WO2018071920A1 - Curable urethane dimethacrylates and dental restorative compositions thereof - Google Patents

Abstract

BisGMA is the most widely used resin in dental composites, however, it is being phased out for use due to potential long-term health effects. The present invention relates to a urethane dimethacrylate replacement candidate based on the reaction products of equal molar amounts of 2-hydroxypropylmethacrylate and 2-hydroxyethylmethacrylate with mixed-MDI. This resin is a viscous liquid at room temperature; however, formulations with reactive diluents produce low viscosity liquid with a refractive index comparable to bisGMA formulations, as well as having Young's modulus comparable to bisGMA formulations. Unlike bisGMA this resin should have no negative health effects.

Description

CURABLE URETHANE DIMETHACRYLATES AND DENTAL RESTORATIVE COMPOSITIONS THEREOF

RELATED APPLICATIONS

[0001] The present application claims the benefit of priority under 35 U.S.C. § 119 to U.S. Provisional Application No. 62/408, 132, filed Oct 14, 2016, the contents of which are herein incorporated by reference in their entirety.

FIELD OF INVENTION

[0002] The present invention relates to novel urethane dimethacrylate resins. In particular, the present invention relates to liquid urethane dimethacrylates based on the isomers of methylene diphenyl diisocyanate. The invention also relates to dental restorative compositions based on the liquid urethane dimethacrylate resins.

BACKGROUND OF INVENTION

[0003] Dental restorative materials are used often in modern dentistry to replace tooth structure loss due to cavities, dental trauma or tooth wear. These materials are also often used to alter an individual's appearance for cosmetic purposes.

[0004] Research and development departments are continuously working on trying to find the ideal dental restorative materials. There are many challenges to be met in finding a proper resin and formulation that can replace the natural tooth structure in appearance, strength, and adherence. [0005] The right candidate dental restorative material would have to fulfill four basic criteria to be usable as a dental restorative material. These criteria are:

biocompatibility; physical properties; application, and aesthetics.

[0006] Biocompatibility: since dental restorative material will be used near and in the mouth, in contact with living tissue, it is absolutely imperative that the material exists in harmony with the tissue without causing damage to the tissue or other deleterious changes.

[0007] Physical properties: dental restorative materials must withstand various forces during mastication such as attrition, abrasion, and must have resistance to chemical erosion. The material also must have low thermal conductivity and coefficient of thermal expansion, this is especially important when drinking hot or cold beverages. The material also needs to be able to have excellent adhesion to the tooth surface under hot, wet conditions and in the presence of various enzymes, saliva, food and drink.

[0008] Application: a dentist or assistant must to be able to easily apply, cure and shape the material in a predictable and controllable manner.

[0009] Aesthetics: ideally, the dental restorative material should match the surrounding tooth structure in shade, translucency and texture in order to satisfy the patient.

[0010] Many materials have historically been used as dental fillings, these include: gold; other various metals and alloys; amalgams; and glass ionomer cements. [0011] Composite resin fillings are used most often in modern dentistry. These materials, also known as white fillings, are typically a combination of curable organic resins and glass filler along with adhesion promoters and light activators. These materials are very popular because they can be made to look identical to the natural tooth in color and appearance.

[0012] By far the most widely used resin used in dental composites around the world is bisphenol A diglycidyl ether methacrylate (bisGMA). This material is synthesized by the reaction of methacrylic acid with bisphenol A diglycidyl ether. BisGMA (Structure 1) is a viscous, clear liquid at room temperature with a high refractive index (1.540). Because of the high viscosity of the resin various reactive diluents are added to allow for easier handling of the formulations.

Formula I. BisGMA

[0013] Bisphenol A, which may be present as a small impurity in some bisGMA samples and has been known for some time in animal or cell cultures to induce changes in estrogen-sensitive organs or cells. Although short-term risk exposure to bisGMA has been determined to be minimal, long-term exposure effects are unknown at this time and are being studied. This determination has led to all out efforts to find a suitable replacement resin for bisGMA. [0014] The properties of the dental composites using bisGMA are very good. The materials provide very hard, yet tough composites with good abrasion resistance, and often with excellent adhesion. The high refractive index allows for composites that match closely with natural teeth to give a more aesthetically pleasing filling.

[0015] The problem to be solved is to find a suitable replacement for bisGMA that retains all of the good properties of bisGMA, but is not a potential endocrine disruptor, or have any other biocompatibility issues.

SUMMARY OF INVENTION

[0016] The present invention is directed toward liquid urethane di(meth)acrylates comprising the reaction product of one equivalent of mixed methylene diphenyl diisocyanate isomers with about 0.5 equivalents of a secondary alcohol (meth)acrylate followed by the addition of about 0.5 equivalents of a primary alcohol (meth)acrylate.

[0017] Mixed methylene diphenyl diisocyanate (MDI) is composed of various isomers of MDI, which include the 4,4'-MDI, the 2,4'-MDI and possibly the 2.2'- MDI. The 2-position is 3 to 4 times slower to react that the 4-position, therefore by adding a sterically hindered secondary alcohol (meth)acrylate in the first step of the synthesis will exclusively react with the 4-position. The remainder of the isocyanate is reacted by the addition of a primary alcohol (meth)acrylate to provide a liquid product. [0018] The liquid urethane di(meth)acrylate is a clear high viscosity liquid with a refractive index above 1.55, which makes it a good candidate for replacing bisGMA as a dental composite resin.

[0019] In certain embodiments the invention provides, dental restorative compositions comprising a liquid urethane dimethacrylate described herein; and at least one filler;

at least one reactive diluent; at least one initiator;

at least one accelerator; at least one free-radical inhibitor; and

at least one adhesion promoter.

[0020] The present invention provides a liquid urethane dimethacrylate comprising the reaction product of one molar equivalent of mixed methylene diphenyl diisocyanate isomers with about 0.5 molar equivalents of a secondary alcohol (meth)acrylate followed by the addition of about molar 0.5 equivalents of a primary alcohol (meth)acrylate.

[0021] The mixed methylene diphenyl diisocyanate isomers can comprise a combination of 4,4'-MDI, 2,4'-MDI and optionally 2.2'-MDI. The secondary alcohol (meth)acrylate can comprise compounds selected from the group consisting of hydroxypropyl (meth)acrylate, hydroxybutyl (meth)acrylate, poly(propylene glycol) mono-(meth)acrylate, 2-hydroxypropyl methacrylamide, and glycerol dimethacrylate. The primary alcohol (meth)acrylate can comprise at least one compound selected from the group consisting of 2-hydroxy ethyl (meth)acrylate, 3-hydroxypropyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, N-(2-hydroxyethyl) methacrylamide, and polyethylene glycol mono-(meth)acrylate.

The liquid urethane di(meth)acrylate can have a structure selected from the group consisting of:

[0022] The invention also provides dental restorative compositions comprising: a) at least one a liquid urethane dimethacrylate; b) at least one filler; c) at leas one reactive diluent; d) at least one initiator; e) at least one accelerator; f) at least one free-radical inhibitor; and g) at least one adhesion promoter.

[0023] In the dental restorative compositions of the invention, the at least one liquid urethane dimethacrylate can comprise at least one compound selected from the group consisting of:

[0024] The liquid urethane dimethacrylate in the dental composition comprises 60 to 80% by weight of the composition based on the total weight of the resin mixture.

[0025] The the at least one filler in the dental composition can be selected from the group comprising of fumed silica, colloidal silica, aluminosilicate glass, fluoro aluminosilicate glass, silica, quartz, strontium silicate, silanated barium borosilicate glass, strontium borosilicate, lithiumsilicate, lithium alumina silicate, amorphous silica, ammoniated or deammoniated calcium phosphate, alumina, Zirconia, tin oxide, titania, and mixtures comprising at least one of the foregoing fillers.

[0026] The at least one filler in the dental restorative composition comprises 60 to 85% by weight of the composition based of the composition on the total weight of the filled composition.

[0027] The at least one reactive diluent in the dental restorative composition can be selected from the group consisting of ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, ethoxylated bisphenol-A dimethacrylate (EBPADMA), hexanediol dimethacrylate, decanediol dimethacrylate, urethane dimethacrylate (UDMA) and combinations thereof.

[0028] The at least one reactive diluents in the dental restorative composition can comprise 20 to 40% by weight of the composition based on the total weight of the resin.

[0029] The at least one initiator in the dental restorative composition can be selected from the group consisting of phenyl bis(2,4,6 trimethyl benzoyl) phosphine oxide, Bis-9-eta 5-2,4 cyclopentadien-l-yl) Bis[2,6-difluoro-3-(lH-pyrrol-l- yl)phenyl]titanium, camphorquinone (CQ), l-hydroxy-cyclohexyl-phenylketone, 2,2- dimethoxy-2-phenylacetophenone, benzoyl peroxide (BPO) and combinations thereof.

[0030] The at least one initiator in the dental restorative composition can comprise 0.1 to 5% by weight of the composition based on the total weight of the composition. [0031] The at least one curing accelerator can be selected from the group comprising of ethyl 4-dimethylaminobenzoate, diethyl aminoethyl methacrylate, 2-[4- (dimethylamino)phenyl]ethanol, N,N dimethyl-p-toluidine, bis-(hydroxyethyl)-p- toluidine, triethanolamine and combinations thereof.

[0032] The at least one curing accelerator can comprise 0.1 to 5% by weight based on the total weight of the composition.

[0033] The at least one free-radical inhibitor can be selected from the group consisting of of butylated hydroxy toluene, hydroquinone, hydroquinone mono- methyl ether, 1,4-benzoquinone, phenothiazine and combinations thereof.

[0034] The at least one adhesion promoter in the dental restorative composition an be is selected from the group comprising of 2 -hydroxy ethyl methacrylate,

hydroxypropyl methacrylate, pyromellitic dianhydride glycerol dimethacrylate adduct, bis(2-methacryloxy)pyromelliate, methacryloxyethyl phthalate,

methacryloxyethyl maleate, methacryloxyethyl succinate, glycerol dimethacrylate maleate, glycerol dimethacrylate succinate, hydroxy ethyl methacrylate phosphate, 10- methacryloxydecane phosphate, and combinations thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

[0035] FIG. 1 illustrates the methacrylate functional group conversion upon photopolymerization of the control resin (70:30 mix BisGMA/TEGDMA) and the BisGMA replacement resin (70:30 mix H1345/TEGDMA). [0036] FIG. 2 illustrates and compares the flexural strength of the two resin systems after photopolymerization in both dry and wet conditions.

[0037] FIG. 3 illustrates and compares the flexural modulus of the two resin systems after photopolymerization in both dry and wet conditions.

[0038] FIG. 4 illustrates and compares the shrinkage % of the two resin systems.

[0039] FIG. 5 illustrates and compares the stress of the two resin systems.

DETAILED DESCRIPTION

[0040] It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention claimed. As used herein, the use of the singular includes the plural unless specifically stated otherwise. As used herein, "or" means "and/or" unless stated otherwise. Furthermore, use of the term "including" as well as other forms, such as "includes," and "included," is not limiting.

[0041] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0042] Unless specific definitions are provided, the nomenclatures utilized in connection with, and the laboratory procedures and techniques of analytical chemistry, synthetic organic and inorganic chemistry described herein are those known in the art, such as those set forth in "IUPAC Compendium of Chemical Terminology: IUPAC Recommendations (The Gold Book)" (McNaught ed.; International Union of Pure and Applied Chemistry, 2ⁿ Ed., 1997) and "Compendium of Polymer Terminology and Nomenclature: IUPAC Recommendations 2008" (Jones et al., eds; International Union of Pure and Applied Chemistry, 2009). Standard chemical symbols are used interchangeably with the full names represented by such symbols. Thus, for example, the terms "hydrogen" and "H" are understood to have identical meaning. Standard techniques may be used for chemical syntheses, chemical analyses, and formulation.

Definitions

[0043] "About" as used herein means that a number referred to as "about" comprises the recited number plus or minus 1-10% of that recited number. For example, "about" 100 degrees can mean 95-105 degrees or as few as 99-101 degrees depending on the situation. Whenever it appears herein, a numerical range such as " 1 to 20" refers to each integer in the given range; e.g., " 1 to 20 carbon atoms" means that an alkyl group can contain only 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 20 carbon atoms (although the term "alkyl" also includes instances where no numerical range of carbon atoms is designated).

[0044] "Adhesive" or "adhesive compound" as used herein, refers to any substance that can adhere or bond two items together. Implicit in the definition of an "adhesive composition" or "adhesive formulation" is the fact that the composition or formulation is a combination or mixture of more than one species, component or compound, which can include adhesive monomers, oligomers, and/or polymers along with other materials, whereas an "adhesive compound" refers to a single species, such as an adhesive polymer or oligomer. [0045] More specifically, adhesive composition refers to un-cured mixtures in which the individual components in the mixture retain the chemical and physical characteristics of the original individual components of which the mixture is made. Adhesive compositions are typically malleable and may be liquids, paste, gel or another form that can be applied to an item so that it can be bonded to another item.

[0046] "Cured adhesive," "cured adhesive composition" or "cured adhesive compound" refers to adhesives components and mixtures obtained from reactive curable original compound(s) or mixture(s) thereof which have undergone a chemical and/or physical changes such that the original compound(s) or mixture(s) is (are) transformed into a solid, substantially non-flowing material. A typical curing process may involve crosslinking.

[0047] "Curable" means that an original compound(s) or composition material(s) can be transformed into a solid, substantially non-flowing material by means of chemical reaction, crosslinking, radiation crosslinking, or the like. Thus, adhesive compositions of the invention are curable, but unless otherwise specified, the original compound(s) or composition material(s) is (are) not cured.

[0048] "Thermoset," as used herein, refers to the ability of a compound, composition or other material to irreversibly "cure" resulting in a single three- dimensional network that has greater strength and less solubility compared to the non- cured product. Thermoset materials are typically polymers that may be cured, for example, through heat (e.g. above 200° Celsius), via a chemical reaction (e.g. epoxy ring-opening, free-radical polymerization, etc or through irradiation (e.g. visible light, UV light, electron beam radiation, ion-beam radiation, or X-ray irradiation). [0049] Thermoset materials, such as thermoset polymers or resins, are typically liquid or malleable forms prior to curing, and therefore may be molded or shaped into their final form, and/or used as adhesives. Curing transforms the thermoset resin into a rigid infusible and insoluble solid or rubber by a cross-linking process. Thus, energy and/or catalysts are typically added that cause the molecular chains to react at chemically active sites (unsaturated or epoxy sites, for example), linking the polymer chains into a rigid, 3-D structure. The cross-linking process forms molecules with a higher molecular weight and resultant higher melting point. During the reaction, when the molecular weight of the polymer has increased to a point such that the melting point is higher than the surrounding ambient temperature, the polymer becomes a solid material.

[0050] "Cross-linking," as used herein, refers to the attachment of two or more oligomer or longer polymer chains by bridges of an element, a molecular group, a compound, or another oligomer or polymer. Crosslinking may take place upon heating or exposure to light; some crosslinking processes may also occur at room temperature or a lower temperature. As cross-linking density is increased, the properties of a material can be changed from thermoplastic to thermosetting.

[0051] The term "monomer" refers to a molecule that can undergo polymerization or copolymerization thereby contributing constitutional units to the essential structure of a macromolecule (a polymer).

[0100] "Polymer" and "polymer compound" are used interchangeably herein, to refer generally to the combined the products of a single chemical polymerization reaction. Polymers are produced by combining monomer subunits into a covalently bonded chain. Polymers that contain only a single type of monomer are known as "homopolymers," while polymers containing a mixture of monomers are known as "copolymers."

[0052] As used herein, "aliphatic" refers to any alkyl, alkenyl, cycloalkyl, or cycloalkenyl moiety.

[0053] "Aromatic hydrocarbon" or "aromatic" as used herein refers to compounds having one or more benzene rings.

[0054] "Alkane," as used herein, refers to saturated straight-chain, branched or cyclic hydrocarbons having only single bonds. Alkanes have general formula

[0055] As used herein, "alkyl" refers to straight or branched chain hydrocarbyl groups having from 1 up to about 500 carbon atoms. "Lower alkyl" refers generally to alkyl groups having 1 to 6 carbon atoms. The terms "alkyl" and "substituted alkyl" include, respectively, substituted and unsubstituted C1-C500 straight chain saturated aliphatic hydrocarbon groups, substituted and unsubstituted C2-C200 straight chain unsaturated aliphatic hydrocarbon groups, substituted and unsubstituted C4-C100 branched saturated aliphatic hydrocarbon groups, substituted and unsubstituted Ci- C500 branched unsaturated aliphatic hydrocarbon groups.

[0056] For example, the definition of "alkyl" includes but is not limited to: methyl (Me), ethyl (Et), propyl (Pr), butyl (Bu), pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, ethenyl, propenyl, butenyl, penentyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, isopropyl (i-Pr), isobutyl (i-Bu), tert-butyl (t-Bu), sec-butyl (s- Bu), isopentyl, neopentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, methylcyclopropyl, ethylcyclohexenyl, butenylcyclopentyl, tricyclodecyl, adamantyl, norbornyl and the like.

[0057] As used herein, the term "acrylate" refers to a compound bearing at least one moiety having the structure:

[0058] As used herein, the term "methacrylate" refers to a compound bearing at least one moiety having the structure:

[0059] As used herein, the term "free radical initiator" refers to any chemical species which, upon exposure to sufficient energy (e.g., light, heat, or the like), decomposes into parts, which are uncharged, but every one of such part possesses at least one unpaired electron.

[0060] As used herein, the term "coupling agent" refers to chemical species that are capable of bonding to a mineral surface and which also contain polymerizably reactive functional group(s) so as to enable interaction with the adhesive composition.

[0061] "Modulus" or "Young's modulus" as used herein, is a measure of the stiffness of a material. Within the limits of elasticity, modulus is the ratio of the linear stress to the linear strain, which can be determined from the slope of a stress-strain curve created during tensile testing.

[0100] "Thixotropy" as used herein, refers to the property of a material which enables it to stiffen or thicken in a relatively short time upon standing, but upon agitation or manipulation to change to low-viscosity fluid; the longer the fluid undergoes shear stress, the lower its viscosity. Thixotropic materials are therefore gel-like at rest but fluid when agitated and have high static shear strength and low dynamic shear strength, at the same time.

[0062] BisGMA (bisphenol A diglycidyl ether methacrylate), which is the most widely used resin in dental composite fillings has some great properties, however, due to potential long-term health effects it is being phased out and replacement resins are being evaluated.

[0063] The present invention provides liquid urethane dimethacrylates based on the reaction products of equal molar ratios of 2-hydroxypropylmethacrylate and 2- hydroxy ethylmethacrylate along with the mixed isomers of MDI according to the following structure :

Liquid Urethane Dimethacrylate Isomers

[0064] Methylene diphenyl diisocyanate (MDI) is an aromatic diisocyanate, with three common isomers positioned around the aromatic rings. These isomers are known as the 4,4'-MDI, the 2,4'-MDI and the 2,2'-MDI, the structures of these isomers are shown below.

4,4' 2,4' 2,2' Mixed MDI

[0065] The 4,4' -MDI isomer is a crystalline solid and is the most widely used isomer for the preparation of various rigid polyurethanes. The mixed isomers, typically commercially available are 50:50 blends of the 4,4'-MDI and the 2,4'-MDI are liquids at room temperature. Not to be bound by any limitations, the mixtures of MDI contemplated for use in the practice of the invention can have variable ratios of the 4,4'-MDI and the 2,4'-MDI isomers, and optionally also contain the 2,2'-MDI isomer that form non-crystalline liquids.

[0066] The position of the isocyanate groups is very important due to the reactivity difference. The isocyanate at the 2-position is more sterically hindered; therefore, it is known to be about 3-4 times less reactive than the isocyanate at the 4-position. This difference in reactivity can be taken advantage of to form unique molecules with special properties.

[0067] Accordingly, in the first step of the synthesis, the mixed-MDI is reacted with about 0.5 equivalents of a methacrylate species that contains a secondary alcohol. The secondary alcohol being less reactive than a primary alcohol will almost exclusively react with the more reactive isocyanate at the 4-position. At this point about 0.5 equivalents or excess of a methacrylate species containing a primary alcohol is added to the reaction mixture, which reacts with the remaining isocyanate groups (either 4-position or 2-position) to complete the urethane synthesis.

[0068] The methacrylate species containing secondary alcohols contemplated for use in the practice of the invention include the following non-limiting examples: Hydroxypropyl methacrylate (HPMA); hydroxybutyl methacrylate; 2-hydroxypropyl methacrylamide; poly(propylene glycol) mono-methacrylate; glycerol dimethacrylate, and such.

[0069] The methacrylate species containing primary alcohols contemplated for use in the practice of the invention include the following non-limiting examples: 2- hydroxy ethyl methacrylate; 3 -hydroxypropyl methacrylate; 4-hydroxybutyl methacrylate; polyethylene glycol mono-methacrylate; N-(2- hydroxyethyl)methacrylamide, and such.

[0070] It is known to those skilled in the art that the all of the acrylated and methacrylated urethane derivatives used in the invention compositions are readily prepared by the reaction of the corresponding isocyante species with a

hydroxyalkylacrylate or hydroxyalkylmethacrylate in the presence of an appropriate catalyst such as dibutyltin dilaurate. Many other metal carboxylates are also used to produce urethanes such as aluminum, bismuth, zinc and zirconium. Tertiary amines such as triethylenediamine, l,4-diazabicyclo[2.2.2]octane, dimethylcyclohexylamine, and dimethylethanolamine are also used to prepare the acrylated urethanes.

[0071] The invention urethane dimethacrylate resin compositions may utilize various initiators and accelerators in the formulations. In one embodiment, the free- radical initiated photopolymerization may be photoinitiated by any light wavelength range within the ultraviolet (about 200 to about 400nm) and/or visible light spectrum (about 380 to about 780nm). The choice of the Wavelength range can be determined by the photoinitiator employed. [0072] The photoinitiators contemplated for use in the practice of the invention are those capable of generating free radicals upon exposure to ultraviolet light. BASF, formerly Ciba and many other companies offer a variety of photoinitiators for use in light curing coatings. All of these photoinitiators are contemplated for use in the practice of the invention.

[0073] In one embodiment, the resin further comprises a polymerization

photoinitiator. In one aspect, any radical photoinitiator may be employed. In another aspect, a photoinitiator responsive to visible light is employed. In a one aspect, the photoinitiator is a bis-acyl phosphine oxide (BAPO). In a specific aspect, the BAPO photoinitiator is phenyl bis(2,4,6 trimethyl benzoyl) phosphine oxide (Irgacure 819, Ciba). In another aspect, the photoinitiator is a metallocene initiator. In a specific aspect, the mettallocene initiator is Bis-9-eta 5-2,4 cyclopentadien-l-yl) Bis[2,6- difluoro-3-(lH-pyrrol-l-yl)phenyl]titanium (Irgacure 784, Ciba). In another aspect, if photopolymerization using visible light is desired, camphorquinone (CQ) may be used as an initiator, in combination with an accelerator, such as, for example, ethyl 4- dimethylaminobenzoate (EDAB). Alternatively, if ultraviolet (UV)

photopolymerization is desired, then an appropriate UV light activated photoinitiator may be employed. For example, the photoinitiator can be selected from an alpha- hydroxyketone, such as 1-hydroxy-cyclohexyl-phenylketone (Irgacure 184, Ciba); a benzyl dimethyl-ketal, such as 2,2-dimethoxy-2-phenylacetophenone (DMPA, e.g. Irgacure 651, Ciba), or a number of other commercially available photoinitiators may be used as an initiator. Photoinitiators can be used in amounts ranging from about 0.1 to about 5 weight percent (wt %). [0074] In another embodiment, one or more accelerators are utilized in the photopolymerization. Amine accelerators may be used as polymerization accelerators, as well as other accelerators. Polymerization accelerators suitable for use are the various organic tertiary amines well known in the art. In visible light curable compositions, the tertiary amines are generally acrylate derivatives such as dimethyl aminoethyl methacrylate and, particularly, diethyl aminoethyl methacrylate

(DEAEMA), EDAB and the like, in an amount of about 0.05 to about 0.5 wt %. The tertiary amines are generally aromatic tertiary amines, preferably tertiary aromatic amines such as EDAB, 2-[4-(dimethylamino)phenyl]ethanol, N,N dimethyl-p- toluidine (commonly abbreviated DMPT), bis (hydroxyethyl)-p-toluidine,

triethanolamine, and the like. Such accelerators are generally present at about 0.5 to about 4.0 wt % in the polymeric component.

[0075] Although most dental composites are light cured materials, there is still a need for two-part systems that can be mixed together to start the initiation process. In some areas of the mouth where the dentist or dental technician is unable to effectively apply a light source to cure the composite a two-part system is employed. Wherein, one part of the formulation contains a free-radical initiator such as benzoyl peroxide(PBO), and the other part of the formulation contains a tertiary amine such as bis(2-hydroxyl)-p-toluidine or N,N-dimethyl-p-toluidine. The two-part type curing initiation is also contemplated for use in the practice of the invention.

[0076] Since the invention formulations are free-radically curable materials, they will also have to contain free-radical inhibitors. The addition of free-radical inhibitors helps to give the product shelf life and prevent premature curing of the material. Many of these free-radical inhibitors are known as antioxidants, these compounds include reducing agents such as thiols, ascorbic acid and polyphenols. In the laboratory phenolic compounds such as butylated hydroxytolune (BHT) and methoxyhydroquinone (MeHQ), hydroquinone (HQ), are added to formulations. The combination of a phenolic inhibitor with benzoquinone derivatives has a synergistic effect and is a more potent inhibitor mix. The addition of certain nitrosyl compounds, certain tertiary amines, nitro-aromatic compounds are known to those skilled in the art to prevent premature free radical curing. The amount of free radical inhibitor contemplated for use in the practice of the invention can vary from 50 ppm (parts per million) to about 5000 ppm.

[0077] In another embodiment, the resin compositions of the disclosure further comprise one or more fillers. In one aspect, fillers are used to increase the viscosity of the dental restorative material, to tailor the hydrophilicity of the dental impression material, and to increase the stiffness (rubbery modulus) of the cured impression. The filled compositions can include one or more of the inorganic fillers currently used in dental restorative materials, the amount of such filler being determined by the specific function of the filled materials. Thus, for example, in one aspect dental impression materials may be mixed with one or more inorganic filler compounds such as barium, ytterbium, strontium, zirconia silicate and/or amorphous silica to match the color and opacity to a particular use or tooth. The filler can be a silanized filler. The filler is typically in the form of particles with a size ranging from 0.01 to 5.0 micrometers. In one aspect, the filler is a hydrophobic fumed silica. In one specific aspect, the hydrophobic fumed silica filler is composed of nanoparticles or nanoclusters. A nanoparticle is defined as any particle less than 100 nanometers (nm) in diameter. A nanocluster is an agglomeration of nanoparticles. In one aspect, utilization of nanoclusters in a nanosized filler can be exploited to increase the load and improve some mechanical properties. Other suitable fillers are known in the art, and include those that are capable of being covalently bonded to the impression material itself or to a coupling agent that is covalently bonded to both. Examples of suitable filling materials include but are not limited to, barium glass, ytterbium nanoglasses and nanoclusters, fumed silica, silica, silicate glass, quartz, barium silicate, strontium silicate, barium borosilicate, strontium borosilicate, borosilicate, lithium silicate, lithium alumina silicate, amorphous silica, ammoniated or deammoniated calcium phosphate and alumina, zirconia, tin oxide, and titania. In one aspect, the filler is a mixture of barium glass, ytterbium nanoglasses and nanoclusters, and fumed silica. The above described filler materials may be combined with the resins of the disclosure to form a dental composite material with high strength along with other beneficial physical and chemical properties. In one aspect, suitable fillers are those having a particle size in the range from about 0.01 to about 5.0 micrometers, mixed with a silicate colloid of about 0.001 to about 0.07 micrometers. The filler may be utilized in the filled resin compositions of the disclosure in the amount of from about 40-wt % to about 90-wt %; preferably about 60-wt % to 85-wt %; more preferably about 70-wt % to about 80-wt % of the total weight of the composition.

[0078] In one aspect, the resin composition further comprises a UV absorber. The UV absorber can be selected from, for example, 5-benzoyl-4-hydroxy-2-methoxy- benzene sulfonic acid, Uvinul® 3000 from BASF Corp., and other various benzophenones, e.g. UV-5411 from America Cyanamid. The UV absorber can be present in from about 0.05 to about 5-wt %; preferably less than about 0.5-wt % of the weight of the total weight of the filled composition.

[0079] Additional ingredient added to the formulation includes compound such as hydroxyethyl acrylate. Not to be bound by any particular theory, but these compounds are often added to boost the adhesion of the material to various substrates or to modify the viscosity of the formulation.

[0080] In another embodiment of the invention certain adhesion promoters are either used as primers or in the dental composite formulation to help adhere the filling to the natural tooth. The adhesion promoters are also contemplated for use in the practice of the invention. Typically, materials such as curable phosphates, borates and the like are used in these applications. Compounds bearing carboxylic acid anhydrides are also contemplated for use in the practice of the invention.

[0081] In another embodiment of the invention reactive diluents or co-monomers are added to the formulation to bring about a lower viscosity and or change other properties such as modulus, cure speed, hydrophobicity, adhesion and such. The reactive diluents or co-monomers are typically based on methacrylate monomers.

[0082] The term "methacrylate monomer" refers to a discrete chemical compound that is an ester of methacrylic acid. Methacrylate monomers suitable for embodiments the present invention include any monomer having one or preferably two or more methacrylate moieties. Unless otherwise specified or implied, the term

"(meth)acrylate" or "methacrylate" includes both the methacrylate and the analogous acrylate. [0083] Specific examples of monofunctional methacrylic ester compounds include methyl methaciylate, ethyl methaciylate, propyl methaciylate, butyl methaciylate, hydroxyethyl methaciylate, benzyl methaciylate, methoxyethyl methaciylate, glycidyl methaciylate, tetrahydrofurfuryl methaciylate, and the hydroxyethyl methaciylate monoester of trimellitic anhydride.

[0084] Specific examples of polyfunctional methacrylic ester compounds include dimethaciylates of ethylene glycol derivatives, such as ethylene glycol

dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, ethoxylated bisphenol-A dimethacrylate

(EBPADMA), hexanediol dimethacrylate, decanediol dimethacrylate and other diol dimethaciylates as well as various polyol methaciylate compounds are also contemplated for use in the invention.

[0085] Other examples of polyfunctional methacrylic ester compounds include, without limitation, Bis-GMA, UDMA, and other urethane dimethaciylates. The polyester dimethaciylates or PEM compounds (Designer Molecules, Inc., San Diego, CA) are also contemplated for use in the practice of the invention.

[0086] In another embodiment of the invention, the dimethacrylate invention compositions are to utilized as dental restorative materials. As such, dental professionals can be provided with the photocurable restorative compositions in a syringe for use. The material would be dispensed and applied to the cavity, followed by photopolymerization using an appropriate light source. The dental professional can then finish or polish the cured material using the appropriate tools. Such dental restoratives can be used for direct anterior or posterior restorations, core-build-ups, and splinting, and for indirect restorations including inlays, onlays and veneers.

EXAMPLES

Example 1

Synthesis of H1345 Reaction Product of Mixed MDI with HPMA and HEMA

[0087] Load a 500-mL jacketed reactor with the MDI blend, Lupranate MI (200.2 g). Add BHT (0.17 g) and dibutyl tin dilaurate (0.07 g). Warm to 40C and stir. Add HPMA (115.3 g). The reaction temperature rises to 60°C. After 49 minutes, the reaction cools to 42°C and the HEMA (114.8 g) can be added. Again, the reaction warms up now to 68°C. After reaction temperature drops to 60°C, the bath around it can be warmed to 60°C and maintained at that temperature until the IR signal of the isocyante (NCO) group disappears. Drain and package product (H1345).

Example 2

Adduct Resin (HI 345) and Formulation Comparison to Bis-GMA

[0088] The following Table 1 shows data for monomer blend ratios, comparing bisGMA/TEGDMA mixtures with the H1345/TEGDMA mixtures.

TABLE 1

Monomer Bled Ratio DataComparison of BisGMA/TEGDMA mixture with H1345/TEGDMA mixtures

DSC Cure

BisGMA (%) TEGDMA (%) RI Viscosity (cpsl Onset (°C) Peak (°Q Heat fJ/g)

70 30 1.5214 276.8 210.93 218.44 118.8 100 1.5501 22,050 236.78

100 1.4610 39.1 178.48 422.5

DSC Cure

Adduct (%) TEGDMA (%) RI Viscosity (cpsl Onset (°C) Peak (°Q Heat fJ/g)

65 35 1.5197 317 168.2 177.5 116.8

66 34 1.5202 351 163.3 171.4 141.5

67 33 1.5187 294 162.2 170.1 211.1

68 32 1.5225 417 165.7 176.5 142.8

70 30 1.5237 549 163.2 171.0 124.7

80 20 1.5329 1,681 163.7 171.3 142.0

100 0 1.5534 153,060 172.1 183.2 83.5

[0089] The HI 345 adduct refractive index and the viscosity are higher than the BisGMA standard. However, the BisGMA is widely utilized in dental composites not as a neat liquid but rather as a 70/30 blend with triethyleneglycol dimethacrylate (TEGDMA). The parameters of that blend closely match the parameters of the 68% HI 345 adduct blend with 32% TEGDMA.

Example 3

Polymer Physical Property Measurements

[0090] Table 2, shows the polymer physical property measurements for the simple blend of 70% bisGMA and 30% TEGDMA versus the 68% H1345 adduct and 32% TEGDMA. TABLE 2

Polymer Physical Properties

Photocured Polymer

BisGMA (%) TEGDMA (%) Tg (°C) Young's Modulus (GPa)

70 30 135.3 2.317

Adduct (%) TEGDMA (%) Tg (°C) Young's Modulus (GPa) 68 32 180.2 2.313

Chemically cured Polymer

BisGMA (%) TEGDMA (%) Tg (°C) Young's Modulus (GPa)

70 30 170.39 3.12

Adduct (%) TEGDMA (%) Tg (°C) Young's Modulus (GPa) 68 32 179.5 3.22

Example 4

Blend of Invention HI 345 Adduct with UDMA

[0091] The HI 345 adduct was also blended with urethane dimethacrylate (UDMA) in various ratios to understand if the viscosity would drop far enough to produce usable blends, as well as to understand the cure profile. The results are summarized in Table 3. The addition of UDMA to the HI 345 adduct appears to give a very high viscosity blend that would not be suitable for many dental composite applications.

TABLE 3 Blends of H 1345 Adduct with UDMA

DSC Cure

Adduct (%) UDMA (%) RI Viscosity (cps) Onset (°C) Peak (°C) Heat (J/g)

60 40 1.5259 12,459 175.3 182.6 96.6

70 30 1.5283 18,413 176.3 184.9 71.6

80 20 1.5395 38,204 171.5 180.6 101.3

0 100 1.4842 1,396 169.9 191.9 109.9

Example 5

HI 345 Project

[0092] The purpose of this project was to evaluate the mechanical properties (flexure strength, flexure modulus, yield strength and fracture toughness), water sorption (Wsp) and solubility (Wsl), polymerization kinetics and degree of conversion (DC) of composites and resins formulated from a novel monomer system.

Materials and methods.

[0093] Control and experimental resins were prepared with a mix of 70-wt% BisGMA (bisphenol A-glycidyl-dimethacrylate) or H1345 adduct, and 30-wt% HDMA (1,6- Hexanediol dimethacrylate). To these mixtures, 0.2-wt% of

Camphorquinone and 0.8-wt% of EdMAB (Ethyl 4-dimethyl aminobenzoate) were added as photoinitiator and accelerator respectively. Control and experimental composites were prepared by mixing the resins with 70.5% of filler, comprised of a 5% silane-treated OX50 and 65.5% of a silanated barium borosilicate glass in a mechanical mixer at 2300 rpm for 2 minutes.

[0094] Degree of conversion (DC) and polymerization kinetics.

[0095] Uncured resins and composites were placed in silicon molds; 10-mm diameter and 1-mm thick, and placed in a Fourier transform infrared spectrometer. Infrared spectra were recorded immediately after placement, and then the specimen was illuminated with a cure unit, 700 mW/cm², for 60s. DC was calculated from the ratio of the C=C peak from the methacrylate group to that of the unchanging C... C peak from the aromatic ring, for the cured and uncured specimens. The

polymerization rate curve was obtained by taking the first derivative of the DC with respect to time. Spectra were obtained until 210s. The maximum value of the derivative was taken as the maximum polymerization rate (Rpmax, ADC%s). Table 4 summarized the functional group conversion for the filled and unfilled control and experimental composites and resins.

TABLE 4

Functional Group Conversion

Formulation Ratio Filler Methacrylate

Conversion (%)

BisGMA/HDMA 70/30 70.5% 62

H1345 HDMA 70/30 70.5% 58

Bis GMA HDMA 70/30 0% 60

H1345 HDMA 70/30 0% 49 [0096] Water sorption (Wsp) and solubility (Wsl).

[0097] Uncured resins and composites were placed in rubber molds (n=3), 10mm diameter and 1mm thick, sandwiched between slide glass, and photoactivated for 60s at 700 mw/cm², only in one side, with the tip in direct contact with the glass. After 24h, specimens were measured, to calculate volume, weighed (mi), and stored in distilled water, at 25(±1) °C for 7 days. In sequence, specimens were removed from storing, gently dried, and weighed again (m₂). After this period, samples were stored in a desiccator, at 37(±1) °C, and weighed each two days until a constant mass was obtained (m₃). Wsp and Wsl were obtained by applying the following calculations: Wsp=(m₂-m₃)/V and Wsl=(mi-m₃)/V. Table 5 summarizes the water sorption and water solubility of the control and experimental composites and resins. It is clear that the HI 345 compositions fair much better than the bisGMA compositions.

TABLE 5

Water Sorption and Solubility

Formulation Ratio Filler Water Sorption («g/mm³) Solubility («g/mm³)

BisGMA/HDMA 70/30 70.5 27 -2

H1345/HDMA 70/30 70.5 13 1

BisGMA HDMA 70/30 0 29 4

H1345/HDMA 70/30 0 14 10 [0098] Flexure strength, flexural modulus, yield strength and fracture toughness.

[0099] Bar-shaped specimens from resins and composites (n=10) were generated by compressing the composite between a stainless-steel mold (2 X 2 X 25mm) and a slide glass. For the fracture toughness, composite samples (n=6) were made into 2 X 5 X 25-mm dimension, as described before. All specimens were divided into three parts and light cured with overlapping exposure of 20s each, in both sides (total 120 s). After curing, specimens were stored in distilled water, for 24h, at 37(±1) °C. In sequence, samples were polished and their width and thickness measured with a micrometer. Flexure strength, flexural modulus, yield strength and fracture toughness was measured using three-point bending method with a universal testing machine, at a crosshead speed of 0.5mm/min (supporting span length 20mm). Tables 6 and 7 show the comparison data for the flexural strength, flexural modulus and yield strength for the compositions.

TABLE 6

Flexural Properties of Control and Experimental Composites and Resins

Formula Ratio Filler Flexural Strength (MPa) Flexural Modulus £GPa)

BisGMA/HDMA 70/30 70.5 88 6.4

H1345/HDMA 70/30 70.5 80 6.7

BisGMA HDMA 70/30 0 82 2.2

H1345/HDMA 70/30 0 62 1.1

TABLE 7 Yield Strength of Control and Experimental Composites and Resins

Formula Ratio Filler Yield Strength (MPa)

Bis GMA HDMA 70/30 70.5 84 H1345 HDMA 70/30 70.5 75 BisGMA/HDMA 70/30 0 70 H1345 HDMA 70/30 0 39

Claims

CLAIMS What is claimed is:

1. A liquid urethane dimethacrylate comprising the reaction product of one molar equivalent of mixed methylene diphenyl diisocyanate isomers with about 0.5 molar equivalents of a secondary alcohol (meth)acrylate followed by the addition of about molar 0.5 equivalents of a primary alcohol (meth)acrylate.

2. The liquid urethane dimethacrylate of claim 1, wherein the mixed methylene diphenyl diisocyanate isomers comprise a combination of 4,4' -MDI, 2,4' -MDI and optionally 2.2' -MDI.

3. The liquid urethane dimethacrylate of claim 1, wherein the secondary alcohol (meth)acrylate comprises compounds selected from the group consisting of hydroxypropyl (meth)acrylate, hydroxybutyl (meth)acrylate, poly(propylene glycol) mono-(meth)acrylate, 2-hydroxypropyl methacryl amide, and glycerol

dimethacrylate.

4. The liquid urethane dimethacrylate of claim 1, wherein the primary alcohol (meth)acrylate comprises at least one compound selected from the group consisting of 2-hydroxy ethyl (meth)acrylate, 3 -hydroxypropyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, N-(2-hydroxyethyl) methacrylamide, and polyethylene glycol mono- (meth)acrylate.

5. The liquid urethane di(meth)acrylate of claim 1, wherein liquid urethane di(meth)acrylate has a structure selected from the group consisting of:

6. A dental restorative composition comprising:

a) at least one a liquid urethane dimethacrylate; b) at least one filler; c) at least one reactive diluent; d) at least one initiator; e) at least one accelerator; f) at least one free-radical inhibitor; and g) at least one adhesion promoter.

7. The dental restorative composition of claim 6, wherein the at least one liquid urethane dimethacrylate comprises at least one compound selected from the group consisting of:

8. The dental composition of claim 7, wherein the liquid urethane dimethacrylate comprises 60 to 80% by weight of the composition based on the total weight of the resin mixture.

9. The dental restorative composition of claim 6, wherein the at least one filler is selected from the group comprising of fumed silica, colloidal silica, aluminosilicate glass, fluoro aluminosilicate glass, silica, quartz, strontium silicate, silanated barium borosilicate glass, strontium borosilicate, lithiumsilicate, lithium alumina silicate, amorphous silica, ammoniated or deammoniated calcium phosphate, alumina, Zirconia, tin oxide, titania, and mixtures comprising at least one of the foregoing fillers.

10. The dental restorative composition of claim 9, wherein the at least one filler comprises 60 to 85% by weight of the composition based of the composition on the total weight of the filled composition.

11. The dental restorative composition of claim 6, wherein the at least one reactive diluent is selected from the group consisting of ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, ethoxylated bisphenol-A dimethacrylate (EBPADMA), hexanediol dimethacrylate, decanediol dimethacrylate, urethane dimethacrylate (UDMA) and combinations thereof.

12. The dental restorative composition of claim 11, wherein the at least one reactive diluents comprise 20 to 40% by weight of the composition based on the total weight of the resin.

13. The dental restorative composition of claim 6, wherein the at least one initiator is selected from the group consisting of phenyl bis(2,4,6 trimethyl benzoyl) phosphine oxide, Bis-9-eta 5-2,4 cyclopentadien-l-yl) Bis[2,6-difluoro-3-(lH-pyrrol- 1 -yl)phenyl]titanium, camphorquinone (CQ), 1 -hydroxy-cyclohexyl-phenylketone, 2,2-dimethoxy-2-phenylacetophenone, benzoyl peroxide (BPO) and combinations thereof.

14. The dental restorative composition of claim 13, wherein the at least one initiator comprises 0.1 to 5% by weight of the composition based on the total weight of the composition.

15. The dental restorative composition of claim 6, wherein the at least one curing accelerator is selected from the group comprising of ethyl 4-dimethylaminobenzoate, diethyl aminoethyl methacrylate, 2-[4-(dimethylamino)phenyl]ethanol, N,N dimethyl-p-toluidine, bis-(hydroxyethyl)-p-toluidine, triethanolamine and

combinations thereof.

16. The dental composition of claim 15, wherein the at least one curing accelerator comprises 0.1 to 5% by weight based on the total weight of the composition.

17. The dental restorative composition of claim 6, wherein the at least one free- radical inhibitor is selected from the group consisting of of butylated hydroxy toluene, hydroquinone, hydroquinone mono-methyl ether, 1,4-benzoquinone, phenothiazine and combinations thereof.

18. The dental restorative composition of claim 6, wherein the at least one adhesion promoter is selected from the group comprising of 2-hydroxy ethyl methacrylate, hydroxypropyl methacrylate, pyromellitic dianhydride glycerol dimethacrylate adduct, bis(2-methacryloxy)pyromelliate, methacryloxyethyl phthalate, methacryloxyethyl maleate, methacryloxyethyl succinate, glycerol dimethacrylate maleate, glycerol dimethacrylate succinate, hydroxyethyl

methacrylate phosphate, 10-methacryloxydecane phosphate, and combinations thereof.