiation of the polymerizalion reaction to initiate a crosslinking reaction without the need to expose the system to visible light. A preferred alternative mode for initiation of the polymerization reaction is the incorporation of an oxidizing agent and a reducing agent as a redox catalyst system to enable the dental composition to cure via a redox reaction. Various redox systems is described in o U S. Patent No. 5,154,762, the disclosure of which is expressly incorporated herein by reference.
The oxidizing agent should react with or otherwise cooperate with the reducing agent to produce free radicals capable of initiating polymerization of the ethyienically unsaturated moiety. The oxidizing agent and the reducing agent preferably are sufficiently shelf stable and free of undesirable coloration to permit their storage and use under typical dental conditions. The oxidizing agent and the reducing agent should also preferably be sufficiently soluble and present in an amount sufficient to permit an adequate free radical reaction rate. This can be evaluated by combining the ethylenically unsaturated moiety, the oxidizing agentand the reducing agent and observing whether or not a hardened mass is obtained.Suitable oxidizing agents include persulfates such as sodium, potassium, ammonium and alkyl ammonium persulfates, benzoyl peroxide, hydroperoxides such as cumene hydroperoxide, tert-butyl hydroperoxide, tert-amyl hydroperoxide and 2,5-dihydroperoxy-2,5-dimethylhexane, salts of cobalt (III) and iron (III), hydroxylamine, perboric acid and its salts, salts of a permanganate anion, and combinations thereof. Hydrogen peroxide can also be used, although it may, in some instances, interfere with the photoinitiator, if one is present. The oxidizing agent may optionally be provided in an encapsulated form as described in U.S.
PatentNo. 5,154,762.
Preferred reducing agents include amines (and preferably aromatic amines), ascorbic acid, metal complexed ascorbic acid, cobalt (Il) chloride, ferrous chloride, CA 0223~80 1998-04-22 W~ 97/18792 PCT/US96116299 ferrous sulfate, hydrazine, hydroxylamine, oxalic acid, thiourea and salts of a dithionite, thiosulfate, benzene sulfinate, or sulfite anion.
When redox initiator systems are used to photoinitiator systems, because care must be taken to keep the reducing agent from reacting with the oxidizing s agent before polymerization is desired. Generally, the use of a redox system necessitates providing the material in a two-part format. One-part dental compositions utili7ing a photoinitiator system are preferred.
For compositions that are polymerized by a cationic mechanism, suitable initiators include salts that are capable of generating cations such as the o diaryliodonium, triarylsulfonium and aryldiazonium salts. Use of electronic donors or peroxides in such systems are also useful for enhancing rate of cure and depth of cure. Simultaneous photoinitiation of cationic and free radical groups may be afforded by, for example, onium salts or organometallic compounds in combinationwith or wtihout oxidizing agents. Organometallic compounds can be selected from 5 compounds that undergo sigma bond cleavage upon photolysis. The sigma bond is usually a metal-metal bond. Examples of suitable organometallic compounds include [Co Fe(Co)~]2, Mn(CO)~0, and Mn2(CO)l(,, in combination with iodonium salts and peroxides.

The acidic component of the compositions of the present invention is provided by compounds that are monomers, oligomers or polymers of molecular weight less than I0,000 and containing at least one acidic group. The acidic group is preferably selected from oxyacids or thio-oxy acids of B, C, N, S, P. More preferably, the acidic component is a compound that is an acid of C or P. If desired, 2~ a precursor to the acid such as an acid anhydride, e.g., 4-Methacryloxyethyl Trimellitate Anhydride (4-~TA), or ester can be used in place of the acid itself, e.g., to generate the desired acid in situ. Suitable acids include, carboxylic acids, sulfonic acids, and phenols, with carboxylic acids, alkylsulfonic acids, arylsulfonic acids, and phosphonic acids being preferred.
Suitable organic acids include acetic acid, oc-chloropropionic acid, 2-acrylamido-2-methylpropane sulfonic acid, acrylic acid, benzenesulfonic acid, benzoic CA 0223~80 1998-04-22 Wo 97118792 PCr/US96/16299 acid, bromoacetic acid, I 0-camphorquinone-sulfonic acid, 1 0-camphorsulfonic acid, chloroacetic acid, citraconic acid, citric acid, dibromoacetic acid, dichloroacetic acid, di-Hema ester of 1,2,4,5 b~n7f~netetracarboxylic acid, 2,4-dinitrophenol, formic acid, fumaric acid, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, maleic acid, methacrylic acid, 2-naphtha1ene sulfonic acid, nitric acid, oxalic acid, p-nitrophenol, phenol, phosphoric acid, phosphorous acid esters (such as 2,2'-bis(a-methacryloxy-b-hydroxypropoxyphenyl) propane diphosphonate (Bis-GMA diphosphonate), dibutyl phosphite, di-2-ethyl-hexyl phosphate, di-2-ethyl-hexyl phosphite, hydroxyethyl methacrylate monophosphate, glyceryl dimethacrylate phosphate, glyceryl-2-phosphate, lo glycerylphosphoric acid, methacryloxyethyl phosphate, pentaerythritol triacrylate monophosphate, pentaerythritol trimethacrylate monophosphate, dipentaerythritol pentaacrylate monophosphate, and dipentaerythritol pentamethacrylate monophosphate), pivalic acid, propionic acid, sulfuric acid, toluene sulfonic acid, tribromoacetic acid, trichloroacetic acid, trifluoroacetic acid, trifluorometh~n~ lfonic acid, and trihydroxybenzoic acid. Mixtures of such acids can be used if desired.Preferred acids are capable of complexing ~,vith a reactive glass.
The mixtures can if necessary also contain other compounds that although they contain acid groups, their salts, or their reactive derivative groups, do not contain polymerizable groups. Preferred in this case are multibasic acids such as tartaric, citric, mellitic, polycarboxylic, polyphosphoric, polyphosphonic, or polysulfonic acids along with chelating agents such as ethylenediamine-tetraacetic acid, and especially their salts.

Particularly preferred compositions of the present invention are those wherein at }east a portion of the polymerizable component and at least a portion of the acidic component of the composition are provided by the same chemical compound. Examples of such compounds are monomers, oligomers or polymers of molecular weight less than 10,000 and containing at least one acidic groups and at least one polymerizable group. Preferably, these compounds hav a molecular weight of between about 300-5000, and more preferably between about 300-]000. The CA 0223~80 1998-04-22 acidic group can be oxyacids or thio-oxy acids of B, C, N, S, P. Preferably it is an acid of C or P.
These preferred compounds are defined by the structure (P)p--(Q)q--(R) r-where P = backbone with acidic functionality Q= backbone with a curable group, e.g. acrylate, methacrylate, epoxy etc R= backbone of a non-reactive modifying unit p > 1, c~> 1, and r=Oormore.

Especially preferable acid groups are carboxylic acids, sulfonic acids, o phoshoric acids, phosphonic acids, and boric acids, the salts of the foregoing acids or precursors of the foregoing acids that are easily converted to these acids inconditions encountered durin;, a dental restorative procedure. Examples of such compounds are acryloyl or methacryloyl substituted polycarboxylic acids, phosphoric acid esters of hydroxyethyl methacrylate, hydroxy propyl meth~crylate, acrylates and methacrylates of pentaerythritol dimethacrylate dipentaerythritol penta-acryalte and glyceroldimethacrylate.
Examples of such preferred compounds include the aliphatic carboxy compounds, such as acrylic acid, methacrylic acid, maleic acid, fumaric acid, itaconic acid, crotonic acid, aconitic acid, glutaconic acid, mesaconic, citraconic acid, acid, tiglicinic acid, 2-chloroacrylic acid, 3-chloroacrylic acid, 2-bromoacrylic acid, I-methacryloyl malonic acid, I-acryloyl malic acid, N-methacryloyl and N-acryloyl derivatives of amino acids, and acids such as tartaric acid, citric acid, malic acid that have been further functionalized with an ethylenic functionality. For example, citric acid may be ethylenically functionalized by substituting with anacryloyl or methacryloyl functionality. These polymerizable groups may be attached directly to the acid containing compound, or may be optionally attached through a linking group. Preferred linking groups include substituted or unsubstituted alkyl, alkoxyalkyl, aryl, aryloxyalkyl, alkoxyaryl, aralkyl or alkaryl groups. Particularly preferred linking groups comprise an ester functionality and most particularly preferred linking groups comprise an amide functionality.

CA 0223~80 1998-04-22 W~ 97/18792 PCT/US96/16299 Other preferred compounds are the aromatic carboxy compounds, such as benzoic acid, and acryloyl or methacryloyl derivatives of salicyclie aeid, trimellitic acid, phthalic acid,and the like.
Reaetive fillers may be included eompositions of the present invention, s which may or may not have the property of releasing fluoride. Such fillers include those that are commonly used with ionomers to form ionomer eements. Examples of suitable reaetive fillers include metal oxides sueh as zinc oxide and magnesium oxide, and ion-leaehable glasses, e.g., as deseribed in U.S. Pat. Nos. 3,655,605, 3,814,717, 4,143,018, 4,209,434, 4,360,605 and 4,376,83~. Sueh reaetive fillers 0 may be incorporated to modify the handling characteristics or to affect the setting properties of the ultimate compostion.
The reactive filler is preferably a finely divided reactive filler. The filler should be sufficiently finely-divided so that it can be conveniently mixed with the other ingredients and used in the mouth. Preferred average particle diameters for the filler are about 0.2 to about 15 micrometers, more preferably about I to 10 micrometers, as measured using, for example, a sedimentation analyzer.
Preferred reactive fillers are acid-reactive. Suitable acid-reactive fillers include metal oxides, metal salts and glasses. Preferred metal oxides include barium oxide, calcium oxide, magnesium oxide and zinc oxide. Preferred metal salts include salts of multivalent cations, for example aluminum acetate, ~luminllm chloride, calcium ehloride, magnesium chloride, zinc ehloride, aluminllm nitrate, barium nitrate, ealeium nitrate, magnesium nitrate, strontium nitrate and ealeium fluoroborate. Preferred glasses inelude borate glasses, phosphate glasses and fluoroaluminosilieate glasses. Fillers that are reactive as deseribed above provide 2s exeellent handling properties and final composition properties because, when reacted, they impart a gel or partial gel structure to the material.
Most preferred of the reactive fillers are those that release fluoride. Fluoridereleasing glasses, in addition to providing good handling and final composition properties as discussed above, provide the benefit of long-term release of fluoride in use, for example in the oral cavity. Fluoroaluminosilicate glasses are particularly preferred. Suitable reactive fillers are also available from a variety of commercial CA 0223~80 1998-04-22 sources familiar to those skilled in the art. For example, suitable fillers can be obtained from a number of commercially available glass ionomer cements, such as "GC Fuji LC" and "Kerr XR" ionomer cement. Mixtures of fillers can be used if desired.
If desired, the reactive filler can be subjected to a surface treatment.
Suitable surface treatments include acid washing, treatment with phosphates, treatment with chelating agents such as tartaric acid, treatment with a silane or silanol coupling agent. Parlicularly preferred reactive fillers are silanol treated fluoroaluminosilicate glass fillers, as described in U.S. Patent Number 5,332,429 the o disclosure of which is expressly incorporated by reference herein.
Non-reactive fillers may be selected from one or more of any material suitable for incorporation in compositions used for medical applications, such as fillers currently used in dental restorative compositions and the like. The filler is finely divided and preferably has a maximum particle diameter less than about 50micrometers and an average particle diameter less than about ]0 micrometers. Thefiller can have a unimodal or polymodal (e.g., bimodal) particle size distribution.
The filler can be an inorganic material. It can also be a crosslinked organic material that is insoluble in the polymerizable resin, and is optionally filled with inorganic filler. The filler should in any event be non-toxic and suitable for use in the mouth.
The filler can be radiopaque, radiolucent or non-radiopaque.
Examples of suitable non-reactive inorganic fillers are naturally-occurring or synthetic materials such as quartz, nitrides (e.g., silicon nitride), glasses derived from, for example Ce, Sb, Sn, Zr, Sr, Ba and Al, colloidal silica, feldspar, borosilicate glass, kaolin, talc, titania, and zinc glass; low Mohs hardness fillers such as those described in U.S. Patent No. 4,695,251; and submicron silica particles (e.g., pyrogenic silicas such as the "Aerosil" Series "OX 50", " 130", " 150" and "200" silicas sold by Degussa and "Cab-O-Sil M5" silica sold by Cabot Corp.).
Examples of suitable non-reactive organic filler particles include filled or unfilled pulverized polycarbonates, polyepoxides, and the like. Preferred non-reactive filler CA 0223~80 1998-04-22 W(~ 97/18792 PCT/US96/16299 particles are quartz, submicron silica, and non-vitreous microparticles of the type described in U.S. Patent ~o. 4,503,169. Mixtures ofthese non-reactive fillers are also contemplated, as well as combination fillers made from organic and inorganic materials.
s Preferably the surface of the filler particles is treated with a coupling agent in order to enhance the bond between the filler and the polymerizable resin. Theuse of suitable coupling agents include gamma-methacryloxypropyltrimethoxysilane, gamma-mercaptopropyltriethoxysilane, gamma-aminopropyltrimethoxysilane, and the like.

If desired, the compositions of the invention can contain adjuvants such as cosolvents, pigments, inhibitors, accelerators, viscosity modifiers, surfactants, rheology modifiers, colorants, medicaments and other ingredients that will be apparent to those skilled in the art. Optionally, the compositions may contain stabilizers. The incorporation of stabilizers serves to further improve the color stability of paste:paste compositions. Suitable stabilizers include oxalic acid,sodium metabisulfite, metaphosphoric acid, sodium bisulfite, sodium thiosulfate, and combinations thereof. Oxalic acid and sodium metabisulfite are preferred stabilizers.
Cosolvents useful in the present invention include, but are not limited to, low molecular weight organic solvents. The word "cosolvent", as used herein refers to a material that aids in the disso1ution of materials in the composition, in order to form a homogeneous composition. Examples of suitable cosolvents include ethanol, propanol, and glycerol.
2s The compositions of this invention can be used in a variety of applications in the dental or medical fields in which a materiai is desired that will adhere well to the surrounding tooth or bone structure. For instance, these compositions can be used as dental restoratives, liners, bases, cements, sealants and as dental or orthodontic adhesives.

-2 l-CA 0223~80 1998-04-22 The present compositions are preferably provided initially as a one-part paste composition. For purposes of the present invention, a paste is defined as a material wherein the inelastic modules is less than the elastic modulus of the material. Preferably, the paste has a viscosity between about 5 I X 102 and I X 10~ Cps. More preferably, the paste has a viscosity between about I X ] o7 and I X 109 Cps. Viscosity is measured using a rheometer at a shear rate between 0.01 and 0.1 sec ' at about 25~C. A preferred test protocol is to utilize a Bohlin CSSO controlled stress rheometer (Metric Group, Inc., Bohlin Instruments Division, Cranbury, NJ) with 20 mm parallel plates and a gap of 2mm.o The stress is ramped from I Pascal up to a stress sufficient to reach a shear rate of approximatelyO.I sec~'.

The present invention will be further understood in view of the following examples which are merely illustrative and not meant to limit the scope of the 5 invention. Unless otherwise indicated, all parts and percentages are by weight.

Water Uptake Test Water uptake was measured by forming each composition into disks 20 mm in diameter and I mm thick. Both sides of each disk were covered with 20 polyethylene terephthalate ("PET") film and light cured for 30 seconds on each side using two oppositely-disposed 3MTM VisiluxTM 2 Visible Light Curing Units with about a I cm distance between the output end of the light guide and the sample.
The film was then removed and the exposed samples allowed to cure for I hour at 37~C/95% relative humidity ("RH"). Each disk was weighed and placed in a glass 25 jar to which was added 25 mL of deionized water. The sample was maintained at 37~C for a specified time period.
At the specified time~ the sample was removed from the jar, the superficial water was removed usin~ a facial tissue or cotton and the sample was immediatelyweighed. The weight was recorded and the sample was returned to the water in the30 sample jar. At periodic designated intervals, the above procedure was repeated and the sample weight recorded. At each specified time interval, water uptake for 3 CA 0223~80 1998-04-22 WO 97/t8792 PCT/US96/16299 samples of each composition was measured and the average reported in grams per 100 grams of cured composition.

The present invention will be further understood in view of the following examples which are merely illustrative and not meant to limit the scope of the invention. Unless otherwise indicated, all parts and percentages are by weight and all mo~ecular weights are weight average molecular weights.

PREPARATORY EXAMPLE I
o Trezlted Fluoro:lluminosilic~te Glass The ingredients set out below in TABLE l were mixed, melted in an arc furnace at about 1350-1450~C, poured from the furnace in a thin stream and quenched using chilled rollers to provide an amorphous single-phase fluoroaluminosilicateglass.

1ngredient P~rts sio2 37 AIF-~ 23 SrCO~ 20 Al20~ 1 0 Na~AlFG 6 The glass was ball-milled to provide a pulverized frit with a surface area of 2.5-3.2 m2/g measured using the Brunauer, Emmet and Teller (BET) method.
A silanol solution was prepared by mixing together 2.4 parts gamma-methacryloxypropyl trimethoxysilane ("A-174", Union Carbide Corp.), 12.6 parts methanol, 36.5 parts water and 0.33 parts acetic acid. Tlle mixture was stirred magnetically for 60 minutes at ambient temperature, added to 60.8 parts ofthe glass powder and slurried for 30 minutes at ambient temperature. The slurry was poured CA 0223~80 1998-04-22 W~ 97/18792 PCT/US96/16299 into a plastic-lined tray and dried for 10 hours at 80~C. The silanol treated dried powder was sieved through a 60 micrometer mesh screen.

s Treated OX-~0 A-174 (3.7gj was added with stirring to 50~ of deionized water acidified to pH 3-3.3 by dropwise addition of trifluoroacetic acid. The resultant mixture wasstirred at about 25~C for 1 hour at which time 95g of OX-50 were added to the mixture with continued stirring for 4 hours. The slurry was poured into a plastic-0 lined tray and dried at 35~C for 36 hours. The silanol treated dried powder was sieved throuah a 74 micrometer mesh screen.

PREPARATORY EXAMPL~ 3 Treated Zirconia:Silica Filler 25.5 Parts silica sol ~"LUDOX" LS, E.I. duPont de Nemours & Co.) were acidified by the rapid addition of 0.255 parts concentrated nitric acid. In a separate vessel, 12.9 parts ion-exchanged zirconyl acetate (Magnesium Elecktron Inc.) were diluted with 20 parts deionized water and the resultant solution acidified with 0.255 parts concentrated nitric acid. The silica sol was pumped into the stirred zirconyl acetate solution and mixed for one hour while filterin~ the stirred mixture through "CUNO" 5 micrometer and 1 micrometer filters (Commercial Intertech Corp.). The stirred, filtered mixture was further filtered though a 1 micrometer "HYTREX"
filter (Osmonics, Inc.) followed by a 0.22 micrometer "BALSTRON" filter (BalstonInc.). The filtrate was poured into trays to a depth of about 25 mm and dried at65~C in a forced air oven for about 24 hours. The resultant dried material was removed from the oven and tumbled through a rotary tube furnace (Harper Furnace Corporation) preheated to 600~C to provide 21 parts of calcined microparticles.
The calcined microparticles were comminuted in a tumbling ball mill until all of the microparticles were less than 10 micrometers in particle diameter. 0.3 Part portions of the milled microparticles were placed in ceramic saggers and fired in an electric kiln (Harper Furnace Corporation) in air at 825~C for I hour. The fired CA 0223~80 1998-04-22 microparticles were allowed to cool in air-. The cooled microparticles were slurried in hydrolyzed A-174 silane at a ratio of 1 1 . 1 parts silane to 100 parts microparticles, dried in a forced air oven and screened through a 74 micrometer mesh screen.

Preparation of Polymerizable Component "A1"
Citric acid (400g) was dissolved in 2 L of tetrahydrofuran ("THF") in a reaction vessel fitted with a mechanical stirrer, condenser, addition funnel and air inlet tube. To the resultant homogenous solution was added 0.52g butylated o hydroxytoluene ("BHT"), 0. 5g of triphenylantimony ("TPS") and 0.98g dibutyltin dilaurate ("DBTDL"). Dry air was introduced into the reaction mixture through the inlet tube. 2-lsocyanatoethyl methacrylate ("IEM", 161.5g, 1.04 moles) was addeddropwise through the addition funnel so as to maintain the reaction temperature at about 40~C. The reaction was followed by infrared spectroscopy ("IR"). After a]ls the IEM had been added and the IR spectrum no longer showed the presence of isocyanate group, the solvent was removed under vacuum from the reaction mixtureand the resultant viscous liquid was dried. Nuclear magnetic resonance spectroscopy ("NMR") confirmed the presence of added methacrylate functionalities and the retention of carboxy groups.

Prepar7~tion Or Polymeriz:lble Component '~A2"
Polyacrylic acid (8.64g, molecular weight 2,000) and 75 mL T~ were added to a reaction flask e~uipped with a stirrer, condenser, addition funnel and air inlet tube. After stirring at a bath temperature of 50-70~C for 2-3 hours, a cloudy solution was obtained. The temperature of the bath was maintained at 40-50~C anda solution containing 0.093g BHT, 0.093g TPS and 0.64g DBTDL in 5 mL of dry THF was added to the reaction mixture. IEM (9.3g) was added dropwise through the addition funnel over a period of 1 hour. The mixture was allowed to stir until 30 the IR spectrum showed complete disappearance of the isocyanate band at which CA 0223~80 1998-04-22 time the reaction mixture was poured into petroleum ether. A white, solid polymer precipitated and was isolated by filtration, washed and dried under vacuum.

Prep~ration Or Met~l Fluorocomplexes Metal fluorocomplexes Dl-DXI were independently prepared by dissolving the quantity of the carboxylic acid complexing agent set out in TABLE 2 in water.
For Complex nos. DI-DIX, zinc fluoride powder was slurried with each aqueous solution for about one-half hour, after which time the slurry was poured into a o shallow tray and dried at 55~C overnight. Each complex was then sieved through a 100 micrometer mesh screen to provide a free-flowing powder.
Complex nos. DX and DXI were prepared as detailed for the zinc complexes except that 20g aluminum trifluoride and 20g zirconium tetrafluoride respectively were substituted for the zinc fluoride and the resultant complexes were sieved through a 74 micrometer mesh screen. Complex no. DXII was prepared by mixing the zinc fluoride with a mixture of acetoacetoxyethylmethacrylate ("AAEM"; Eastman Chemicals, TN), ~ 0~ ethanol and Sg deionized water. The resultant mixture was allowed to stir for 12 hours at ambient temperature. The solid was then collected by filtration and dried under vacuum at 45~C for 12 hours. The dried solid was crushed with a mortar and pestle to yield a fine powder of Complex no. DXII.

CA 0223~80 1998-04-22 W(~ 97/18792 PCT/US96/16299 ComplexNo. Complexing A8ent Water zr~2 Type Amount (g)(g) (g DI Tartaric acid 20 20 20 DII Tartaric acid 20 20 80 DIII Tartaric acid 30 20 20 DIV Tartaric acid 20 20 30 DV N-methacryloyl glutamic acid 20 20 20 DVI Itaconic acid 20 300 80 DVII Itaconic acid 20 300 40 DVIIl Itaconic acid 25 350 25 DIX Itaconic acid 30 380 20 DX Tartaric acid 20 20 ---DXI Tartaric acid 20 20 ---Prep:lration orHydrophilic Component "Cl"
A glass reaction flask equipped with magnetic stirrer, two addition funnels connected to peristaltic pumps, thermometer, gas inlet tube and reflux condenserwas charged with 300 mL of dry THF. One addition funnel was charged with a solution of ethylmethacrylate (18.24g; 0.16 moles~, acrylic acid (28.8g; 0.4 moles), N-vinylpyrrolidone ("NVP"; 26.98g; 0.24 moles) and THF to a volume of 200 mL.
The second addition funnel was charged with a solution of 0.82g azobisisobutyronitrile ("A~BN") in 60 mL THF. Both solutions were purged with dry nitrogen for I ~ minutes. The reaction vessel was heated to 60~C and the charges from both addition funnels were added via the peristaltic pumps over a course of 6 hours. After addition was complete, the reaction was stirred at 60~Covernight. Then 300 rnL of dry dimethylformamide ("DMF") was added to the reaction vessel and the temperature lowered to 40~C. BHT (0.094g), TPS (0.094g) and DBTDL (0.644g) were added to the reaction mixture and the nitrogen in the inlet tube was switched to dry air. A solution of IEM (18.6g; 0.12 mole) in 45 rnL
TH~ was added dropwise to the reaction mixture over 2 hours. The reaction -3n-CA 0223~80 1998-04-22 WO 97/18792 P~T/US96tl6299 mixture was then allowed to stir at 4()~C -for an additional hour. The solvents were partially removed under vacuum to reduce the volume to about one-half of the original and the resultant solution poured into ethyl acetate. The precipitated polymer was collected by filtration, washed and dried under vacuum.

Preparation of Hydrophilic Con ponellt "C2"
A glass reaction flask equipped with magnetic stirrer, two addition funnels connected to peristaltic pumps, thermometer, gas inlet tube and reflux condenserwas charged with 500 mL of dry THF. One addition fiJnnel was charged with a solution of ethylmethacrylate (34.25 g; 0.3 moles), acrylic acid (50 4g; 0.7 moles) and T~ to a volume of 200 mL. The second addition funnel was charged with a solution of 0.82g AIBN in 60 mL THF. The solutions were purged with dry nitrogen for 15 minutes. The reaction vessel was heated to 60~C and the charges s from both addition fi~nnels were added via the peristaltic pumps over a course of 6 hours. After addition was complete, the reaction was stirred at 60~C overnight.
Then the reaction temperature was lowered to 35~C. BHT (0.165g), TPS (0.165g) and DBTDL ( 1.1 3g) were added to the reaction mixture and the nitrogen in the inlet tube was switched to dry air. A solution of IEM (32.55g; 0.21 moles) in 200 20 rnL T~ was added dropwise to the reaction mixture over 2 hours. The reaction mixture was then allowed to stir at 35-40~C for an additional hour. The solventswere partially removed under vacuum to reduce the volume to about one-third of the original and the resultant solution poured into ethyl acetate. The precipitated polymer was collected by filtration, washed and dried in under vacuum.
E~AMPLE 6 PrepArAtion of Hydrophil~c Component "C3"
A glass reaction flask equipped with magnetic stirrer, two addition funnels connected to peristaltic pumps, thermometer, gas inlet tube and reflux condenser30 was charged with 500 mL of dry THF. One addition funnel was charged with a solution of ethylmethacrylate (17.12g; 0.15 moles), acrylic acid (50.4g; 0.7 moles), CA 0223~80 1998-04-22 wo 97118792 PCT/US96/16299 methacrylic acid (12.9g; 0.15 moles) and THF to a volume of 200 mL. The second addition funnel was charged with a solution of 0.82g of AIBN in 60 mL THF. Both solutions were purged with dry nitrogen for 15 minutes. The reaction vessel was heated to 60~C and the charges from the addition funnels were added via the peristaltic pumps over a course of 6 hours. After the addition was complete, thereaction was stirred at 60~C overnight. Then the reaction temperature was lowered to 35~C. BHT (0.165g), TPS (0.165g) and DBTDL (1.13~~,) were added to the reaction mixture. The nitrogen in the inlet tube was switched to dry air. A solution of IEM (32.55g, 0.21 mole) in 200mL THF was added dropwise to the reaction o mixture over 2 hours. The mixture was then allowed to stir at 35-40~C for anadditional hour. The solvents were partially removed under vacuum to reduce the volume to about one-third of the original and the resultant solution poured intoethyl acetate. The precipitated polymer was collected by filtration, washed and dried under vacuum.

Prep~ration of Hydrophilic Componellt '~C4"
A glass reaction flask equipped with magnetic stirrer, two addition funnels connected to peristaltic pumps, thermometer, gas inlet tube and reflux condenserwas charged with 210 mL of dry THF. One addition funnel was charged with a solution of acrylic acid (50.4g; 0.7 moles), NVP (33.3g, 0.3 moles) and T~ to a volume of 250 mL. The second addition funnel was charged with a solution of 0.82g AIBN in 60 mL THF. Both solutions were purged with dry nitrogen for 15 minutes. The reaction vessel was heated to 60~C and the charges from both addition funnels were added via the peristaltic pumps over a course of 4 hours.
After addition was complete, 22 mL of dry DMF was added and the reaction was stirred at 60~C overnight. The reaction temperature was then lowered to 35~C.
BHT (0.15g), TPS (0.15g) and DBTDL (1.03g) were added to the reaction mixture and the nitrogen in the inlet tube was switched to dry air. A solution of IEM
(32.55g; 0.21 mole) in 200 mL THF was added dropwise to the reaction mixture over 2 hours. The reaction mixture was then allowed to stir at 35-40~C for an CA 0223~80 1998-04-22 additional 24 hours. The solvents were partially removed under vacuum to reduce the volume to about one-third of the original and the resultant solution poured into ethyl acetate. The precipitated polymer was collected by filtration, washed and dried under vacuum.

Pastes were prepared by mixing the ingredients shown in TABLE 3. The specified quantities of polymerizable component Al of EXAMPLE 1, glycerol dimethacrylate ("GDMA"; Rohm Tech, Inc., Malden, MA) and I . I g or no poly(N-0 vinyl pyrrolidone) ("PVP"; International Specialty Products, Wayne, NJ) werethoroughly mixed with 0.095g camphor~uinone ("CPQ") and 0.37g ethyl(4-dimethylamino)benzoate ("EDMAB'~). A portion of the resultant mixture was combined with the specified amounts of the glass of PREPARATORY EXAMPLE
1 ("PEI") + 2% OX-50 of PREPAR~TORY EXAMPLE 2 ("PE2") and 4g or no 5 Complex D~ from TABLE 2. The pastes were either hand-mixed or mechanically mixed using a double planetary mixer.
~ABLE 3 Run Component Al GDMA PVP Glass of PEI + 2% ComplexDI
No. of Ex. 1 (g) (g) (~)OX-50 of PE2 (g) of Ex. 3 (g) 7.0 13.9 1.1 74.0 4 2 7.0 13.9 1.1 78.0 0 3 7.3 14.7 0 74.0 4

4 7.3 14.7 0 78.0 0 Water uptake of each composition in TABLE 3 as well as that of DyractTM
20 Light Cured Compomer ("Dyract"; Dentsply International Inc.) was measured on day 7 and day 14 using the procedure described in the Water Uptake Test. The results are set out in TABLE 4.
Incremental fluoride release of each composition was measured after 3 days and compared with that of Dyract. Disks of each composition were prepared and 2s cured as described for the Water Uptake Test. Each disk was placed in a jar containing 25 mL of deionized water at 37~C

"

CA 0223~80 1998-04-22 W ~ 97/18792 PCT~US96/16299 A fluoride-selective electrode, Orion Model 96-09-00 (from Orion Research Inc., Cambridge, MA) was used to quantify the amount of fluoride ion released from the sample in the water. The electrode was calibrated using Fluoride Activity Standards #940907 and #040908, a 100 parts per million ("ppm") and a 10 pprn

5 respectively, fluoride standard fluid ~both from Orion Research Inc.).
For the measurement of fluoride ions released into the water, 10 mL of the sample solution was transferred on the day specified to a 60 mL beaker and 10 mLof TISAB solution (total ionic strength adjustment buffer; Orion Research Inc., Cambridge, MA) was added to the beaker. The contents were mixed for 10 0 seconds. The calibrated fluoride-selective electrode was placed in the solution and the ppm F- were recorded and converted to micro~rams of F per cmZ of the cured disk The residual liquid was then removed from the sample jar and replaced with a fresh 25 mL quantity of deionized water. The sample jar was transferred to a 37~C
oven for the specified interval in days, at which time, the sample )ar was removed 5 from the oven and the ppm F- released during that interval were measured as described above. Micrograms of F per cm2 of the cured disk were again calculatedand these values were reported as a function of time of storage in the water.
Fluoride release values for 3 samples of each composition were measured and the average recorded. The results are set out in TABLE 4 Run No. Water Uptake in g/lOOg of Cured ~g/cm2 F- Released Composition Measured on Day After 3 Days 1.7 1.9 43.38 2 1 .9 2. 1 26.03 3 1.5 1.8 34.70 4 1.6 1.9 19.52 Dyract I.1 1.2 2.2 The data in TABLE 4 show that the compositions of Run nos. 1-4 of the invention in general took up significantly more water than a commercial one-paste 25 fluoride releasing material, Dyract, and correspondingly released much higherquantities of fluoride. Furthermore, the incremental fluoride release data show that -3~-CA 0223~80 1998-04-22 WO 97/18792 PCT/~JS96/16299 although a fluoroaluminosilicate glass in a hydrophilic resin matrix exhibited enhanced fluoride release compared to Dyract, the addition of a metallo-fluorocomplex to the compositions of Run nos. I and 3 substantially increased the fluoride release.

Pastes were prepared by mixing the ingredients shown in TABLE 5. The specified quantities of polymerizable component A I of EXAMPLE 1, GDMA and component C were thoroughly mixed with CPQ at a concentration of 0.42 patts per hundred and EDMAB at a concentration of ~.65 parts per hundred. A portion of o the resultant mixture was combined with the specified amounts ofthe glass of PEI+
2% OX-50 of PE2 and the Complex of EXAMPLE 3 as outlined in TABLE 5. The pastes were either hand-mixed or mechanically mixed using a double planetary mlxer.
For determination of compressive strength ("CS") and diametral tensile 5 strength ("DTS"), the composition of each run no. was packed into a 4 mm inside diameter glass tube, capped with silicone rubber plugs and axially compressed atabout 0.28 MPa for 15 minutes, then light cured for 80 seconds by exposure to two oppositely-disposed Visilux units. Each sample was then irradiated for 30 seconds using a Dentacolor XS unit (Kulzer). Cured samples were cut on a diamond saw to 20 form cylindrical plugs 8 mm long for measurement of CS and 2 mm long for measurement of DTS. The plugs were stored in distilled water at 37~C for 24 hours.
CS and DTS values for each composition were measured according to ADA
("American Dental Association") specification No. 9 and ADA specification No. 27tespectively.

-3~-CA 0223ss80 1998-04-22 RunComponentAl GDMA ComponentC GiassofPEI~ ComplexofEx.3 CS DTS
No. E~;. 1 (g) (L~)E.~. Amount(~) 2% OX-50 ~O Arnount(g) (MPa) (MPa) of PE2( ~ ) 7.15 14.30 4 0.5S 76 Di 2 346 44.8 7 7 00 13.90 ~ 1.] 76 Dl 7 367 54.8 3 7.1~ 14.30 j 0.55 76 Dl '' 376 ~0.~
4 7.1~ 14.30 6 0.55 76 Dl 7 37~ 55.5 7.00 13.90 6 1.10 76 DV 7 28~ 37.6

6 7.0() 13.90 PVP~1.10 76 Dl 7 368 57.7

7 7.00 13.90 PVP1.10 74 Dl 4 341 47.7

8 7.00 13.90 PVP1.10 72 Dl 6 348 43.6

9 7.00 13.90 P~P1.10 76 DV 2 338 47.6 7.00 13.90 PVP1.10 77 DV 6 336 34.5 11 700 13.90 PVP1.10 77 Dl 6 34~ 52.3 17 7.00 13.90 ~ I .10 76 Dl 7 37~ 50.7 13 7 00 14.0 7 0.5~ 78 Dl 4 290 4~.3 * Poly(N-vinyl pvrrolidone); ~nternational Specialty Products~ Wayne, NJ.

The CS and DTS ofthe paste compositions of ~un nos 1-13 were superior to the mechanical properties of two commercial fluoride releasin~ materials, 3M~M
VitremerTM Glass lonomer Core Build-up Restorative ("Vitremer'', 3M) with a CS
of 214 MPa and Dyract with a CS of 267 MPa Water uptake of the compositions of Run nos. 7, 4 and 6 in TABLE ~ as well as thal of Dvract was measured on days ~. I 7 and 7~ usin~ the procedure described in the ~hater Upta~e Test Tile resulls are set OUt in TABLE 6.
Incremental fluoride release of the compositions of Run nos. 1, 2, 6, 9 and

10 as weli as that of Dyract and Vitremer was measured on days 4, ~, 14, 2 I and 27 using the procedure described in EXAMPLE ~. The resuits are set out in TABLE 6.

, (, Run l~io. ~ cr Upl~ike In L~ u~ of Cured Incrclllc~ l F Rcleasc in ~ /CIll- Measured on D~
Composltioll Mcasurcd on n~,~
1~ 2X I ~ 1~ 21 27 28. - 17.(, 3~.~25.3 2~.8 2 I.fi2.0' 2 ~7 17. 1 1 I.~ 20.:~20.~ 19.3 I .6 ~ 2.0'~ 2.~6 ---------- --------G 1 ( 2.17 2.~ 1 16.-23 ~ 5 21.' 2'.~20.4 1(~ --- --- --- ~2.1 31 X4X.I 4".13~fi Dvr~c~ ' I 0~ 1.2(, X I 10 ~13 ~ 13.116.'3 Vitremcr --- --- -~ 17 (~ 3~ 27.

The data in TABLE 6 show Ihat composilions of the invention exhibited hi~her water uptake and higher fluoride release compared to a commercial one-paste fluoride releasin(~ malerial. Dvracl The rate of fluoride release was comparable to a water-based powder.liquid ~lass ionomer. ~itremer Three resin mixtures were prepared by mixing together 7.0~ polymerizable 0 component Al of EXAMPLE 1, 1~.9~ GDMA, 1.1~ P~'P, 0.095~ CPQ and 0.37g EDMAB to provide a homo~eneous mixture. Pastes were then compounded by adding to each mixture 74g of a blend of the ~lass of PE I . ~~~ OX-50 of PE2 and 4.0g of the desi_nated Complex from TABLE ~. All three resultant pastes were stable at room temperature whereas control pasles prepared uShlg untreated zinc fluoride showed substantial thickenin(~ on standino and became crumblv after 24 hours.
Usin~g the procedure described in EXAMPLE 8, incremental fluoride release of the compositions of Run nos. 1-3 was measured and compared with that of Dyract and Vitremer. The results are set out in TABLE 7 Run No. Comple~; from Incremental F Released in ll~cm2 Measured on Day Table ~ I 7 3 4 ~ 6 7 14 21 Dll 79.-~ 2X.2() 3~ X.()x 17 3~ 6 ~.6~ 3~ 20.24 Dl 7g.~,2().2~ 21.6~13.()1 9~ .1? 7.23 27.83 17.21 3 DVII 79.~ 36.1~ 26.7~ 2().~ 16.6~ l 10.8~ 44.:~4 22.27 Dyract --- 7.9~ 1.9~ 2.0' 1.37 2.46 1.4~ 1.4~ 4.~ 3.54 Vitremer --- 6~.07 16.6, 13.011().l? ~.6X 6.~1 j.06 27.8~ 16.70 The incremental fluoride release results hl TABLE 7 show that paste compositions of the invention containin~ a hydrophiiic matrix showed much higher~ fluoride release than a commercial one-paste fluoride-releasin(~ material Dyract. The amount of fluoride released was comparable to a water-based powder:liquid ~lass ionomer Vitremer EXAMPLE Il Four resin mixtures were prepared by mixin~ 7.3~ polvmerizable component Al of EXAMP~E 1~ 14.6~, GDMA~ 0.095~ CPQ and 0.~7~ EDMAB
to provide a homo-~eneous mixture. Pastes were then compounded b~ adding to each mixture the filler type and amount and '.Og or none of Complex D ] from TABLE 2 as set out in TABLE 8.
I~ Cumulative fluoride release was measured on disks of she compositions prepared and cured as described for the Water Uptake Tes~ Each disk was placed in a jar of phosphate buffer prepared by mixin~ 0.7n KH~PO~ and 0.71~ I~ia2HPO~
in I liter of deionized water to provide a 0.01 M solution havin~ a pH of 6.8-7.0 at 37~C.
A calibrated fluoride-selective electrode as described for incremental fluoride release in EXAMPLE 8 was placed in the buffer solution containin ~ the disk on the days desiPnated in TABLE 8 anA ppm F recorded Micro_rams of F
per cm2 of the cured dis~ were then calculated and these values were reported as a function of time of stora(~e in the bufl'er. Fluoride release values for 3 samples of 2~ each composition were measured and the avera~e reported in TABLE 8 The compoSition of Run no. 4 showed no measurable fluoride release.

Run FillerComplex Dl Cumulalive F- Release in No. Type Amount(g) Ex. 3(~cm2 Measured on Day Glass of PEI + 2% OX-SC) of PE' 78 0 1 30 4 2 Glass of PEl ~ 2% OX-50 of PE276 2 ~ 45 9 3 PREPARATORY EXAMPLE 3 76 ~ 1 20 3 The data in TABLE 8 show that the incorporation of a fluorocomplex ~ increased the fluoride release of the compositions of Run nos. ~ and 3. This effect was exhibited even when no other acid-reactive filler was incorporated into the system.
Thus both Run nos. 3 and 4 contained a non-acid reactive filler~ but onlv Run no. ,, which contained a fluorocomplex salt. showed appreciable fluoride release lo EXAMPLE 12 A stocl~ liguid was made up by blendin~ 719~ polYmerizable component A1 of EXAMPLE 1, 400g~ GDMA, 30~ PVP, ] lo EDMAB and '.8~ CPQ. Six pastes were then forrnulated usin~ 12.6g ofthe stock liquid 43.8~, ofthe _lass of PE1~ 1.2 g of OX-50 of PE~ and 2 4 ~ of the Compiex of EXAMPLE, identified in TABLE 9. The CS and DTS of the compositions were measured accordin(~ to the procedure detailed in EXAMPLE 9 ~un. No.¦ Compiex of Ex. 3 CS (MPa) DTS (MPa) Dl 324 53.8 2 DII1 324 51.7 3 DTV 331 51.0 4 DVII 310 53.1 DVIII 3~3 48., 6 DIX 317 55.2 The data in TABLE 9 show that one-paste compositions containing a 20 hydrophiiic resin matrix and zincfluorocompiexes provided cured specimens exhibitin~ excellent mechanical properties.

CA 02235580 l998-04-22 WCj 97/18792 PCT/IJS96/16299 E,~AMPLE 13 Two pastes were formulated usin~ 12.~g ofthe stocl; liquid of EXAMPLE 12, 43.8g ofthe glass of PEI, 1.2g of OX-50 of PE2 and 2.4~ ofthe aluminumfluorocomplex or tlle zirconiumfluorocomplex of EXAMPLE, . A third paste was formulated as described for the first two pastes. except that 12.6g ofthe stock liquid of EXAMPLE 12 was used and the fluorocomplex was DXII. CS and DTS was measured according to the procedure described h1 EXAMPLE 9 and incremental fluoride release was measured according to the procedure detaiied inl() EXAMPLE 8.

TABLE. lO
Run ¦ Complex of CS DTS lncremental F Reiease in tl~cm2 Measured on Day No. ¦ Ex. 3 (MPa)(M~'a) ~ 7 DX 304 52.2 24.5 4.8 2 DXI 312 51 7 44.8 14.2 3 DXII 34~ 50.3 88.9 13. l The data in TABLE l 0 show additional examples of pastes containing a 1~ hydrophilic matrix and various metallo-fluorocomplexes. These pastes exhibited excellent mechanical properites as well as very high fluoride rele~se.

EXAMPI,E 1 1 A stock solution was prepared bv dissolYing 40g GDMA, 3g PVP. 1. Ig 2() benzoyl peroxide and 0.088g BHT. Then 8.4g ofthe stock solu~ion was combined with 4.2g of the polymerizable component A 1 of EXAMPLE I . The resulting homogeneous liquid was combined with 43.8g ofthe glass of PE1, 1.2g OX-50 of PE2 and 2.4g of Complex Dl of EXAMPLE 3 to provide a Paste "A"
Three Paste "B" formulations were prepared bv combining 43.8g of the glass 2~ of PEl, 1.2g OX-50 of PE2 and 2.4g of Complex Dl of EXAMPLE 3 with 12.6g of the ineredients set out below in TABLE 1 l.

-- 1()-wb 97/18792 PCT/US96/16299 TABLE I ]
Paste B Liquid Paste B 1 PasIe B~ Paste B' lneredients (g) ( CD-S4 1 1 47. 5 --~
PEG,",~,DMA~ 2 3 . 7 ---~JDMA ' --- 23 . 7 3 5 IEMA~ 10 10 12.5 DMAPE5 1.5 1.5 1.
' Sartomer, Exton, PA.
2 Polyethvleneglycol-600 dimethacrylate (Sartomer).
-' Urethane dimethacrylate ~Rohm Tech, Inc, Malden, MA) 2-Hvdroxyethyl methacrylate.
' 4-(Dimethvlamino)phenethanol Compositions were prepared bv combinin~ four parts of I'aste A with one part of Paste B I, B2 and B3 respectively. Set time was measured accordiny to ISO
n specification 9917 and CS and DTS were measured accordin~ to the procedure described in EXAMPLE 9 Run. No. Paste BSet Time Imin.:sec.) CS (MPa) DTS (MPa) B] 4:00 310 44.8 2 B2 3:30 303 37.9 3 B3 2:30 255 27~6 The data in TABLE I ~ illustrate two-paste compositions containing a hydrophilic resin matrix and a fluorocomplex that cured upon mixin~ to yield materials exhibitin~ eood physical properties and set times thal were clinicallyacceptable.

Claims (17)

What is Claimed:

1. A dental composition comprising a) a polymerizable component, b) a fluoride-releasing material, c) a hydrophilic component, d) a polymerization initiator, e) an acidic component, said dental composition being substantially free of added water, said composition having a Water Uptake Value of at least about 1.5 g of water per 100g composition in 2 weeks.

2. A dental composition according to claim 1, wherein said polymerizable component and said hydrophilic component are provided as a single compound.

3. A dental composition according to claim 1, wherein said polymerizable component and said acidic component are provided as a single compound.

4. A dental composition according to claim 1, wherein said hydrophilic component and said acidic component are provided as a single compound.

5 A dental composition according to claim 1, wherein said polymerizable component is a free radically polymerizable material.

6 A dental composition according to claim 1, wherein said polymerizable component has a molecular weight of between about 100 to 5000.

7. A dental composition according to claim 1, wherein said fluoride releasing material comprises a metal complex described by formula M(G)g(F)n or M(G)g(ZFm)n where M represents an element capable of forming a cationic species and having avalency 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 F is a fluoride atom g, m and n are at least 1 .

8. A dental composition according to claim 7, wherein M is selected from group consisting of Ca2, Mg'+2, SR+2 Zn'2, Al'3, Zr'4, Sn+2, Yb+3, Y+3, and Sn+4

9. A dental composition according to claim 7, wherein M is Zn+2.

10. A dental composition according to claim 1, wherein said hydrophilic component is selected from monomers or polymers comprising functionalities selected from the group consisting of pyrrolidone, sulfonate (SO3), sulfonic (SO2), N-oxysuccinimide, N-vinylacetamide and acrylamide functionalities.

11. A dental composition according to claim 1, wherein said hydrophilic component is selected from from the group consisting of polyalkyleneoxides, polyethers, polyethyleneimines, polyacrylamides, polymethacrylamides, polyvinylalcohol, saponified polyvinylacetate, polyvinylpyrrolidone, polyvinyloxazolidone, polymers containing N-oxysuccinimdo groups, ionic or ionizable polymers and copolymers containing polyacrylic acid, polymethacrylic acid in unionized, partially neutralized or fully neutralized forms, polyethyleneimine and its salts, polyethylene sulfonic acid and polyaryl sulfonic acids in unionized, partially neutralized or fully neutralized form, and polyphoshoric and phosphonic acids in unionized, partially neutralized or fully neutralized form.

12. A dental composition according to claim 1, wherein said hydrophilic component is selected from from the group consisting of polyoxymethylene, polyethyleneoxide, polypropylene oxide and polyvinylmethyl ether.

13. A dental composition according to claim 1, wherein said acidic component is selected from are monomers, oligomers or polymers of molecular weight less than 10,000 and containing at least one acidic group selected from oxyacids or thio-oxy acids of B, C, N, S, P.

14. A dental composition according to claim 13, wherein said acidic component is a compound that is an acid of C or P.

15. A dental composition according to claim 1, said composition comprising a) a polymerizable component containing acid functionality defined by the structure (P)p--(Q)q--(R)r-where P= backbone with acidic functionality Q= backbone with a polymerizable functionality, R= backbone of a non-reactive modifying unit p> 1,q>1, and r=0 or more;
b) a fluoride-releasing material, c) a hydrophilic component, d) a polymerization initiator, said dental composition being substantially free of added water, said composition having a Water Uptake Value of at least about 1.5 g of water per 100 g composition in 2 weeks.

16. A dental composition according to claim 1, additionally comprising a reactive filler.

17. A dental composition according to claim 1, additionally comprising a non-reactive filler.