WO2000069394A1

WO2000069394A1 - One-part fluoride releasing dental materials

Info

Publication number: WO2000069394A1
Application number: PCT/US1999/021995
Authority: WO
Inventors: Byron C. Shen
Original assignee: 3M Innovative Properties Company
Priority date: 1999-05-18
Filing date: 1999-09-22
Publication date: 2000-11-23
Also published as: AU6397899A

Abstract

Stable one-part dental materials are provided comprising resin comprising a compound having only one acid functionality and at least one polymerizable functionality on each compound. The material does not contain storage-deleterious quantities of poly-acid compounds. The material also contains a fluoride source containing polyvalent metal ions, and a photopolymerization initiator.

Description

One-Part Fluoride Releasing Dental Materials

Field of Invention

This invention relates to dental materials. More specifically, this invention relates to fluoride-releasing dental materials.

Background of the Invention It is desired to prepare materials for use in the process of repairing or cosmetically treating teeth, wherein the materials contain fluoride. Recently, a new class of material was introduced, named the "compomer.^" which is a type of dental restorative material aimed at combining the fluoride release of glass ionomer chemistry with the ease-of-use and better physical properties of composite technology. Commercially available compomer materials do provide a certain amount of fluoride release and ease of use as they are a one-part system with no mixing required. However, these compomer materials have several shortcomings: their fluoride release level is very low compared to the traditional resin-modified glass ionomer. and their physical properties are relatively poor compared to the traditional composite materials. Their uses and clinical indications are therefore somewhat limited.

Other classes of dental materials, such as adhesives and traditional dental restoratives, also would benefit from incorporation of fluoride.

Summary of the Invention A stable one-part dental material is provided comprising resin comprising a compound (i.e.. a monomer, oligomer or polymer) having a molecular weight between about 80-5.000. The compound has only one acid functionality on each compound, and at least one polymerizable functionality on each compound. The material does not contain storage-deleterious quantities of poly-acid compounds. The material also contains a fluoride source containing polyvalent metal ions, and a photopolymerization initiator. Detailed Description of the Invention Compositions of the present invention provide surprising benefits, because they surprisingly release significant amounts of fluoride from the cured composition. Further, these compositions are surprisingly storage stable before cure and have excellent physical properties after cure. For example, superior strength properties of the cured materials may be demonstrated by diametral tensile strength and compressive strength measurements.

It has been found that the acid appears to facilitate release of fluoride. Further, the storage stability is benefitted by the presence of only one acid on each compound.

The acid functionality is preferably provided by a mono-acid compound having a molecular weight between about 80-5.000. In addition to having only one acid functionality, this compound has at least one polymerizable functionality.

Examples of such mono-acid compounds include acrylic acids, methacrylic acids, (preferably acrylic acid and methacrylic acid) and N-substituted amino acids such as N-acryloyl alanine. N-methacryloyl alanine. N-acryloyl glycine. N- methacryloyl glycine. N-acryloyl serine. N-methacryloyl serine. N-acryloyol leucine. N-methacryloyol leucine, N-acryloyol valine. N-methacryloyol valine, N-acryloyl tyrosine. N-methacryloyl tyrosine and the like. Additionally, mono-acid functionalities may include carboxylic acid. phosphoric acid, phosphonic acid, sulfonic acid, boric acid functionalities, and the like.

Preferred mono-acid compounds have the formula:

O O

H OC (A) — OC C CH₃

CH₂ Wherein A is bridging alkyl group that is optionally interrupted with one or more heteroatoms. ester, urethane or amide linkages. Preferably, the bridging alkyl group is a C₂_6 alkyl group, which is optionally interrupted by an ether linkage, sulfur linkage or a secondary or tertiary amine linkage. Preferred mono-acid compounds are the reaction products of cyclic anhydrides and hydroxy alkyl methacrylates.

A particularly preferred mono-acid compound has the formula

wherein n is 0.1 or 2 m is 1.2 or 3 and n + m = 3:

R is independently. ]_]2 alkyl. -O- Cj_i2 alkyl: C1-12 alkyl-OH:

-C_M2 alkyl — O — C_M2 a-kylA-R

R^v=alkyl or -OH

R is independently

-(-CH₂

CH.CH.CH. -O

arvl-

aryl— CH-.-)-

A≡A P

wherein p is 1-12 or any combination thereof

R is independently

CR . I'V^V = CH,

-f-OCH=CH₂

-acrylamide -methacrvlamide

R _• ι^,v^v is independently H. Cl-12 alkyl.

Of the compounds described above, one preferred class of compounds has the formula:

wherein n is 1 m is 1

one of R¹ is C_{M 2} alkyl-OH: and the other of R¹ is C j . j i alkyl. -0- C \ . j i alkyl:

^■ C ._n alkyl — O — C,.₁₂ alkyl-)— R" R^V=C, -i₂ alkyl

R¹¹ is independently

^CH, . \ /' P

CH₂CH₂CH₂ O

arvl

- CH.— arvl-

wherein p is 1-12 or anv combination thereof

R is independently

-f-OCH=CH₂

-acrN'lamide — methacrvlamide

R ,ι^,v^v is independently H. Cl-12 alkyl.

Another preferred class of compounds has the formula:

wherein n is 1

R .1' _ is Cι_i2 alkyl. -O- C ₂ alkyl;

-CM ^■> alkvl — O — C,.p atkvlA— R'

R^V=C,.|. alkvl

R is independently

-(-CI CH.O-+- V /p

CH.CH.CH.- -O

-AA

C Hary

aryl— CH- -(-HC=CH-)- ^v φ

A≡A P

wherein p is 1-12 or any combination thereof

R is independently

CR^1V = CH,

-OCH = CH₂

— acrylamide — methac π'lamide

R .ι'v^v i •s independently H. C 1 -12 alkyl.

A particularly preferred class of compounds of the present invention is wherein

m

R' = CH₃:

R" -CH-.CH-.

Another particularly preferred class are the compounds wherein n=2. m= one of R¹ is 5 CCHH₂.--OOHH ; and the other R¹ is -CH,. R" is

and R¹" is

Another particularly preferred class of compounds is where n is 2 and one of R .1' :is- CH₂-OH.

Most preferably, the polymerizable carboxylic acid compound is selected from 2.2-di(N-methacryloxyethyl carbamoylmethyl) propionic acid ("PDMA^") and

2-hydroxymethyl-2-[(N-methacryloxyethyl) carbamoylmethyl] propionic acid

("PAMA^"). The resin does not contain storage-deleterious quantities of poly-acid compounds. For purposes of the present invention, a poly-acid would be considered to be present in a storage-deleterious amount if a viscous composition increased in extrusion force more than 50% upon storage at 45° C temperature for

60 days. A poly-acid would be considered to be present in a storage-deleterious amount in a non-viscous composition if upon storage at 45° C temperature for 60 days the composition exhibited lumpiness from undesired agglomeration of the composition over time.

Preferably, the resin contains no more than 5% by weight of compounds having more than one acid functionality per compound in the composition based on the resin component of the material, and more preferably contains no more than

2% by weight of compounds having more than one acid functionality per compound.

The present compositions preferably comprise co-polymerizable materials. which do not contain acid functionality. Preferred co-polymerizable materials are the esters of acrylic or methacrylic acid. Examples of these compounds are methyl acrylate: methyl 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 ("BisGMA^"): glycerol mono- and di- acrylate: glycerol mono- and di- methacrylate; ethyleneglycol diacrylate: ethyleneglycol dimethacrylate; polyethyleneglycol diacrylate (where the number of repeating ethyiene oxide units vary from 2 to 30); polyethyleneglycol dimethacrylate [where the number of repeating ethyiene oxide units vary from 2 to 30. especially triethv ene glycol dimethacrylate ("TEGDMA^")]; neopentyl glycol diacrylate: neopentylglycol dimethacrylate: trimethyloipropane triacrylate: trimethylol propane trimethacrylate: mono-, di-. tri-. and tetra- acrylates and methacrylates of pentaen'thritol and dipentaerythritol: 1.3-butanediol diacrylate: 1.3-butanediol dimethacrylate; 1.4-butanedioldiacrylate; 1. 4-butanediol dimethacrylate: 1 ,6- hexane diol diacrylate; diurethane dimethacrylate ("DUDMA.^" CAS No. 44137- 60-4); 1.6-hexanediol dimethacrylate: di-2-methacryloyloxethyl hexamethylene dicarbamate: di-2-methacryloxyethyl trimethylhexanethylene dicarbamate; di-2- methacryloyl oxyethyl dimethylbenzene dicarbamate: methylene-bis-2- methacryloxyethyl-4-cyclohexyl carbamate: di-2-methacryioxyethyl- dimethylcyclohexane dicarbamate: meth\ ene-bis-2-methacryloxyethyl-4- cyclohexyl carbamate: di- 1 -methyl-2-methacr\ oxyethyl-trimethyl-hexamethylene dicarbamate: di-l -methyl-2-methacryloxyethyl-dimethylbenzene dicarbamate; di- l -methyl-2-methacryloxyethyl-dimethylcyclohexane dicarbamate: methylene-bis- l-methyl-2-methacryloxyethyl-4-cyclohexyl carbamate: di-l -chloromethyI-2- methacryloxyethyl-hexamethylene dicarbamate: di- 1 -chloromethyl-2- methacryloxyethy 1-trimethylhexamethylene dicarbamate: di- 1 -chloromethyl-2- methacryloxyethyl-dimethylbenzene dicarbamate: di- 1 -chloromethyl-2- methacryloxyethyl-dimethylcyclohexane dicarbamate: methylene-bis-2- methacryloxyethyl-4-cyclohexyl carbamate: di- 1

hexamethvlene dicarbamate; di- 1

trimethylhexamethylene dicarbamate; di- 1 -methyl-2-methacryloxyethyl- dimethylbenzene dicarbamate: di-l -methyl-2-methacryloxyethyl- dimethylcyclohexane dicarbamate: 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- 1 -chloromethy 1-2-methacryloxyethyl- dimethylbenzene dicarbamate; di- 1 -chloromethyl-2-methacryloxyethyl- dimethylcyclohexane dicarbamate: methylene-bis- 1 -chloromethyl-2- methacryloxyethyl-4-cyclohexyl carbamate; 2A-bis(4- methacryioxypheny 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:

ethoxy)_nphenyl )propane ( wherein n=l -5) ("BisEMA^"); 2.2^,-bis(4-acryloxyethoxyphenyl)propane: 2.2"-bis(4- methacr 'loxypropoxyphenyl)propane: 2.2^"-bis(4-acryloxypropoxyphenyl)propane; 2.2'-bis(4-methacryloxydiethoxyphenyl)propane: 2.2'-bis(4- acryloxydiethoxypheny propane; 2.2'-bis[3(4-phenoxy)-2-hydroxypropane-l - methacrylate]propane; 2.2^"-bis[3(4-phenoxy)-2-hydroxypropane-l - acrylatejpropane; and the like.

Other preferred co-polymerizable materials include substituted acrylamides and methacrylamides. Examples are acrylamide. methylene bis-acry amide. methylene bis-methacryiamide. diacetone/acrylamide. diacetone methacylamide. N-alkyl acrylamides and N-alkyl methacr lamides where alkyl is a lower hydrocarbyl unit of 1 -6 carbon atoms. Other suitable examples of co- polymerizable materials are isopropenyl oxazoline. vinyl azalactone. vinyl pyrrolidone. styrene. divinylbenzene. urethane acrylates or methacrylates. epoxy acrylates or

and polyol acrylates or methacπ ates.

Particularly preferred co-polymerizable materials that do not contain an acid functionality are BisGMA. TEGDMA. HEMA. BisEMA. DUDMA and mixtures thereof. The fluoride-releasing material of the present invention is a polyvalent fluoride source. Such sources, which have more than one fluoride ion associated with each species, provides more efficient fluoride deliver)', and additionally provides bener physical properties in the ultimate cured restoration.

The polyvalent fluoride source may be naturally occurring 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 described in U.S. Pat. No. 3.814.717. which may be optionally treated as described in U.S. Pat. No. 5.332.429.

Storage stability and strength properties are particularly enhanced when the fluoride releasing material 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:

F is a fluoride atom; g is 0 or 1 or more: and m and n are at least 1.

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"\ Sr^"2. ZA\ A1A Zr^{^4}. SA². YbA A³. SA⁴. Most preferably. M is ZnA 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. 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.

Compositions of the invention 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 sufficiently shelf stable and free of undesirable 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 651 ") 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 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

Particularly preferred compositions of the present invention are prepared such that thev are comparatively thick in consistency , and perform well as dental composite mateπals A preferred formulation

be made according to the following a) 10-25% by weight of a resin, which resin in turn comprises l) 5-30%o of a free radically polymerizable compound having one acid functionality. n) 65-95 5%> of a dimethacrylate compound free ot acid functionality , in) 0-5% of p-NVP b) 65-89 75% by weight of a filler. c) 0 25-10% by weight of a fluoride source containing polyvalent ions. Additional preferred compositions of the present invention are formulated such that their consistency is less thick These formulations may find usefulness particularly flowable composites, resin cements, filled adhesn es or sealants Particularly preferred compositions of this type may be formulated as follows a) 30-69 75%o by weight of a resin, which resin in turn comprises 0 5-30%) of a free radically poly merizable compound having one acid functionality . n) 65-95 5% of a dimethacrylate compound free ot acid functionality .

b) 30-69 75% by weight of a filler. c) 0 25-10% by weight of a fluoride source containing polyvalent ions Compositions of the present invention may be substantially free ot added water A particularly preferred composition of the present invention is a stable one-part paste dental composite comprising a) resin comprising PDMA. b) reactn e filler, and c) polymerization initiator, which composition is substantialh free of added water

- 1 J>- For purposes of the present invention, the term substantialh free of added water^" means that the composition does not contain water that is intentionally added as a non-complexed or coordinated entity It 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 water that is present in the composition, regardless of source, should not be present in amounts such that the water will have a deleterious effect ot the long term properties of the composition For example, water should not be present in an amount that would facilitate reaction of the acid - reactive filler with the acidic component so that lumpiness or graimness of the material dev elops during commercialh required storage time

Surprisingly some water may be tolerated in the instant compositions despite the presence of both acid and fluoride releasing functionality in the composition which often undergo a cement reaction in other sy stems Therefore, up to about 5% water may optionally be present in the compositions of the present invention

One embodiment of the present invention is compositions specifically designed to additionally utilize a cement reaction as an additional curing mode of the compositions These compositions incorporate reactive fillers that react with acid functionality present in the resin portion ot the composition to undergo a cement reaction The reactiv e filler mav or av not ha e the propertv of releasing fluoride Such fillers include those that are commonly used with lonomers to form ionomer cements Examples of suitable reactiv e fillers include metal oxides such as zinc oxide and magnesium oxide, and lon-leachable glasses, e g . as described in

U S Pat Nos 3.655.605. 3.814.717. 4 143.018. 4.209.434. 4.360.605 and 4.376,835 Such reactiv e fillers may be incorporated to modify the handling characteristics or to affect the setting properties of the ultimate composition Compositions that hav e a sufficient amount of reactiv e filler to undergo the cement reaction are generally less tolerant of the presence of water in the uncured state, because the cement reaction prematurely begins before use by the practitioner when water is present. Preferably, compositions containing reactive filler are substantially free of added water.

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 1 to 10 micrometers, as measured using, for example, a sedimentation analyzer.

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, aluminum chloride, calcium chloride, magnesium chloride, zinc chloride, aluminum nitrate, barium nitrate, calcium nitrate, magnesium nitrate. strontium nitrate and calcium fluoroborate. Preferred glasses include borate glasses, phosphate glasses and fluoroaluminosilicate glasses. Most preferred of the acid reactive fillers are those that release fluoride.

Fluoride releasing 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 acid reactive fillers are also available from a variety of commercial sources familiar to those skilled in the art. For example. suitable fillers can be obtained from a number of commercially available glass ionomer. Mixtures of fillers can be used if desired.

If desired, the acid 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. Particularly preferred acid reactive fillers are silanol treated fluoroaluminosilicate glass fillers, as described in U.S. Patent Number

5.332.429.

Non-acid 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 restorativ e compositions and the like. The filler is finely divided and preferably has a maximum particle diameter less than about 10

- 1 3- micrometers and an average particle diameter less than about 1.0 micrometers. More preferably, the filler has a maximum particle diameter less than about 1.0 micrometers and an average particle size of diameter less than about 0.1 micrometer. The filler 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-acid 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-acid reactive filler particles are quartz, submicron silica, and non-vitreous microparticles of the type described in U.S. Patent No. 4,503.169. Mixtures of these non-acid reactive fillers are also contemplated, as well as combination fillers made from organic and inorganic materials.

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. The use 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, stabilizers, viscosity modifiers. surfactants, rheology modifiers, colorants, medicaments and other ingredients that will be apparent to those skilled in the art. In a preferred embodiment of the present invention, dental restorative materials of the present invention exhibit fluoride release levels that are close or comparable to that of the traditional resin-modified glass ionomer material, and have physical properties close to or comparable with those of the traditional composite material Surprisingly, these properties are provided in a single- component (that is. no mixing of parts is required by the dental practitioner) system that is storage stable Specifically, the physical properties of the present materials include wear resistance, compressive strength, dimetral tensile strength

The compositions of the present invention may be formulated for use as dental adhesives. sealants, orthodontic cements and adhesives. liners, restoratives, mill blanks and dental prosthetics. as will be apparent to those skilled in the art

The following examples are provided for purposes of illustrating the present invention, and are not intended to be limiting of the broadest concepts of the present invention Unless otherwise indicated, all parts and percentages are by weight and all molecular weights are weight average molecular weight

Tests

Diametral Tensile Strength

Diametral tensile strength (DTS) was measured using the following method The mixed, uncured composite samples were injected into a glass tube having a 4 mm inner diameter The filled tube was subjected to 2 88 kg/cm- (40 psi) pressure followed by curing while under pressure, by exposure to a Visilux™ 2

(3M, St Paul) dental curing light They were then cut on a diamond saw to form cylindrical plugs approximately 2 mm long for measurement of diametral tensile strength Seven samples were prepared for DTS The DTS was determined according to ISO specification 7489 (or American Dental Association ("ADA") specification No 27) using an Instron Mechanical Testing Instrument (Model

4500 Series)

Extrusion force test Four to seven custom made 3 cc syringe dispensers (length of barrel - 61.47mm. length of tip at the end of the barrel - 5.72mm. inside diameter of the barrel - 7.90mm. diameter of tip orifice - 4.06mm) were filled with approximately 4.0 grams of the sample pastes. A piston was placed in the open end of each 3 cc syringe. Each syringe was tested for extrusion force. A filled syringe was placed in an Instron™ Model 4505 testing machine and the sample paste was extruded from the discharge end of the syringe at a crosshead speed of 5 mm/'min. The force required to extrude the paste was measured, and the average of five independent determinations was recorded. The extrusion force is taken to be the average force observed when taken at two minutes at which a plateau is reached.

Below is a list abbreviations used in the examples.

BisGMA. 2.2-bis[4-(2-hydroxy-3-methacryloyloxy- propoxy)phenyl]propane

BHT. 2.6-Di-tert-butyl-4-methylphenol

CDMA, an adduct of citric acid with isocyanatoethyl methacrylate as described in Preparatory Example No. 5 WO 9846197.

CPQ, Camphorquinone DPI PF6. Diphenyl Iodonium Hexafluorophosphate

DTIHFP. ditolyl iodonium hexafluoro phosphate.

EDMAB . Ethyl 4-dimethy aminobenzoate

GDMA. Glycerol dimethacrylate p-NVP, N- Polyvinyl pyrrolidinone (38.000 MW) PDMA 2.2-di( -methacry oxyethyl carbamoylmethyl) propionic acid

TEGDMA. Triethyleneglycol dimethacrylate

ZnF . Zinc difluoride

Examples

Preparatory Filler Example 1

A sol-gel derived filler was prepared as follows: 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 v essel. 12.9 parts ion- exchanged zirconyl acetate (Magnesium Elektron. 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. The stirred mixture was filtered through a 3 micrometer filter followed by a 1 micrometer filter. The filtrate was poured into trays to a depth of about 25 mm and dried at 65°C in a forced air oven for about 35 hours (hrs). The resultant dried material was removed from the oven and tumbled through a rotary tube furnace (Harper Furnace Corp.) . which was preheated to 950°C. The calcined material was comminuted in a tumbling ball mill with VA alumina media until an average particle size of 0.5-1.2 micrometers (as measured on a Micromeritics 5100 sedigraph ) was achieved. The mill charge included 75 parts calcined material. 3 parts methanol. 1.9 parts benzoic acid, and 1.1 parts deionized water. The filler was then loaded into ceramic saggers and fired in an electric furnace (L&L Furnace Corp.) in air at 880-900°C for approximately 8 hrs. The fired filler was then ball-milled for 4-5 hrs. The mill charge included 32 parts fired filler. 1.25 parts ethanol. and 0.3 parts deionized water. Next, the filler was passed through a 74 micrometer nylon screen in a vibratory screener (Vortisiv V/S 10010). The filler was then blended in a V-blender (Patterson-Kelly Corp.) for about 15 min. Silane treatment was as follows: 32 parts by weight (pbw) of the filler was added to 48.94 pbw of deionized water under vigorous stirring. Trifluoroacetic acid (TFAA ). 0.104 pbw. was added slowly . The pH was then adjusted to 3.0 - 3.3. by adding further 5 pbw increments of TFAA. Then. 3.56 pbw of silane A- 174 silane was added. After stirring vigorously for 2 hrs a solution of 0.0957 pbw of calcium hydroxide and 200 grams (g) of deionized water was added and stirred an additional 5 minutes. The slurry was poured into a tray lined with a plastic sheet, and then dried in an oven set at 90°C for 13 hours. The cakes of dried filler were crushed and passed through a 74 um screen. Preparatory Filler Example 2

Treated Fluoroaluminosilicate Glass

The ingredients set out below in TABLE 1 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 fluoroaluminosilicate glass.

Table 1

The glass was ball-milled to provide pulverized frits with surface areas shown in Table 2 measured using the Brunauer. Emmet and Teller (BET) method.

A silanol solution was prepared by mixing together the required parts of gamma-methacryloxypropyl trimethoxysilane ("A- 174". OSi Specialties. Inc.) as defined in Table 2. 12.6 parts methanol. 36.5 parts water and 0.33 parts acetic acid. The mixture was stirred magnetically for 60 minutes at ambient temperature, added to 60.8 parts of the glass powder and slurried for 30 minutes at ambient temperature. The slurry was poured 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.

Table 2

Preparatory Glass Surface Parts A- 174 Example Area (m2/g)

1A 3.20 2.43

I B 7.83 2.95

I C 3.85 1.51

I D 3.85 5.19

I E 1 1.50 1.51 Preparatory Filler Example 3

Treated Fumed Silica (OX-50) was made as follows: a solution of 3312 g MeOH and 720 g deionized water was premixed for 1 minute. Glacial Acetic Acid, 1024 g. was slowly added to the water followed by 4968 g A- 174 silane. The above solution was mixed for 1 hour. At the end of the hydrolysis step, the solution was clear. The solution was used within 30 minutes after hydrolysis. The above solution and 20700 g OX-50 powder were blended for approximately 40 minutes and the treated filler was immediately discharged into drying trays, and was dried at 67 C for 3.75 hours and then another 1.25 hours at 100 C. The dried filler was screened through a 74 mm nylon screen in a v ibratory screener (Vortisiv V/S

10010).

Preparatory Example - Preparation of PDMA

Bis(hydroxymethyl)propionic acid di(N-methacryIoxyethyl)carbamate (PDMA) is synthesized by reacting 2.2-Bis(hydroxymethyl)propionic acid

(BHMPA) and two equivalents of Isocyanatoethylmethacrylate (IEM) as follows 2,2-Bis(hydroxymethyl)propionic acid (BHMPA. 225.21 g, 1.679 mole), small amounts of stabilizer(s) such as 2,6-Di-tert-butyl-4-methylphenol (BHT, 1.6781 g, 7.615 mmole) and/or Triphenyl antimony (TPS, 1.3463 g. 3.813 mmole), and a catalytic amount of Dibutlytin dilaurate (2.4396 g, 3.863 mmole) and dry THF or other suitable solvents were added first to the reactor. After the solution was stirred for a short while. IEM (592.64 g. 3.823 mole) was added. The reaction was heated to 65 °C for about 30 hours while stirring constantly. The solvent was stripped off after the conversion was completed. The final product. PDMA. was a colorless, viscous liquid.

Example 1

Comparative Resin Formulation A (this sample contains no acid functional materials) was mixed with the following ingredients as listed in Table 3: Table 3

Resin Formulation B (contains acid functional compound PDMA) was mixed with the following ingredients as listed in Table 4:

Table 4

Comparative PI and P2 pastes were made by adding filler constituents, as listed in Table 5. to Resin Formulations A and B.

Table 5

r>ι. The Diametral Tensile Strength (DTS) was measured for Comparative PI and P2 as described above, and the change in the DTS of these materials were compared after the cured samples were aged in water at 60 C for 10 days.

Table 6

One-tail Two-Sample t-test assuming unequal variances NS = no significant difference ** = significant difference

Prior to aging both samples in water at 60C. fresh DTS samples were tested to obtain the initial DTS values. The mean initial DTS values of Comparative P (8725 psi) and P2. (8848 psi) were essentially indistinguishable and the small difference between the numbers is statistically insignificant. After the DTS samples had been aged in water at 60 C for 10 days, the DTS values for both samples were lower than their respective initial values. However, the t-test showed that the large difference between the mean DTS values of Comparative PI and P2 after aging was statistically significant. The DTS value of Comparative P I is now approximately 50% lower compared to its initial value. In comparison, the percentage DTS value decrease for P2 after aging was approximately 34% which showed that Paste P2 had better aging performance.

Example 2

Resin Formulation C according to the present invention was prepared as follows: Table 7

Comparative Resin Formulation D with CDMA and GDMA was prepared as follows:

Table 8

Paste formulations. P3 and Comparative P4. using resins C and Comparative D were prepared by mixing in the resin and filler components as listed in Table 9.

Table 9

Table 1 1 is a comparison of aging stability of uncured pastes with PDMA (a mono-acid compound) versus with CDMA (a polyacid compound) as determined by the previously described Extrusion Force Test. Table 11

*Extrusion force in kg.

The uncured polyacid-containing paste required the application of an increasing extrusion force as measured over a 10 day interval. Over a four-fold increase of extrusion force was observed at the end often days. In contrast, the extrusion force for the uncured mono-acid-containing paste remained relatively constant over a 21 day measurement interval, which demonstrates much improved paste stability.

Example 3

Resin ingredients were mixed according to the scheme exhibited in Table 12 to make pastes P5 and P6. Table 13. Table 14 shows the final contributions made by each of the ingredients to the formulations of the two pastes.

Table 12

Table 13

Table 15 illustrates the effect of high and low amounts of PDMA on fluoride release. Incremental fluoride release of each paste was measured after 24 hours. Samples were prepared by light curing (XL-3000™ Curing Light; 3M, St. Paul) 20 mm in diameter by 1 mm thick disks for 40 seconds on both sides. The cured disks were placed in ajar containing 25 mL of deionized water at 37°C. A fluoride-selective electrode. Orion Model 96-09-BN (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 of 10 parts per million ("ppm"). 5 ppm. 2 ppm, and 1 ppm (from Orion Research Inc.).

For the measurement of fluoride ions released into the water. 10 mL of the sample solution was transferred after 24 hours to a 60 mL beaker and 10 mL of

TISAB II solution (total ionic strength adjustment buffer; Orion Research Inc.. Cambridge, MA) was added to the beaker. The contents were mixed for 10 seconds. The calibrated fluoride-selective electrode was placed in the solution and the ppm F^" were recorded and converted to micrograms of F^" per gram of the fluoride containing sample disks. The results are set out in Table 15.

Table 15

Claims

Claims:

1. A stable one-part dental material comprising a) resin comprising a mono-acid compound having a molecular weight between about 80-5.000. said compound comprising only one acid functionality and further comprising at least one polymerizable functionality. b) a fluoride source containing polyvalent metal ions, and c) photopolymerization initiator said composition being free of a storage stability-deleterious amount of a compound having more than one acid functionality.

2. The one-part dental material according to claim 1. said material having no more than 5% of a compound or compounds having more than one acid functionality based on the resin component of the material.

3. The one-part dental material according to claim 1. said mono-acid compound being selected from the group consisting of acrylic acids, methacrylic acids, and N-substituted amino acids.

4. The one-part dental material according to claim 1. said mono-acid compound being selected from the group consisting of N-acryloyl alanine. N- methacryloyl alanine. N-acryloyl glycine. N-methacryloyl glycine. N-acryloyl serine. N-methacryloyl serine, N-acryloyol leucine. N-methacryloyol leucine. N- acryloyol valine. N-methacryloyol valine. N-acryloyl tyrosine. and N-methacryloyl tyrosine.

5. The one-part dental material according to claim 1. wherein the acid functionality of said mono-acid compound is selected from the group consisting of carboxylic acid, phosphoric acid, phosphonic acid, sulfonic acid, and boric acid functionalities.

6. The one-part dental material according to claim 1. said mono-acid compound being selected from the group consisting of compounds of the formula:

O O

wherein A is bridging alkyl group optionally interrupted with one or more heteroatom, ester, urethane. or amide linkages.

7. The one-part dental material according to claim 6. wherein the A bridging alkyl group is a C2-6 alkyl group, which is optionally interrupted by an ether linkage, sulfur linkage or a secondary or tertiary amine linkage.

8. The one-part dental material according to claim 1. said mono-acid compound being selected from the group consisting of the reaction products of cyclic anhydrides and hydroxy alkyl methacrylates.

9. The one-part dental material according to claim 1. said mono-acid compound being selected from the group consisting of compounds having the formula

wherein n is 0. 1 or 2 m is 1. 2 or 3 and n + m = 3; R¹ is independently. C j.j2 alkyl. -O- C \.\2 alkyl; C M2 alkyl-OH;

— (-d.,₂ alkyl — O — C ₂ a-kyl-A- R^v R^v=alkyl or -OH R is independently

A^HA

CH₂CH₂CH₂ O p

-(-CH-.— aryl— CH,-)- ^X Φ

-f CH,— arvl-

P

4^HC=CH ;

wherein p is 1-12 or any combination thereof

R¹" is independently

CR^IV = CH,

-f-OCH=CH₂

— acrylamide — methacrvlamide R ,ι^,v^v i •s independently H. Cl-12 alkyl.

10. The one-part dental material of claim 9, wherein n = 1 ; m = 2; R¹ = CH₃; R" = CH₂CH₂: and

1 1. The one-part dental material of claim 9. wherein n=2. m=l, one of R is

CH₂-OH a inndd tthhee ootthheerr 1 R¹ is -CH₃, R^M is

and R¹" is

12. The one-part dental material of claim 9. wherein n is 2 and one of R is CH₂-OH.

13. The one-part dental material of claim 9. wherein the polymerizable carboxylic acid compound is selected from 2.2-di(N-methacryloxyethyI carbamoylmethyl) propionic acid and 2-hydroxymethyl-2-[(N- methacryloxyethyl) carbamoylmethyl] propionic acid.

14. The one-part dental material according to claim 1. said material further comprising a filler.

15. The one-part dental material of claim 1. comprising no more than about 2% of compounds having more than one acid functionality per compound based on the resin component of the material.

16. The one-part dental material of claim 1. wherein the fluoride source containing polyvalent metal ions comprises 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; F is a fluoride atom; g is 0 or 1 or more; and m and n are at least 1 .

17. The one-part dental material of claim 1 , wherein the fluoride source containing polyvalent metal ions comprises zinc difluoride.

18. The one-part dental material of claim 1 , said material additionally comprising a non-acidic co-polymerizable material.

19. The one-part dental material of claim 18. wherein said non-acidic co- polymerizable material is selected from one or more esters of acrylic or methacrylic acid.

20. The one-part dental material of claim 1. comprising a) 10-25%) by weight of a resin, which resin in turn comprises i) 5-30% of a free radically polymerizable compound having one acid functionality.

i - ii) 65-95.5%) of a dimethacrylate compound free of acid functionality, iii) 0-5% of p-NVP b) 65-89.75% by weight of a filler; c) 0.25-10%) by weight of a fluoride source containing polyvalent ions.

21. The material of claim 20. wherein said dimethacrylate compound free of acid functionality is selected from Bis-GMA. TEGDMA. HEMA, Bis-EMA, DUDMA and mixtures thereof.

22. The one-part dental material of claim 1, comprising a) 30-69.75%) by weight of a resin, which resin in turn comprises i) 5-30% of a free radically polymerizable compound having one acid functionality, ii) 65-95.5% of a dimethacrylate compound free of acid functionality, iii) 0-5% of p-NVP b) 30-69.75% by weight of a filler; c) 0.25-10%) by weight of a fluoride source containing polyvalent ions.

23. A stable one-part paste dental composite comprising a) resin comprising PDMA b) reactive filler c) polymerization initiator said composition being substantially free of added water.

24. A method of restoring a tooth in need of restoration, comprising a) preparing a tooth in need of treatment, b) applying to said prepared tooth a dental material of claim 1.