WO2010033515A1 - Single-container dental adhesive - Google Patents

Abstract

Compositions of the invention are mixtures of acid-free polymerizable (meth)acrylate monomers and polymerizable phosphate (meth)acrylate monomers, all having minimized amounts of carbamyl groups, and polymerization initiation systems that are optionally in the form of solutions in non-hydroxylic water-miscible solvents to provide single-container dental adhesives with improved storage stability that exhibit reduced microleakage and excellent bond strength to dentin, enamel, metals, composite, ceramic and porcelain without requiring a pre-treatment of tooth surfaces such as etching or priming.

Description

SINGLE-CONTAINER DENTAL ADHESIVE

I. CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit under 35 U.S.C. § 119(e) of United States Provisional Patent Application No. 61/097,473 filed on September 16, 2008, which is hereby incorporated by reference in its entirety.

II. INTRODUCTION

A. Field of the Invention

[0002] This invention relates to stable adhesive compositions. This invention also relates to stable dental adhesive compositions for adhering dental restoratives to dentin, enamel and other common dental substrates. More specifically, this invention provides an all-in-one- container, self-etching, self-priming dental adhesive for adhering dental restorative materials such as metal, porcelain, filling composites, filling compomers, fissure sealants, root coating materials, lining, luting, and other resin cements to each other and to dental substrates such as enamel and dentin through a simple procedure.

B. Background of the Invention

[0003] Former dental adhesive systems require the application of at least two mixtures from separate containers or sources (such as bottles, impregnated brushes, syringes, or packets) to tooth surfaces in techniques requiring one or more steps. Total-etch (three-step) and self-etch (two-step) products have come into general use.

[0004] In total-etch systems the tooth is first treated with an acid solution or gel that preferentially dissolves part of the tooth enamel to create microporosities known as tags. It dissolves the smear layer, a layer created when dentin is cut, and opens the tubules. In the second step the surface is then rinsed and at least partially dried. Thirdly, the resin monomer-based adhesive is applied to the surface using a brush or swab so that it penetrates the tags and tubules to provide some mechanical as well as chemical bonding. The adhesive, which may also contain a solvent, is air-thinned and then cured with a light- emitting dental curing unit.

[0005] In self-etch systems an acidic primer solution partially dissolves and penetrates tooth surfaces. The volatile portion of the solution evaporates during placement. The organic residue remains until the adhesive is placed over it. The adhesive and the primer intermix at the surface during adhesive placement. In some cases volatile solvents from the adhesive are again removed before curing the layers with a strong blue light. Restorative application and curing follows to complete the treatment procedure.

[0006] Unlike two-container self-etch systems that must be dispensed and separately applied, the inventors realized that an adhesive that features one container dispensing and can be directly applied to the tooth surface in one application step would be desirable. Such an adhesive would not substantially penetrate into dentinal tubules. Instead, it reinforces the dentinal tubule smear plugs by hybridization of the smear layer. The smear layer is a mixture of organic and inorganic components left on a tooth surface after removal of decayed and healthy tooth tissue by, for example, a dental laser, a dental drill, bur, or reamer, or by abrasion by powders or particle slurries.

[0007] Compared to the conventional adhesive types (three-step or two-step techniques), a strong adhesive composition for adhering a restorative device to tooth structure through a one-step process is greatly desired. Most recently, several companies developed one-part self-etching adhesives to provide bond strength to dentin and enamel such as Clearfil S

Bond (Kuraray Medical), G-Bond (GC), Xeno IV (Dentsply), I-Bond (Heraeus Kulzer), and OptiBond All-in-One (Kerr). These commercial products each include a monomer having a phosphate acid group that demineralizes or etches the tooth surface.

[0008] Though these one-container self-etch products are less time consuming, the inventors found their bond strength to enamel, especially to un-cut enamel, does not compare well to the three-step total-etch and two-step self-etch techniques. The three-step total-etch adhesive is still the "gold standard" for enamel bonding.

[0009] Also, the inventors have found that these commercial products do not exhibit adequately long shelf lives, that is, more than two years, when stored at normal room temperatures of 21 - 25⁰C. [0010] Moreover, according to a recent clinical evaluation, the current commercial one- container adhesives show higher microleakage than those systems requiring three-step and two-step processes.

[0011] Microleakage is defined as the passage of bacteria, fluids, molecules, or ions through the space between a cavity wall and the restorative material. Microleakage can lead to staining, post-operative sensitivity, and/or recurrent caries. Since these conditions may shorten the longevity of a restoration they should be minimized or preferably eliminated.

[0012] In order to overcome these clinical problems, it would be advantageous to provide a long-term-stable single-container self-etching adhesive with high bond strength to dentin, enamel, metal, ceramic and porcelain that also minimizes microleakage.

[0013] To overcome some of the stability issues, many adhesives are presented in two parts that must either be 1) mixed just prior to use or 2) used sequentially. Both types present clinical challenges; the former because dosing to the proper mix ratio may be imprecise and the latter because contamination of the surface by blood or saliva may occur in the interim between steps. Both are less desirable because in order to use one part, the matching part must be available. Some manufacturers have designed multi-segmented packages to separate incompatible components to help increase shelf life. The user manipulates the package to break seals between the compartments causing admixture of the separated components just prior to use. While this has been a successful solution, the cost of such packaging is far greater than that of a simple dropper bottle or unit dose container suitable for use with one patient. Such additional costs are certainly passed on to the recipient of the adhesive service, that is, the patient.

[0014] US Patent 5,834,532 describes a curable composition comprising a polymerizable unsaturated monomer having an acidic group in its molecule, a polymerizable unsaturated monomer having a hydroxyl group in its molecule, a polymerization initiator, and an amine compound. There is no data on shelf-stability of these compositions.

[0015] US Patent 6,812,266 describes dental adhesives that use acidic polymerizable (meth) acrylamides to prevent hydrolysis, however no data is presented to substantiate the claim of improved shelf stability and no teaching against the use of hydroxylic solvents is given therein. [0016] US Patent 6,916,858 describes a one-pack type dental adhesive that does not require tooth pretreatment and is comprised of a polymerizable monomer containing a phosphoric acid group and a polymerizable monomer containing a plurality of carboxyl groups, however it specifically requires 15-50% by weight of water in the formulation. [0017] US Patent 7,129,281 describes dental adhesives that use radical polymerizable monomers having a phosphoric ester and/or pyrophosphoric ester group therein and another polymerizable monomer, however no data is presented for shelf stability and this patent actually teaches using polymerizable monomers having carbamyl groups with hydrogen bonded to the carbamyl nitrogen and hydroxylic solvents. [0018] US Pub. No. 2007/0197683 describes dental composition that does not require a separate etching and bonding step and comprises a polymerizable (meth)acrylate carboxylic acid/anhydride; a copolymerizable multi-functional (meth)acrylate resin; a copolymerizable diluent monomer; and a curing system. However, the reported shear bonding strength was low. Also, there is no data on shelf-stability of these compositions.

III. SUMMARY OF THE INVENTION

[0019] The object of the present invention is to provide a long-term stable, single container adhesive composition. This composition can also be used as a dental adhesive composition that requires no pre-treatment such as etching or priming of the tooth surface, requires no mixing of two or more components at the time of use, and provides an excellent bond strength and minimal microleakage. After extensive and intensive investigations, the present inventors have designed a long-term stable adhesive composition. This long-term stable single-container adhesive composition can be used as a bonding agent or an adhesive for a variety of medical applications. It can be used as an adhesive for hard animal tissues, preferably for hard tissues of human body such as bones and teeth, and more preferably for human teeth. This long-term stable single-container adhesive composition is capable of being applied to tooth surfaces in one step that when cured shows minimized microleakage and exhibits high adhesive strength to natural tooth surfaces such as dentin, enamel, and cementum as well as to various other dental materials such as dental resins, composites, cements, coatings, fissure sealants, noble and non-noble metals, porcelain, and ceramic, allowing these various restorations and restorative materials to be strongly adhered to tooth surfaces and to each other. [0020] In one embodiment, the present invention provides a stable single-container adhesive composition comprising:

a) at least one phosphate (meth)acrylate monomer;

b) at least one acid-free polymerizable monomer having vinyl or (meth)acryl groups;

c) at least one polymerization initiator;

d) at least one polymerization inhibitor; and optionally

e) a water-miscible non-hydroxylic organic solvent.

[0021] In another embodiment, the present invention provides a a stable single-container adhesive composition consisting essentially of:

a) at least one phosphate (meth)acrylate monomer;

b) at least one acid-free polymerizable monomer having vinyl or (meth)acryl groups;

c) at least one polymerization initiator;

d) at least one polymerization inhibitor; and optionally

e) a water-miscible non-hydroxylic organic solvent.

[0022] In another embodiment, the present invention provides a process of preparing an adhesive, wherein the process comprises blending together at least one phosphate (meth)acrylate monomer, at least one acid-free polymerizable monomer having vinyl or (meth)acryl groups, at least one polymerization initiator, at least one polymerization inhibitor optionally in a water-miscible non-hydroxylic organic solvent in a container non- porous to acetone and water.

[0023] In another embodiment, the present invention provides a method of tooth restoration wherein the method involves: i) transferring an effective amount of water to a tooth surface via an applicator to provide a wet tooth surface;

ii) applying the dental adhesive composition as described above to the wet tooth surface to provide an adhesive layer on the tooth surface; and

iii) adhering a dental material to the adhesive layer on the tooth surface.

[0024] The adhesive composition of the present invention can be dispensed in containers of various sizes. In another embodiment, the present invention also provides a container having a volume of 0.05 to 50 ml, from which can be dispensed an adhesive composition comprising:

a) at least one phosphate (meth)acrylate monomer;

b) at least one acid-free polymerizable monomer having vinyl or (meth)acryl groups;

c) at least one polymerization initiator;

d) at least one polymerization inhibitor; and optionally

e) a water-miscible non-hydroxylic organic solvent.

[0025] In another embodiment, the present invention provides a kit comprising:

i) a dental adhesive composition as described above;

ii) one or more delivery devices calibrated to administer the composition of i) in an amount sufficient to coat at least one tooth surface for the purpose of restoration; and

iii) instructions. [0026] In another embodiment, the present invention provides a dental adhesive composition comprising:

a) at least one phosphate (meth)acrylate monomer in an amount sufficient to provide adhesion to a natural tooth surface or artificial surfaces encountered during tooth restoration procedures; b) at least one acid-free polymerizable monomer having a vinyl or (meth)acryl group in an amount sufficient to interact with the monomer of (a) to provide acceptable mechanical properties of the composition on a natural tooth surface or artificial surfaces encountered during tooth restoration procedures, while providing stability of the dental adhesive composition for at least 90 days at room temperature; c) a polymerization initiator in an amount sufficient to initiate polymerization of the monomers by light irradiation of the composition; d) a polymerization inhibitor in an amount sufficient to aid in providing stability to the composition during storage prior to use for at least 90 days at room temperature; e) a water-miscible, hydroxyl-free organic solvent in an amount sufficient to solubilize the monomers a) and b), the initiator c), and the inhibitor d).

IV. DETAILED DESCRIPTION OF THE INVENTION

A. Compositions

[0027] As used herein, the term "comprising" is intended to mean that the compositions and methods include the recited elements, but do not exclude others. "Consisting essentially of when used to define compositions and methods, shall mean excluding other elements of any essential significance to the combination for the intended use. Thus, a composition consisting essentially of the elements as defined herein would not exclude trace contaminants from the isolation and purification method and pharmaceutically acceptable carriers, such as phosphate buffered saline, preservatives, and the like. "Consisting of shall mean excluding more than trace elements of other ingredients and substantial method steps for administering the compositions of this invention. Embodiments defined by each of these transition terms are within the scope of this invention.

[0028] As used herein, the term "an effective amount" refers to the amount of the defined component sufficient to achieve the desired result.

[0029] This invention provides a long-term stable single-container adhesive composition that can be used for hard animal tissues, preferably for hard tissues of human body such as bones and teeth, more preferably for human teeth. This composition etches, primes, and adheres to hard tissue surfaces in one application step. [0030] In one embodiment, this invention provides an adhesive composition comprising:

a) at least one phosphate (meth)acrylate monomer; b) at least one polymerizable monomer having vinyl or (meth)acryl groups; c) at least one polymerization initiator; d) at least one polymerization inhibitor; and optionally e) a water-miscible non-hydroxylic organic solvent.

[0031] In one embodiment, the adhesive composition comprises a water-miscible non- hydroxylic organic solvent. In another embodiment, the adhesive composition does not comprise a water-miscible non-hydroxylic organic solvent. In another embodiment, the adhesive composition does not comprise a water-miscible hydroxylic organic solvent. In another embodiment, the adhesive composition is a dental adhesive composition.

[0032] In another embodiment, this composition has the following components:

a) at least one phosphate (meth)acrylate monomer, such a monomer containing a hydrogen phosphate functional group with two organic substituents having polymerizable groups such as vinyl, acryl, or methacryl functional groups;

b) at least one polymerizable monomer having one or more vinyl or (meth)acryl groups and being substantially free of carbamyl functionality, where a hydrogen atom is directly bonded to the carbamyl nitrogen; c) at least one polymerization initiator;

d) at least one polymerization inhibitor; and optionally,

e) a water-miscible non-hydroxylic organic solvent.

[0033] The hydrogen phosphate-containing polymerizable monomer(s) a) is a primary component for achieving excellent adhesive properties in dental applications. It includes at least one member selected from polymerizable monomers having a hydrogen phosphate functional group. Not only acting as adhesion promoter, these monomers also provide the properties of partial dissolution of a smear layer of a tooth surface, dentinal decalcification, and penetration and hybridization of the protein layer, which is essential for a successful dental adhesive composition.

[0034] The component(s) described in a) above, the phosphate-containing monomers, must exhibit a high acidity, especially when mixed with water on a wet tooth surface, to promote the dissolution of hydroxyapatite in enamel, cementum and the dentin smear layer of a tooth surface by decalcification to improve adhesive properties to dentin and enamel. They also act as excellent adhesion promoters that increase the ability of the composition to adhere to noble and non-noble metals, composite, porcelain and ceramic.

[0035] Favorable examples of the phosphate-containing monomers include di(methacryloyloxyalkyl) hydrogen phosphates and di(methacryloyloxyaryl) hydrogen phosphates and oligomers and polymers made from them. The alkyl portions can be branched, cyclic, or straight-chain and may have oxygens in the chains to form ether or ester linkages and be the same or different. The aryl portions may include alkyl portions as just described or be bonded directly to the phosphate oxygen. By proper formulation with components b) through e), above, and specific methods of application, these products have found great use as dental adhesives. [0036] Many phosphate monomers have been previously suggested for use in adhesives, including dental adhesives. These include 2-(meth)acryloyloxyethyl dihydrogen phosphate, 3-(meth)acryloyloxypropyl dihydrogen phosphate, 4-(meth)acryloyloxybutyl dihydrogen phosphate, 5-(meth)acryloyloxypentyl dihydrogen phosphate, 6-(meth)acryloyloxyhexyl dihydrogen phosphate, 7-(meth)acryloyloxyheptyl dihydrogen phosphate, 8- (meth)acryloyloxyoctyl dihydrogen phosphate, 9-(meth)acryloyloxynonyl dihydrogen phosphate, 10-(meth)acryloyloxydecyl dihydrogen phosphate, 12- (meth)acryloyloxydodecyl dihydrogen phosphate, 16-(meth)acryloyloxyhexadecyl dihydrogen phosphate, di(meth)acryloyloxyethyl hydrogen phosphate, di(meth)acryloyloxypropyl hydrogen phosphate, di(meth)acryloyloxybutyl hydrogen phosphate, di(meth)acryloyloxypentyl hydrogen phosphate, di(meth)acryloyloxyhexyl hydrogen phosphate, di(meth)acryloyloxyheptyl hydrogen phosphate, di(meth)acryloyloxyoctyl hydrogen phosphate, di(meth)acryloyloxynonyl hydrogen phosphate, di(meth)acryloyloxydecyl hydrogen phosphate, l,3-di(meth)acryloyloxypropyl- 2-dihydrogen phosphate, 2-(meth)acryloyloxyethyl phenyl hydrogen phosphate, and (meth)acryloyloxyethyl ethyl phenyl phosphate. Some commercial phosphate monomers include Sipomer® PAMlOO, Sipomer® PAM200, and Sipomer® PAM 300 (all from Rhodia Novecare),

[0037] Examples of known pyrophosphate-containing monomers include tetra(meth)acryloyloxyethyl pyrophosphate, di(meth)acryloxyethyl pyrophosphate, di(meth)acryloyloxybutyl pyrophosphate, di(meth)acryloyloxyhexyl pyrophosphate, di(meth)acryloyloxyoctyl pyrophosphate, di(meth)acryloyloxynonyl pyrophosphate, di(meth)acryloyloxydecyl pyrophosphate.

[0038] Many of the above phosphates have not found their way into general use in single- container adhesives, including dental adhesives. The inventors believe that many phosphate monomers previously suggested, including the di(meth)acryloyloxyalkyl hydrogen phosphates listed above, could not form shelf-stable compositions with many monomers and solvents commonly used in dental adhesives and so have been excluded by manufacturers from further consideration. However, when formulated according to the invention, excellent stability results and strong bonds to tooth surfaces are formed. Conversely, the (meth)acryloyloxyalkyl dihydrogen phosphates have acceptable storage stability when formulated with hydroxylic monomers or hydroxylic solvents such as ethanol or water, but such formulations do not provide the strongest bonds to tooth surfaces upon a single application, especially to enamel surfaces. Such facts may indicate that these phosphates may not be as acidic as the preferred phosphate monomers of the invention. [0039] In one preferred embodiment, the phosphate-containing monomer or monomers, component a) of the present invention as referred herein, do not include pyrophosphate(s). [0040] The preferred di(meth)acryloyloxyalkyl hydrogen phosphate monomers may be used either alone or in a mixture of at least two kinds of phosphate to form an all-in-one container adhesive as disclosed herein. The presence of (meth)acryloyloxyalkyl dihydrogen phosphates in compositions of the current invention can be tolerated and in fact may be expected to be present as a bi-product of the manufacture of the preferred di(meth)acryloyloxyalkyl hydrogen phosphates. The quantity of (meth)acryloyloxyalkyl dihydrogen phosphates is not counted as part of the content of preferred phosphate (meth)acrylate monomers described in a), above, rather, they are counted as part of the polymerizable (meth)acrylate monomers b). [0041] The content of the phosphate containing monomer(s) a) in the adhesive composition of the present invention should be in the range of about 1 to about 99% by weight, preferably about 5 to about 50% by weight, and more preferably about 10 to about 20% by weight of the combined non-solvent components a) through d).

[0042] The polymerizable (meth)acrylate monomer(s) b) that are substantially free of carbamyl groups having hydrogen directly bonded to the carbamyl nitrogen may have one or more polymerizable (meth)acryl or vinyl functional groups. This polymerizable monomer or mixture of two or more similar monomers not only provide essential mechanical properties, but help to form a hybrid layer within an oral cavity and also provide the long-term stability of the adhesive composition. [0043] Another purpose of the polymerizable monomer(s) b) in the present invention is to increase the functionality and provide long-term durability of the hybrid layer within oral environment.

[0044] According to the present invention, examples of such monomers may comprise mono- (meth)acrylates such as methyl (meth)acrylate, ethyl (meth)acrylate, isopropyl (meth)acrylate, n-butl- (meth)acrylate, isobutyl (meth)acrylate, tetrahydro fur fury 1 (meth)acrylate, glycidyl (meth)acrylate, benzyl (meth)acrylate. Examples of such monomers, may also comprise bifunctional (meth)acrylates, such as ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acylate, triethylene glycol di(meth)acrylate, butylene glycol di(meth)acrylate, neopentyl glycol di(meth)acrylate, propylene glycol di(meth)acrylate, 1,3-butanediol di(meth)acrylate, 1 ,4-butanediol di(meth)acrylate, 1,6- hexanediol di(meth)acrylate, 2,2-bis[(meth)acryloyloxyphenyl]propane, 2,2-bis{4-[3- (meth)acryloyloxy]-2-hydroxypropoxyphenyl}propane (hereinafter abbreviated as bis- GMA), 2,2-bis[4-(meth)acryloyloxyphenyl]propane, 2,2-bis[4- (meth)acryloyloxypolyethoxyphenyl]propane, 2,2-bis[4- (meth)acryloyloxydiethoxyphenyl]propane, 2,2-bis[4- (meth)acryloyloxytetraethoxyphenyl]propane, 2,2-bis[4- (meth)acryloyloxypentaethoxyphenyl]propane, 2,2-bis[4-

(meth)acryloyloxydipropoxyphenyl]propane, 2- [4-(meth)acryloyloxyethoxyphenyl] -2- [4- (meth)acryloyloxydiethoxyphenyl]propane, 2-[4-(meth)acryloyloxydiethoxyphenyl]-2-[4- (meth)acryloyloxyditriethoxyphenyl]propane, 2- [4-(meth)acryloyloxydipropoxyphenyl] -2- [4-(meth)acryloyloxytriethoxyphenyl]propane, 2,2-bis[4- (meth)acryloyloxypropoxyphenyl]propane, 2,2-bis[4-

(meth)acryloyloxyisopropoxyphenyl]propane; and ethoxylated trimethylolpropane triacrylate.

[0045] The polymerizable monomer or monomers having vinyl or (meth)acryl groups, component b) of the present invention as referred herein, do not include (meth)acryl amides and monomers containing a plurality of carboxyl groups. It also does not include any monomer that can readily react with water to generate a plurality of carboxyl groups.

[0046] Another preferred embodiment of the invention utilizes trifunctional, tetrafunctional, or multifunctional vinyl or (meth)acrylate monomers such as trimethylolpropane tri(meth)acrylate, trimethylolethane tri(meth)acrylate, pentaerythritol tri(meth)acrylate, trimethylolmethane tri(meth)acrylate, pentaerythritol tetramethacrylate and pentaerythritol tetraacrylate; and those adducts obtained by the addition reaction of glycidyl (meth)acrylates to molecules containing carboxylic acid functionality.

[0047] In the adhesive composition according the present invention, it is important to understand that methacrylate monomers containing hydroxyl groups, such as hydroxyethyl methacrylate (HEMA) and BisGMA, may react slowly with the preferred phosphate- containing monomer(s) leading to a shorter shelf life of the adhesive composition of the current invention. Therefore, the content of hydroxyl group containing monomer(s) in the adhesive composition of the present invention should be controlled. In the dental adhesive compositions according the present invention, in order to improve its permeability into tooth structure and increase its polymerizability, it is preferable to mix a hydrophilic monomer such as triethylene glycol dimethacrylate with a hydrophobic monomer such as ethoxylated bisphenol A dimethacrylate monomer or BisGMA. Small amounts of hydroxyl group- containing monomers, such as HEMA and BisGMA, can be added to the composition without extensive loss of storage stability. HEMA and BisGMA can be used alone or as a mixture of hydroxyl group-containing monomers. The amount of hydroxyl group- containing monomers may be in the range of about 1 to about 70% by weight of total (meth)acrylate monomers or be completely absent.

[0048] Even more important to the success of the invention is the avoidance within the disclosed composition of monomers that contain carbamyl functionality, especially those that have a hydrogen atom bonded directly to the carbamyl nitrogen. Compounds with carbamyl functional groups are also known as urethanes. The urethane monomers may be formed by preparing an adduct or diadduct by the combination of one or more polymerizable monomers having a hydroxyl group such as 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 3-chloro-2-hydroxypropyl (meth)acrylate, or BisGMA with one or more isocyanate or diisocyanate compounds having an aliphatic or aromatic group, such as diisocyanatomethyl benzene, 4,4'-diphenylmethane diisocyanate, hexamethylene diisocyanate, trimethylhexamethylene diisocyanate, diisocyanatomethylcyclohexane, isophorone diisocyanate, or methylenebis(4-cyclohexyl isocyanate) where essentially all of the hydroxyl groups have been reacted.

[0049] The content of (meth)acrylate monomer b) in the adhesive composition of the present invention should be in the range of about 1 to about 99% by weight, preferably about 50 to about 95% by weight, and more preferably 80 to 90% by weight of the combined non-solvent components a) through d).

[0050] The adhesive composition of the present invention contains a polymerization initiator c), which is part of a photopolymerization initiation system. The polymerization initiator is present in an amount sufficient to initiate the polymerization of the monomers by light irradiation. The photopolymerization initiation system includes photosensitizing and reducing agents. Useful types of photosensitizers include, for instance, α-diketones, ketals, thioxanthones, acylphosphine oxides, and like.

[0051] Examples of the α-diketones include camphorquinone, benzyl, 2,3-pentadione, and the like. Examples of the ketals include benzyl dimethyl ketal, benzyl diethyl ketal, and the like. Examples of the thioxanthones include 2-chlorothioxanthone, 2,4-diethylthioxanthone, and the like. Examples of the acylphosphine oxide include, for instance, 2,4,6- trimethylbenzoyldiphenylphosphine oxide, 2,6-dimethoxybenzoyldiphenylphosphine oxide, 2,6-dichlorobenzoyldiphenylphosphine oxide, 2,3,5,6- tetramethylbenzoyldiphenylphosphine oxide, benzoyl di-(2,6-dimethylohenyl)phosphonate, 2,4,6-trimethylbenzoylethoxyohenylphosphine oxide, and the like.

[0052] The above photosensitizer can be used alone or in combination. Of these are particularly preferred camphorquinone and 2,4,6-trimethylbenzoylphenyl diphenylphosphine oxide.

[0053] Usually the photosensitizer is used together with a reducing agent for improving the initiator efficiency. The reducing agent includes tertiary amines and aldehydes, etc. Useful types of tertiary amines are aromatic and aliphatic tertiary amines.

[0054] Examples of the aromatic tertiary amines include N,N-dimethylaniline, N ,N- dimethyl-p-toluidine, N,N-dimethyl-m-toluidine, N,N-diethyl-p-toluidine, N,N-dimethyl- 3,5-dimethylaniline, N,N-dimethyl-3,4-dimethylaniline, N,N-dimethyl-4-ethylaniline, N₅N- dimethyl-4-i-propylaniline, N,N-dimethyl-4-t-butylaniline, N,N-dimethyl-3,5-di-t- butylaniline, N,N-bis(2-hydroxyethyl)-3 ,5 -dimethyl aniline, N,N-di(2-hydroxyethyl)-p- toluidine, N,N-bis(2-hydroxyethyl)-3 ,4-dimethylaniline, N,N-bis(2-hydroxyethyl)-4- ethylaniline, N,N-bis(2-hydroxyethyl)-4-i-propylaniline, N,N-bis(2-hydroxyethyl)-4-t- butylaniline, N,N-bis(2-hydroxyethyl)-3,5-di-i-propylaniline, N,N-bis(2-hydroxyethyl)-3,5- di-t-butylaniline, n-butoxyethyl 4-dimethylaminobenzoate, (2-methacryloyloxy)ethyl 4- dimethylaminobenzoate, and the like.

[0055] Examples of the aliphatic tertiary amines include trimethylamine, triethylamine, N- methyldiethanolamine, N-ethyldiethanolamine, N-n-butyldiethanolamine, N- lauryldiethanolamine, triethanolamine, (2-dimethylamino)ethyl methacrylate, N- methyldiethanolamine dimethacrylate, N-ethyldiethanolamine dimethacrylate, triethanolamine monomethacrylate, triethanolamine dimethacrylate, triethanolamine trimethacrylate, and the like.

[0056] Specific preferred examples of the reducing agent that can be used include N₅N- dimethyl-p-toluidine, N,N-bis(2-hydroxyethyl)-p-toluidine, N,N-dimethylaminoethyl methacrylate, N,N-dimethylaminopentyl (meth)acrylate, methyl 4-dimethylaminobenzoate, ethyl 4-dimethylaminobenzoate, and octyl 4-dimethylaminobenzoate. These reducing agents may be used alone or in a mixture of two or more.

[0057] The polymerization initiator c) such as a photo-polymerization initiator, including photosensitizer and reducing agent, in the adhesive composition of the present invention should be in the range of about 0.05 to about 10% by weight, preferably about 0.1 to about 3%, and, more preferably, in the range of about 0.5 to about 2% by weight of the combined non-solvent components a) through d).

[0058] Most commercially available methacrylate and acrylate monomers that can be used in the composition of the invention are supplied with polymerization inhibitor(s) d) to provide those components with good shelf life. Additional inhibitors may be added to the composition of the invention to prevent excessive acceleration of the polymerization reaction within the adhesive composition so that polymers having desired molecular weights are produced. Also, the level of inhibitor, if needed, is adjusted to provide the composition with long-term shelf life stability. The amount and type of inhibitor are selected so that they do not interfere with the desired level of polymerization.

[0059] Examples of polymerization inhibitors useful in the present invention are t- butylhydroxytoluene, hydroquinone, and the methyl ether of hydroquinone. Other useful examples are well known to those familiar with the art. The polymerization inhibitor(s) d) can be present in the range of about 0.001-1% by weight, preferably about 0.005-0.5% by weight, and more preferably about 0.01-0.2% by weight of the combined non-solvent components a - d.

[0060] For component e), a water-miscible organic solvent may be added in the adhesive composition to increase the solubility of the phosphate-containing monomers, the acid- free (meth)acrylate monomers, the polymerization initiators, and the polymerization inhibitors in the adhesive composition. The water-miscible solvent also can improve the miscibility between adhesive components and water. The water on the wet tooth surface helps ionize the acidic group in the phosphate-containing monomer(s) that etches the tooth surfaces by demineralization.

[0061] It is desired to use a volatile solvent with a boiling point less than 100⁰C at atmospheric pressure. Some examples of water-miscible organic solvent include alcohols such as ethanol, 1-propanol, isopropyl, isobutyl or butyl alcohol, and ketones such as acetone or methylethylketone. Any of above described solvents may be used alone or as a mixture of at least two kinds. For improved storage stability of the composition, the amount of alcohols used should be minimized. Thus, a water-miscible non-hydroxylic organic solvent is preferable. From the viewpoint of safety and long-term stability of the adhesive composition, acetone is the most preferable water-miscible solvent.

[0062] The content of the water-miscible organic solvent in the adhesive composition of the present invention can be in a range of about 0 to about 90% by weight of the total adhesive composition. Preferably, the water-miscible organic solvent is in a range of about 0 to about 70% by weight, and more preferably in the range of about 0 to about 50 % by weight.

[0063] The adhesive composition of the present invention may contain a filler to provide radiopaque property and increase the hardness and abrasion resistance of the adhesive layer after curing. Fillers may also help to regulate the thickness of the adhesive layer during application and prevent over-thinning during the solvent removal step that is accomplished by applying an air stream to the composition. The filler may be inorganic, organic, or mixtures thereof. The inorganic filler may include minerals, ceramics, silica, talc, alumina, apatite, clay, oxides of silicon, titanium, zirconium, and strontium, barium glass, borosilicate glass, bio-active glass, and hydroxyapatite. The inorganic filler may be a colloidal stable sol, such as Zirconia sol or organosilicasol (IPA-ST, IPA-ST-MA, IPA-ST- L, IPA-ST-ZL, MEK-ST, MEK-ST-MS, and MIBK-ST, from Nissan Chemical) with the size range from 5-150 nm. The organic filler may be poly(methyl methacrylate), polyamide, or polystyrene. It is also possible to add a mixture of inorganic and organic fillers. The size of the organic or inorganic fillers may be in the range of about 0.005-50 microns. [0064] A colorant, a fluorescent, an ultraviolet absorbent and the like may be added to the adhesive composition of the present invention.

[0065] In addition, other components may be also added into the adhesive composition of the present invention without much loss of its essential qualities previously described. For example, antimicrobial compounds produced by microorganisms to inhibit cell wall synthesis, cell membrane organization, protein synthesis, nucleic acid metabolism, or metabolism by enzyme competition, and similar inhibitory pathways can be added. Antimicrobial additives can also be produced by chemical synthesis such as small molecule antibacterials, nanotubes, nanosilver, or various inorganic ionic species such as fluoride or potassium.

[0066] In addition, a compound that releases a fluorine ion, such as sodium fluoride, lithium fluoride, or cetylamine hydrofluoride, or a fluoride-releasing (meth)acrylate monomer, may also be added to the adhesive composition to make surrounding dentition less soluble in acids by formation of fluoroapatite. In one embodiment, the composition of the present invention does not contain any compound that releases a fluoride ion.

[0067] The optional components mentioned above might be present in the composition alone or in combination with other optional components.

[0068] Viscosity is an important feature of the composition since an adequate viscosity imparts better handling properties and allows a uniform application of the composition on the tooth surface. The preferable viscosity of the composition of the present invention at the moment of application is such that it forms a film when scrubbed on a wet tooth surface. It is the shear viscosity of the composition that is important if thinning fillers are added. When a solvent is added, the viscosity of the composition with the solvent when the adhesive composition is dispensed, is important. The preferred viscosity of the composition of the present invention in the range of about 800,000 centipoise (cps) to about 1 million cps, or alternatively, in the range of about 600,000 cps to about 800,000 cps, or alternatively, in the range of about 400,000 cps to about 600,000 cps, or alternatively, in the range of about 200,000 cps to about 400,000 cps, or alternatively, in the range of about 100,000 cps to about 200,000 cps, or alternatively, in the range of about 50,000 cps toabout 100,000 cps, or alternatively, in the range of about 25,000 cps to about 50,000 cps, or alternatively, in the range of about 5,000 cps to about 25,000 cps, and preferably less than 5,000 cps, or alternatively in the range of about 4,000 cps to about 5,000 cps, or alternatively in the range of about 3,000 cps to about 4,000 cps, or alternatively in the range of about 2,000 cps to about 3,000 cps, or alternatively in the range of about 1,000 cps to about 2,000 cps, or alternatively less than 1000 cps.

[0069] In another embodiment, this invention provides an adhesive composition as described above that optionally comprises viscosity modifiers. Some examples of viscosity modifiers include, but are not limited to, fumed silica, aluminum oxide, titanium dioxide, glass powder, and the like.

[0070] In another embodiment, this invention provides a dental adhesive composition that comprises:

f) at least one phosphate (meth)acrylate monomer in an amount sufficient to provide adhesion to a natural tooth surface or artificial surfaces encountered during tooth restoration procedures; g) at least one acid-free polymerizable monomer having a vinyl or

(meth)acryl group in an amount sufficient to interact with the monomer of (a) to provide acceptable mechanical properties of the composition on a natural tooth surface or artificial surfaces encountered during tooth restoration procedures, while providing stability of the dental adhesive composition for at least 90 days at room temperature; h) a polymerization initiator in an amount sufficient to initiate polymerization of the monomers by light irradiation of the composition; i) a polymerization inhibitor in an amount sufficient to aid in providing stability to the composition during storage prior to use for at least 90 days at room temperature; j) a water-miscible, hydroxyl-free organic solvent in an amount sufficient to solubilize the monomers a) and b), the initiator c), and the inhibitor d).

[0071] In a further embodiment, the phosphate monomer contains at least one alkyl or aryl group. In another embodiment, the acid- free, polymerizable monomer is free of a carbamyl group having hydrogen directly bonded to nitrogen. In another embodiment, the light irradiation is visible or UV light. [0072] In another embodiment, this invention provides a dental adhesive composition comprising:

a) about 10-20% of at least one phosphate (meth)acrylate monomer; b) about 80-90% of at least one polymerizable monomer having vinyl or

(meth)acryl groups; c) about 0.5-2% of at least one polymerization initiator; d) about 0.01-0.2% of at least one polymerization inhibitor; and optionally e) a water-miscible non-hydroxylic organic solvent.

[0073] In a further embodiment, the above dental composition of components a) through d) further comprises:

e) about 0%-50% of water-miscible non-hydroxylic organic solvent, by weight of components a) through e).

[0074] In a preferred embodiment, the water-miscible non-hydroxylic organic solvent is acetone. [0075] The adhesive composition of the present invention can be easily prepared from the above components by mixing and be stored in a single container. The composition can also be divided into two containers where the initiator system is designed so that by mixing the two parts a polymerization reaction is begun. Such a curing mechanism is known as self- curing or dual-curing and is effected by mixing the two parts, one containing a radical former and the other containing an accelerator. Mixing just prior to use forms the single composition that is the intent of this invention. Tooth surfaces contacted by this mixture of two stored compositions still do not require any pretreatment such as etching or priming.

[0076] In another embodiment, this invention provides a container having a volume of 0.05 to 50 ml from which can be dispensed a dental adhesive composition comprising:

a) at least one phosphate (meth)acrylate monomer; b) at least one acid-free polymerizable monomer having vinyl or (meth)acryl groups; c) at least one polymerization initiator; d) at least one polymerization inhibitor; and optionally

e) a water-miscible non-hydroxylic organic solvent.

[0077] In another embodiment, the container has a volume of 5 ml. The container is not particularly limited insofar it is capable of blocking external light and water. It is favorable that the container is designed in such a manner that the composition therein is easily withdrawn and directly dropped onto the tooth surface, since it makes coating of the composition in a desired amount.

[0078] In another embodiment, this invention provides a kit containing at least one container. In another embodiment, this invention provides a kit comprising:

i) a dental composition as described above; ii) one or more delivery devices calibrated to administer the composition of i) in an amount sufficient to coat at least one tooth surface for the purpose of restoration; and

iii) instructions. [0079] In another embodiment, this invention provides a kit as described above, wherein the dental adhesive composition is in the form of a unit dose of about 0.05 to about 0.25 ml. In another embodiment, this invention provides a kit as described above, wherein the dental adhesive composition is in the form of a unit dose of 0.125 ml.

[0080] In another embodiment, the adhesive composition is in the form of a unit dose of about 0.05 to about 0.25 ml, more preferably in the form of a unit dose of 0.125 ml. The term "unit dose" as used herein, refers to an amount of adhesive composition in a sealed container that is used on a single patient during a surgical operation where the container is not resealed and excess adhesive is not kept for subsequent procedures.

[0081] While not wanting to be limited in the invention by any specific theory, it is believed by the inventors that when the adhesive is applied onto the wet surface of a tooth, the phosphate (meth)acrylate monomer of the adhesive composition of the present invention reacts with water to activate its acidic function that effectively demineralizes and etches the tooth, providing a strong bond in a thin coating between the tooth and dental restoration. Preferably, the phosphate (meth)acrylate monomer contains a dialkyl hydrogen phosphate functional group.

[0082] According to the invention, the phosphate-containing monomer also acts as an adhesion promoter to cured dental composites, metals, porcelain and ceramic. When applied over or together with commercial porcelain or metal primers, the adhesive composition provides excellent bond strengths to these surfaces that may be present in a patient's mouth or whose installation into a patient by their dentist may be desired, improving their retention and durability.

B. Examples

[0083] The following examples are presented to demonstrate more detail about the present invention, but it should be understood that the examples are not intended to limit the scope of the invention in any way.

[0084] The abbreviated names and symbols in the following tables are interpreted as follows:

BisGMA: Bisphenol A diglycidyl methacrylate; DMEHP: di(methacryloyloxyethyl) hydrogen phosphate, an example of a phosphate monomer preferred for the described invention;

DAEHP: di(acryloyloxyethyl) hydrogen phosphate, an example of a phosphate monomer preferred for the described invention;

EBPADM: Ethoxylated BisPhenol A Dimethacrylate; EEEA: 2-ethoxyethyl acrylate

ETMPTA: ethoxylated trimethylolpropane triacrylate;

EtOH: Ethanol.

GPDM: Glycerol phosphate dimethacrylate;

HEMA: 2-Hydroxyethyl methacrylate; SR368: tris (2-hydroxy ethyl) isocyanurate triacrylate from Sartomer;

TEGMA: triethylene glycol dimethacrylate;

UDMA: [2,2,4-trimethylhexamethylenebis(2-carbamoyloxyethyl)]dimethacrylate;

OP: OptiBond All-in-One, commercial one container dental adhesive from Kerr;

GB: G-Bond, commercial one container dental adhesive from GC; XE: Xeno IV, commercial one container dental adhesive from Dentsply;

CL: Clearfϊl S³ Bond, commercial one container adhesive from Kuraray Medical. Table 1. Examples 1 - 18 and Comparative Examples 1 - 5

[0085] Conventional additives such as polymerization initiator(s), polymerization inhibitor(s), etc. can be added to each of the above example formulations. For example, camphorquinone (CQ) can be added in a range from 0.5-2%, more preferably 0.7% of the total composition. Further, octyl p-dimethylaminobenzoate (ODMAB) can be added in a range from about 0.5-2%, more preferably 0.8% of the total composition. Also, 2,6-di-tert- butyl-4-methylphenol (BHT) can be added in a range from about 0.01-0.2%, more preferably 0.1% of the total composition. Table 2. Comparative Examples 6 - 9

Table 3. Comparative Examples 10 - 12

[0086] The polymerizable monomers and phosphate monomers shown in each of the

Examples 1-11 above and Comparative Examples were mixed by stirring until they became homogeneous monomer mixtures. Then to 984 parts of each individual monomer mixture 8 parts CQ, 7 parts ODMAB, and 1 part BHT were added and dissolved by further agitation. Five parts of Examples 1 - 10 and Comparative Examples 1 - 5 and 9 were each individually combined with 4 parts of acetone to form the tested compositions. Five parts of Comparative Examples 6 - 8 and 10 - 12 were each individually combined with 4 parts of a 50:50 weight percent mixture of acetone and ethanol to form the tested compositions. No solvent was added to Example 11. In Examples 12-18, addition of solvent is optional and in one embodiment, no solvent is added.

C. Bond Strength Test

[0087] Shear bond strength (SBS) tests were performed after storage in water at 37⁰C of test specimens prepared on dentin or enamel according to ISO/TS 11406, Annex 3.2 (Watanabe Shear Test Method) using an Instron 4411. Shear bond strength was calculated in megapascals (MPa) using Series IX Software for Windows. Experimental specimens were prepared by following steps:

[0088] Human teeth were wet polished by the use of silicon carbide abrasive paper #320 and #600 (3M) to expose the enamel and dentin surfaces and then water was blown off of these surfaces by means of a dental air syringe. A Mylar tape having a 3 mm diameter hole was affixed over the center of the enamel or dentin surface of each test piece. The tooth surface of each test piece defined by the hole was covered with fresh water, then brush- coated with each of the adhesive compositions prepared in Examples 1 to 11, scrubbed for 20 seconds, and dried by air from a dental air syringe (10-15 seconds). Each Example formulation was applied to at least five test pieces for a total of at least 55 prepared test specimens. The tooth surface preparation has an important function in the success of the bonding. The tooth surface should not be dry, nor should it be very wet. A convenient method for applying just the correct amount of water is to dip a fresh applicator brush into water and touch this to the surface of the tooth that will receive the adhesive. A second fresh applicator brush, preferably of the same kind, is used to carry adhesive to the tooth surface for scrubbing. At this point, the surface of the dentin or enamel is shiny. Using an Optilux 501 curing gun at -770 mW/cm², the adhesive layer is cured for 10 seconds (the light gun is ~ 0.5-1 cm above the test piece assembly). Comparative Examples were prepared in the same way as the Examples. Commercial one-container adhesives were applied according to manufacturer's instructions. On the top of the adhesive layer, a commercial photopolymerizable flowable dental composite, StarFlow A2 (Danville Materials), was applied in two layers of 1 - 2 mm; each layer was polymerized by exposure to visible light from the Optilux gun for 30 seconds. The prepared teeth were immersed in water at 37⁰C for 24 hours. Bond strengths were determined at a crosshead speed of 1 mm/min.

Table 4. Shear Bond Strength Results for Examples, Comparative Examples, and Commercial Products on Dentin and Enamel Immediately after Preparation of

Compositions and after 90 Days Storage in Ambient Room Conditions in Polyethylene Bottles (Commercial Products were tested within 10 days of receipt).

[0089] Compositions of the present invention are exemplified in Examples 1 - 18. By comparison, these examples show better strength after storage for 90 days at ambient room temperatures than do Comparative Examples 1 - 8, even though all of these Comparative Examples contain examples of the phosphate monomers preferred by this invention. Examples of the present invention also provide better shear bond strength to enamel than Comparative Examples 9 - 12 that contain a well-known dental adhesion monomer, glycerol phosphate dimethacrylate (GPDM). Furthermore, examples of the present invention also have better shear bond strengths to human dentin and enamel than the currently available commercial products, Optibond All-in-One, G-Bond, Xeno IV, and Clearfil S3 Bond, even after storage of compositions of the present invention for 90 days. [0090] Each of the formulations containing the preferred surface-active monomers of the present invention provide good bond strength to both enamel and dentin in fresh compositions as illustrated by Comparative Examples 6 - 8, but also provide better storage stability when ethanol is not used as a solvent, as shown by Example 4, therefore, it is best to avoid using hydroxylic solvents like ethanol when formulating with these preferred monomers. In Comparative Example 7, half of the solvent present in Example 4 was replaced with ethanol, causing a comparatively greater loss of shear bond strength after storage of the composition for 90 days in ambient conditions. By ambient conditions is meant typical temperatures and humidity commonly found in offices, clinics, and laboratories. Temperatures were mostly in the range of 20 - 25⁰C. Relative humidity was generally 20 to 60%.

[0091] While hydroxylic solvents are counter-indicated in compositions of the invention, hydroxylic monomers can be tolerated as shown by Examples 4 - 9 as compared to Examples 1 - 3 that do not contain such monomers. Especially illustrative is the comparison between Examples 4 and 3 that differ only in the type of monomers used. In fact, these examples show that the hydroxylic monomers may provide slightly better adhesion to dental surfaces. Without being bound by a theory, it is likely these monomers, being more hydrophilic, may wet those surfaces more completely. However, the amount of hydroxylic monomers does affect the storage life as shown by the trend in reduced bond strengths upon storage for 90 days as the total amount of these types of monomers were increased relative to total monomers used. Example 3, having no hydroxylic monomers, provides shear bond strengths to dentin and enamel of 34.5 MPa and 36.2 MPa, respectively after 90 days storage. Examples 7, 6, 5, and 4 have progressively more hydroxylic monomers in their compositions and provide progressively lower shear bond strengths to both dentin and enamel after storage. At 90 days storage, Example 4, having the most hydroxylic monomers, provides bond strengths to dentin and enamel of 30.0 MPa and 33.0 MPa, respectively, representing more than a 10% reduction in strength. Additional storage time causes the bonds strengths to continue to drop into the foreseeable future (data not shown). While being detrimental, use of hydroxylic monomers can be tolerated in the present invention since the initial bond strengths are so much higher than those of other commercial products. We have found that an amount of hydroxylic monomer whose mole ratio with the phosphate-containing monomer does not exceed 1 will have stability in the presence of solvent, but at this 1 : 1 mole ratio, formulations not having solvent already show reduced shelf life.

[0092] Compared to GPDM-containing compositions, adhesive compositions comprised of DMEHP and DAEHP show excellent adhesive strength to both dentin and enamel. Though GPDM based formulations show excellent bond strength to dentin, the bond strengths to enamel are comparatively low. This is especially clear when comparing Example 4 to Comparative Example 9 whose only difference is the active monomer and the diluent monomer ETMPTA.

[0093] Another illustration of the difference between the preferred monomers and GPDM can be seen by comparing Examples 8 and 9 to Comparative Examples 11 and 12. The GPDM-containing compositions have very good storage stability, but their bond strengths to enamel are not initially very high.

[0094] Example 3 differs from Comparative Example 1 in that it contains EBPDMA and no UDMA, while Comparative Example 1 contains UDMA and no EBPDMA. Example 3 illustrates that excellent bond strengths are obtained to both dentin and enamel that are not affected by storage time. By comparison, Comparative Example 1 shows the detrimental effect that UDMA has on the storage stability of its composition.

[0095] A distinguishing feature of UDMA and urethanes in general that is not found in monomers used in Examples 1 - 7 is that they have a nitrogen atom next to a carbonyl carbon. A similar characteristic is found in SR368, which is used in successful compositions of Examples 8 and 9, except that in this case, the nitrogen atom does not have a hydrogen atom attached. Furthermore, since the nitrogens and carbonyls of SR368 are bound in a ring, the reactivity around nitrogen may be diminished so that compounds of this type do not cause loss of storage stability of compositions comprising them. SR368 is used again in Comparative Examples 2 - 5, but in these compositions UDMA is also present so that the storage stability is negatively affected as indicated by loss of shear bond strength after only 90 days. Ideally, a dental adhesive should be able to provide at least 90% of its original bond strengths well beyond 90 days storage in ambient conditions, preferably 360 days, and more preferably at least 720 days. This allows time for the product to get from the manufacturer to the dentist who will use it and time for the dentist to consume it before any noticeable degradation takes place. It also means that the distribution system and the dentist do not have to handle the product in any special way such as by refrigeration during transport or storage.

[0096] In order to illustrate the difference between typical dental adhesive monomers such as GPDM and the monomers preferred for the instant invention described herein, compare Comparative Example 10 comprising GPDM and UDMA with Comparative Example 5. Comparative Example 10 shows good bond strength to dentin, less bond strength to enamel, and excellent storage stability. Comparative Example 5 comprising DMEHP and UDMA has excellent adhesion to dentin and enamel when fresh, but very poor storage stability. While UDMA has no noticeable effect on GPDM, its affect on DMEHP is dramatic making that combination quite undesirable.

[0097] To illustrate the effect of elimination to the solvent within compositions of the instant invention, compare Example 10 having 44.4 wt% acetone to Example 11 having no acetone or other solvent. These compositions have the same relative ratio of monomers, initiators, and inhibitors. One can deduce that exclusion of the solvent has no perceptible affect on shear bond strength to enamel or on shelf stability over 90 days. The shear bond strength to dentin is lower when acetone is not present, but not substantially so.

[0098] As described above in detail, the dental adhesive composition according to the present invention is a long-term stable all-in-one container dental adhesive composition to be used for adhering dental restoration materials to tooth structure that does not require an etching treatment or a priming treatment, can be used in one step, and provides high bond strengths to dentin and enamel.

[0099] The present invention also produces a high strength bond to un-cut enamel, even without pumice-cleaning the enamel, and to dental restoration materials such as metal, porcelain, filling composites, filling compomers, fissure sealants, root coating materials, lining, luting, and other resin cements (data not shown).

[0100] While the present invention has been described in detail, it should be understood that the examples are not intended to limit the scope of the invention in any way. D. Methods and Uses

[0101] The composition of the present invention is usually prepared by mixing the components, for example, by stirring, shaking, or blending. In one embodiment, this invention provides a process of preparing a dental adhesive, wherein the process comprises blending together at least one phosphate (meth)acrylate monomer, at least one acid-free polymerizable monomer having vinyl or (meth)acryl groups, at least one polymerization initiator, at least one polymerization inhibitor optionally in a water-miscible non-hydroxylic organic solvent in a container non-porous to acetone and water.

[0102] In one embodiment, this invention provides a method of hard animal tissue restoration, wherein the method involves applying the adhesive composition as described above on the hard animal tissue surface to provide an adhesive layer adhering any material to the adhesive layer on the hard animal tissue surface. Examples of hard animal tissues are bones, teeth, and the like.

[0103] In another embodiment, this invention provides a method of tooth restoration, wherein the method involves:

i) transferring an effective amount of water to a tooth surface via an applicator to provide a wet tooth surface; ii) applying the dental adhesive composition as described above to the wet tooth surface to provide an adhesive layer on the tooth surface; and iii) adhering a dental material to the adhesive layer on the tooth surface.

[0104] In another embodiment, the present invention provides use of a composition for tooth restoration wherein the composition comprises:

a) at least one phosphate (meth)acrylate monomer; b) at least one acid-free polymerizable monomer having vinyl or (meth)acryl groups; c) at least one polymerization initiator; d) at least one polymerization inhibitor; and optionally e) a water-miscible non-hydroxylic organic solvent. [0105] It will be appreciated by one of skill in the art that the embodiments summarized above may be used together in any suitable combination to generate additional embodiments not expressly recited above, and that such embodiments are considered to be part of the present invention.

Claims

WHAT IS CLAIMED IS:

1. An adhesive composition comprising: a) at least one phosphate (meth)acrylate monomer; b) at least one acid-free polymerizable monomer having vinyl or (meth)acryl groups; c) at least one polymerization initiator; d) at least one polymerization inhibitor; and optionally e) a water-miscible non-hydroxylic organic solvent.

2. The adhesive composition according to claim 1 comprising a water-miscible non- hydroxylic organic solvent.

3. The adhesive composition according to claim 1 wherein the adhesive composition does not comprise a water-miscible non-hydroxylic organic solvent.

4. The adhesive composition according to claim 1, wherein the adhesive composition is a dental adhesive composition.

5. The adhesive composition according to claim 1, wherein the phosphate (meth)acrylate monomer is in a range of about 1% to about 99% by weight of components a) through d).

6. The adhesive composition according to claim 5, wherein the phosphate (meth)acrylate monomer is in the range of about 5% to about 50% by weight of components a) through d).

7. The adhesive composition according to claim 6, wherein the phosphate (meth)acrylate monomer is in the range of about 10% to about 20% by weight of components a) through d).

8. The adhesive composition according to any one of claims 1-7, wherein the phosphate (meth)acrylate monomer is selected from the group consisting of di((meth)acryloyloxyalkyl) hydrogen phosphates, di((meth)acryloyloxyaryl) hydrogen phosphates, and (meth)acryloyloxyalkyl (meth)acryloyloxyaryl hydrogen phosphates.

9. The adhesive composition according to claim 8, wherein the phosphate (meth)acrylate monomer is di(meth(acryloyloxy)alkyl) hydrogen phosphate.

10. The adhesive composition according to claim 9, wherein the phosphate (meth)acrylate monomer is di(methacryloyloxyethyl) hydrogen phosphate or di(acryloyloxyethyl) hydrogen phosphate.

11. The adhesive composition according to claim any one of claims 1-10, wherein the acid- free polymerizable monomer is in a range of about 1% to about 99% by weight of components a) through d).

12. The adhesive composition according to claim 11, wherein the acid- free polymerizable monomer is in the range of about 50% to about 95 % by weight of components a) through d).

13. The adhesive composition according to claim 12, wherein the acid- free polymerizable monomer is in the range of about 80% to about 90% by weight of components a) through d).

14. The adhesive composition according to claim 11, wherein the acid- free polymerizable monomer is free of a carbamyl group having hydrogen bonded to the carbamyl nitrogen.

15. The adhesive composition according to claim 11, wherein the acid- free polymerizable monomer is selected from the group consisting of triethylene glycol di(meth)acrylate, ethoxylated trimethylolpropane triacrylate, BisPhenol A diglycidyl methacrylate, ethoxylated BisPhenol A dimethacrylate, and hydroxyethyl methacrylate.

16. The adhesive composition according to any one of claims 1-15, wherein the polymerization initiator is a photopolymerization initiator.

17. The adhesive composition according to claim 16, wherein the photopolymerization initiator comprises a photosensitizer and a reducing agent.

18. The adhesive composition according to claim 17, wherein the photopolymerization initiator is in a range of about 0.05% to about 10% by weight of components a) through d).

19. The adhesive composition according to claim 18, wherein the photopolymerization initiator is in a range of about 0.1% to about 3% by weight of components a) through d).

20. The adhesive composition according to claim 19, wherein the photopolymerization initiator is in a range of about 0.5% to about 2% by weight of components a) through d).

21. The adhesive composition according to any one of claims 1-20, wherein the polymerization inhibitor is selected from the group consisting of t-butylhydroxytoluene, hydroquinone, and hydroquinone methyl ether.

22. The adhesive composition according to claim 21, wherein the polymerization inhibitor is in a range of about 0.001% to about 1% by weight of components a) through d).

23. The adhesive composition according to claim 22, wherein the polymerization inhibitor is in a range of about 0.005% to about 0.5% by weight of components a) through d).

24. The adhesive composition according to claim 23, wherein the polymerization inhibitor is in a range of about 0.01% to about 0.2% by weight of components a) through d).

25. The adhesive composition according to any one of claims 1-24, wherein the water- soluble non-hydroxylic organic solvent is methylethylketone or acetone.

26. The adhesive composition according to claim 25, wherein the water-soluble non- hydroxylic organic solvent is acetone.

27. A process of preparing an adhesive, wherein the process comprises blending together at least one phosphate (meth)acrylate monomer, at least one acid-free polymerizable monomer having vinyl or (meth)acryl groups, at least one polymerization initiator, at least one polymerization inhibitor optionally in a water-miscible non-hydroxylic organic solvent in a container non-porous to acetone and water.

28. A method of tooth restoration wherein the method involves: i) transferring an effective amount of water to a tooth surface via an applicator to provide a wet tooth surface; ii) applying the dental adhesive composition according to claim 4 to the wet tooth surface to provide an adhesive layer on the tooth surface; and iii) adhering a dental material to the adhesive layer on the tooth surface.

29. A container having a volume of about 0.05 to about 50 ml from which can be dispensed an adhesive composition comprising: a) at least one phosphate (meth)acrylate monomer; b) at least one acid-free polymerizable monomer having vinyl or (meth)acryl groups; c) at least one polymerization initiator; d) at least one polymerization inhibitor; and optionally e) a water-miscible non-hydroxylic organic solvent.

30. The container of claim 29 having a volume of about 5 ml.

31. The adhesive composition as in any one of claims 1 -26 in the form of a unit dose of about 0.05 to about 0.25 ml.

32. The adhesive composition according to claim 31 in the form of a unit dose of 0.125 ml.

33. A kit containing at least one container according to claim 29.

34. A kit comprising: i) the dental adhesive composition of claim 4; ii) one or more delivery devices calibrated to administer the composition of i) in an amount sufficient to coat at least one tooth surface for the purpose of restoration; and iii) instructions.

35. The kit of claim 34, wherein the adhesive composition is in the form of a unit dose of about 0.05 to about 0.25 ml.

36. The kit of claim 34, wherein the adhesive composition is in the form of a unit dose of 0.125 ml.

37. A dental adhesive composition comprising: k) at least one phosphate (meth)acrylate monomer in an amount sufficient to provide adhesion to a natural tooth surface or artificial surfaces encountered during tooth restoration procedures;

1) at least one acid-free polymerizable monomer having a vinyl or

(meth)acryl group in an amount sufficient to interact with the monomer of (a) to provide acceptable mechanical properties of the composition on a natural tooth surface or artificial surfaces encountered during tooth restoration procedures, while providing stability of the dental adhesive composition for at least 90 days at room temperature; m) a polymerization initiator in an amount sufficient to initiate polymerization of the monomers by light irradiation of the composition; n) a polymerization inhibitor in an amount sufficient to aid in providing stability to the composition during storage prior to use for at least 90 days at room temperature; o) a water-miscible, hydroxyl-free organic solvent in an amount sufficient to solubilize the monomers a) and b), the initiator c), and the inhibitor d).

38. The dental adhesive composition of claim 37, wherein the phosphate (meth)acrylate monomer contains at least one alkyl or aryl group.

39. The dental adhesive composition of claim 37, wherein the acid-free, polymerizable monomer is free of a carbamyl group having hydrogen directly bonded to nitrogen.

40. The dental adhesive composition of claim 37, wherein the light irradiation is visible or UV light.

41. The dental adhesive composition of claim 4 comprising: a) about 10-20% of at least one phosphate (meth)acrylate monomer; b) about 80-90% of at least one acid- free polymerizable monomer having vinyl or (meth)acryl groups; c) about 0.5-2% of at least one polymerization initiator; d) about 0.01-0.2% of at least one polymerization inhibitor; and optionally e) a water-miscible non-hydroxylic organic solvent.