Dental composition and method of use

Abstract

To provide a high performance dental restorative composition, particularly a two-part composition having good self-hardening time. [Solution] A dental composition comprising a first part and a second part, wherein the first part comprises a hydroperoxide and a polymerizable monomer comprising an ethylene group, and the second part comprises thiourea and a polymerizable monomer comprising an ethylene group, the first part and the second part are physically separated from each other, and the first part and / or the second part comprises a copper(II) catalyst.

Description

[Technical Field]

[0001] cross reference This application claims the interests of U.S. Provisional Application No. 62 / 113,899, filed on 9 February 2015, and U.S. Provisional Application No. 62 / 260,193, filed on 25 November 2015, both of which are incorporated herein by reference in their entirety.

[0002] Field of Invention Its intended applications are dental compositions, particularly those useful for dental restorative purposes. [Background technology]

[0003] Dental restorations or fillings are dental restorative materials used to restore the function, integrity, and form of missing tooth structures. Structural loss is typically caused by caries or external trauma (collectively referred to herein as cavities). Sometimes, tooth structures are intentionally damaged during tooth preparation to improve the aesthetic or physical integrity of the intended restorative material. Direct restoration requires placing a soft or malleable filling into the prepared tooth and constructing the tooth before the material hardens. Due to their desirable aesthetic properties, resin-based dental restorative materials are becoming the preferred material by dentists.

[0004] Among all different types of dental fillings, molar fillings are often the largest in size. In some cases, molar fillings are also subject to compressive loads. Restorations that are subject to compressive loads, such as Class I and Class II fillings in molars, require the use of mechanically strong restorative materials to withstand the forces generated during chewing. Such restorative materials are typically very viscous, making it difficult to accurately place the restorative material and requiring delicate and highly skilled techniques. Molar cavities are often deep, sometimes reaching depths of more than 7 mm. Currently, most dental filling materials for molars are cured by blue light with a wavelength of approximately 468 nm. The effective penetration of light is often less than 5 mm in depth, and such techniques are not suitable for filling deeper cavities (e.g., without using more complex and / or time-consuming techniques). These materials also shrink during curing, introducing stress thereby. The nature of light-initiated curing is that polymerization occurs very rapidly, which usually results in significant stress on the tooth structure.

[0005] In some cases, it may be possible to reduce these drawbacks and risks by incrementally filling the cavity in thin layers. After individually curing each increment layer, subsequent layers are placed to mitigate the effects of polymerization stress and light penetration depth. Thus, this method is relatively time-consuming and increases the risk of leaving voids between layers, which can significantly weaken the restoration and pose a risk of restoration failure.

[0006] Inadvertently, if the cavity filling is insufficient and the adaptation of the restorative material to the cavity wall is incomplete, a gap may occur between the restoration and the tooth structure, which can lead to an increase in sensitivity, fluid, and bacterial invasion, potentially causing continued tooth decay and premature damage to the restoration. Most clinical studies have shown that the annual failure rates (AFR) for tooth-colored fillings in molars are between 1% and 3%. SUMMARY OF THE INVENTION

[0007] In some examples, an ideal filling material (e.g., a molar filling material, or other filling materials, such as those for filling larger cavities, etc.) can be filled in bulk rather than incrementally and cures relatively slowly from the bottom of the restoration such that stress and voids are very low. In certain embodiments, such processes and materials suitable for such uses are provided herein.

[0008] Provided herein in certain embodiments is a dental composition comprising a polymerizable monomer and a hydroperoxide and / or a thiourea. In some embodiments, the composition further comprises copper(II) (e.g., as a catalyst). In certain embodiments, the dental composition comprises a first part and a second part, the first part comprising a hydroperoxide, and the second part comprising a thiourea. In certain embodiments, the first part and / or the second part comprise a polymerizable monomer (e.g., one comprising an ethylene group as described herein). In some embodiments, the first part and / or the second part comprise copper(II) (e.g., a copper(II) catalyst such as the copper(II) compounds described herein).

[0009] In a specific embodiment, provided herein is a dental composition comprising a first part and a second part, the first part comprising copper(II) (e.g., a copper(II) catalyst); a hydroperoxide; and a polymerizable monomer comprising an ethylene group, and the second part comprising copper(II) (e.g., a copper(II) catalyst); a thiourea; and a polymerizable monomer comprising an ethylene group. In a specific embodiment, the first part and the second part are physically separated (e.g., until the time the dental composition is used to repair a dental cavity).

[0010] In some embodiments, provided herein are dental compositions comprising a first part and a second part, the first part and the second part collectively comprising copper(II) (e.g., a copper(II) catalyst); a hydroperoxide; a polymerizable monomer comprising an ethylene group; and thiourea. In specific embodiments, the first part comprises the hydrogen peroxide, the second part comprises the thiourea, and the first and second parts are physically separated from each other (e.g., until the time the dental composition is used to repair a tooth cavity). In more specific embodiments, both the first and second parts comprise copper(II). In other specific embodiments, the second part (e.g., comprising thiourea) comprises copper(II). In more specific embodiments, the second part comprises copper(II), and the first part does not comprise copper(II). In some embodiments, the second portion comprises more copper(II) than the first portion (for example, at least twice, at least four times, at least five times, or at least ten times by weight).

[0011] In some embodiments, provided herein are dental compositions, portions thereof, or resin precursors thereof, comprising a hydroperoxide and a polymerizable monomer (e.g., a polymerizable monomer comprising an ethylene group). In specific embodiments, provided herein are dental compositions, portions thereof, or resin precursors thereof, comprising copper(II) (e.g., a copper(II) catalyst); a hydroperoxide; and a polymerizable monomer (e.g., a polymerizable monomer comprising an ethylene group). Similarly, in certain embodiments, provided herein are dental compositions, portions thereof, or resin precursors thereof, comprising copper(II) (e.g., a copper(II) catalyst); thiourea; and a polymerizable monomer (e.g., a polymerizable monomer comprising an ethylene group).

[0012] In some embodiments, provided herein is a dental composition (e.g., a fast-curing, copper-free, acid-free composition) comprising a first part and a second part, wherein the first part and the second part collectively comprise a hydroperoxide (e.g., the hydroperoxide is a tertiary aryl hydroperoxide (e.g., HOOCR'3 (wherein each R' is independently alkyl or aryl, and at least one R' is aryl (e.g., substituted or unsubstituted aryl)), e.g., cumene hydroperoxide (e.g., where the first and second R' are methyl and the third R' is phenyl)); a polymerizable monomer (e.g., a polymerizable monomer comprising an ethylene group); and thiourea. In some embodiments, the first part comprises hydrogen peroxide and the second part comprises thiourea, and the first part and the second part are physically separated from each other. In specific embodiments, the hydro The hydroperoxide is present in the dental composition at a concentration of approximately 1.5% (w / w) or more (for example, relative to the entire composition (e.g., concentration = (weight of hydroperoxide / weight of composition) * 100%) or the composition excluding the weight of all fillers (e.g., concentration = (weight of hydroperoxide / (weight of composition - weight of fillers)) * 100%), or at a concentration of approximately 1.5% (w / w) or more relative to the monomer (e.g., concentration = (weight of hydroperoxide / weight of monomer) * 100%). In a specific embodiment, the hydroperoxide is present at a concentration of about 2% (w / w) or more in the dental composition (for example, the entire composition or the composition excluding the filler), or at a concentration of about 2% (w / w) or more relative to the monomer. In a more specific embodiment, the hydroperoxide is present at a concentration of about 2.5% (w / w) or more in the dental composition (for example, the entire composition or the composition excluding the filler), or at a concentration of about 2.5% (w / w) or more relative to the monomer.In further or alternative embodiments, the thiourea is present in the dental composition at a concentration of about 1.5% (w / w) or more (e.g., relative to the entire composition (e.g., concentration = (weight of thiourea / weight of composition) * 100%) or relative to the composition excluding the filler (e.g., concentration = (weight of thiourea / (weight of composition - weight of filler) * 100%)), or at a concentration of about 1.5% (w / w) or more relative to the monomer (e.g., concentration = (weight of thiourea / weight of monomer) * 100%). More specific implementation In some embodiments, the thiourea is present in a concentration of about 2% (w / w) or more in the dental composition (e.g., the entire composition or the composition excluding the filler), or in a concentration of about 2% (w / w) or more relative to the monomer. In more specific embodiments, the thiourea is present in a concentration of about 2.5% (w / w) or more in the dental composition (e.g., the entire composition or the composition excluding the filler), or in a concentration of about 2.5% (w / w) or more relative to the monomer. In further or additional embodiments, The total weight of the hydroperoxide and thiourea is such that the concentration in the dental composition (e.g., the entire composition or the composition excluding the filler) is about 3% (w / w) or more, or the concentration relative to the monomer is about 3% (w / w) or more. In a more specific embodiment, the total weight of the hydroperoxide and thiourea is such that the concentration in the dental composition (e.g., the entire composition or the composition excluding the filler) is about 4% (w / w) or more, or the concentration relative to the monomer is about 4% (w / w) or more. In an even more specific embodiment, the total weight of the hydroperoxide and thiourea is such that the concentration in the dental composition (e.g., the entire composition or the composition excluding the filler) is about 5% (w / w) or more, or the concentration relative to the monomer is about 5% (w / w) or more. In a particular example, the amount of thiourea and hydroperoxide present in the composition is less than the amount that would result in poor curing of the composition and / or failure of the restorative material resulting from the combined curing of parts of the composition.In certain embodiments, the amount of thiourea and / or hydroperoxide (individually or in combination) in the dental composition (e.g., the entire composition or the composition excluding the filler) is less than 50% (w / w) of the monomer, less than 30% (w / w) of the monomer, less than 20% (w / w) of the monomer, less than 10% (w / w) of the monomer, and so on.

[0013] In certain embodiments, the copper(II) or copper(II) catalyst comprises copper(II) ions and / or copper(II) compounds (e.g., copper(II) salts, complexes, or other dentally acceptable compounds). In specific embodiments, the copper(II) compound or catalyst comprises copper(II) sulfate, copper(II) acetate, copper(II) chloride, copper(II) acetylacetonate, or a combination thereof. In some embodiments, the copper(II) (e.g., copper(II) compound or catalyst) is present in the composition (e.g., the entire composition or the composition excluding the filler) in an amount of about 5% by weight or less (e.g., about 1% by weight or less, or about 0.1% by weight or less). In specific embodiments, the copper(II) compound is present in the composition (e.g., the entire composition or the composition excluding the filler) in an amount of about 5% by weight or less (e.g., about 1% by weight or less, or about 0.1% by weight or less). In certain embodiments, the amount of copper(II) present in the composition is sufficient to promote a desired curing time (for example, of the composition provided herein, which is a combination of the first and second parts thereof), such as any desired curing time described herein.

[0014] In some embodiments, the hydroperoxide is a hydrocarbon substituted with one or more -OOH groups (e.g., C4-C4). 20The composition comprises hydrocarbons. In specific embodiments, the hydroperoxide is a tertiary hydroperoxide (for example, the -OOH group is substituted with a carbon having a tertiary substituent). In more specific embodiments, the hydroperoxide is t-butyl hydroperoxide, t-amyl hydroperoxide, p-diisopropylbenzene hydroperoxide, cumene hydroperoxide, pinan hydroperoxide, p-menthane hydroperoxide, 1,1,3,3-tetramethylbutyl hydroperoxide, or a combination thereof or comprising them. In further or alternative embodiments, the hydroperoxide is present in the composition (for example, the entire composition or the composition excluding the filler) in an amount of about 0.01% (w / w) to about 10% (w / w). In more specific embodiments, the hydroperoxide is present in the composition in an amount of about 0.1% (w / w) to about 6% (w / w), for example, about 0.1% (w / w) to about 5% (w / w). In some embodiments, the hydroperoxide is present in the composition such that the ratio of hydroperoxide to polymerizable monomer is about 1:9999 to about 1:9. In more specific embodiments, the ratio of hydroperoxide to polymerizable monomer is about 1:99 to about 5:95.

[0015] In certain embodiments, the monomer is a dentally acceptable monomer. In some embodiments, the monomer comprises vinyl, acrylate, methacrylate (e.g., dimethacrylate), or a combination thereof. In further or alternative embodiments, the monomer is present in an amount of about 10% (w / w) to about 60% (w / w) (e.g., by weight of the total composition including any filler). In more specific embodiments, the polymerizable monomer is present in an amount of about 20% (w / w) to about 50% (w / w).

[0016] In certain embodiments, the thiourea is a (hetero)arylthiourea, a (hetero)arylcarbonylthiourea, a (hetero)alkylcarbonylthiourea, a (hetero)alkylthiourea, and the like. In specific embodiments, the thiourea is 1-(2-pyridyl)-2-thiourea (PTU), 1-benzoyl-2-thiourea (BTU), 1-acetyl-2-thiourea (ATU), 1-(2-tetrahydrofurfuryl)-2-thiourea (TTU), or a combination thereof, or comprising them. In further or alternative embodiments, the thiourea is present in the composition in a ratio of thiourea to polymerizable monomer of about 1:999 to about 100:900. In more specific embodiments, the ratio of thiourea to polymerizable monomer is about 1:99 to about 10:90.

[0017] In specific embodiments, the hydroperoxide is cumene hydroperoxide. In further or alternative embodiments, the thiourea is 1-(2-pyridyl)-2-thiourea (PTU). In more specific embodiments, the hydroperoxide is cumene hydroperoxide and the thiourea is 1-(2-pyridyl)-2-thiourea (PTU). Other specific hydroperoxides and thioureas, as well as their combinations, are described in the examples. In addition, specific embodiments, specific monomers, and their combinations included in the compositions herein are as described in the examples. Other specific agents and agent combinations described in the examples and included in the disclosure herein are illustrated in any combination.

[0018] In specific embodiments, the dental compositions provided herein comprise a filler. In more specific embodiments, the first and second portions comprise a filler. In even more specific embodiments, the filler is a microfiller. In some embodiments, the microfiller comprises a plurality of particles. In specific embodiments, the particles have an average size (e.g., diameter) of about 0.02 microns to about 30 microns, for example, about 0.2 microns to about 10 microns. In further or alternative embodiments, the filler comprises an inorganic filler, a prepolymerized filler, or a combination thereof. Examples of fillers, though not limited to them, include metal oxides, metal nitrides, metal fluorides, silicates, silica (e.g., colloidal silica, precipitated silica, fused quartz), aluminosilicates, aluminoborosilicates, fluoroaluminosilicates, barium silicates, barium aluminosilicates, barium aluminoborosilicates, strontium aluminosilicates, barium fluoroaluminosilicates, strontium fluoroaluminosilicates, strontium zinc fluoroaluminosilicates, zinc aluminosilicates, prepolymerized fillers, and combinations thereof. In some embodiments, the filler is present in an amount of about 10% (w / w) to about 90% (w / w) of the total composition (e.g., including all components). In more specific embodiments, the filler is present in an amount of about 40% (w / w) to about 80% (w / w). In a more specific embodiment, the filler is present in an amount of approximately 60% (w / w) to approximately 80% (w / w).

[0019] In some embodiments, the composition comprises a photoinitiator, a stabilizer, a solvent, or any combination thereof. In some embodiments, the photoinitiator is present in an amount of about 5% (w / w) or less (e.g., by weight relative to the total weight of the composition or the weight of the composition excluding the filler). In further or alternative embodiments, the stabilizer is present in an amount of about 1% (w / w) or less (e.g., by weight relative to the total weight of the composition or the weight of the composition excluding the filler).

[0020] In some embodiments, the compositions provided herein are acid-free or substantially acid-free. In specific embodiments, the composition (and / or portion thereof) contains an acid and / or anhydride—either alone or in combination—in less than 10% (w / w) (e.g., less than 8% (w / w), less than 5% (w / w), less than 3% (w / w), less than 1% (w / w), or less than 0.5% (w / w)) (e.g., by weight of the entire composition or by weight of the composition excluding the fillers). In some embodiments, the composition and / or portion thereof is non-acidic (e.g., having a pH of about 5 or higher).

[0021] In various embodiments, the compositions provided herein have good performance characteristics, for example, when used in restorative dental applications (e.g., restoration of teeth with Class I or Class II cavities). In specific embodiments, when the first and second parts are combined, the total volume of the composition (e.g., when it solidifies) is reduced by less than 10% (e.g., less than 8%, less than 6%, or less than 4%). In some examples, minimizing such reduction reduces the occurrence of void formation between the filling and the tooth, and reduces the occurrence of damage to the tooth during and after restoration (e.g., cracking). In further or alternative embodiments, when the first and second parts are combined, the hygroscopicity of the composite is 100 μg / mm³. 3 Less than (for example, 50 μg / mm³) 3 Less than 25 μg / mm³ 3 Less than 20 μg / mm³ 3 Less than 15 μg / mm³ 3 It is less than ). In some cases, minimizing this hygroscopicity can reduce the expansion of the restorative material after hardening into the resulting composite, which in turn can reduce the occurrence of tooth damage (e.g., cracking) and the detachment of the filling from the tooth.

[0022] Also provided herein are dental composites comprising, for example, partially or fully cured mixtures resulting from the mixing of the compositional components described herein. In some embodiments, the composite comprises a partially or fully cured resin (for example, comprising a polymer such as a polymer monomer described herein), a filler, and copper. In specific embodiments, the composite comprises the cured resin in an amount of about 10% (w / w) to about 60% (w / w), the filler in an amount of about 10% (w / w) to about 90% (w / w), and the copper in an amount of about 1 elemental weight percent or less. Also provided herein are mixtures comprising copper(II) (for example, a copper(II) catalyst); hydroperoxide; polymerizable monomers comprising an ethylene group; and thiourea. The reaction mixture may partially cure, with some of their monomer units forming monomers and others forming their oligomers or polymers.

[0023] In some embodiments, the two-component compositions provided herein are housed in a dual-chamber device comprising a housing body, the housing body comprising a first chamber containing a first portion of the composition described herein and a second chamber containing a second portion of the composition described herein. In specific embodiments, the dual-chamber device is configured to simultaneously extrude and / or mix the first and second portions.

[0024] Also provided herein are methods for restoring teeth in an individual. In some embodiments, the process comprises combining a first composition (e.g., a first part of the dental composition described herein) and a second composition (e.g., a second part of the dental composition described herein) to form a mixed composition. In specific embodiments, the first composition comprises a hydroperoxide, the second composition comprises thiourea, and one or both of the first composition and / or the second composition comprises copper(II) (e.g., a copper(II) catalyst), a polymerizable monomer (e.g., a polymerizable monomer comprising an ethylene group), and a filler. In some embodiments, the method further comprises administering the mixed composition to an individual (e.g., a Class I or Class II cavity in the tooth of the individual). In some embodiments, the process further comprises curing the mixed composition (e.g., a self-curing step of the composition, and / or a step of using dental curing light to photocur the composition). In specific embodiments, the curing of the mixed composition results in the formation of a restorative composite (for example, in the form of a filling in the cavity of the solid tooth). In preferred embodiments, the curing step (e.g., self-curing) is carried out relatively quickly to facilitate the restorative process. In specific embodiments, the curing step (e.g., self-curing or solidification) is carried out within 10 minutes, 4 minutes, 2 minutes, etc.

[0025] In some embodiments, the method includes a step of removing caries from within and around the cavity to be filled (for example, a step of drilling the tooth to remove the caries). In certain embodiments, the cavity into which the composition is administered is a Class I or Class II cavity. In some specific embodiments, the cavity into which the composition is administered has a depth of at least 3 mm, for example, at least 4 mm, at least 5 mm, 5 mm to 7 mm.

[0026] The compositions, parts thereof, their precursors, resulting composites, and methods disclosed herein, as well as their respective purposes, features, and properties, and methods of production, will become more apparent by considering the following description and the accompanying claims with reference to the accompanying drawings, all of which constitute part of this specification. However, it should be clearly understood that the drawings are for illustrative and illustrative purposes only and do not define the limitations of the invention. As used herein and in the claims, the singular forms "a," "an," and "the" refer to plural subjects unless otherwise explicitly indicated in the context. [Brief explanation of the drawing]

[0027] [Figure 1] Figure 1 shows a cross-sectional image of a cavity filling using the compositions described herein and commercially available restorative compositions. [Figure 2] Figure 2 shows images demonstrating the absence of microleakage observed when filling a cavity with the compositions described herein, compared to the microleakage observed when filling a cavity with commercially available restorative compositions. [Figure 3] Figure 3 shows an example monomer (diacrylate) used herein that contains an ethylene group. [Figure 4] Figure 4 shows an example monomer (tetraacrylate) used herein that contains an ethylene group. Detailed description of the invention

[0028] Provided in certain embodiments herein are dental compositions. Also provided in certain embodiments herein are their component parts, dental restorative processes, resins used in the preparation of dental compositions, dental composites (e.g., filling materials), etc. In specific embodiments herein, the dental composition comprises two parts, for example, two parts that are physically separated from each other. In some examples, when the two parts are combined, for example, when the dental composition is used in a dental restorative process (as described herein), the composition forms a composite (e.g., a filling material used to restore teeth).

[0029] In some embodiments, provided herein is a dental composition comprising two parts (for example, where free radical polymerization is initiated upon mixing thereof), the two-part dental composition comprising, in some embodiments, (1) at least one monomer having at least one ethylene-based unsaturated group (for example, as herein also referred to as a polymerizable monomer comprising an ethylene group, as described herein); (2) one part comprising at least one hydroperoxide group; and (3) one part comprising at least one substituted thiourea. In a more specific embodiment, the two-component dental composition comprises: (1) at least one monomer having at least one ethylene-unsaturated group; (2) one portion comprising at least one hydroperoxide group; (3) one portion comprising at least one substituted thiourea; and (4) at least one portion comprising at least one copper(II) compound (for example, a copper(II) compound that, when combined with the first and second portions, catalyzes, promotes, and / or accelerates, the curing of the composition (e.g., polymerization of its monomer components).

[0030] In specific embodiments, provided herein are dental compositions comprising a first part and a second part, wherein the first part comprises a polymerizable monomer comprising (1) copper(II) (e.g., a copper(II) catalyst); (2) a hydroperoxide; and (3) an ethylene group, and the second part comprises a polymerizable monomer comprising (1) copper(II) (e.g., a copper(II) catalyst); (2) thiourea; and (3) an ethylene group. Also provided herein are the individual first and second parts, for example, dental compositions comprising a polymerizable monomer comprising (1) copper(II) (e.g., a copper(II) catalyst); (2) a hydroperoxide; and (3) an ethylene group, and / or dental compositions comprising a polymerizable monomer comprising (1) copper(II) (e.g., a copper(II) catalyst); (2) thiourea; and (3) an ethylene group. Alternatively, in some embodiments, the first part does not contain copper(II).

[0031] In certain embodiments, provided herein is a dual-chamber device comprising a housing body, the housing body comprising a first chamber containing a first portion of the composition described herein and a second chamber containing a second portion of the composition described herein. In some embodiments, the dual-chamber device is any suitable device suitable for simultaneously extruding the first and second portions to enable mixing of the first and second portions and to promote the initiation and polymerization of their monomer components. In specific embodiments, the dual-chamber device is a dual-barrel syringe comprising nozzles configured to facilitate mixing of the first and second portions when a first plunger and a second plunger are pressed down (simultaneously) (for example, here the first and second plungers move the first and second portions of the composition out of the dual-chamber device when they are pressed down).

[0032] In certain embodiments, the monomer having at least one ethylenically unsaturated group or the polymerizable monomer comprising an ethylene group is a compound comprising at least one >C=C< group. In specific embodiments, the monomer is of the formula R2C=CR2, where each R is independently selected from H, COOR 1 , or an optionally substituted hydrocarbon, such as alkyl, aryl, etc., for example, at least one R is not H). In specific embodiments, at least one R is COOR 1 or aryl (such as phenyl, etc.). In some embodiments, R 1The monomer is one of the following: H, (hetero)alkyl (e.g., C1-C6 alkyl) (wherein "(hetero)alkyl" means either alkyl or heteroalkyl as used herein), (hetero)alkylaryl, aryl(hetero)alkyl, (hetero)alkylaryl(hertero)alkyl, etc. In more specific embodiments, the alkyl is a C1-C6 alkyl (e.g., methyl, ethyl, etc.). In certain embodiments, the alkyl is acyclic (e.g., branched or linear) or cyclic, saturated or unsaturated alkyl. In some embodiments, optional substituents include, but are not limited to, -OH, alkyl, and / or aryl. In certain embodiments, the monomer comprises one or more parts represented by the formula R'2C=CR'L (wherein each of the R' and L groups is independently as described above for the R group). In specific embodiments, adjacent L groups bond to form any preferred group, such as -COO-(hetero)alkyl-OOC-, -COO-(hetero)alkylaryl(hetero)alkyl-OOC-, -COO-(hetero)alkylarylalkylaryl(hetero)alkyl-OOC-, (hetero)alkyl, (hetero)alkylaryl(hetero)alkyl, (hetero)alkylarylalkylaryl(hetero)alkyl, etc. In certain embodiments, the L group(s) are replaced by any preferred group(s), such as one or more alkyl groups, one or more -OH groups, one or more oxo (i.e., =O) groups, or a combination thereof. Figure 3 shows, for example, an exemplary embodiment in which adjacent L groups bond to form a -COO-heteroalkylarylalkylarylheteroalkyl-OOC- group. In a particular embodiment, the monomer comprises two or more R'2C=CR'L groups, where the L group is as shown in formula I below (for example, R'2C=CR'L-(LCR'=CR'2) a (In the formula, a > 0, 1 to 5, for example, 1 to 2) are concatenated together. [ka]

[0033] For example, in some embodiments, the monomer may be R'2C=CR'-COO((CH2) m (CHOH) n ) p OOC-R'C=CR'2 (for example, where each L group is COOR, and each R group is an alkyl which may be substituted together and / or individually with OH) (wherein m is 1 to 6 (e.g., 2 to 4), n is 0 to 1, and p is 1 to 30 (e.g., 1 to 10)). Figure 4 shows another exemplary monomer comprising an acrylate (tetraacrylate, ethoxylated (4) pentaerythritol tetraacrylate) (where each L is -COOR' (R' = heteroalkyl group) and a = 3).

[0034] In specific embodiments, the monomer is an acrylate (for example, where three R groups = H and one R group = COOR). 1 ), methacrylate (for example, where two R groups = H, one R group = methyl, and another R group (on the same carbon as the methyl) is COOR 1The monomer is a acrylate, a methacrylate, and / or a vinyl group (where at least one R group is a hydrocarbon). In some embodiments, the monomer comprises an acrylate, a methacrylate, and / or a vinyl group. In specific embodiments, the ethylene-unsaturated group is selected from acrylate and methacrylate groups.Examples of polymerizable monomers include, but are not limited to, glycerol di(meth)acrylate, glycerol mono(meth)acrylate, hydroxyethyl(meth)acrylate {(meth)acrylate = acrylate or methacrylate}, hydroxypropyl(meth)acrylate, methyl(meth)acrylate, ethyl(meth)acrylate, propyl(meth)acrylate, octyl(meth)acrylate, decyl(meth)acrylate, 2-ethoxyethyl(meth)acrylate, 2'-ethoxy-2-ethoxyethyl(meth)acrylate, ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate; polyethylene glycol mono-(meth)acrylate, polyethylene glycol di-(meth)acrylate, polypropylene glycol mono-(meth)acrylate, polypropylene glycol di(meth)acrylate, polytetramethylene glycol mono-(meth)acrylate, polytetramethylene Glycol di(meth)acrylate, hexanediol di(meth)acrylate, octanediol di(meth)acrylate, decanediol di(meth)acrylate, trimethyloylpropane tri(meth)acrylate, urethane dimethacrylate (e.g., reaction adduct of 2-hydroxyethyl methacrylate and 2,4,4-trimethylhexanediisocyanate), 2,2-bis[4-(2-hydroxy-3-methacryloylpropoxy)-phenyl]-propane (Bis-GMA), ethoxy Examples include ethoxylated bisphenol A dimethacrylate (where the total number of moles of ethylene oxide in the molecule can be in the range of 2 to 30 units, for example, Figure 3 shows ethoxylated bisphenol A dimethacrylate, where n is, for example, 2 to 30) (e.g., ethoxylated (6) bisphenol A dimethacrylate (E6BAD) or ethoxylated (3) bisphenol A dimethacrylate (EBPADM)), tetrahydrofurfuryl (meth)acrylate, or mixtures or copolymers thereof. As referred to herein, “(meth)acrylate” includes disclosures of both methacrylate and acrylate.

[0035] In certain embodiments, the amount of monomer present in the composition is any preferred amount (for example, to promote the curing of the composition into a dentally acceptable restorative material). In certain embodiments, the dental composition provided herein contains monomer in a weight percentage (for example, between 10% and 60% of the total composition). In more specific embodiments, the weight percentage is between 20% and 50%.

[0036] In certain embodiments, the compositions provided herein contain copper(II) (e.g., a copper(II) catalyst), for example, in the form of a copper(II) compound. In specific examples, copper(II) (e.g., a copper(II) compound) is used to catalyze the curing (e.g., hardening, otherwise solidification) of the composition (e.g., to accelerate, otherwise promote, the polymerization of the monomer). In specific examples, when two parts of the composition of the present invention are mixed, the presence of copper(II) (e.g., its compound) accelerates the polymerization process (e.g., thereby promoting the initiation of polymerization, which is accelerated by the presence of copper(II), by the combined action of the separated hydroperoxide and thiourea). The copper(II) catalyst may be in a dissociated form, a bonded form (e.g., in the form of a copper(II) compound), or a partially bonded form. In various embodiments, the copper(II) compound is any suitable compound having at least one copper(II) in its molecular formula. Examples of copper(II) compounds include, but are not limited to, copper(II) sulfate, copper(II) acetate, copper(II) chloride, copper(II) acetylacetonate, and combinations thereof. In a specific embodiment, the copper(II) compound is copper(II) acetate. In another specific embodiment, the copper(II) compound is copper(II) acetylacetonate. In a specific embodiment, the weight percentage of copper(II) (or its compounds) is less than 1% (e.g., about 0.001% to 1%). In a more specific embodiment, the weight percentage of copper(II) (or its compounds) is less than 0.1% (e.g., about 0.001% to about 0.1%). In an even more specific embodiment, the copper(II) (or its compounds) is provided in or combined in a composition herein in an amount of about 0.001% to about 0.05%. In specific embodiments, such a weight percentage is determined with respect to the total weight of the composition, or the total weight of the composition minus the weight of any filler (e.g., an inorganic filler).

[0037] In certain embodiments, the hydroperoxide is any suitable agent, particularly dentally acceptable, that, when combined with the thiourea provided herein, initiates and / or otherwise promotes the polymerization of the monomer herein, for example, at a rate suitable for dental applications, particularly restorative applications. In some embodiments, the hydroperoxide is of the formula HOO-R 2 (In the formula, R 2 R is represented by any suitable organic group. In specific embodiments, R 2 This refers to hydrocarbons, for example, C4-C 20 This includes hydrocarbons (which may be substituted with any preferred group, e.g., alkyl groups, aryl groups (e.g., phenyl), alkylaryl groups, additional -OOH groups, etc.). In some embodiments, R 2 is, formula: -CR 3 R 4 R 5 (In the formula, R 3 , R 4 , and R 5 Each of these is independently represented by H, alkyl (cyclic and / or acyclic, and branched or linear), aryl (e.g., phenyl), arylalkyl (e.g., bonded to the alkyl carbon), alkylarylalkyl, etc., where such groups may be substituted or unsubstituted. In some embodiments, R 3 , R 4 , and R 5 At least two of them are not H. In a specific embodiment, the hydroperoxide is a tertiary hydroperoxide, i.e., where R 3 , R 4 , and R 5 None of these are H. In a particular example, R 3 , R 4 , and / or R 5 Any one or more of the following are R 3 , R 4 , and R 5They may combine with another or both to form a cyclic (monocyclic or polycyclic) alkyl group (which may be substituted or unsubstituted, as discussed herein). Any preferred hydroperoxide compound having at least one hydroperoxide group may be used as desired, as discussed herein. In specific embodiments, the hydroperoxide compound comprises two or more hydroperoxide groups. Examples of hydroperoxide compounds that are not limited to include, but are, t-butyl hydroperoxide, t-amyl hydroperoxide, p-diisopropylbenzene hydroperoxide, cumene hydroperoxide, pinan hydroperoxide, p-methane hydroperoxide, and 1,1,3,3-tetramethylbutyl hydroperoxide.

[0038] In some embodiments, any preferred concentration of hydroperoxide is used as desired in the compositions and methods provided herein. In specific embodiments, the total hydroperoxide compound is in the range of about 0.01% (w / w) to about 10.0% (w / w) (e.g., of the whole composition). In certain embodiments, the hydroperoxide is present in the range of about 0.1% (w / w) to about 5.0% (w / w) of the composition (e.g., of the whole composition). In some embodiments, the hydroperoxide is present in the composition in an amount of about 1.5% (w / w) to about 5% (w / w). In specific embodiments, such a weight percentage is determined relative to the total weight of the composition, or the total weight of the composition minus the weight of any fillers (e.g., inorganic fillers). In certain examples, the hydroperoxides provided herein are, for example, stable under various conditions and have a long shelf life, among those described above.

[0039] Any suitable thiourea may be used as desired in the compositions described herein (e.g., at least one part of the two-component compositions described herein). In some embodiments, the thiourea is a substituted thiourea, e.g., dentally acceptable thiourea. In some embodiments, the thiourea is an organic thiourea, e.g., a thiourea substituted with an organic group (e.g., pyridyl, acetyl). In specific embodiments, the thiourea is structure R 6 R 7 NC(=S)NR 8 R 9 (In the formula, R 6 , R 7 , R 8 , and R 9 H, COR 10 Selected from heterocycloalkyl and heteroaryl (for example, the heterocycloalkyl or heteroaryl is substituted or unsubstituted), R 10 is alkyl, heteroalkyl (cyclic or acyclic (acylic)), aryl, or heteroaryl (R 10 R is represented by (which is substituted or unsubstituted). In specific embodiments, the thiourea group is bonded to the heterocycloalkyl or heteroaryl α-carbon of the heteroatom of the ring. In some embodiments, R 6 , R 7 , R 8 , and R 9 At least one or more of the atoms are not H. In specific embodiments, the substituted thiourea is selected from the group consisting of 1-(2-pyridyl)-2-thiourea (PTU), 1-benzoyl-2-thiourea (BTU), 1-acetyl-2-thiourea (ATU), 1-(2-tetrahydrofurfuryl)-2-thiourea (TTU) and any mixture thereof (i.e., any one or more of PTU, BTU, ATU, and / or TTU).

[0040] In certain embodiments, a combination of two parts of a composition provided herein results in the curing of that composition. In specific examples, the combination of the two parts, particularly the hydroperoxide and thiourea, facilitates the initiation of polymerization of the monomer components of the composition. In certain embodiments, the inclusion of the copper(II) catalyst accelerates the curing process (e.g., polymerization of the monomer components) to obtain a solidification time fast enough to be suitable for dental applications. In some examples, once the two parts are mixed, the mixed composition cures (e.g., solidifies or hardens). In one embodiment, the solidification time is less than 20 minutes (e.g., without the need for photocuring using a photocuring device that emits most light having wavelengths in the blue range (e.g., 400 nm to 530 nm, e.g., about 470 nm, etc.)). In one embodiment, the solidification time is less than 10 minutes. In one embodiment, the solidification time is less than 5 minutes. In a more preferred embodiment, the curing (e.g., solidification) time is about 250 seconds or less. In a preferred embodiment, the curing (e.g., solidification) time is about 180 seconds or less. In further or alternative embodiments, the composition, when the two parts are combined, has a working time of about 200 seconds or less, for example, about 150 seconds or less. Furthermore, in some embodiments, the working time is at least 30 seconds (for example, to enable the restoration or filling of a dental cavity, particularly a Class I or Class II cavity).

[0041] In certain embodiments, additional additives are included in the composition and / or parts thereof. In some embodiments, any suitable additives, such as, but not limited to, photoinitiators, fillers, stabilizers, solvents, or combinations thereof, may be included. In specific embodiments, the dental composition (or part thereof) comprises a resin composition and a filler (for example, the resin composition comprises the materials of the dental composition described herein). In more specific embodiments, each part of the composition provided herein comprises a resin composition (for example, a composition comprising the monomers described herein) and a filler. In specific embodiments, the agents and additives used in the compositions and composites provided herein are generally dentally acceptable (e.g., have sufficiently low toxicity and perform their intended purpose under oral conditions).

[0042] In specific embodiments, the compositions (or portions thereof) provided herein comprise fillers, for example, at least one microfiller. In some examples, the fillers may reduce polarization shrinkage, improve mechanical properties, and increase the radiopaqueness of the dental composite. In further or alternative examples, the fillers may modify the rheological properties of the dental composition. Exemplary fillers include, but are not limited to, metal oxides, metal nitrides, metal fluorides, silicate glass, colloidal silica, precipitated silica, fused quartz, aluminosilicate glass, aluminoborosilicate glass, fluoroaluminosilicate glass, barium silicate, barium aluminosilicate, barium aluminoborosilicate, strontium aluminosilicate, barium fluoroaluminosilicate, strontium fluoroaluminosilicate, strontium zinc fluoroaluminosilicate, zinc aluminosilicate pre-polymerized composite filler, and any one or more combinations thereof. Examples of metal oxides and fluorides include, but are not limited to, barium oxide, strontium fluoride, barium fluoride, ytterbium fluoride, yttrium fluoride, zinc oxide, and bismuth(III) oxide. In one embodiment, the filler is treated with a coupling agent, such as γ-methacryloyloxypropyltrimethoxysilane (MPTMS). In some examples, such treatment enhances the interfacial bonding between the filler and the resin matrix and improves the mechanical properties.

[0043] In some embodiments, the filler is a fine filler, for example, a filler comprising or consisting of a plurality of solid particles. In a particular embodiment, the fine filler (e.g., its particles) has any preferred average dimensions, for example, an average size (e.g., particle size) between 0.02 microns (μm) and 30 microns. In a specific embodiment, the average size is between 0.2 microns and 10 microns.

[0044] In certain embodiments, the filler is present in any preferred amount in the composition provided herein. In some embodiments, the filler (e.g., a fine filler) is present in the composition in an amount between 10% and 90% by weight. In specific embodiments, the weight percentage is between 40% and 80%.

[0045] In certain embodiments, the compositions (or portions thereof) provided herein further comprise at least one photoinitiator. Any suitable photoinitiator may be included. Examples of photoinitiators, but not limited to, include benzoin and derivatives, 2,2-diethoxyacetophenone, camphorquinone, 1-phenyl-1,2-propanedione, monoacylphosphine oxides, bisacylphosphine oxides, and mixtures thereof. In addition, activators can be used with the photoinitiators. Examples of activators, but not limited to, include 2-ethyl-4-(N,N-dimethylamino)benzoate, 2-amyl-4-(N,N-dimethylamino)benzoate, 2-octyl-4-(N,N-dimethylamino)benzoate; 2-(ethylhexyl)-4-(N,N-dimethylamino)benzoate, N,N-dimethylaminoethyl methacrylate, N,N-dimethylaminophenethyl alcohol, and mixtures thereof. In one embodiment, the photoinitiator system comprises camphorquinone and a tertiary amine selected from the group consisting of 2-ethyl-4-(N,N-dimethylamino)benzoate, 2-amyl-4-(N,N-dimethylamino)benzoate, 2-octyl-4-(N,N-dimethylamino)benzoate; 2-(ethylhexyl)-4-(N,N-dimethylamino)benzoate, N,N-dimethylaminoethyl methacrylate, N,N-dimethylaminophenethyl alcohol, and any mixture of one or more thereof. In one embodiment, the weight percentage of the photoinitiator is less than 5%. In another embodiment, the weight percentage of the photoinitiator is less than 3%. In a specific embodiment, such a weight percentage is determined relative to the total weight of the composition, or the total weight of the composition minus the weight of any fillers (e.g., inorganic fillers).

[0046] In certain embodiments, the compositions provided herein comprise at least one stabilizer. In some examples, the stabilizer is a polymerization inhibitor, such as a monomer component of the compositions described herein. In certain examples, such an agent is useful for improving the shelf life of the compositions provided herein (e.g., inhibiting the polymerization of monomers before use). Any suitable stabilizer or polymerization inhibitor (e.g., a free radical scavenger) is available herein as desired. Examples of stabilizers, not limited to, include 2,6-di-(tert-butyl)-4-methylphenol (BHT) and 4-methoxyphenol (MEHQ). Any suitable amount of stabilizer, such as less than 1% by weight, is available as desired. In specific embodiments, such a weight percentage is determined relative to the total weight of the composition, or the total weight of the composition minus the weight of any fillers (e.g., inorganic fillers).

[0047] In various embodiments, the first and / or second parts provided herein are provided in any preferred ratio, as desired, to provide, for example, an entire composition having the properties provided herein. In certain embodiments, the ratio of the first part to the second part (for example, present in the composition herein and / or provided by the process herein) is about 99:1 to about 1:99. In some embodiments, the ratio of the first part to the second part is about 9:1 to about 1:9. In specific embodiments, the ratio of the first part to the second part is about 4:1 to about 1:4 or about 2:1 to about 1:2. In more specific embodiments, the ratio of the first part to the second part is about 1:1.

[0048] In certain embodiments, what is provided herein are methods of using and preparing such compositions, for example, in dental applications. In general examples, such compositions are prepared in a dentally acceptable manner (i.e., in a manner suitable for administration to an individual, a patient, or a person's mouth (or its dental cavity)). In specific embodiments, what is provided herein is a method of administering the compositions described herein to an individual, for example, to restore the teeth of the individual. In specific embodiments, the compositions described herein are provided, any part thereof is combined to form a mixed composition (e.g., monomers of the compositions are polymerized), this mixed composition is administered to an individual (e.g., into a cavity of the individual), and the mixed composition is cured (e.g., until solidified).

[0049] In specific embodiments, the method is used to restore teeth (e.g., teeth containing cavities). In some embodiments, the composition is administered, delivered, and / or used to restore teeth containing Class I or Class II cavities (e.g., based on the GV Black classification system), or cavities in molar teeth. In certain embodiments, Class I cavities are cavities located in the occlusal surfaces of molars and premolars, the buccal two-thirds of the occlusal surface of molars, the lingual surface of maxillary incisors, or the pits and fissures of the lingual surface of maxillary molars. In some embodiments, Class II cavities are cavities in the interproximal surfaces of molars or premolars. In certain embodiments, the composition is particularly useful in providing an effective mechanism for filling large cavities—an area not found in other restorative compositions. In specific embodiments, the cavities treated by the processes described herein have a depth of about 3 mm or more (e.g., about 4 mm or more, about 5 mm or more, about 5 mm to about 7 mm, etc.) from any surface of the tooth (e.g., the filling surface of the tooth, or the surface of the tooth that previously had or did not have a cavity).

[0050] In a specific example, two parts of the composition are mixed, and the mixture is then delivered to a Class I or Class II cavity (or any other cavity type described herein). After waiting for a certain period of time, the mixture eventually solidifies. In one embodiment, the solidification time is between 1 and 5 minutes (e.g., under oral conditions (e.g., in the mouth of the individual to whom the composition is administered)). In one embodiment, the solidification time is between 0.2 and 5 minutes (e.g., under oral conditions). In one embodiment, the solidification time is between 0.5 and 3 minutes (e.g., under oral conditions).

[0051] In some embodiments, the mixture is further cured with dental curing light after it has solidified, for example, under intraoral conditions. In further or alternative embodiments, an additional layer of the dental composition provided herein is placed on top of the solidified or cured mixture and subsequently cured with dental curing light.

[0052] In specific embodiments, portions of the composition provided herein are mixed (e.g., passively brought into contact with each other or actively integrated) to form a mixed composition, which is administered to a solid (e.g., a tooth cavity of a solid), and the mixed composition is cured (or self-curable) for up to 5 minutes (e.g., 0.2 to 5 minutes, 30 to 250 seconds, or 0.5 to 3 minutes) under ambient (e.g., oral) conditions. In alternative embodiments, a first or second portion is administered, followed by the remainder of the first or second portion (e.g., thereby mixing the two portions in, for example, a tooth cavity of a solid), followed by curing as described herein. In specific examples, curing under ambient conditions comprises curing the composition in the absence of a photoinitiator, e.g., a device that emits light, for example, a device whose majority has a blue wavelength (e.g., in the range of 400 to 530 nm, or about 470 nm). In specific embodiments, the cured (e.g., self-cured or solidified) composite is further cured using a photoinitiator device, such as a device that emits light, the majority of which has a blue wavelength (e.g., in the range of 400-530 nm, or about 470 nm). In more specific embodiments, an additional mixed composition is administered to the cavity prior to photocuring. In some examples, photocuring at the surface is desirable to promote complete curing of the filler at the surface (e.g., here, radical groups—e.g., living polymers and / or initiators—may interact and disappear, for example, as a result of chemical reactions with agents, in the surrounding environment (e.g., air), for example, in water, etc., prior to complete polymerization / curing).

[0053] In some embodiments, one or more of the desirable restorative material properties described herein are achieved by any preferred method, for example, by using the concentrations of the materials described herein. In certain embodiments, provided herein is a composition (e.g., a two-component composition) comprising copper(II) as described herein. In some embodiments, the presence of copper(II) catalyzes the hardening (e.g., self-hardening) of the composition at a rate sufficient to be dentally effective (e.g., longer hardening times may reduce the proper use of the product and increase the failure rate of the restorative material). In some embodiments, the amount of copper(II) (or its compounds) present is not very necessary to produce the effect. For example, in some embodiments, less than 0.1% by weight or less than 0.01% by weight of copper(II) (or its compounds) is used. In further or alternative embodiments, a good hardening rate is achieved by using higher concentrations of hydroperoxide and / or thiourea (e.g., not so high as to result in excessive temperature and / or defects in the hardened restorative material). In some embodiments, the compositions provided herein consist of a total concentration of a hydroperoxide and thiourea (for example, the hydroperoxide and thiourea are provided in separate parts of the composition). This total concentration is about 2.5% by weight or more (as a percentage of the total weight of the monomers - i.e., {{weight hydroperoxide + weight thiourea} / total weight monomer}*100%), about 3% by weight or more, about 4% by weight or more, or about 5% by weight or more (for example, up to about 50% by weight, up to about 30% by weight, up to about 20% by weight, up to about 10% by weight, up to about 8% by weight, etc.).

[0054] Provided in certain embodiments herein are dental composites (e.g., restorative materials described herein) comprising a curing combination of a first and second part of any composition described herein, or a curing combination of any composition comprising thiourea and any composition comprising a hydroperoxide described herein. In certain embodiments, one or both parts of the compositions described herein comprise a copper(II) catalyst. In some embodiments, the composites provided herein comprise a curing resin (e.g., comprising a polymerization monomer described herein), a filler, and copper (e.g., any oxidation state, such as the oxidation state of the copper(II) catalyst). In specific embodiments, the composite comprises the curing resin in any suitable amount, for example, the amount described herein for the monomer-containing composition (e.g., about 10% to about 60% by weight), and the filler in any suitable amount, for example, the amount described herein for the filler-containing composition (e.g., about 10% to about 90% by weight). The composite comprises such materials, and contains copper in an amount of about 1 elemental weight percent or less (for example, based on the amount of copper present on an elemental basis) (for example, about 0.1% by weight or less, about 0.05% by weight or less, etc.). In a specific embodiment, the dental composite comprises a filler in an amount of about 60% (w / w) to about 80% (w / w) and a hardening resin in an amount of about 20% (w / w) to about 40% (w / w). In a specific embodiment, such weight percentages are determined relative to the total weight of the composite, or the total weight of the composite after subtracting the weight of any filler (for example, an inorganic filler). In a specific embodiment, the dental composite is a restorative material (for example, one that is fixed to and / or bonded to a dental cavity, or may be suitable for that purpose) having a thickness of, for example, more than 3 mm, more than 4 mm, more than 5 mm, or about 5 mm to about 7 mm.

[0055] In certain embodiments, the compositions and methods provided herein are useful for restoring teeth, wherein the restorative material has a good curing / hardening time, good adhesion, low shrinkage during hardening (e.g., hardening, in some examples, creates a gap between the filling and the tooth, resulting in leakage of fluid and / or bacteria), little leakage after hardening, little expansion after hardening (e.g., hardening, in some examples, causes cracking or other deformation of the filling and / or tooth), and / or a low or reduced failure rate. Figure 1 shows cross-sectional images of cavity fillings using the compositions described herein (left) and commercially available restorative compositions (right). As shown on the left, exemplary restorative materials prepared by the processes herein and / or using the compositions provided herein provide good cavity filling. As indicated by the arrows in the left panel of Figure 1, the composite material exhibits good adhesion and good volume retention (low shrinkage) (e.g., in cavities with depths greater than 5 mm, e.g., about 7 mm). In contrast, as shown (indicated by arrows) in the right panel of Figure 1, other commercially available materials exhibit poor adhesion to the subcavity, resulting in the formation of a gap between the composite and the subcavity (e.g., in cavities with depths greater than 5 mm, e.g., approximately 7 mm). Figure 2 shows images demonstrating the absence of microleakage (left) observed when a cavity is filled with an exemplary composition (after curing) described herein, compared to the microleakage (right) observed when a cavity is filled with a commercially available restorative composition (after curing).

[0056] In some embodiments, the compositions provided and used herein exhibit little to no shrinkage during curing. In certain examples, minimal shrinkage is desirable to avoid poor fit between the filling and the tooth, such as the formation of a gap between the filling and the tooth. Such gaps can lead to leakage of fluids and / or bacteria, which can further lead to tooth decay. In some embodiments, when the compositions herein cure, the shrinkage is about 10% or less (e.g., about 8% or less). In more specific embodiments, the shrinkage is about 6% or less, about 5% or less, about 4% or less, about 3% or less, about 2% or less, about 1% or less, and so on.

[0057] In certain embodiments, the compositions provided and used herein have zero to low acid and / or anhydride content. In specific embodiments, the acid and / or anhydride content is less than 5% by weight of the composition. In more specific embodiments, the acid and / or anhydride content is less than 3% by weight of the composition, less than 2% by weight of the composition, less than 1% by weight of the composition, less than 0.5% by weight of the composition, less than 0.1% by weight of the composition, and so on. In specific embodiments, such weight percentages are determined relative to the total weight of the composition, or the total weight of the composition minus the weight of any fillers (e.g., inorganic fillers). In some embodiments, the composition is substantially neutral or alkaline, for example, with a pH of about 5 or higher, a pH of about 5.5 or higher, a pH of about 6 or higher, a pH of about 6.5 or higher, or a pH of about 7 or higher. In specific examples, the acid content of the composition is preferably minimized for any reason, such as to minimize the hygroscopicity or moisture absorption of the resulting composite. In some cases, when used as a restorative material, high levels of moisture absorption into the composite can lead to volume expansion of the restorative material, which can result in deformation of the restorative material and ultimately lead to detachment of the restorative material, tooth damage, and / or other undesirable consequences.

[0058] In certain embodiments, the composition provided herein has a concentration of approximately 100 μg / mm³.3 The following moisture-absorbing composites harden (or the composites provided herein have a moisture content of approximately 100 μg / mm³). 3 (Having the following moisture sorption). In a specific embodiment, the moisture sorption is approximately 50 μg / mm³. 3 Below, approximately 25μg / mm 3 Below, about 20μg / mm 3 The following, or approximately 15 μg / mm³ 3 That is the case.

[0059] In some embodiments, the composites described herein (e.g., those formed from combinations of the compositional parts described herein) have good physical parameters for dental applications. In some embodiments, such composites have good flexural strength (e.g., greater than 50 MPa, greater than 100 MPa, greater than 125 MPa, etc.). In further or alternative embodiments, the composites have good compressive strength (e.g., greater than 100 MPa, greater than 150 MPa, greater than 200 MPa, greater than 250 MPa, etc.). In certain embodiments, the composites have good diametrical strength (e.g., greater than 30 MPa, greater than 40 MPa, greater than 45 MPa, etc.). In some embodiments, the composites provided herein have good water solubility (e.g., 1 μg / mm³). 3 (less than). In certain embodiments, the composites provided herein have good radiopaqueness (e.g., greater than 200% Al, greater than 300% AI, etc.). To determine such parameters, any suitable process may be used as desired, for example, by testing a film comprising such a composite (e.g., a film having a thickness of about 10 to 15 microns, e.g., about 14 microns, etc.).

[0060] Furthermore, this specification provides methods for producing the compositions described herein. In some embodiments, the component parts of the compositions described herein are combined in any preferred order. Exemplary processes are shown in the examples. In specific embodiments, the components of the compositions provided herein are prepared by combining monomers, hydroperoxides, an optional stabilizer, and an optional photoinitiator. In some embodiments, the combination is mixed to form a resin, to which fillers are added and blended or ground. Similarly, in specific embodiments, the components of the compositions provided herein are prepared by combining monomers, thiourea, an optional stabilizer, and an optional photoinitiator. In some embodiments, the combination is mixed to form a resin, to which fillers are added and blended or ground. Examples of specific agents (and corresponding component class types) described in the examples should be understood to be included in the disclosure of compositions and methods described herein.

[0061] In some examples, as used herein, “solidification time” is the amount of time that a mixed composition provided herein (i.e., a composition combining both parts of the two-component compositions described herein) forms a solid or hard composite (which is partially or completely cured) in the absence of an auxiliary device designed to accelerate the curing of restorative materials, such as dental curing light (also referred to herein as “self-curing”). Dental curing light is part of a dental apparatus used for polymerization of photocurable resin composites. It can be used with several different dental materials that are curable by light. The light used falls into the visible blue light spectrum. This light is delivered over a range of wavelengths and differs for each type of apparatus. There are four basic types of dental curing light: tungsten halogen, light-emitting diode (LED), plasma arc curing (PAC), and laser. In certain examples, “working time” is the length of time that a mixed composition loses its malleability using typical dental techniques and / or apparatus.

[0062] As used herein, weight percentage (wt%) or %(w / w) means the percentage of the weight of an ingredient relative to the total weight of a composition or composite, unless otherwise specified. For non-monomer and non-filler ingredients, whether considered as whole, one-component, or two-component, the disclosure of weight percentage (wt%) or %(w / w) also includes the disclosure of the percentage of the weight of the ingredient relative to the total weight of the composition or composite, minus the weight of any fillers in the composition or composite (e.g., inorganic fillers). In some embodiments, weight percentage means the weight of an ingredient relative to the weight of a two-component composition (e.g., a first part and a second part that are physically separated) and / or the weight of an ingredient relative to the weight of one part of a two-component composition. In some examples, the weight percentage of an ingredient may be the same or similar in both parts of a two-component system, while in other examples, the ingredient may have different weight percentages in each part of a two-component system. For example, in a typical case, the hydroperoxide and thiourea each have different weight percentages in each of the aforementioned parts, with the hydroperoxide being present entirely or predominantly in the first part of the composition, and the thiourea being present entirely or predominantly in the second part of the composition.

[0063] As used herein, the term "alkyl" refers to a substituted linear or substituted branched saturated or unsaturated hydrocarbon monoradical, either alone or in combination, having, for example, 1 to about 10 carbon atoms, more preferably 1 to 6 carbon atoms. Examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, tert-amyl and hexyl, as well as long-chain alkyl groups such as heptyl and octyl. Whenever it appears herein, a numerical range such as “C1-C6 alkyl” means, in some embodiments, that the alkyl group consists of one carbon atom; in some embodiments, two carbon atoms; in some embodiments, three carbon atoms; in some embodiments, four carbon atoms; in some embodiments, five carbon atoms; or in some embodiments, six carbon atoms; however, this definition also includes the existence of the term “alkyl” without a specified numerical range. In addition, in some examples where the alkyl is substituted on either side (for example, as described for L above), alkyl may refer to a diradical derived from the alkyl of the monoradical defined above. Examples include, but are not limited to, methylene (-CH2-), ethylene (-CH2CH2-), propylene (-CH2CH2CH2-), and isopropylene (-CH(CH3)CH2-). "Alkyl" can also refer to a cyclic alkyl group that may be substituted, a saturated hydrocarbon monoradical ring containing, for example, 3 to about 15 ring carbon atoms or 3 to about 10 ring carbon atoms, but in some embodiments, additional acyclic carbon atoms may be included as substituents (e.g., methylcyclopropyl).This term includes condensing groups, non-condensing groups, crosslinking groups, and spiro groups. In some embodiments, a condensed cycloalkyl group comprises 2 to 4 condensed rings, the bonding ring being a cycloalkyl ring. Examples, but not limited to, include cyclopropyl, cyclopentyl, cyclohexyl, cumene, and pinan ring systems.

[0064] As used herein, the term "aryl" refers to an aromatic hydrocarbon group, either alone or in combination, which may have 6 to about 20 substituted ring carbon atoms, and includes fused and unfused aryl rings. A fused aryl ring group includes 2 to 4 fused rings in which the bonding ring is an aryl ring and the other individual rings are alicyclic, heterocyclic, aromatic, heteroaromatic, or any combination thereof. Furthermore, the term aryl includes fused and unfused rings containing 6 to about 12 ring carbon atoms, as well as those containing 6 to about 10 ring carbon atoms. An unfused biaryl group is biphenyl.

[0065] As used herein, the term “heteroaryl” means an optionally substituted aromatic monoradical, either alone or in combination, containing about 5 to about 20 skeletal ring atoms, wherein one or more of the ring atoms are heteroatoms independently selected from, but not limited to, oxygen, nitrogen, and sulfur, provided that the ring of the group does not contain two adjacent O or S atoms. In embodiments where two or more heteroatoms are present in the ring, the two or more heteroatoms are either identical to each other or some or all of the two or more heteroatoms are different from each other. The term heteroaryl includes optionally substituted condensed and uncondensed heteroaryl groups having at least one heteroatom. The term heteroaryl also includes condensed and uncondensed heteroaryls having 5 to about 12 skeletal ring atoms, as well as those having 5 to about 10 skeletal ring atoms. In certain examples, the bond to the heteroaryl group is via carbon atoms or heteroatoms; not limited examples of monocyclic heteroaryl groups include pyridyl or furanyl.

[0066] As used herein, the term "heteroalkyl" refers to an alkyl structure in which one or more carbon atoms (and any associated hydrogen atoms, as needed) of the skeletal chain are independently substituted with heteroatoms (i.e., atoms other than carbon, such as, but not limited to, oxygen, nitrogen, sulfur, or combinations thereof), as described above. Examples of heteroalkyl groups include linear groups, such as ethylene oxide (e.g., -CH2CH2On-), or cyclic groups, such as tetrahydrofuran. [Examples]

[0067] The following are abbreviations for specific materials used in certain embodiments provided herein, such as the exemplary and non-limiting examples provided below:

[0068] PTU: 1-(2-pyridyl)-2-thiourea BTU: 1-Benzoyl-2-thiourea ATU: 1-acetyl-2-thiourea TTU: 1-(2-tetrahydrofurfuryl)-2-thiourea CHP: Cumene hydroperoxide THPO:tert-butyl hydroperoxide Cu(acac)2: Copper(II) acetylacetonate CuAc: Copper(II) acetate GPDM: Glycerol dimethacrylate MDP: 12-Methacryloyldodeylphosphate; Saccharin: o-Sulfimide benzoate R202: AEROSIL (registered trademark) Fumed Silica R812S: AEROSIL (registered trademark) fumed silica GM27884-K6: Schott GM27884 dental glass, 3 μm GM39923-706: Schott GM39923 dental glass, 0.7 μm Ba-Glass-15-23: Dental barium glass, 1.5 μm YbF3: Ytterbium fluoride BYK W9010: Wetting and dispersing agent (flow modifier) CQ: Camphorquinone SR494: Ethoxylated (4) Pentaerythritol Tetraacrylate EDMAB: Ethyl-4-dimethylaminobenzoate UDMA: Urethane dimethacrylate E6BAD: Ethoxylated (6) bisphenol A dimethacrylate EBPADM: Ethoxylated (3) bisphenol A dimethacrylate BisGMA: Bisphenol A-glycidyl methacrylate TEGDM: Triethylene glycol dimethacrylate BHT: Butylated hydroxytoluene

[0069] Example 1 The compositions listed in Table 1 are prepared from Cu(acac)2 paste. All components are mixed and ground using a three-roll kneading machine.

[0070] [Table 1]

[0071] Examples 2-19 The compositions listed in Table 2 are prepared from a resin containing a hydroperoxide. All components are mechanically mixed or magnetically stirred to form a homogeneous mixture or solution.

[0072] [Table 2]

[0073] Using the resin examples described above (resin examples are indicated with "R") (Table 2), prepare the following paste compositions listed in Table 3. Mix all the components and disperse them using a three-roll mixer.

[0074] [Table 3]

[0075] The compositions listed in Table 4 are prepared from a resin containing a thiourea compound. All components are mechanically mixed or magnetically stirred to form a homogeneous mixture or solution.

[0076] [Table 4]

[0077] Using the resin examples described above, prepare the following paste compositions listed in Table 5. Mix all the components and disperse them using a three-roll mixer.

[0078] [Table 5]

[0079] Examples of two-component pastes containing either the chemical reducing agent (thiourea) or oxidizing agent (hydroperoxide) compound described above are combined (for example, in a ratio of approximately 1:1), and the resulting working / solidifying times are measured for each initiator system. The working / solidifying times are determined under ambient conditions (for example, at 22°C, without the use of dental curing light). Exemplary working / solidifying times are shown in Table 6.

[0080] [Table 6]

[0081] As shown in Table 6, compared to otherwise similar compositions that do not contain copper(II), compositions containing copper(II) achieve faster working / solidifying times, even at very low concentrations.

[0082] Examples 20-26 The compositions listed in Table 7 are prepared from a resin containing a hydroperoxide. All components are mechanically mixed or magnetically stirred to form a homogeneous mixture or solution.

[0083] [Table 7]

[0084] Using the resin examples described above, the following paste compositions listed in Table 8 were prepared. All components were mixed and dispersed using a three-roll mixer.

[0085] [Table 8]

[0086] The compositions listed in Table 9 are prepared from a resin containing a thiourea compound. All components are mechanically mixed or magnetically stirred to form a homogeneous mixture or solution.

[0087] [Table 9]

[0088] Using the resin examples described above, prepare the following paste compositions listed in Table 10. Mix all the components and disperse them using a three-roll mixer.

[0089] [Table 10]

[0090] As described above, examples of two-component pastes containing either the chemical reducing agent or oxidizing agent compound were combined (for example, in a ratio of approximately 1:1), and the resulting work / solidification times were measured for each initiator system. The results are shown in Table 11.

[0091] [Table 11]

[0092] As shown in Table 11, good working / solidification times were achieved with various thiourea compounds when copper was present, with TTU and PTU yielding excellent results.

[0093] Examples 27-44 The compositions listed in Table 12 are prepared from a resin containing a hydroperoxide. All components are mechanically mixed or magnetically stirred to form a homogeneous mixture or solution.

[0094] [Table 12]

[0095] Using the resin examples described above, prepare the following paste compositions listed in Table 13. Mix all the components and disperse them using a three-roll mixer.

[0096] [Table 13]

[0097] The compositions described in Table 14 are prepared from a resin containing a thiourea compound. All components are mechanically mixed or magnetically stirred to form a homogeneous mixture or solution.

[0098] [Table 14]

[0099] Using the resin examples described above, prepare the following paste compositions listed in Table 15. Mix all the components and disperse them using a three-roll mixer.

[0100] [Table 15]

[0101] For example, combine the examples of two-component pastes containing either the chemical reducing agent or oxidizing agent compound described above, and measure the work / solidification time obtained for each initiator system. Exemplary results are shown in Table 16.

[0102] [Table 16]

[0103] As shown in Table 16, good working / solidification times were achieved by using a combination of PTU and CHP, and the best results were obtained with compositions containing higher concentrations of PTU+CHP and / or copper(II).

[0104] Example 45 In addition, good physical parameters are obtained for composites prepared according to the previous examples. For example, when filling deep cavities, good adhesion of the restorative material to the underlying layer is obtained without the formation of a void between the restorative material and the underlying layer, as shown in Figure 1. On the other hand, when using competing materials, void formation occurs, and adhesion to the underlying layer is very poor, especially at the bottom of the cavity (which is 7 mm deep). In addition, as shown in Figure 2, no interdental leakage is observed in restorative material composites prepared using the compositions provided herein. On the other hand, microleakage occurs along the interdental margins with competing light-curing bulk filling composite materials.

[0105] In addition, the composite described in the previous example exhibits, for example, very little volume loss during curing (e.g., less than 5%), good flexural strength (e.g., greater than 100 MPa), good compressive strength (e.g., greater than 150 MPa), good diametrical strength (e.g., greater than 30 MPa), and low water absorption (e.g., 20 μg / mm³). 3 (less than), good water solubility (e.g., 1 μg / mm³) 3 It offered good physical parameters, such as having a value less than 300% and good radiopaqueness (e.g., greater than 300% Al).

Claims

1. A dental composition for use in restoring a tooth cavity in an individual, comprising a first portion and a second portion, which are physically separated from each other until the time the dental composition is used to restore a tooth cavity. The first portion comprises a hydroperoxide and a copper(II) catalyst, The second portion comprises thiourea and a copper(II) catalyst, The first portion and the second portion comprise a polymerizable monomer and a filler, The polymerizable monomer comprises an ethylene group, The combined amount of the hydroperoxide and thiourea is greater than 3% (w / w) of the dental composition excluding all fillings. A dental composition wherein the cavity of the tooth has a depth of at least 5 mm.

2. The dental composition for use according to claim 1, wherein the hydroperoxide comprises a tertiary aryl hydroperoxide and optionally cumene hydroperoxide.

3. The dental composition for use according to claim 1 or 2, wherein the hydroperoxide is present in a concentration of more than 2% by weight in the dental composition, excluding the weight of all fillers.

4. The copper(II) catalyst comprises copper(II) ions and / or copper(II) compounds; and / or The dental composition according to any one of claims 1 to 3, wherein the copper(II) catalyst comprises copper(II) sulfate, copper(II) acetate, copper(II) chloride, copper(II) acetylacetonate, or a combination thereof.

5. The dental composition for use according to any one of claims 1 to 4, wherein the copper(II) catalyst is present in the composition in an amount of 5% by weight or less, excluding the weight of all the fillers, and optionally, the copper(II) catalyst is present in the composition in an amount of 0.1% by weight or less, excluding the weight of all the fillers.

6. The aforementioned hydroperoxide is comprising hydrocarbons substituted with one or more -OOH groups; and / or A dental composition for use according to any one of claims 1 to 5, comprising t-butyl hydroperoxide, t-amyl hydroperoxide, p-diisopropylbenzene hydroperoxide, cumene hydroperoxide, pinan hydroperoxide, p-menthane hydroperoxide, and 1,1,3,3-tetramethylbutyl hydroperoxide, or a combination thereof.

7. The dental composition for use according to any one of claims 1 to 6, wherein the ethylenic monomer comprises a vinyl monomer, an acrylate monomer, a methacrylate monomer, or a combination thereof.

8. The polymerizable monomer is present in an amount of 10% (w / w) to 60% (w / w); or A dental composition for use according to any one of claims 1 to 7, wherein the polymerizable monomer is present in an amount of 20% (w / w) to 50% (w / w).

9. The dental composition for use according to any one of claims 1 to 8, wherein the thiourea comprises 1-(2-pyridyl)-2-thiourea (PTU), 1-benzoyl-2-thiourea (BTU), 1-acetyl-2-thiourea (ATU), 1-(2-tetrahydrofurfuryl)-2-thiourea (TTU), or a combination thereof.

10. The thiourea is present in the composition such that the ratio of thiourea to polymerizable monomer is 1:999 to 100:900; or The ratio of thiourea to polymerizable monomer is 1:99 to 10:

90. A dental composition for use according to any one of claims 1 to 9.

11. The filler is present in an amount of 10% (w / w) to 90% (w / w); or The filler is present in an amount of 40% (w / w) to 80% (w / w); or The filler is present in an amount of 60% (w / w) to 80% (w / w). A dental composition for use according to any one of claims 1 to 10.

12. A dental composition for use according to any one of claims 1 to 11, further comprising a photoinitiator, wherein optionally the photoinitiator is present in an amount of 5% (w / w) or less, excluding the total weight of the filler.

13. A dental composition for use according to any one of claims 1 to 12, further comprising a stabilizer, wherein optionally the stabilizer is present in an amount of 1% (w / w) or less, excluding the weight of all the fillers.

14. A dental composition for use according to any one of claims 1 to 13, wherein the tooth cavity is a Class I or Class II cavity.

15. The aforementioned filler comprises an inorganic filler or a prepolymerized filler, or A dental composition for use according to any one of claims 1 to 14, wherein the filler comprises an inorganic filler selected from the group consisting of metal oxides, metal nitrides, metal fluorides, silicates, silica (e.g., colloidal silica, precipitated silica, fused quartz), aluminosilicate, aluminoborosilicate, fluoroaluminosilicate, barium silicate, barium aluminosilicate, barium aluminoborosilicate, strontium aluminosilicate, barium fluoroaluminosilicate, strontium fluoroaluminosilicate, strontium zinc fluoroaluminosilicate, zinc aluminosilicate, prepolymerized fillers, and combinations thereof.

16. A dual-chamber device for use in the restoration of a dental cavity, comprising a housing body, wherein the housing body comprises a first chamber containing a first portion of the composition according to any one of claims 1 to 15, and a second chamber containing a second portion of the composition according to any one of claims 1 to 15, and is configured to simultaneously extrude the first portion and the second portion. The cavity of the tooth has a depth of at least 5 mm. The combined amount of hydroperoxide and thiourea is greater than 3% (w / w) of the dental composition, excluding all fillings. Dual-chamber device.

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