Hardenable dental compositions comprising basic core material encapsulated in inorganic shell and dispensing devices therewith

Abstract

To provide a hardenable composition comprising an encapsulated material.SOLUTION: The encapsulated material comprises a basic core material and an inorganic shell material having certain viscosity criteria. Also described are dispensing devices and kits are described comprising a hardenable composition comprising a liquid material and an encapsulated material, the encapsulated material comprising a basic core material and an inorganic shell material comprising a metal oxide surrounding the core. The dispensing devices and kits can facilitate methods of applying the hardneable composition. The hardenable or hardened composition can provide various technical effects such as a delayed release of a basic core material, a delayed increase in basicity, promoting remineralization of a tooth or bone structure, and increasing average alkaline phosphatase (ALP) activity of pulp cells. In some embodiments, the composition is a dental composition for application to a tooth structure.SELECTED DRAWING: Figure 1

Description

[Background technology]

[0001] Various cements suitable for medical and dental use have been described, see, for example, U.S. Patent No. 5,154,762 to Mitra et al., WO 2016 / 005822, and U.S. Patent Application Publication No. 2008 / 0058442. [Brief explanation of the drawings]

[0002] [Figure 1] FIG. 1 is a perspective view of an exemplary syringe. [Figure 2] FIG. 1 is a cross-sectional view of an exemplary syringe. [Figure 3] FIG. 1 is a cross-sectional view of an exemplary syringe. [Figure 4] FIG. 1 is a side view of an exemplary static mixer. Summary of the Invention

[0003] In some embodiments, hardenable (e.g., dental) compositions are described that include an encapsulated material. The encapsulated material includes a basic core material and an inorganic shell material that includes a metal oxide surrounding the core.

[0004] In some embodiments, the hardenable (eg, dental) compositions described have certain viscosity criteria.

[0005] In one embodiment, a two-part curable composition is described, the two-part curable composition comprising: a first part comprising a composition including a liquid material and an encapsulated material, the encapsulated material comprising a basic core material and an inorganic shell material comprising a metal oxide surrounding the core; and a second part comprising a composition including the liquid material. The composition of the first part has a first viscosity, and the composition of the second part has a second viscosity, the first and second viscosities being the same or differing by no more than 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20, 15, or 10% of the higher viscosity part.

[0006] In another embodiment, a two-part curable composition is described, comprising: a first part comprising a composition having a viscosity of 6500 cps or less, comprising a liquid material and an encapsulated material, wherein the encapsulated material comprises a basic core material and an inorganic shell material comprising a metal oxide surrounding the core; and a second part comprising a composition having a viscosity of 6500 cps or less, comprising a liquid material.

[0007] In another embodiment, the curable composition comprises a one-part composition comprising a liquid material and an encapsulated material, wherein the encapsulated material comprises a basic core material and an inorganic shell material comprising a metal oxide surrounding the core, and the one-part composition is viscous at 23° C. and a shear rate of 100 s s using a Brookfield viscometer and a Type A T-bar spindle. -1 Curable compositions are described having a viscosity of less than 25,000 cps, or, for one-part compositions, greater than 40,000 cps, as measured by HPLC.

[0008] The viscosity of the curable composition (e.g., the lower viscosity one) is measured using a Brookfield viscometer and a Type A T-bar spindle at 23°C and a shear rate of 100 s -1 In some embodiments, the viscosity criteria are appropriate for the end use of the hardenable (e.g., dental) composition and / or the dispensing device for such composition and / or the method for applying such composition.

[0009] In other embodiments, two-part hardenable (eg, dental) compositions are described that include a redox cure system.

[0010] In one embodiment, a curable composition is provided, comprising: a first part comprising an encapsulated material, the encapsulated material comprising a basic core material and an inorganic shell material comprising a metal oxide surrounding the core; a non-aqueous second part; Redox curing system, The second part may comprise a (e.g., liquid) polymerizable resin.

[0011] In another embodiment, a hardenable composition is described that includes: a first part including an encapsulated material and a reducing agent, where the encapsulated material includes a basic core material and an inorganic shell material including a metal oxide surrounding the core; and a second part including an oxidizing agent selected from peroxide compounds, persulfate compounds, perborate compounds, and perchlorate compounds.

[0012] In other embodiments, dispensing devices and kits are described that include a hardenable (e.g., dental) composition that includes a liquid material and an encapsulated material, where the encapsulated material includes a basic core material and an inorganic shell material that includes a metal oxide surrounding the core. The dispensing devices and kits can facilitate a method of applying the hardenable composition.

[0013] In some embodiments, the hardenable or hardened composition comes into contact with water, acidic components, or biological fluids during use.

[0014] In an exemplary embodiment, when the first and second parts are combined, the composition initially has an acidic or neutral pH. The shell is degradable by water or the acidic component of the second part. The basic core material releases -OH upon decomposition of the shell, thereby increasing the pH.

[0015] In some embodiments, the basic core material is settable, such as in the case of calcium silicate. In some embodiments, the composition further comprises at least one second filler, such as a fluoroaluminosilicate (FAS) glass and / or a nanoscopic particulate filler. In some embodiments, the first and / or second portions comprise a polymerizable (e.g., liquid) material.

[0016] Various methods of use are also described, including providing a hardenable or hardened (e.g., cured) composition described herein and applying the composition to a tooth or bone structure.

[0017] In some embodiments, the composition comprises a polymerizable material, and the method further comprises hardening the composition by exposing it to a radiation source and / or using a redox cure system. The hardenable or hardened (e.g., hardened) composition can provide various technical effects, such as delayed release of a basic core material, delayed increase in basicity, promoting remineralization of tooth or bone structures, and increasing mean alkaline phosphatase (ALP) activity of dental pulp cells. In some embodiments, the composition is a dental (e.g., sealant) composition for application to tooth structures. In other embodiments, the composition is a dental restorative. DETAILED DESCRIPTION OF THE INVENTION

[0018] Described herein are encapsulated materials. The encapsulated materials are suitable for use in biocarrier materials, such as hardenable dental compositions. The encapsulated materials include a chemically basic core material and an inorganic shell material surrounding the core. The shell material and shell thickness can be selected to allow for controlled and / or delayed release or reaction of the basic core material. In some embodiments, release of the basic core material is utilized to increase basicity after an extended period of time.

[0019] The encapsulated filler comprises a basic core material. The basic core material, as well as the materials (e.g., compounds) from which the core is formed, are generally solid at 25°C.

[0020] The basic core material may be a single particle or multiple smaller associated particles. As used herein, the term "associated" refers to a group of two or more primary particles that are aggregated and / or agglomerated. Similarly, the term "non-associated" refers to a group of two or more primary particles that does not include aggregation and / or agglomeration.

[0021] In some embodiments, the basic core may comprise a plurality of agglomerated particles. "Agglomeration" or "agglomerated" refers to a strong association between primary particles. For example, the primary particles may be chemically bonded to one another. Breaking down the agglomerates into smaller particles (e.g., primary particles) is typically not achieved during the preparation and encapsulation of the core material, such that the agglomerated core particles remain as agglomerates. Similarly, the term "non-aggregated" refers to primary particles that do not comprise strong associations with other primary particles.

[0022] In other embodiments, the basic core may comprise a plurality of agglomerated particles. As used herein, the terms "agglomeration" or "agglomeration" refer to a weak association of primary particles. For example, the primary particles may be held together by charge or polarity. Breaking down the agglomerates into smaller particles (e.g., primary particles) may occur during the preparation of the core material and its encapsulation. Similarly, the term "non-agglomerated" refers to primary particles that do not contain weak associations with other primary particles.

[0023] The average (e.g., primary, associated, or agglomerated) particle size of the core is typically at least 0.2, 0.5, 1, 2, 3, 4, or 5 micrometers, and typically no greater than 1 mm, 750 micrometers, or 500 micrometers, as measured, for example, using a sedimentation analyzer. In some embodiments, such as in the case of hardenable dental compositions, the basic core material typically has an average (e.g., primary, associated, or agglomerated) particle size of no greater than 250, 200, 150, 100, or 50 micrometers. In some embodiments, the average particle size of the basic (e.g., core) material (e.g., of primary particles, associated particles, or agglomerated particles) is typically no greater than 45, 40, 35, 30, 25, or 20 micrometers. Because the shell is typically thin, the encapsulated material may also fall within the average particle size ranges described herein.

[0024] The core material is basic. A chemically basic material is one that will donate electrons and accept protons, typically providing hydroxyl ions in aqueous solution.

[0025] Cores of encapsulated material are considered basic if they have or exhibit one or more of the properties described below, including containing a sufficient amount of a high pKa component, resulting in a basic pH when added to deionized water (according to the test methods further described in the Examples), or resulting in a basic pH when added to an acidic buffer (according to the test methods further described in the Examples).

[0026] The basic material functions to react with acids and acidic buffer solutions to produce an increase in pH, with the change in pH and rate of pH change depending on the strength of the basic component, the chemical and physical form of the basic component therein, and the amount of basic component within the core material.

[0027] In some embodiments, the core of the encapsulated material is strongly basic. Strongly basic materials typically include and are prepared from a sufficient amount of a strongly basic material (e.g., compound) having a pKa in the range of about 11 to 14. Examples of strongly basic compounds include oxides and hydroxides of alkali and alkaline earth metals, as well as strongly basic salts such as alkali phosphates. Specific examples of strongly basic core compounds include oxides and hydroxides of Na, K, Ca, Sr, and Ba; silicates of Na, K, Ca, Sr, and Ba; and aluminates of Na, K, Ca, Sr, and Ba. Strongly basic silicates and glasses typically contain, on a cation mole basis, at least 1, 2, or 3 moles of strongly basic core compound (e.g., CaO) per mole of silica. Similarly, strongly basic aluminates typically contain, on a cation mole basis, at least 1, 2, or 3 moles of strongly basic core compound (e.g., CaO) per mole of alumina.

[0028] In some embodiments, the strongly basic material can be a heterogeneous physical mixture of at least one strongly basic compound in combination with a weakly basic or neutral material. For example, the strongly basic material can be a physical mixture of silica and sodium hydroxide. Sodium hydroxide is a strongly basic material with a pKa of 13.8. A 0.1N aqueous solution of sodium hydroxide has a pH of 13. On a weight percent basis, 1 gram of a mixture of 96% by weight silica and 4% by weight sodium hydroxide in 1 liter of water would provide a 0.1N aqueous solution of sodium hydroxide. When the encapsulated material is a physical mixture, substantially all of the strongly basic compound is accessible upon disintegration of the shell. Thus, in this embodiment, the basic core material may contain a small amount (e.g., at least 1, 2, or 3% by weight of the strongly basic material) to provide a delayed pH of at least 8.5 or 9 in deionized water (according to the test methods described in the Examples). However, a higher concentration of the chemically basic core material may be required to provide a delayed pH of at least 8.5 or 9 in an acidic buffer solution. For example, depending on the pKa of the strongly basic material, the amount of strongly basic material can be at least 5, 6, 7, 8, 9, or 10% by weight of the total encapsulated material.

[0029] In other embodiments, the core of the encapsulated material is a multi-component crystalline compound that includes and is prepared from at least one strongly basic material (e.g., compound) and other components (such as alkaline earth silicates). In yet other embodiments, the core of the encapsulated material can be characterized as a multi-component amorphous glass prepared from at least one strongly basic material (e.g., compound). The strongly basic material (e.g., compound) can be homogeneously or heterogeneously distributed within the glass structure. When the core of the encapsulated material is a molten multi-component material such as a glass, the concentration of the strongly basic compound (which can be measured by X-ray fluorescence (XRF) or inductively coupled plasma (ICP)) is typically in the range of at least 25, 30, 35, 40, 45, or 50% by weight, up to 75% by weight or more, based on the total basic core material.

[0030] In some preferred embodiments, the core comprises and is prepared from CaO, which has a pKa of 11.6. CaO can be utilized to provide both a delayed increase in pH in combination with providing a source of calcium ions. The amount of CaO is typically at least 5, 10, 15, 20, or 25% by weight, and can range up to 75% by weight or more. The amount of Ca is approximately 71% of such value.

[0031] Specific examples of strongly basic multi-component core materials containing CaO include Portland cement (reported to contain 60-70% by weight CaO), tricalcium silicate (containing about 75% by weight CaO), and bioactive glass such as that available from 3M Advanced Materials Division (containing about 25% by weight CaO and about 25% by weight NaO).

[0032] In other embodiments, the core of the encapsulated material is weakly basic. A weakly basic material comprises a substantial amount of at least one material (e.g., compound) having a pKa in the range of at least 8 but less than 11. Examples of weakly basic core compounds include oxides of Cu, Zn, and Fe, as well as weakly basic salts such as NaF, Ca acetate, and hydrogen phosphate.

[0033] Alternatively, the weakly basic core material may contain or be prepared from a smaller amount of a strongly basic compound. A weakly basic core material alone typically cannot provide a sufficient amount of hydroxyl ions to adequately increase the pH of an acidic solution. However, a weakly basic core material alone can provide a sufficient amount of hydroxyl ions to adequately increase the pH of water. Furthermore, an encapsulated weakly basic core material can be used in combination with an encapsulated strongly basic core material.

[0034] The encapsulated basic material is typically not the reducing agent of the redox curing system. In some preferred hardenable (e.g., dental or medical) materials, the desired technical effect is to control the pH so that the composition is initially acidic for a time sufficient to promote adhesion, and then becomes basic to promote remineralization. This pH change is delayed sufficiently so that it occurs after curing. The encapsulation of the reducing agent will delay the redox curing reaction. Furthermore, because the reducing agent is typically a weak base utilized in relatively low concentrations, the encapsulated reducing agent alone does not produce the desired increase in pH.

[0035] In preferred embodiments, the core material further comprises, and is prepared from, one or more neutral compounds, defined herein as having a pKa of at least 6, 6.5, or 7 and less than 8. In some embodiments, such neutral compounds exhibit low solubility in deionized water and / or weak acid and / or weak base solutions. Weak acid solutions typically have a pH of less than 7 but greater than 4. Weak base solutions typically have a pH of greater than 7 but less than 10. Low solubility means that less than 100 grams per liter (i.e., 10% by weight) dissolves. In some embodiments, less than 50, 25, 5, or 1 grams per liter dissolves. Neutral compounds include, for example, silica, zirconia, titania, alumina, and combinations thereof. While a pKa greater than 7 is slightly basic, such basicity is less than that of a weakly basic core material and significantly less than that of a strongly basic core material, as discussed above.

[0036] When a core material includes and is prepared from only basic materials (e.g., compounds) or a combination of basic and neutral materials, the basicity of the core material can be estimated based on the weight of the components, such that the core material includes the amount of basic material (e.g., compounds) described above.

[0037] However, if the core material further comprises an acidic material (e.g., a compound), estimating basicity can be difficult. Particularly for embodiments where it is difficult to estimate the basicity of a core material based on its composition or compositional analysis, the basicity of a core material or encapsulated core material can be defined by the change in pH of a specific amount of the material in deionized water or in an acidic (e.g., buffer) solution. These tests can also be used to confirm that the core material or encapsulated core material is indeed basic.

[0038] For example, fluoroaluminosilicate (FAS) glass is a homogeneous glass structure prepared from approximately 19% by weight of a strongly basic compound (SrO), with the remainder being prepared from neutral (SiO) and other compounds. Referring to Table 11, when tested in deionized water according to the test method described in the Examples, FAS glass reduces the pH to 6.5 within 15 minutes and is therefore considered a weakly acidic core material.

[0039] In some embodiments, the basicity of a core material or encapsulated core material can be measured by the change in pH of a specific amount (0.25 g) of the material in 25 g of deionized water. Unencapsulated core materials typically change the pH of deionized water from neutral to a pH of at least 8.5 or 9. This typically occurs within 1, 2, 3, 4, or 5 minutes, but may take up to 1 or 24 hours. For example, referring to Table 10, an unencapsulated (e.g., bioactive glass) core material can achieve a pH of 10 in water within 20 seconds. The same encapsulated core material would require a longer time to achieve such a pH, because the core material cannot release hydroxyl ions until the inorganic shell material is sufficiently decomposed, such as by dissolution. However, even encapsulated material can experience small but rapid pH changes in DI water when only a small portion of the unencapsulated material or less than the bulk of the sample is present.

[0040] In a preferred embodiment, the basicity of a core material or encapsulated material can be measured by the change in pH of a specific amount (0.25 g) of material in a buffer solution, where the solution is 15 g of deionized water and 10 g of an aqueous potassium hydrogen phthalate buffer solution (e.g., buffer BDH5018) having a pH of 4, adjusted (with hydrochloric acid) to a pH of 4.00 at 25°C. This test is referred to herein as the "buffer test." When a strongly basic core material or encapsulated material is subjected to the buffer test, it may reach a pH of at least 8.5 or even 9. It is understood that more hydroxyl ions are required to change an acidic solution to a basic pH compared to deionized water. Therefore, this pH change may take longer compared to the same material in deionized water. In some embodiments, such a pH change occurs within 5, 10, or 15 minutes, but may take up to 1 hour or 24 hours. The same encapsulated core material takes even longer to effect such a pH change because the core material cannot release hydroxyl ions to react with acid until the inorganic shell material has sufficiently degraded, such as by dissolution and / or decomposition. In one embodiment, referring to Table 8, an unencapsulated (e.g., bioactive glass) core material achieves a pH of 8.5 according to the buffer test within 15 minutes and a pH of 9 within 40 minutes. The same encapsulated (e.g., bioactive glass) core material achieves a pH of 8.5 according to the buffer test within 35 minutes, with the pH continuing to rise after 1 hour.

[0041] A weakly basic core material may provide a small increase in pH when tested according to the Buffer Test. For example, the pH may increase from 4 to 5. However, a weakly basic core material does not provide a sufficient amount of hydroxyl ions to cause the pH to reach a pH of at least 8.5 or 9 when tested according to the Buffer Test.

[0042] Thus, when the encapsulated basic core material is added to water or a buffer solution, as described herein, it does not initially change the pH (i.e., immediately after immersion of the material in the water or buffer solution), but the pH increases at varying rates depending on the shell and basic core material.

[0043] In some embodiments, the basic core material is settable or self-setting when mixed with water, such as in the case of various natural and synthetic cements. Conventional natural (e.g., Portland) and synthetic cements typically contain large amounts of calcium silicate (e.g., 3CaO-SiO2, 2CaO-SiO2), alone or in combination with one or more calcium aluminates (e.g., 3CaO-Al2O3, 4CaO-Al2O3-Fe2O3). When the basic core material is settable or self-setting, it may be the only hardenable material of the hardenable composition. Thus, the first portion of the composition may contain 100% encapsulated basic core material.

[0044] Water-based medical and dental cements, such as those described in U.S. Patent No. 5,154,762 to Mitra et al., typically do not contain significant amounts of calcium silicate. Rather, such compositions generally contain particulate materials that can be characterized as acid-reactive metal oxides or acid-reactive glass fillers (e.g., FAS glass). These types of fillers do not self-harden when mixed with water. However, such acid-reactive fillers can be combined with a polyfunctional acid component to provide a hardenable material.

[0045] In some embodiments, the encapsulated material is an encapsulated (e.g., dental) filler. The encapsulated (e.g., dental) filler may contain a significant amount of a neutral metal oxide having low solubility, as described above, in water or an acidic solution having a pH of 3 to 4. Neutral metal oxides include, for example, silica, zirconia, titania, and alumina. The amount of neutral metal oxide may range from at least 10, 15, 20, 25, or 30% by weight, up to 50, 60, 70, 80, or 90% by weight of the total weight of the basic core material. Encapsulated calcium silicate may also be characterized as a filler due to its silica content.

[0046] The hardenable dental composition or other suitable (e.g., biological) carrier material includes a material that promotes remineralization, such as a material that releases calcium ions, phosphorus-containing ions (e.g., phosphate), fluoride ions, or a combination thereof. These materials can be present within the core of an encapsulated filler, can be provided as a second filler such as an FAS glass, or can be provided as a separate component in the hardenable dental composition.

[0047] In some embodiments, the core of the encapsulated (e.g., filler) material preferably comprises a material that promotes remineralization, such as a material that releases calcium ions, phosphorus ions, fluoride ions, or a combination thereof. CaO, as described above, can function as both a highly basic material (e.g., a compound) and a calcium ion source. When the basic core material comprises a (e.g., strongly) basic material that does not release calcium ions, the core may further comprise another calcium material, such as a calcium salt (e.g., calcium glycerophosphate). Examples of other calcium salts include calcium carbonate, calcium chloride, calcium caseinate, calcium citrate, calcium glubionate, calcium gluceptate, calcium gluconate, calcium hydroxide, calcium hydroxyapatite, calcium lactate, calcium oxalate, calcium oxide, calcium pantothenate, calcium phosphate, calcium polycarbophil, calcium propionate, calcium pyrophosphate, and calcium sulfate.

[0048] In some embodiments, the core of the encapsulated (e.g., dental) filler further comprises, and is prepared from, a material that promotes remineralization by the release of fluoride ions. In other embodiments, the (e.g., dental) composition further comprises a second filler comprising a material that promotes remineralization by the release of fluoride ions. The core or second filler material comprises, and is prepared from, a fluoride compound, such as AlF3, Na2AlF3, and mixtures thereof, in an amount ranging from about 5-40% by weight. In some embodiments, the amount of AlF3 ranges from 10-30% by weight of the core or second filler material. In some embodiments, the amount of Na2AlF3 ranges from 2-10% by weight of the core or second filler material.

[0049] In some embodiments, the core of the encapsulated (e.g., dental) filler further comprises a material that promotes remineralization through the release of phosphorus ions. In other embodiments, the (e.g., dental) composition further comprises a second filler comprising a material that promotes remineralization through the release of fluoride ions. In some embodiments, the core or second filler material comprises and is prepared from phosphorus compounds, such as P2O5, AlPO4, and mixtures thereof, in an amount ranging from 2 to 25% by weight. In some embodiments, the amount of P2O5 ranges from 2 to 15% by weight of the core or second filler material. In some embodiments, the amount of AlPO4 ranges from 2 to 10% by weight of the core or second filler material.

[0050] The basic core can be encapsulated with an inorganic shell comprising a metal oxide by any suitable method, such as vapor deposition, atomic layer deposition (ALD), sputtering, or evaporation, techniques well known in the art.

[0051] In some embodiments, a method for producing an encapsulated material includes providing a basic core particle, as described above, and encapsulating the basic core particle with a (e.g., continuous, non-particulate) inorganic coating using at least one vapor deposition technique, including chemical vapor deposition (CVD), such as atmospheric pressure chemical vapor deposition (APCVD), hydrolytic CVD, and plasma CVD.

[0052] Advantages of vapor deposition techniques for producing coatings include that the coating is constructed from molecular-sized species without interference from a solvent or liquid medium. Some coating methods (e.g., ALD and CVD) tend to produce coatings composed of conformal layers on irregular materials (e.g., powders or porous particulates).

[0053] ALD and CVD are coating processes that involve chemical reactions, and the chemical reactants used are called chemical precursors. That is, they are precursors (i.e., coating precursors) to the coating material (e.g., metal oxide coating) that is being formed. In some embodiments, a single coating precursor is used, while in other embodiments, at least two coating precursors are used. At least one coating precursor contains at least one metal cation required for the coating (e.g., metal oxide coating).

[0054] A single coating precursor can be used when simple decomposition (e.g., thermal or plasma-enhanced decomposition) of the precursor is sufficient to form the coating. At least two coating precursors (e.g., metal oxide precursors) are used when at least one coating precursor contains at least one metal cation and chemically reacts with at least one additional precursor (i.e., co-reactant) to form the coating (e.g., a metal oxide coating). The additional coating precursor is a co-reactant for the coating precursor containing at least one metal cation. The co-reactant chemically reacts with the coating precursor containing at least one metal cation to form the coating.

[0055] ALD coatings generally deposit one monolayer at a time through alternating pulses of chemical precursors (e.g., coating precursors comprising at least one metal cation), absorption of a monolayer of precursor, removal of excess precursor, and pulsing of a co-reactant (e.g., co-reactant into a coating precursor comprising at least one metal cation). Therefore, these coatings tend to be conformal and uniform. Alternatively, for example, ALD systems can also deposit thicker, non-self-limiting coatings, where significantly more than a monolayer of each chemical reactant adsorbs to the substrate during each pulse or cycle, resulting in the deposition of a much larger amount of coating.

[0056] CVD coatings can involve similar chemical reactions, but both precursors are typically delivered simultaneously and sequentially. Uniformity can be improved by continuously mixing the powders being coated.

[0057] An effective coating method for making the encapsulated materials described herein is atmospheric pressure chemical vapor deposition (APCVD). APCVD can be performed with simple equipment such as glassware. In some embodiments, a hydrolysis reaction is used to form (e.g., continuous) metal oxide coatings at temperatures ranging from room temperature (about 22°C) to about 180°C.

[0058] Exemplary precursors for ALD and CVD processes include coating precursors (e.g., metal oxide precursors) containing at least one metal cation, such as metal alkyls (e.g., trimethyl or triethyl aluminum, diethyl zinc), volatile metal chlorides (titanium tetrachloride, silicon tetrachloride, aluminum trichloride), silanes, metal alkoxides (titanium isopropoxide, aluminum isopropoxide, silicon ethoxide), compounds with mixed alkyl, halide, hydride, alkoxy, and other groups, and other volatile metal-organic compounds. Exemplary co-reactants for coating precursors containing at least one metal cation (e.g., metal oxide precursors containing at least one metal cation) include water, oxygen, ozone, ammonia, and alkylamines. In addition to metal oxides, other inorganic, non-metallic coating materials have been deposited using chemical reactions between coating precursors and co-reactants for the coating precursor (e.g., metal nitride coatings have been deposited using metal nitride precursors containing at least one metal cation and a co-reactant for the metal nitride precursor).

[0059] Exemplary (e.g., continuous) coatings include non-metallic inorganic materials such as metal (e.g., Al, Si, Ti, Zr, Mg, and Zn) oxides. In some embodiments, the shell material includes at least 50, 60, 70, 80, 90, or 100 wt. % of a single metal oxide or a combination thereof. Exemplary metal oxides include hydroxides and hydrous oxides, as well as forms containing mixed anions (e.g., oxides plus halides, hydroxyls, small amounts of alkyls, or carboxylates). The shell material is primarily inorganic with a carbon content of 20, 10, 5, or 1 wt. % or less. Furthermore, the encapsulated basic material can also have a carbon content of 20, 10, 5, or 1 wt. % or less. The shell material may further include metal nitrides, metal sulfides, metal oxysulfides, and metal oxynitrides. The coating can be amorphous, crystalline, or mixed, single-phase, or multiphase, and can contain one or more cations and one or more anions. In some embodiments, the coating is amorphous alumina, with or without some hydroxyls or bound water.

[0060] The shell material may be a weakly basic material, provided that the shell material is not sufficiently basic to produce the desired pH change, particularly according to the aforementioned buffer test or disk buffer test (as described subsequently).

[0061] In some embodiments, encapsulating the basic particles with a continuous coating is accomplished via an APCVD coating process, in which an alumina-based coating is produced using trimethylaluminum (TMA) and water. The precursors can be introduced into the reaction chamber by flowing a carrier gas through a bubbler for each liquid precursor. Generally, as is typical for CVD processes, the carrier gas with each component is delivered simultaneously and sequentially into the reaction chamber. The desired flow rates and ratios can be adjusted to produce the desired amount and properties of the coating. In some embodiments, the trimethylaluminum (TMA) flow rate and the water flow rate are independently at least 50 or 100 cm . 3 / min ~ 1000, 1500, or 2000 cm 3 / min range. The water flow rate is typically higher than the TMA flow rate by a factor ranging from 2 to 10 or more times. In some embodiments, the flow of either precursor can be initiated or maintained individually for a period of time in the absence of the flow of the other precursor. In some embodiments, the flow of the precursors can be changed or adjusted one or more times throughout the process.

[0062] In some embodiments, the ratio of co-reactant (e.g., water) to coating precursor comprising at least one metal cation (e.g., TMA) is higher early in the process than later. In other embodiments, the ratio of co-reactant (e.g., water) to coating precursor comprising at least one metal cation is lower early in the process than later. In some embodiments, the composite particles are exposed to only co-reactant (e.g., water) for an initial period before being exposed to the coating precursor comprising at least one metal cation. In some embodiments, the composite particles are exposed to only the coating precursor comprising at least one metal cation before being exposed to the second reactant (e.g., co-reactant for the coating precursor). In some embodiments, the different flow conditions are maintained for at least 5 minutes (or in other embodiments, at least 10, 15, 20, 30, 45, 60, or 90 minutes), up to a maximum of 150 minutes.

[0063] In some embodiments, a coating of a first composition is deposited, followed by a coating of a second composition, for example, an alumina-based coating can be deposited from TMA and water, followed by a titania-based coating deposited from TiCl4 and water.

[0064] In some embodiments, the shell, or in other words the encapsulant, has an average thickness of at least 5, 10, 15, 20, or 25 nm. The shell thickness may range up to 250, 500, 750, or 1000 nm (1 micrometer). In some embodiments, for example, in the case of encapsulated dental fillers, the shell thickness is typically up to 50, 75, 100, 150, or 200 nm.

[0065] On a weight percent basis, the shell material is typically at least 0.1, 0.2, 0.3, 0.4, or 0.5 weight percent of the total encapsulated material. The amount of shell material on a weight percent basis can range up to 15 or 20 weight percent of the total encapsulated material, but is more typically no more than 10, 9, 8, 7, 6, or 5 weight percent.

[0066] In preferred embodiments, the shell material and shell thickness can be selected to allow for controlled and / or delayed release or reaction of the basic core material, hi some embodiments, the amount of shell material on a weight percent basis is 4.5, 4, 3.5, 3, 2, or 1 weight percent or less.

[0067] In a preferred embodiment, the shell is initially impermeable (i.e., materials from the composition and the core material cannot interact by simple diffusion through the shell). The interaction occurs after the shell is altered by interaction with other materials (e.g., degradation, erosion, or dissolution). The composition (e.g., a two-part composition) can be designed to include a component, such as water or acid, that degrades the shell. In other embodiments, shell degradation can occur upon contact with water or an acidic component during use. In this embodiment, the source or water or acidic component can be a biological fluid (e.g., saliva or water held within the soft tissue surrounding the tooth or bone). In the case of dental sealants and restoratives, it is speculated that the basic component can neutralize acids from bacteria or food sources that come into contact with the hardened dental sealant.

[0068] Referring to Tables 4-7 in the following Examples, in one embodiment, an unencapsulated (e.g., Portland cement or tricalcium silicate) basic material provides a basic pH (e.g., at least 8.5, 9, 9.5, 10, or 10.5) within 1 minute when subjected to the aforementioned buffer test. However, an encapsulated (e.g., Portland cement or tricalcium silicate) basic material does not provide a basic pH (e.g., at least 8.5, 9, 9.5, 10, or 10.5) for 2, 3, 4, 5, 6, 7, 8, 9, or 10 minutes or more according to this buffer test. In some embodiments, an encapsulated (e.g., Portland cement) basic material does not provide a basic pH (e.g., at least 8.5, 9, 9.5, 10, or 10.5) for 15, 20, 25, 30, 35, 40, or 45 minutes. In some embodiments, the encapsulated (e.g., Portland cement) basic material does not provide a basic pH (e.g., at least 8.5, 9, 9.5, 10, or 10.5) for 100, 200, or 300 minutes.

[0069] Referring to Table 8 in the following Examples, in another embodiment, an unencapsulated (e.g., bioactive glass) basic material, when subjected to the aforementioned buffer test, provides a basic pH (e.g., at least 8.5, 9, 9.5, 10, or 10.5) within 5 minutes. However, an encapsulated (e.g., bioactive glass) basic material does not provide a basic pH (e.g., at least 8.5, 9, 9.5, 10, or 10.5) for 30 to 40 minutes according to this buffer test.

[0070] Referring to Table 9 in the following examples, in another embodiment, an unencapsulated (e.g., Portland cement) basic material will achieve a basic pH of 11.5 within 20 seconds when tested in deionized water. However, an encapsulated (e.g., Portland cement) basic material will achieve a basic pH of at least 8.5 within 20 seconds when tested in deionized water. Referring to Table 10 in the following examples, in another embodiment, an unencapsulated (e.g., bioactive glass) basic material will achieve a basic pH of 10.5 within 20 seconds when tested in deionized water. However, an encapsulated (e.g., bioactive glass) basic material will achieve a basic pH of at least 9.8 within 20 seconds. Thus, changes in pH of an acidic (e.g., buffer) solution can occur at a significantly slower rate than deionized water.

[0071] In a preferred embodiment, the delayed release or reaction of a basic core material is utilized to increase the basicity of a (e.g., biological) carrier material, such as a hardenable dental material, at a later time point, such as after application to a tooth or bone structure, typically after hardening. An unencapsulated basic material can cause a desirably large (but undesirably rapid) increase in pH. An encapsulated version of the same basic material can cause a desired increase in pH, but after a long period of time, i.e., release the basic material (e.g., hydroxyl ions) slowly and continuously.

[0072] The basicity of a (e.g., biological) carrier material, such as a hardenable (e.g., dental) composition containing an encapsulated basic material, can be assessed by measuring the pH change of a disk (3.1 mm × 1.3 mm high) of hardened (i.e., cured) material immersed in 1.5 mL of 10 mM NaHPO (commonly known as PBS) buffer solution contained in a 2 mL plastic centrifuge tube. PBS buffer can be prepared by dissolving 8 g NaCl, 0.2 g KCl, 1.44 g NaHPO, and 0.24 g KHPO in 800 mL distilled HO, adjusting the pH to 7.4 with HCl, adjusting the volume to 1 L with additional distilled water, and sterilizing by autoclaving. This test is hereafter referred to as the "Disk Buffer Test."

[0073] A representative two-part curable (e.g., dental) composition that can be utilized for purposes of evaluating encapsulated (e.g., dental) basic materials includes a first part described below and a second part containing the encapsulated basic material. The first and second parts are combined (1:1 by weight) and radiation-cured as described in more detail in the Examples. In one embodiment, the second part contains 65 wt. % of the encapsulated basic material described herein, 33.7 parts hydroxyethyl methacrylate (HEMA), and 1 wt. % fumed silica. In another embodiment, the second part contains 33.7 parts hydroxyethyl methacrylate (HEMA), 16.25 to 65 wt. % (e.g., 32.5 wt. %) of the encapsulated basic material described herein, 0 to 32.5 wt. % FAS glass, and 1 wt. % fumed silica.

[0074] [Table 1]

[0075] In some embodiments, the concentration of the encapsulated basic material is typically at least 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, or 65% by weight of the second portion of the hardenable (e.g., dental) composition, up to 100%. The entire hardenable (e.g., dental) composition contains half of that concentration of the encapsulated basic material. Thus, the concentration of the encapsulated basic material is typically at least 1, 1.5, 2, 2.5, 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, or 32.5% by weight of the entire hardenable (e.g., dental) composition, up to 50% by weight. The formulation with 16.25 wt% bioactive glass in the second portion (8 wt% total) showed marginal performance, but it is speculated that the concentration of highly basic materials (CaO, NaO) in the bioactive glass could be increased so that smaller concentrations could provide a delayed rise to a pH of at least 8.5 or 9.

[0076] Referring to Tables 12-22 in the following Examples, in one embodiment, the encapsulated basic material provides a basic pH (e.g., at least 8.5, 9, 9.5, 10, or 10.5) within 46, 72, 100, 147, 260, 360, or 500 hours for compositions greater than 16.25% by weight of the encapsulated basic material.

[0077] Hardenable (e.g., dental) compositions are typically acidic (pH of 1, 2, 3, 4, 5, or 6) prior to hardening by including an acidic component for a time sufficient to provide good adhesion to bone or tooth structure. While this period can vary somewhat, they are initially acidic (immediately after immersion of the hardenable or hardened composition in water or buffer), typically for at least 30 seconds, 1, 2, 3, 4, or 5 minutes. In other embodiments, the hardenable or hardened (e.g., dental) composition is initially neutral (pH of 7-7.5) and becomes more basic (e.g., at least 8, 8.5, 9, 9.5, 10, 10.5, or 11) after a period ranging from 1 hour to 1 day, and in some embodiments, up to 2, 3, 4, 5, 6, or 7 days, or longer. However, when the released base neutralizes acids present in the oral environment, the hardened (e.g., dental) composition can remain neutral (pH 7-7.5) due to the neutralization reaction proceeding at a rate equal to the release rate of the basic (e.g., core) material.

[0078] In another embodiment, a representative non-aqueous, two-part curable composition may be utilized in a disk cushioning test, as further described in the following examples.

[0079] In some embodiments, the hardened dental composition comprising an encapsulated basic material increases the pH of a buffer solution by at least 0.05, 0.10, 0.15, 0.20, 0.25, or 0.30 within 15 or 39 hours.

[0080] In some embodiments, the hardenable (e.g., dental) composition can be characterized as a cement with multiple cure modes. In some embodiments, the cement cures through a first mechanism via an ionic reaction between the acid and an acid-reactive filler (e.g., FAS glass). The reaction of encapsulated basic (e.g., filler) materials is delayed as described above and therefore typically does not impair the cure reaction. The cement also cures through a second mechanism via photoinitiated free radical crosslinking of ethylenically unsaturated components. The cement may optionally cure through a third mechanism via redox-initiated free radical crosslinking of ethylenically unsaturated components.

[0081] Such cements are typically formulated as two-part systems, with the first part typically being a powder or liquid containing an encapsulated basic filler and an acid-reactive (e.g., FAS-glass) filler for hardening. The second part is typically an aqueous liquid containing an acidic polymer and water. In some cases, the encapsulated filler can be designed to provide controlled hardening followed by a continued increase in pH.

[0082] The cement may optionally contain a water-soluble reducing agent and a water-soluble oxidizing agent in separate portions. If the reducing agent is present in the liquid portion, then the oxidizing agent is typically present in the powder portion, and vice versa. Suitable reducing agents include ascorbic acid, sulfinic acids, barbituric acid and its derivatives, cobalt(II) chloride, ferrous chloride, ferrous sulfate, hydrazine, hydroxylamine (depending on the choice of oxidizing agent), oxalic acid, thiourea, and salts of dithionite or sulfite anions.

[0083] In another embodiment, the hardenable (eg, dental) composition may be free of water, such as in the case of a dental sealant, and the reducing and oxidizing agents need not be water soluble.

[0084] Suitable reducing agents include functional groups selected from amines, mercaptans, or mixtures thereof. When two or more functional groups are present, they may be part of the same compound or may be provided by different compounds.

[0085] Preferred reducing agents are aromatic tertiary amines. Examples of useful tertiary amines include those of the formula: [ka] wherein each R group can be H or an organic group that does not adversely affect the initiation of hardening of the dental material. The organic group generally does not sterically or electronically interfere with the function of the reducing agent. Examples of such compounds are disclosed in WO 97 / 35916, published October 2, 1997.

[0086] Preferably R 1 is an aliphatic group, and R 2 and R 3 are independently (i.e., may be the same or different) H, aromatic groups, and / or aliphatic groups (preferably containing 20 carbon atoms). Preferably, R 2 and R 3 and R are each independently an aromatic group. 1 is an alkyl group (preferably containing up to 10 carbon atoms) optionally substituted with a hydroxy group, and R 2 and R 3 is H or an alkyl group (preferably containing up to 10 carbon atoms) optionally substituted with a hydroxyl group. In certain preferred embodiments, R 1 , R 2 , and R 3 R may also contain polymerizable functional groups that react with the functional groups of the resin. 1 , R 2 , and R 3 At least one of the groups contains a functional group such as acrylate, methacrylate, acrylamide, vinyl, or other functional group present in the resins described above.

[0087] Preferably, R 4 , R 5 , R 6 , R 7 , and R 8 are independently H or an aliphatic group (preferably containing up to 20 carbon atoms). More preferably, R 4 , R 5 , R 6 , R 7 , and R 8 are independently H or an alkyl group (preferably containing up to 10 carbon atoms) optionally substituted with a hydroxy group. In certain preferred embodiments, R 4 , R 5 , R 6 , R 7 , and R 8 R may also contain polymerizable functional groups that react with the functional groups of the resin. 4 , R 5 , R 6 , R 7 , and R 8 At least one of the groups contains a functional group such as acrylate, methacrylate, acrylamide, vinyl, or other functional group present in the resins described above.

[0088] Particularly preferred aromatic tertiary amines are N,N-bis(2-hydroxyethyl)-p-toluidine (DHEPT), 2-(4-dimethylaminophenyl)ethyl alcohol (DMAPE), and 4-tertbutyldimethylaniline. Other suitable compounds include, for example, DMAPE with a difunctional or polyfunctional acid compound such as adipic acid, sebacic acid, 1,3,5-benzenetricarboxylic acid, or 1,2,4,5-benzenetetracarboxylic acid, or compounds derived from DMAPE with a difunctional or polyfunctional isocyanate such as hexamethylene diisocyanate, isophorone diisocyanate, and Desmodur N-330 (a trifunctional isocyanate).

[0089] The tertiary amine may be polymerizable. Particularly preferred polymerizable aromatic tertiary amines include, but are not limited to, an adduct of N,N-bis(2-hydroxyethyl)-p-toluidine (DHEPT-di-IEM or bis-N,N-[2-(2-methacryloloxyethylaminocarbonyloxy)ethyl]-p-toluidine) with IEM (2-isocyanatoethyl methacrylate), VDM (2-vinyl-4,4-dimethylazlactone) (DMAPE-VDM or 4- These include the adduct of DMAPE to [2(2-acrylamido-2-methylpropionyloxy)ethyl]-N,N-dimethylaniline), the adduct of methacrylate diester to DHEPT (DHEPT-di-ester or bis-N,N-(2-methacryloxyethyl)-p-toluidine), and the adduct of DHEPT to VDM (DHEPT-di-VDM or bis-N,N-[2-(2-acrylamido-2-methylpropionyloxy)ethyl]-p-toluidine).

[0090] Another preferred reducing agent is a mercaptan, which can contain aromatic and / or aliphatic groups and, optionally, a polymerizable group. Preferred mercaptans have a molecular weight greater than about 200 because they have low odor. Particularly preferred mercaptans are isooctylthioglycolate (IOTG) and pentaerythritol tetrakis(3-mercaptopropionate) (PETMP).

[0091] The tertiary amine and mercaptan may be used alone or in mixture with each other. For example, the first initiator system may include one aromatic tertiary amine and one mercaptan, two aromatic tertiary amines, two mercaptans, one polymerizable aromatic tertiary amine, etc. Other reducing agents, such as sulfinic acid, formic acid, ascorbic acid, hydrazine, and their salts, may also be used herein to initiate free radical polymerization. However, preferably, the first initiator system includes an aromatic tertiary amine, a mercaptan, or a mixture thereof. Such reducing agents may function as both a component of the first initiator system and a component of the second initiator system.

[0092] When more than one reducing agent is used, they are preferably selected so that at least one has a faster activation rate than the other reducing agents.

[0093] The encapsulated basic core material is typically combined with the portion of the dental composition that includes the reducing agent.

[0094] Suitable oxidizing agents include peroxide compounds (i.e., peroxy compounds), including hydrogen peroxide and inorganic and organic peroxide compounds (e.g., "per" compounds, i.e., salts with peroxonians). Suitable oxidizing agents include, but are not limited to, peroxides such as benzoyl peroxide, phthaloyl peroxide, substituted benzoyl peroxides, acetyl peroxide, caproyl peroxide, lauroyl peroxide, cinnamoyl peroxide, acetylbenzoyl peroxide, methyl ethyl ketone, sodium peroxide, hydrogen peroxide, di-tert-butyl peroxide, tetralin peroxide, urea peroxide, and cumene peroxide; hydroxides such as p-methane hydroxide, di-isopropyl-benzene hydroxide, tert-butyl hydroxide, methyl ethyl ketone, and 1-hydroxycyclohexyl hydroperoxide-1.

[0095] Other oxidizing compounds include persulfate compounds (e.g., ammonium persulfate, potassium persulfate), perborate compounds (e.g., sodium perborate), perchlorate compounds (e.g., sodium perchlorate), ozone, ozonants, etc. These oxidizing agents may be used alone or in mixtures with each other.

[0096] Small amounts of transition metal compounds may be added to accelerate the redox cure rate. In some embodiments, it may be preferable to include a second ionic salt to enhance the stability of the polymerizable composition, as described in U.S. Patent Application Publication No. 2003 / 0195273 (Mitra et al.).

[0097] The amount of reducing agent and oxidizing agent is sufficient to provide the desired degree of polymerization of the ethylenically unsaturated component and the desired rate of hardening, hi some embodiments, the hardenable (e.g., dental) composition hardens within 5, 4, 3, 2, or 1 minute.

[0098] The amount of reducing agent typically ranges from at least 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, or 1 weight percent, and up to 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, or 10 weight percent, based on the total weight (including water) of the unset cement or other hardenable (e.g., dental) composition. In some embodiments, the hardenable (e.g., dental) composition includes at least 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, or 5 weight percent reducing hardener.

[0099] The amount of oxidizing agent typically ranges from at least 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, or 1 wt. % to up to 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, or 10 wt. % based on the total weight (including water) of the unset cement or other hardenable (e.g., dental) composition.

[0100] In some embodiments, the hardenable (e.g., dental) composition comprises at least 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, or 5 wt. % oxidative hardener. The reducing or oxidizing agent can be encapsulated with the polymer, as described in U.S. Pat. No. 5,154,762 to Mitra et al. When the hardenable (e.g., dental) composition hardens through redox-initiated free radical crosslinking of ethylenically unsaturated components, the composition contains a sufficient amount of oxidizing agent for the crosslinking reaction that is not encapsulated within an inorganic shell comprising a metal oxide. The hardenable (e.g., dental) composition may also contain an oxidizing agent encapsulated within an inorganic shell comprising a metal oxide for the purpose of increasing the pH over a period of time.

[0101] The cement is not limited to two-part powder-liquid compositions. For example, one-part anhydrous formulations can be prepared. These are sold in dry form and can be prepared for use by adding water. Two-part paste-paste formulations can also be prepared by adding a suitable polymerizable liquid (e.g., 2-hydroxyethyl methacrylate, or "HEMA") that does not react with the encapsulated basic and / or additional acid-reactive (e.g., FAS glass) filler to obtain a first paste. The acidic polymer described above is combined with a suitable filler (e.g., crushed quartz) that does not react with the acidic polymer to obtain a second paste. The two pastes are prepared for use by stirring them together.

[0102] The cement contains water at the time of use. The water may be present in the composition at the time of sale or may be added immediately before use. The water may be distilled water, deionized water, or ordinary tap water. The amount of water is generally sufficient to provide adequate handling and mixing properties and to allow for the transport of ions in the filler-acid reaction. The amount of water is typically at least 1, 2, 3, 4, or 5% of the total weight of the cement (i.e., the combination of the first and second parts and any added water), and typically no more than 20 or 25%.

[0103] Cements are typically ionically hardenable, i.e., capable of reacting to produce a hardened mass by ionic reactions, which occur primarily between acid groups on the polymer and acid-reactive (e.g., FAS glass) fillers.

[0104] In some embodiments, an acid-reactive (FAS) glass is utilized in combination with an encapsulated basic (e.g., filler) material. In some embodiments, the amount of FAS glass ranges from at least 5, 10, 15, 20, 25, 30, 35, or 40% by weight of the first part of the two-part composition, up to about 50, 55, or 60% by weight. Because the first part typically represents half of the entire hardenable (e.g., dental) composition, the total concentration of acid-reactive (FAS) glass is half of the concentrations just listed. In addition to participating in ionic reactions, FAS glass releases phosphorus and fluoride ions, which are known to promote remineralization.

[0105] In some embodiments, the concentration of the acid-reactive (FAS) glass is greater than the concentration of the encapsulated basic (e.g., filler) material. In other embodiments, the concentration of the encapsulated basic (e.g., filler) material is greater than the concentration of the acid-reactive (FAS) glass. In some embodiments, the weight ratio of encapsulated basic filler to unencapsulated acid-reactive (FAS) glass in the second part of the two-part composition is typically at least 1:1 or greater than 1:1, e.g., 1.5:1, 2:1, 2.5:1, or 3:1, up to 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1.

[0106] The cement may further comprise at least one ethylenically unsaturated moiety, which may be present as a separate component (e.g., as an acrylate- or methacrylate-functional monomer) or may be present as a group on another component, such as an acidic polymer.

[0107] The ethylenically unsaturated group is typically a (e.g., terminal) free-radically polymerizable group, including (meth)acrylics such as (meth)acrylamides (HC=CHCON- and HC=CH(CH)CON-) and (meth)acrylates (CHCHCOO- and CHC(CH)COO-). Other ethylenically unsaturated polymerizable groups include vinyls (HC=C-), such as vinyl ethers (HC=CHO-). The ethylenically unsaturated terminal polymerizable group is preferably a (meth)acrylate group, particularly for compositions cured by exposure to actinic radiation (e.g., UV or blue light). Furthermore, methacrylate functionality is typically preferred over acrylate functionality in dental hardenable compositions.

[0108] In some embodiments, the ethylenically unsaturated component is a water-miscible or water-soluble (meth)acrylate such as 2-hydroxyethyl methacrylate, hydroxymethyl methacrylate, 2-hydroxypropyl methacrylate, tetrahydrofurfuryl methacrylate, glycerol mono- or di-methacrylate, trimethylolpropane trimethacrylate, ethylene glycol dimethacrylate, polyethylene glycol (e.g., 400 and other molecular weight) dimethacrylate, urethane methacrylate, acrylamide, methacrylamide, methylene bis-acrylamide, or methacrylamide, with diacetone acrylamide and methacrylamide being preferred. If desired, a mixture of ethylenically unsaturated moieties may be used. Preferably, the ethylenically unsaturated moiety is present as a group on an acidic polymer, as described in more detail below.

[0109] The second portion comprises an organic or inorganic acid component. In some embodiments, the acid component is a polycarboxylic acid, such as poly(maleic) acid or poly(itaconic) acid. In other embodiments, the acid component is a polyacrylic acid or a phosphorus-containing acid.

[0110] In some embodiments, the acid component is an acidic polymer. Suitable acidic polymers include those listed in U.S. Pat. No. 4,209,434, column 2, line 62 to column 3, line 6. Preferred acidic polymers include homopolymers and copolymers of alkenoic acids such as acrylic acid, itaconic acid, and maleic acid.

[0111] In some embodiments, the acidic polymers can be characterized as photocurable ionomers, i.e., polymers having pendant ionic groups capable of undergoing a curing reaction and pendant free-radically polymerizable groups that can cause the resulting mixture to polymerize, i.e., cure, upon exposure to radiant energy.

[0112] For example, as described in U.S. Pat. No. 5,130,347, photocurable ionomers have the general formula: B(X) m (Y) n and During the ceremony, B represents an organic backbone chain; each X is independently an ionic group; each Y is independently a photocurable group; m is a number having an average value of 2 or greater; n is a number having an average value of 1 or greater.

[0113] Preferably, backbone B is an oligomeric or polymeric backbone of carbon-carbon bonds, optionally containing non-interfering substituents such as oxygen, nitrogen, or sulfur heteroatoms. As used herein, the term "non-interfering" refers to substituents or linking groups that do not unduly interfere with any of the photocuring reactions of the photocurable ionomer.

[0114] Preferred X groups are acidic groups, with carboxyl groups being especially preferred.

[0115] Suitable Y groups include, but are not limited to, polymerizable ethylenically unsaturated groups and polymerizable epoxy groups. Ethylenically unsaturated groups are preferred, especially those that can be polymerized by a free radical mechanism, examples of which include substituted and unsubstituted acrylates, methacrylates, alkenes, and acrylamides.

[0116] The X and Y groups can be attached to the backbone chain B directly or by using any non-interfering organic linking group such as a substituted or unsubstituted alkyl, alkoxyalkyl, aryl, aryloxyalkyl, alkoxyaryl, aralkyl, or alkaryl group.

[0117] Preferred photocurable ionomers are those in which each X is a carboxyl group and each Y is an ethylenically unsaturated group, such as a (meth)acrylate group, that can be polymerized by a free radical mechanism. Such ionomers include polyalkenoic acids (e.g., those of formula B(X) m+n (wherein each X is a carboxyl group) with a coupling compound containing both an ethylenically unsaturated group and a group reactive with a carboxylic acid group, such as an NCO group. The resulting photocurable ionomer preferably has at least one free-radically polymerizable group (e.g., a (meth)acrylate group) attached to the ionomer by an amide bond. The molecular weight of the resulting photocurable ionomer is typically about 1,000 to about 100,000 g / mol.

[0118] The (e.g., photocurable ionomer) acidic polymer typically has a (weight average) molecular weight in the range of at least 5000 g / mol and up to about 100,000 g / mol, as measured by gel permeation chromatography and polystyrene standards. In some embodiments, the (e.g., photocurable ionomer) acidic polymer has a molecular weight of less than 50,000 or 25,000 g / mol.

[0119] The concentration of the acidic component, such as the photocurable ionomer, is typically at least 5, 6, 7, 8, 9, or 10% by weight of the first part of the two-part composition, and typically no more than 30, 25, 20, or 15% by weight. Because the first part typically represents only half of the entire hardenable (e.g., dental) composition, the total concentration of the acidic component, such as the photocurable ionomer, is approximately half of the concentrations just recited.

[0120] In some embodiments, the acid component is a curable component in the form of an ethylenically unsaturated compound having acid and / or acid precursor functional groups. Acid precursor functional groups include, for example, anhydrides, acid halides, and pyrophosphates. Acid functional groups can include phosphoric acid functional groups, phosphonic acid functional groups, sulfonic acid functional groups, or combinations thereof. Typically, the adhesive compositions described herein contain little (e.g., less than 10 wt%, 5 wt%, or 1 wt%) or no ethylenically unsaturated compounds having carboxylic acid functional groups when the composition contains a radiopaque filler having a basic surface, such as zirconia.

[0121] Examples of ethylenically unsaturated compounds having an acid functional group include α,β-unsaturated acidic compounds such as glycerol phosphate mono(meth)acrylate, glycerol phosphate di(meth)acrylate, hydroxyethyl (meth)acrylate phosphate (e.g., HEMA-P), bis((meth)acryloxyethyl)phosphate, ((meth)acryloxypropyl)phosphate, bis((meth)acryloxypropyl)phosphate, bis((meth)acryloxy)propyloxyphosphate, (meth)acryloxyhexyl phosphate, bis((meth)acryloxyhexyl)phosphate (e.g., MHP), (meth)acryloxyoctyl phosphate, bis((meth)acryloxyoctyl)phosphate, (meth)acryloxydecyl phosphate, bis((meth)acryloxydecyl)phosphate, and caprolactone methacrylate phosphate.

[0122] In some embodiments, the (e.g., dental) composition further comprises another (i.e., second) filler in addition to the encapsulated filler described herein. The second filler typically does not comprise a (e.g., strongly) basic core material as described herein. The second filler typically comprises a neutral metal oxide with low solubility, as described above. The second filler may also be weakly basic or weakly acidic.

[0123] In some embodiments, the second filler is an acid-reactive (FAS glass) filler, as described above.

[0124] In some embodiments, the other fillers include nanoparticles (e.g., inorganic metal oxides). Such nanoparticles, or "nanoscopic fillers," can be used as viscosity and thixotropy modifiers. Such nanoparticles can also contribute, in part, to the mechanical properties of the dental hardenable composition. Due to their size, such nanoparticles also contribute to the refractive index of the polymerizable resin.

[0125] In some embodiments, inorganic oxide nanoparticles have a primary particle size of 100 nm or less. Primary particle size typically refers to the size of discrete, non-agglomerated particles. In other, less common, embodiments, nanoparticles may be aggregates of two or more particles bonded (e.g., fused or covalently) together, with the aggregates having a particle size of 100 nm or less. The average particle size can be measured by cutting a thin section sample of the hardened dental composition, measuring the particle sizes of approximately 50-100 particles using transmission electron micrographs at 300,000 magnification, and calculating the average. The nanoparticles can have a unimodal or multimodal (e.g., bimodal) particle size distribution. In some embodiments, the (e.g., zirconia) nanoparticles have an average particle size of at least about 2, 3, 4, or 5 nanometers (nm). In some embodiments, the (e.g., zirconia) nanoparticles have an average particle size of about 50, 40, 30, 25, 15, or 10 nanometers (nm) or less.

[0126] The dental composition optionally further comprises nanoparticles (e.g., inorganic metal oxides) having a relatively low refractive index, such as silica. The inclusion of low refractive index nanoparticles can reduce the refractive index of the polymerizable resin. Suitable silica nanoparticles are available from Ecolab (St. Paul, MN) under the trade name NALCO COLLOIDAL SILICAS. For example, preferred silica particles can be obtained using NALCO products 1034A, 1040, 1042, 1050, 1060, 2327, and 2329.

[0127] Silica nanoparticles are preferably prepared from an aqueous colloidal dispersion (i.e., sol or aquasol) of silica. Colloidal silica is typically present in the silica sol at a concentration of about 1 to 50 weight percent. Colloidal silica sols with different colloidal sizes that can be used are commercially available; see Surface & Colloid Science, Vol. 6, ed. Matijevic, E., Wiley Interscience, 1973. Preferred silica sols for use in preparing fillers are supplied as dispersions of amorphous silica in aqueous media (e.g., Nalco colloidal silica from Ecolab) and those with low sodium concentrations that can be acidified by admixture with a suitable acid (e.g., Ludox colloidal silica from EI Dupont de Nemours & Co., or Nalco 2326 from Ecolab).

[0128] In some embodiments, the dental composition comprises at least 0.5, 1, 1.5, or 2 wt. % low refractive index (e.g., silica) nanoparticles. The amount of low refractive index (e.g., silica) nanoparticles is typically no more than 30, 25, 20, 15, or 5 wt. % of the dental composition. In other embodiments, the dental composition comprises less than 1, 0.5, 0.25, 0.1, or 0.005 wt. % low refractive index (e.g., silica) nanoparticles, or is substantially free of low refractive index (e.g., silica) nanoparticles.

[0129] When low-refractive-index (e.g., silica) nanoparticles are included in a dental composition, the concentration of the low-refractive-index (e.g., silica) nanoparticles is generally less than the concentration of the high-refractive-index (e.g., zirconia) nanoparticles. Thus, the weight or volume concentration of the high-refractive-index (e.g., zirconia) nanoparticles is typically greater than the weight or volume concentration of the low-refractive-index (e.g., silica) nanoparticles. In some embodiments, the weight or volume ratio of the high-refractive-index (e.g., zirconia) nanoparticles to the low-refractive-index (e.g., silica) nanoparticles is at least 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, or 2:1. In some embodiments, the weight or volume ratio of the high-refractive-index (e.g., zirconia) nanoparticles to the low-refractive-index (e.g., silica) nanoparticles is at least 2.1:1, 2.2:1, 2.3:1, or 2.4:1. In some embodiments, the weight or volume ratio of high refractive index (e.g., zirconia) nanoparticles to low refractive index (e.g., silica) nanoparticles is 100:1, 75:1, 50:1, 25:1, 10:1, or 5:1 or less.

[0130] Some suitable low refractive index (e.g., silica) nanoparticles and high refractive index (e.g., zirconia) nanoparticles are disclosed in U.S. Pat. Nos. 6,387,981 (Zhang et al.) and 6,572,693 (Wu et al.), as well as PCT Publication Nos. WO 01 / 30304 (Zhang et al.), WO 01 / 30305 (Zhang et al.), WO 01 / 30307 (Zhang et al.), WO 03 / 063804 (Wu et al.), U.S. Pat. Nos. 7,090,721 (Craig et al.), 7,090,722 (Budd et al.), 7,156,911 (Kangas et al.), 7,241,437 (Davidson et al.), and 7,649,029 (Kolb et al.).

[0131] The dental compositions described herein preferably contain an appreciable amount of inorganic metal oxide filler. Fillers used in dental applications are typically ceramic in nature.

[0132] The filler can be selected from one or more of a wide range of materials suitable for incorporation into compositions used for dental applications, such as fillers currently used in dental composites and dental articles (e.g., crowns). Fillers are generally non-toxic and suitable for use in the oral cavity. Fillers can be radiopaque, radiolucent, or non-radiopaque. In some embodiments, the filler typically has a refractive index of at least 1.500, 1.510, 1.520, 1.530, or 1.540.

[0133] To enhance radiopacity, it is common to include up to about 5% by weight of a component such as YbF. In some embodiments, the hardened dental composition is radiopaque with aluminum at least 3 mm thick.

[0134] Fillers can be either particulate or fibrous in nature. Particulate fillers can generally be defined as having a length-to-width ratio or aspect ratio of 20:1 or less, more commonly 10:1 or less. Fibers can be defined as having an aspect ratio of greater than 20:1, or more commonly greater than 100:1. Particle shapes can vary, ranging from spherical to ellipsoidal, or more planar, such as flakes or discs. Macroscopic properties can be highly dependent on the shape of the filler particles, particularly the uniformity of the shape.

[0135] The dental composition described herein comprises inorganic metal oxide filler material that is larger in size than nanoparticles.As described above, nanoparticles are typically discrete, non-agglomerated particles with a particle size of 100 nm or less.In contrast, inorganic metal oxide fillers are particulate or fibrous materials with at least one dimension greater than 100 nm, such as at least 150 nm or at least 200 nm.For particulate fillers, the average particle size of the discrete, non-agglomerated particles or agglomerated particles is at least 200 nm.Inorganic metal oxide fillers are very effective for improving wear properties after curing.

[0136] In some embodiments, the filler may comprise a crosslinked organic material that is insoluble in the polymerizable resin, and may optionally be filled with inorganic fillers. Examples of suitable organic filler particles include filled or unfilled ground polycarbonates, polyepoxides, poly(meth)acrylates, and the like.

[0137] In some embodiments, the dental compositions described herein include non-acid-reactive fillers such as quartz, fumed silica, non-vitreous particulates of the type described in U.S. Pat. No. 4,503,169 (Randklev), and nanocluster fillers, such as those described in U.S. Pat. No. 6,730,156 (Windisch et al.), U.S. Pat. No. 6,572,693 (Wu et al.), and U.S. Pat. No. 8,722,759 (Craig).

[0138] In an exemplary embodiment, a suspending agent such as fumed silica can be used. Fumed silica is commercially available from Cabot Corporation under the trade name "Cab O-Sil" and from Degussa, Inc. under the trade name "Aerosil." The suspending agent can thicken the composition, thereby increasing its viscosity.

[0139] The concentration of the suspending agent is typically at least 0.05, 0.10, 0.15, or 0.2% by weight and may range up to 5% by weight. In some embodiments, the concentration of the suspending agent may be reduced when higher concentrations of encapsulated basic material are employed.

[0140] In some embodiments, the filler comprises nanoparticles, i.e., nanoclusters, which are in the form of groups of two or more particles held together by intermolecular forces that are relatively weak but sufficient to cause the particles to agglomerate even when dispersed in a curable resin. Preferred nanoclusters may include lightly agglomerated, substantially amorphous clusters of non-heavy metal oxide (e.g., silica) particles and heavy metal oxides (i.e., having an atomic number greater than 28), such as zirconia. The zirconia may be crystalline or amorphous. In some embodiments, the zirconia may be present as particles. The particles forming the nanoclusters preferably have an average diameter of less than about 100 nm. However, the average particle size of lightly agglomerated nanoclusters is typically significantly larger.

[0141] In some embodiments, the (e.g., dental) composition further comprises a second filler comprising a neutral metal oxide, such as a zirconia / silica nanocluster filler. In the case of a two-part dental composition, the filler comprising a neutral metal oxide is present in a substantial amount in either the first or second liquid-containing portion. In some embodiments, the neutral or non-reactive filler is present in either or both the acidic and non-acidic portions, while the acid-reactive filler (e.g., FAS glass) and / or encapsulated basic core is present in the non-acidic portion and reacts with the acidic portion after mixing.

[0142] In some embodiments, a first portion of the hardenable (e.g., dental) composition comprises a second filler comprising a neutral metal oxide, such as a zirconia / silica nanocluster filler, in an amount ranging from at least 5, 10, 15, or 20 wt % to up to 30, 35, or 40 wt %, and the entire hardenable (e.g., dental) composition comprises about half of such concentration of a second filler comprising a neutral metal oxide, such as a zirconia / silica nanocluster filler.

[0143] In some embodiments, the (e.g., one-part) hardenable (e.g., dental restorative) composition includes a second filler comprising a neutral metal oxide, such as a zirconia / silica nanocluster filler, in an amount of at least 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50% by weight of the total hardenable (e.g., dental restorative) composition. The amount of second filler is typically no more than 80, 75, 70, 65, or 60% by weight of the total hardenable (e.g., dental restorative) composition.

[0144] In some embodiments, the second filler may also be encapsulated with a shell material comprising a metal oxide, such as described in US Pat. No. 7,396,862.

[0145] Mixtures of fillers may also be used.

[0146] In a typical embodiment, the second filler may include a surface treatment to strengthen the bond between the nanoparticles, the inorganic oxide filler, and the resin. Various surface treatments have been described in the art, including organometallic coupling agents and carboxylic acids, such as those described in U.S. Pat. No. 8,647,510 (Davidson et al.). The encapsulated basic material may also optionally include a surface treatment.

[0147] Suitable copolymerizable organometallic compounds have the general formula: CH2=C(CH3) m Si(OR) n or CH2=C(CH3) m C=OOASi(OR) n where m is 0 or 1, R is an alkyl group having 1 to 4 carbon atoms, A is a divalent organic linking group, and n is 1 to 3. The organometallic coupling agent may be functionalized with reactive curing groups such as acrylate, methacrylate, vinyl groups, and the like. Preferred coupling agents include γ-methacryloxypropyltrimethoxysilane, γ-mercaptopropyltriethoxysilane, γ-aminopropyltrimethoxysilane, and the like.

[0148] In some embodiments, a combination of surface modifiers may be useful, with at least one of these agents having a functional group that is copolymerizable with the curable resin. Other surface modifiers that do not generally react with the curable resin may be included to enhance dispersibility or rheological properties. Examples of this type of silane include, for example, aryl polyether, alkyl, hydroxyalkyl, hydroxyaryl, or aminoalkyl functional silanes.

[0149] The surface modification can be carried out either subsequent to or after mixing with the monomer. Typically, it is preferred to combine the organosilane surface treatment compound with the nanoparticles before incorporation into the resin. The amount of surface modifier required depends on several factors, such as particle size, particle type, molecular weight of the modifier, and type of modifier. Generally, it is preferred to deposit approximately a monolayer of modifier on the surface of the particles.

[0150] Various ethylenically unsaturated monomers can be used in dental compositions. The ethylenically unsaturated monomers of dental compositions are typically stable liquids at about 25°C, meaning that the monomers do not substantially polymerize, crystallize, or otherwise harden when stored at room temperature (about 25°C) for a typical shelf life of at least 30, 60, or 90 days. The viscosity of the monomers typically does not change (e.g., increase) by more than 10% of the initial viscosity.

[0151] In particular, for dental restorative compositions, ethylenically unsaturated monomers generally have a refractive index of at least 1.50. In some embodiments, the refractive index is at least 1.51, 1.52, 1.53, or greater. The inclusion of a sulfur atom and / or the presence of one or more aromatic moieties can increase the refractive index (compared to a monomer of the same molecular weight that does not contain such substituents).

[0152] Hardenable (eg, dental) compositions can include a wide variety of other ethylenically unsaturated compounds (with or without acid functionality), epoxy-functional (meth)acrylate resins, vinyl ethers, and the like.

[0153] The (e.g., photopolymerizable) dental composition may include free-radically polymerizable monomers, oligomers, and polymers having one or more ethylenically unsaturated groups. Suitable compounds contain at least one ethylenically unsaturated bond and are capable of undergoing addition polymerization. Examples of useful ethylenically unsaturated compounds include acrylic acid esters, methacrylic acid esters, hydroxy-functional acrylic acid esters, hydroxy-functional methacrylic acid esters, and combinations thereof.

[0154] Such free radically polymerizable compounds include mono-, di-, or poly-(meth)acrylates (i.e., acrylates and methacrylates), such as methyl(meth)acrylate, ethyl(meth)acrylate, isopropyl(meth)acrylate, n-hexyl(meth)acrylate, stearyl(meth)acrylate, allyl(meth)acrylate, glycerol tri(meth)acrylate, ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate, 1,3-propanediol di(meth)acrylate, trimethylolpropane tri(meth)acrylate, 1,2,4-butanetriol tri(meth)acrylate, 1,4-cyclohexanediol di(meth)acrylate, pentaerythritol tetra(meth)acrylate, sorbitol hexa(meth)acrylate, methyl ... Examples of suitable free-radical polymerizable compounds include acrylates, tetrahydrofurfuryl (meth)acrylate, bis[1-(2-acryloxy)]-p-ethoxyphenyldimethylmethane, bis[1-(3-acryloxy-2-hydroxy)]-p-propoxyphenyldimethylmethane, ethoxylated bisphenol A di(meth)acrylate, and trishydroxyethyl-isocyanurate tri(meth)acrylate; (meth)acrylamides (i.e., acrylamides and methacrylamides), such as (meth)acrylamide, methylene bis(meth)acrylamide, and diacetone (meth)acrylamide; urethane (meth)acrylates; bis(meth)acrylates of polyethylene glycol (preferably having a molecular weight of 200 to 500); and vinyl compounds, such as styrene, diallyl phthalate, divinyl succinate, divinyl adipate, and divinyl phthalate. Other suitable free-radical polymerizable compounds include siloxane-functional (meth)acrylates. If desired, a mixture of two or more free-radically polymerizable compounds can be used.

[0155] The hardenable (e.g., dental) composition may contain a monomer having a hydroxyl group and an ethylenically unsaturated group in a single molecule. Examples of such materials include hydroxyalkyl (meth)acrylates, such as 2-hydroxyethyl (meth)acrylate and 2-hydroxypropyl (meth)acrylate; glycerol mono- or di-(meth)acrylate; trimethylolpropane mono- or di-(meth)acrylate; pentaerythritol mono-, di-, and tri-(meth)acrylate; sorbitol mono-, di-, tri-, tetra-, or penta-(meth)acrylate; and 2,2-bis[4-(2-hydroxy-3-ethacryloxypropoxy)phenyl]propane (bisGMA). Suitable ethylenically unsaturated compounds are available from a wide range of commercial suppliers, such as Sigma-Aldrich (St. Louis).

[0156] In some embodiments, the first part of the two-part hardenable (e.g., dental) composition comprises a monomer having a hydroxyl group and an ethylenically unsaturated group in a single molecule, such as HEMA. In some embodiments, the amount of the ethylenically unsaturated compound having an acidic functional group (e.g., HEMA) ranges from at least 5, 10, 15, 20, 25, or 30% by weight, up to about 35, 40, 45, or 50% by weight of the first part of the two-part composition. Because the first part represents only half of the entire hardenable (e.g., dental) composition, the total concentration of the ethylenically unsaturated compound having an acidic functional group (e.g., HEMA) is approximately half of the concentration just described.

[0157] The (e.g., dental) compositions described herein may include one or more hardenable components in the form of an ethylenically unsaturated compound having acid functionality. Such components contain both an acid group and an ethylenically unsaturated group in a single molecule. When present, the polymerizable component optionally includes an ethylenically unsaturated compound having acid functionality. Preferably, the acid functionality comprises an oxyacid (i.e., an oxygen-containing acid) of carbon, sulfur, phosphorus, or boron. However, in some embodiments, the dental composition is substantially free (less than 1, 0.5, 0.25, 0.1, or 0.005 wt. %) of an ethylenically unsaturated compound having acid functionality.

[0158] As used herein, the term "ethylenically unsaturated compound having acid functionality" is intended to include monomers, oligomers, and polymers having ethylenic unsaturation and acid and / or acid precursor functional groups. Acid precursor functional groups include, for example, anhydrides, acid halides, and pyrophosphates. Acid functional groups can include carboxylic acid functional groups, phosphoric acid functional groups, phosphonic acid functional groups, sulfonic acid functional groups, or combinations thereof.

[0159] Examples of ethylenically unsaturated compounds having an acid functional group include α,β-unsaturated acidic compounds, such as glycerol phosphate mono(meth)acrylate, glycerol phosphate di(meth)acrylate (GDMA-P), hydroxyethyl (meth)acrylate (e.g., HEMA) phosphate, bis((meth)acryloxyethyl)phosphate, ((meth)acryloxypropyl)phosphate, bis((meth)acryloxypropyl)phosphate, bis((meth)acryloxy)propyloxyphosphate, (meth)acryloxyhexyl phosphate, bis((meth)acryloxyhexyl)phosphate, and (meth)acryloxyoctyl phosphate. Examples of compounds that can be used as components include bis((meth)acryloxyoctyl)phosphate, (meth)acryloxydecylphosphate, bis((meth)acryloxydecyl)phosphate, caprolactone methacrylate phosphate, citric acid di- or tri-methacrylate, poly(meth)acrylated oligomaleic acid, poly(meth)acrylated polymaleic acid, poly(meth)acrylated poly(meth)acrylic acid, poly(meth)acrylated polycarboxyl-polyphosphonic acid, poly(meth)acrylated polychlorophosphonic acid, poly(meth)acrylated polysulfonate, poly(meth)acrylated polyboric acid, and the like. Monomers, oligomers, and polymers of unsaturated carbonic acid, such as (meth)acrylic acid, aromatic (meth)acrylated acids (e.g., methacrylated trimellitic acid), and their anhydrides can also be used.

[0160] The dental composition may include an ethylenically unsaturated compound having an acid functional group with at least one P-OH moiety. Such compositions are self-adhesive and non-aqueous. For example, such compositions may include at least one (meth)acryloxy group and at least one -OP(O)(OH) x A first compound comprising a group, wherein x=1 or 2, and at least one —OP(O)(OH) xa first compound, wherein the at least one (meth)acryloxy group and the at least one -OP(O)(OH) group are linked together by a C1-C4 hydrocarbon group; x a second compound comprising a group, where x=1 or 2, and at least one —OP(O)(OH) x The group and at least one (meth)acryloxy group are linked together by a C5 to C12 hydrocarbon group, and may include a second compound; an ethylenically unsaturated compound without acid functionality; an initiator system; and a filler.

[0161] The initiator is typically added to the mixture of polymerizable components. The initiator is sufficiently miscible with the resin system so as to be readily soluble in (and prevent separation from) the polymerizable composition. Typically, the initiator is present in the composition in an effective amount, such as from about 0.1 weight percent to about 5.0 weight percent, based on the total weight of the composition.

[0162] In some embodiments, the mixture of monomers is photopolymerizable, and the composition contains a photoinitiator (i.e., a photoinitiator system) that initiates polymerization (or curing) of the composition upon exposure to actinic radiation. Such photopolymerizable compositions may be free-radically polymerizable. Photoinitiators typically have an effective wavelength range of about 250 nm to about 800 nm. Photoinitiators (i.e., photoinitiator systems comprising one or more compounds) suitable for polymerizing free-radically photopolymerizable compositions include two-component and three-component systems. Typical three-component photoinitiators include an iodonium salt, a photosensitizer, and an electron donor compound, as described in U.S. Pat. No. 5,545,676 (Palazzotto et al.). Iodonium salts include diaryliodonium salts, such as diphenyliodonium chloride, diphenyliodonium hexafluorophosphate, and diphenyliodonium tetrafluoroborate. Some preferred photosensitizers include monoketones and diketones (e.g., alpha diketones) that absorb some light within the range of about 300 nm to about 800 nm (preferably about 400 nm to about 500 nm), such as camphorquinone, benzil, furil, 3,3,6,6-tetramethylcyclohexanedione, phenanthraquinone, and other cyclic alpha diketones. Among these, camphorquinone is typically preferred. Preferred electron donor compounds include substituted amines, such as ethyl 4-(N,N-dimethylamino)benzoate.

[0163] Other photoinitiators suitable for polymerizing free radically photopolymerizable compositions include the class of phosphine oxides, which typically have an effective wavelength range of about 380 nm to about 1200 nm. Preferred phosphine oxide free radical initiators with an effective wavelength range of about 380 nm to about 450 nm are the acyl and bisacyl phosphine oxides.

[0164] Commercially available phosphine oxide photoinitiators capable of initiating free radical reactions upon irradiation with wavelengths in the range of greater than about 380 nm to about 450 nm include bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide (IRGACURE 819, Ciba Specialty Chemicals, Tarrytown, NY), bis(2,6-dimethoxybenzoyl)-(2,4,4-trimethylpentyl)phosphine oxide (CGI 403, Ciba Specialty Chemicals), and a 25:75 by weight mixture of bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentylphosphine oxide and 2-hydroxy-2-methyl-1-phenylpropan-1-one (IRGACURE 1700, Ciba Specialty Chemicals). Examples of suitable methylbenzylphenylphosphine compounds include a 1:1 by weight mixture of bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide and 2-hydroxy-2-methyl-1-phenylpropan-1-one (DAROCUR 4265 (Ciba Specialty Chemicals)), and ethyl 2,4,6-trimethylbenzylphenylphosphinate (LUCIRIN LR8893X (BASF Corp., Charlotte, NC)).

[0165] Tertiary amines may be used in combination with acylphosphine oxides. Exemplary tertiary amines include ethyl 4-(N,N-dimethylamino)benzoate and N,N-dimethylaminoethyl methacrylate. When present, the amine reducing agent is present in the photopolymerizable composition in an amount of about 0.1 weight percent to about 5.0 weight percent, based on the total weight of the composition. In some embodiments, the dental hardenable composition may be irradiated with ultraviolet (UV) light or blue light. In this embodiment, suitable photoinitiators include those available from Ciba Specialty Chemical Corp. (Tarrytown, NY) under the IRGACURE and DAROCUR tradenames, including 1-hydroxycyclohexyl phenyl ketone (IRGACURE 184), 2,2-dimethoxy-1,2-diphenylethan-1-one (IRGACURE 651), bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide (IRGACURE 819), 1-[4-(2-hydroxyethoxy)phenyl]-2-hydroxy-2-methyl-1-propan-1-one (IRGACURE 2959), 2-benzyl-2-dimethylamino-1-(4-morpholinophenyl)butanone (IRGACURE 369), 2-methyl-1-[4-(methylthio)phenyl]-2-morpholinopropan-1-one (IRGACURE 369), and 2-methyl-1-[4-(methylthio)phenyl]-2-morpholinopropan-1-one (IRGACURE 369). 907), and 2-hydroxy-2-methyl-1-phenylpropan-1-one (DAROCUR 1173).

[0166] Photopolymerizable compositions are typically prepared by mixing the various components of the composition. In embodiments where the photopolymerizable composition does not cure in the presence of air, the photoinitiators are combined under "safe light" conditions (i.e., conditions that do not lead to premature curing of the composition). If desired, a suitable inert solvent may be used in preparing the mixture. Examples of suitable solvents include acetone and dichloromethane.

[0167] Curing occurs by exposing the composition to a radiation source, preferably a visible light source. Light sources that emit actinic light in the range of 250 nm to 800 nm (especially blue light with wavelengths of 380 to 520 nm), such as quartz halogen bulbs, tungsten halogen bulbs, mercury arcs, carbon arcs, low, medium, and high pressure mercury lamps, plasma arcs, light emitting diodes, and lasers, are conveniently used. Generally, useful light sources have a radiation intensity of 0.200 to 6000 mW / cm. 2 for 20 seconds with an intensity in the range of 1000mW / cm 2 The intensity of the light can generally provide the desired cure. A variety of conventional lights for curing such compositions can be used.

[0168] Optionally, the composition may contain solvents (e.g., alcohols (e.g., propanol, ethanol), ketones (e.g., acetone, methyl ethyl ketone), esters (e.g., ethyl acetate), other non-aqueous solvents (e.g., dimethylformamide, dimethylacetamide, dimethyl sulfoxide, 1-methyl-2-pyrrolidinone)), and water. In some embodiments, (e.g., one-part) dental compositions typically contain water in an amount of 5% or less by weight of the total dental composition.

[0169] If desired, the composition can contain additives such as indicators, dyes such as photobleachable dyes, pigments, inhibitors, accelerators, viscosity modifiers, humectants, buffers, radical and cationic stabilizers (e.g., BHT), and other similar ingredients that will be apparent to those skilled in the art.

[0170] Additionally, pharmaceuticals or other therapeutic substances can be optionally added to the dental composition. Examples include, but are not limited to, fluoride sources, whitening agents, anticaries (e.g., xylitol), calcium sources, phosphorus sources, remineralizing agents (e.g., calcium phosphate compounds), enzymes, breath fresheners, anesthetics, coagulants, acid neutralizers, chemotherapeutic agents, immune response modifiers, thixotropic agents, polyols, anti-inflammatory agents, antibacterial agents (in addition to antibacterial lipid components), antifungal agents, xerostomia treatment agents, desensitizing agents, and the like, of the type often used in dental compositions. Combinations of any of the above additives may also be used. One skilled in the art can select any one of such additives and the amount thereof to achieve the desired results without undue experimentation.

[0171] Dental hardenable compositions can be used to treat oral surfaces, such as teeth, as is known in the art. In some embodiments, the composition can be hardened by applying the dental composition and then curing it. For example, when the dental hardenable composition is used as a restorative material, such as a dental filling, the method generally includes applying the hardenable composition to an oral surface (e.g., a cavity) and allowing the composition to harden. In some embodiments, a dental adhesive may be applied before applying the hardenable dental restorative material described herein. Additionally, the dental adhesive is typically hardened by curing simultaneously with the curing of the highly filled dental restorative composition. A method of treating an oral surface can include preparing a dental article and adhering the dental article to an oral (e.g., tooth) surface.

[0172] In one embodiment, the hardened dental composition can be used for dental pulp capping. In this embodiment, cell proliferation of dental pulp stem cells contacted with the hardened dental composition (e.g., the same molded disc used in the buffer disc test) was evaluated as described in more detail in the Examples. The mean cell proliferation was at least 75% of the control (no hardened dental composition disc was present). In some embodiments, the mean cell proliferation was at least 80, 85, or 90% of the control. The mean alkaline phosphatase (ALP) activity was also increased compared to the control. In some embodiments, the mean ALP activity was in the range of at least 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or 1.0 mU / mL, up to 1.1 or 1.2 mU / mL or greater.

[0173] In another embodiment, the hardened dental composition can be used as an adhesive. The hardened dental composition can exhibit an adhesion of at least 1, 2, 3, 4, 5, 6, 8, 9, or 10 MPa when measured according to the test methods described in the Examples. In some embodiments, the adhesion can range up to 20 MPa or more.

[0174] As used herein, "dental composition" refers to a material, including a filler, that is capable of adhering or bonding to an oral surface. Dental hardenable compositions can be used to bond dental articles to tooth structures, to form coatings (e.g., sealants or varnishes) on tooth surfaces, as restoratives that are placed directly in the oral cavity and allowed to harden in place, or alternatively, to create prostheses extraorally that are then bonded in the oral cavity.

[0175] Dental hardenable compositions include, for example, adhesives (e.g., dental and / or orthodontic adhesives), cements (e.g., two-part cements), primers (e.g., orthodontic primers), liners (applied to the base of cavities to reduce tooth sensitivity), root repairs and pulp capping, coatings such as sealants (e.g., pit and fissure sealants), and varnishes; and resin restoratives such as dental fillings (also called direct composites), as well as articles for crowns, bridges, and dental implants. Highly filled dental compositions are also used in mill blanks from which crowns can be milled. Composites are highly filled pastes designed to be suitable for filling substantial defects in tooth structure. Dental cements are somewhat less filled and less viscous materials than composites and typically act as bonding agents for additional materials such as inlays, onlays, etc., or as filling materials themselves when applied and hardened as a layer. Dental cements are also used to permanently bond dental restorative articles such as crowns, bridges, or orthodontic appliances to tooth surfaces or implant abutments.

[0176] In one embodiment, a two-part (e.g., dental sealant) composition is described, with each part comprising a polymerizable resin. In some embodiments, neither part contains water or an acidic component. The polymerizable resin is typically a mixture of acrylic monomers. One common acrylic monomer is described in U.S. Pat. No. 3,066,112. Such an acrylic monomer is the reaction product of bisphenol A or other bisphenols with glycidyl methacrylate; the reaction product is commonly referred to in the art as Bis-GMA monomer. Typically, this monomer is combined with various other (e.g., low molecular weight, low viscosity) monomers, such as di(meth)acrylate monomers (e.g., tetraethylene glycol dimethacrylate, ethylene glycol dimethacrylate, triethylene glycol dimethacrylate, etc.) or other (meth)acrylate monomers.

[0177] The two-part (e.g., dental sealant) compositions described herein, as previously described, comprise a "redox" cure system, optionally combined with a second initiator that utilizes free radical polymerization. The second initiator is preferably a free radical photoinitiator that can be activated upon exposure to actinic radiation (using a conventional dental curing light) to initiate polymerization (or hardening) of the free radically polymerizable composition.

[0178] In another embodiment, one-part (e.g., dental restorative) compositions are described. Such compositions may also include a polymerizable resin containing Bis-GMA (e.g., 15-35 wt%), as described above, along with various other (e.g., lower molecular weight, lower viscosity) monomers. However, one-part (e.g., dental restorative) compositions typically also include a significant amount of filler. The filler includes an encapsulated basic material described herein, typically in combination with a second filler, as described above. The total amount of filler is typically at least 50, 55, 60, 65, 70, 75, or 80 wt%.

[0179] Hardenable (e.g., dental) compositions can have a variety of viscosity standards depending on the end use, dispensing equipment, and method of application. Overall viscosities can range from 200 cps to 100,000 cps or more at 23° C.

[0180] For example, if the composition is a two-part hardenable (e.g., dental) composition including a liquid (e.g., polymerizable resin) material, the difference in viscosity between the first and second parts is typically no more than 90, 85, 80, 75, 70, 65, 60, 55% of the higher viscosity composition / part. In some embodiments, when the composition is applied using a dispensing (e.g., syringe) device including a static mixer, the difference in viscosity between the first and second parts is typically no more than 50, 45, 40, 35, 30, 25, 20, 15, or 10%.

[0181] In yet another example, when the composition is a two-part curable (e.g., dental) composition that includes a liquid (e.g., polymerizable resin) material intended to fill fissures (e.g., on a tooth surface), it is important that the composition have a very low viscosity. In some embodiments, each part has a viscosity of 6500, 6000, 5500, or 5000 cps or less at 23°C. In some embodiments, each component has a viscosity of 4500, 4000, 3,500, or 3000 cps or less at 23°C. Each component typically has a viscosity of at least 200, 300, 400, or 500 cps at 23°C.

[0182] In another embodiment, when the composition is a highly filled hardenable (e.g., dental) composition comprising a liquid (e.g., polymerizable resin) material for dental restorative applications, the viscosity may be at least 40,000 cps, 45,000 cps, or 50,000 cps.

[0183] If the viscosity is less than about 50,000 cps, the viscosity is measured using a Brookfield viscometer and a Type A T-bar spindle at 23°C and a shear rate of 100 s. -1 It may be measured at.

[0184] Highly filled hardenable (e.g., dental) compositions, including liquid (e.g., polymerizable resin) materials for dental restorative applications, can also have higher viscosities. If the hardenable (e.g., dental) composition has a viscosity that is too high to measure with a Brookfield viscometer, other methods can be used to measure the viscosity.

[0185] Rheological viscosity measurements can be performed on an AR-G2 rheometer (TA Instruments) using an 8 mm diameter plate geometry at a controlled temperature of 25 °C. Self-adhesive sandpaper (9 micron grit) can be placed on both the geometry (8 mm diameter circular sandpaper) and the stage (a wide 15 x 15 mm square piece of sandpaper). A hardenable (e.g., dental) material can be placed on the stage, and the geometry can be pressed against the material until a gap of 1000 microns is left between the geometry and the stage. Excess material can be trimmed off using a razor blade. Measurements can be performed using the following procedure: The material is allowed to rest for 3 minutes during the conditioning step. Next, with the rheometer operating in oscillatory mode, a frequency sweep step can be used to measure the viscosity of the material at various shear rates. The angular frequency can be stepped between 0.1 and 10.0 rad / s at 0.4% strain and 5 points per decade. The material is then allowed to rest for 2 minutes to reach equilibrium. Finally, the yield stress of the material can be measured through another oscillatory measurement. In a stress sweep measurement, the oscillatory stress can be varied in steps from 0.1 to 10,000 Pa, recording 15 points per decade. The angular frequency can be maintained fixed at 10 rad / s. The modulus of elasticity (G') can be monitored. The yield stress is defined as the intersection of a horizontal line drawn through the portion of the data where G' is constant with stress (low stress values) and a line corresponding to the maximum slope of the portion of the curve where G' decreases rapidly with increasing stress. The yield stress can be measured as the minimum amount of force required to move (yield) the material. The collected data can be analyzed using the "Rheology Advantage Data Analysis" software provided with the instrument.

[0186] In some embodiments, the highly filled hardenable (e.g., dental) composition has a shear strength of up to 1, 1.1, 1.2, 1.3, 1.4, or 1.5×10 at a shear rate of 0.1 rad / s. 6In some embodiments, the highly filled hardenable (e.g., dental) composition can have a viscosity in the range of up to 2, 2.1, 2.2, 2.3, 2.4, or 2.5×10 at a shear rate of 1 rad / s. 5 In some embodiments, highly filled hardenable (e.g., dental) compositions can have viscosities in the range of up to 20,000, 30,000, 40,000, or 50,000 (Pa·s) at a shear rate of 10 rad / s.

[0187] In some embodiments, the dental hardenable compositions described herein are provided in a (e.g., pre-filled) dispensing device. Various dispensing devices suitable for storing and applying hardenable (e.g., dental) compositions are known, such as those described in U.S. Patent Nos. 4,632,672, 5,100,320, and 5,848,894, which are incorporated herein by reference. Such devices generally include a cartridge or syringe, a dispensing nozzle with an outlet at one end of the cartridge, and a plunger at the opposite end of the cartridge. In some embodiments, the cartridge has two chambers for containing separate portions of the two-part composition.

[0188] 1 shows an exemplary syringe device 1 suitable for dispensing a two-part (e.g., dental) sealant material. The syringe device comprises a (e.g., cylindrical) cartridge 10, a plunger 20, and a dispensing nozzle 17.

[0189] Cartridge 10 typically has a cylindrical outer shape. In a typical embodiment, the cartridge further includes finger plate 113. Finger plate 113 is shaped to include a flat portion or support point that prevents cartridge 10 from rolling when placed on a flat surface. Thus, when syringe 1 is placed on a flat surface such as a table, the flat portion of finger plate 113 of cartridge 10 can prevent the syringe from rolling off the table.

[0190] The cartridge 10 of the syringe 1 is pre-filled with a two-component composition. One portion of the two-component composition is contained in a first chamber 111 and a second portion of the two-component composition is contained in a second chamber 112.

[0191] 2, syringe 1 has a plunger 20 comprising a first plunger rod 121 and a second plunger rod 122. One end of each rod 121, 122 is configured to seal a first and second portion of the composition in chamber 111 and chamber 112. The opposite ends of the plunger rods are connected at rear end 16 of plunger 20.

[0192] The cartridge contains a sufficient amount of the two-component composition to fill one or more teeth. Typically, the amount of the two-component composition is sufficient to fill all of a patient's teeth. In some embodiments, the amount of the two-component composition is sufficient to fill all of two or more patients' teeth, and the removable nozzle is replaced for each patient. In a typical embodiment, the syringe is pre-filled with the two-part composition by the manufacturer. In some embodiments, the (e.g., pre-filled) syringe, the two-part composition, and one or more removable dispensing nozzles are combined into a kit for storing and applying the composition. The kit typically further includes instructions for using the kit and for attaching the removable nozzle to the syringe.

[0193] The syringe device is relatively small to facilitate use in the mouth and minimize waste of the composition. In some embodiments, the overall length of the filled syringe (without nozzle) before engaging the plunger, as shown in Figures 1 and 2, is 200 mm, 190 mm, 180 mm, 170 mm, 160 mm, 150 mm, or 140 mm or less. The overall length of the filled syringe (without nozzle) is typically at least 100 mm, 110 mm, 120 mm, or 130 mm. In some embodiments, the overall length of the cartridge is typically 100 mm, 95 mm, 90 mm, 85 mm, 80 mm, or 75 mm or less. The overall length of the cartridge is typically at least 50 mm, 55 mm, 60 mm, or 65 mm. The length of the internal chamber is shorter than the overall length of the cartridge. In some embodiments, the overall length of the internal chamber is 70 mm or 65 mm or less. The cartridge typically has an outer diameter of 15 mm, 14 mm, 13 mm, 12 mm, 11 mm, 10 mm, 9 mm, or 8 mm or less. The outer diameter is typically at least 5 mm, 5.5 mm, 6 mm, 6.5 mm, 7 mm, or 7.5 mm. The cartridge typically has a total internal volume of 5, 4.5, 4, 3.5, 3, or 2.5 cc or less.

[0194] In a typical embodiment, the first chamber and the second chamber have a volume ratio of about 1:1. Other volume ratios can be used. For example, the volume ratio of the chambers can range from 1:1 to about 2:1 or 3:1.

[0195] When a 1:1 volumetric mixing of the first and second parts is intended, the first and second chambers comprise approximately half of the total cartridge volume. Thus, in the case of the miniature syringe device described above, the total internal volume of each chamber is typically 2.5, 2, 1.75, 1.5, or 1.25 cc or less.

[0196] 3 shows a cross-sectional view of syringe 1 through cartridge 10. Cartridge 10 has two chambers 111, 112 extending through cartridge 10. In some embodiments, the chambers have a generally D-shaped cross-section, such as those described in U.S. Patent Application Publication No. 2016 / 0270879, which is incorporated herein by reference.

[0197] Specifically, the periphery of the D-shape is defined solely by a plurality of segments 19a, 19b, 19c, and 19d. (Segments 19a, 19b, 19c, and 19d correspond to the first, third, second, and fourth segments, respectively.) Segment 19a adjacent to the separation wall has a different radius than segment 19c adjacent to the outer wall 17. Specifically, segment 19a has a larger radius than segment 19c. Thus, while the approximate D-shape is achieved, having a cross section based solely on circular structures allows for a more reliable seal compared to a cross section having one or more linear structures. Furthermore, segments 19a, 19b, 19c, and 19d join at the junction of two segments such that the tangents of each segment passing through the junction coincide. That is, segments 19a, 19b, 19c, and 19d merge smoothly with one another to form a closed line that together defines the periphery of the cross section.

[0198] In a preferred embodiment, the radius of the first arc may be in the range of 10 mm to 20, 30, 40, or 50 mm, the radius of the second arc may be in the range of 2 mm to 5, 10, 15, or 20 mm, and the radii of the third and fourth arcs may be in the range of 0.3 mm to 1, 2, or 3 mm. In one embodiment, radius 19a is about 14 mm, radius 19b is about 1 mm, and radius 19c is about 4 mm.

[0199] As shown, the two generally D-shaped shapes are mirror-aligned relative to one another such that cartridge 10 defines an outer wall 117 having a generally cylindrical profile at one end and a separating wall 118 at the other end, the separating wall having a generally uniform wall thickness. The generally uniform wall thickness facilitates manufacturing of the cartridge, for example, by injection molding (e.g., polypropylene).

[0200] In some embodiments, plunger rods 121 and 122 are each configured to be pressed into a respective chamber of the cartridge. The plunger rods may comprise a material that is more rigid than the cartridge. In some embodiments, the plunger rods are injection molded from 50% glass-filled polypropylene. The cross-sectional shape of each plunger rod typically corresponds to the cross-sectional shape of the respective chamber. Thus, if the chambers have a generally D-shaped cross-section, the plunger rods also have a generally D-shaped cross-section.

[0201] In some embodiments, the end portions of plunger rods 121 and 122 that seal the two-part composition within the chambers are preferably larger in dimension than the cross-sectional shape of their respective chambers, specifically enlarged in two dimensions by a fixed offset. In one embodiment, plunger rods 121 and 122 each have a skirt-type lip seal, as described in more detail in the above-cited U.S. Patent Application Publication No. 2016 / 0270879.

[0202] The chambers and plunger rod can have a variety of other designs and cross-sectional shapes so that the two-component compositions are sealed within their respective chambers prior to use.

[0203] Dispensing nozzle 17 is removably mounted to front end 15 of cartridge 10. In some embodiments, the nozzle is rotatably mounted to the front end of cartridge 10. The cartridge, nozzle, or a combination thereof includes a valve capable of providing or preventing fluid communication between the two-part composition of cartridge 10 and dispensing nozzle 17. In some embodiments, the combination of cartridge 10 and nozzle 17 forms a rotary slide valve. Further details regarding valves are described in WO 2018 / 057503 and U.S. Pat. No. 9,427,290, which are incorporated herein by reference.

[0204] Dispensing nozzle 17 further comprises a cannula 172 containing static mixer 40 (not shown in FIG. 1, but shown in FIGS. 2 and 4).

[0205] The volume and design can be selected to maximize mixing efficiency and reduce waste. In some embodiments, the total volume of the dispensing nozzle without the static mixer is typically 0.25, 0.20, 0.15, or 0.10 cc or less. In some embodiments, the total volume of the dispensing nozzle is 0.09, 0.08, 0.07, 0.06, 0.05, 0.04, or 0.03 cc or less. The cannula has an outer diameter of 2, 2.5, or 3 mm wide and approximately 75-150 mm long.

[0206] Various static mixers are available. Figure 4 shows a preferred static mixer 40 that may be disposed within the dispensing nozzle shown in Figures 1 and 2. Such a static mixer is described in International Publication No. WO 2015 / 205181, which is incorporated herein by reference. The static mixer 40 has a series of mixing elements 41a / 41b. Each mixing element 41a / 41b is based on a helix or spiral. The structure of such a helical mixing element can essentially be envisioned as a planar sheet of material held at both ends and twisted or rolled 180 degrees, although other methods (e.g., injection molding) are typically used to manufacture such structures. The overall shape of such mixing elements 41a / 41b is based on a cylindrical helix. Thus, each mixing element has an outer diameter D. Each mixing element has a material inlet edge 42a / 42b and an outlet edge 43a / 43b. Regarding the flow F of dental material through the mixing unit, the material enters each mixing element 41a / 41b at an inlet edge 42a / 42b and exits each mixing element 41a / 41b at an outlet edge 43a / 43b. The static mixer 40 has multiple mixing elements 41a / 41b arranged in series. The inlet edges 42a / 42b and outlet edges 43a / 43b of two adjacent mixing elements 41a / 41b are offset at an angle relative to each other. Thus, the flow of the two components of the dental material is split as the dental material flows through the mixing unit 40, and the split partial flows merge multiple times. Thus, the dental material (e.g., two portions) is mixed. The offset angle between the inlet edge 42a / 42b and the outlet edge 43a / 43b is measured at a point on the longitudinal axis A of the mixing unit in a plane perpendicular to the longitudinal axis A. In the example, the offset angle between the inlet edge 42a / 42b and the outlet edge 43a / 43b is 90 degrees, in other words, the inlet edge 42a / 42b and the outlet edge 43a / 43b of adjacent mixing elements 41a / 41b are arranged to intersect with each other.

[0207] As shown, the mixing unit 40 has right-handed mixing elements 41a and left-handed mixing elements 41b arranged alternately in series along the longitudinal axis A. The right-handed and left-handed mixing elements 41, 41b differ in the winding direction of the spiral on which the mixing elements 41a / 41b are based.

[0208] In some embodiments, the mixing elements 41a / 41b of the mini-syringe device have an outer diameter D of 1.5 mm to 1.6 mm. Additionally, each mixing element has a length L of 0.6 mm to 1.2 mm, preferably 0.78 mm. The outer diameter D and length L are preferably the same for all mixing elements 41a / 41b of the mixing unit 40. This particular range of diameter D for the mixing elements 41a / 41b can improve mixing.

[0209] The dispensing nozzle tip 173 of the dispensing nozzle can be rigid or flexible. The nozzle tip can be formed of a thermoplastic material or can be a hollow metallic needle. In some embodiments, the dispensing nozzle tip extends from the cannula at an included angle ranging from 90° to 180°. In some embodiments, the included angle is at least 95, 100, 105, or 110°. In some embodiments, the included angle is no greater than 170, 160, 150, 140, or 130°. In some embodiments, the tip length of the mini-syringe device can range from about 5 mm to 15 mm or 20 mm. In some embodiments, the tip length is no greater than 14, 13, 12, 11, or 10 mm. The outlet is typically rounded and has a narrower diameter than the cannula. In some embodiments, the diameter of the outlet is at least 0.5, 0.6, 0.7, or 0.8 mm and in the range of up to 1, 1.1, 1.2, 1.3, 1.4, or 1.5 mm.

[0210] Syringe 1 may optionally include an actuator for incrementally engaging the plunger toward the front end of the syringe. The inclusion of an actuator is useful for dispensing a predetermined amount (e.g., a single dose) of composition material. This feature can be useful for accurately applying the correct amount, i.e., enough to fill the pits and fissures, but not so much that the patient detects the cured sealant during chewing. An example of a syringe with an actuator is further described in WO 2017 / 180545, which is incorporated herein by reference.

[0211] During use of the syringe device, the nozzle rotates to open the slide valve and allow fluid contained in the chamber to be delivered through the nozzle. Fingers (e.g., index and middle fingers) contact the finger plate 113, and the thumb typically presses against the rear end 16 of the plunger, moving the first plunger rod 121 and the second plunger rod 122 toward the front end 15 of the syringe device. Such movement delivers the first and second portions through the static mixer and outlet onto the enamel of the tooth surface.

[0212] In some embodiments, the two components are combined by confluence in a static mixer. For the miniature syringe device described above, each component preferably has a viscosity of 6,500, 6,000, 5,500, or 5,000 cps or less at 23°C, as measured according to the test methods described in the Examples. In some embodiments, the viscosity of each component is 4,500, 4,000, 3,500, or 3,000 cps or less at 23°C. The viscosity of each of the components is typically at least 200, 300, 400, or 500 cps at 23°C.

[0213] Furthermore, the viscosities of the two components are typically similar, e.g., the difference between the viscosity of the higher viscosity material is no more than 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20, 15, or 10%. When the viscosities and viscosity difference of the mixed components are within a suitable range, a sufficiently homogeneous mixture can be dispensed through an outlet. Furthermore, the components can be transported through a static mixer with a relatively low extrusion force. Such low extrusion forces can typically be generated by manually operated systems.

[0214] As used herein, "dental article" refers to an article that can be adhered (e.g., bonded) to a tooth structure or a dental implant. Dental articles include, for example, crowns, bridges, veneers, inlays, onlays, fillings, orthodontic appliances and devices.

[0215] "Orthodontic appliance" refers to any device intended to be bonded to tooth structure, including, but not limited to, orthodontic brackets, buccal tubes, lingual anchoring devices, orthodontic bands, mouth gag devices, buttons, and cleats. The appliance has a base that receives an adhesive, which may be a flange made of metal, plastic, ceramic, or a combination thereof. Alternatively, the base may be a custom base formed from a hardened adhesive layer (i.e., a single or multi-layer adhesive).

[0216] "Oral surfaces" refers to soft or hard surfaces in the oral environment. Hard surfaces typically include, for example, dental structures, including natural and artificial tooth surfaces, bone, and the like.

[0217] "Hardenable" and "curable" describe a material or composition that can be hardened (e.g., polymerized or crosslinked) by heating to induce polymerization and / or crosslinking; by exposure to actinic radiation to induce polymerization and / or crosslinking; and / or by mixing one or more components to induce polymerization and / or crosslinking. "Mixing" can be performed, for example, by combining and mixing two or more components to form a homogeneous composition. Alternatively, two or more parts can be prepared as separate layers, and the layers can be intermixed at their interface (e.g., spontaneously or by application of shear stress) to initiate polymerization.

[0218] "Cured" refers to a material or composition that has been hardened (e.g., polymerized or crosslinked).

[0219] "Hardening agent" refers to an agent that initiates the hardening of a resin. Hardening agents can include, for example, polymerization initiator systems, photoinitiator systems, thermal initiator systems, and / or redox initiator systems.

[0220] "(Meth)acrylate" is shorthand for acrylate, methacrylate, or a combination thereof, "(meth)acrylic acid" is shorthand for acrylic acid, methacrylic acid, or a combination thereof, and "(meth)acrylic" is shorthand for acrylic, methacrylic, or a combination thereof.

[0221] As used herein, "a," "an," "the," "at least one," and "one or more" are used interchangeably.

[0222] Also herein, the recitations of numerical ranges by endpoints include all numbers subsumed within that range (eg, 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, 5, etc.).

[0223] Illustrative Embodiments 1. A two-part hardenable dental composition, a first part comprising a composition including a liquid material and an encapsulated material, the encapsulated material including a basic core material and an inorganic shell material including a metal oxide surrounding the core; a second portion comprising a composition comprising a liquid material; The first portion composition has a first viscosity, the second portion composition has a second viscosity, and the difference between the first viscosity and the second viscosity is measured using a Brookfield viscometer and a Type A T-bar spindle at 23°C and a shear rate of 100 s -1 is no more than 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20, 15, or 10% of the higher viscosity composition when measured by 2. A two-part hardenable dental composition, Using a Brookfield viscometer and a Type A T-bar spindle, the viscosity was measured at 23°C and a shear rate of 100 s. -1 a first portion having a viscosity of 6500 cps or less when measured at 1000 rpm, the first portion comprising a composition including a liquid material and an encapsulated material, the encapsulated material including a basic core material and an inorganic shell material including a metal oxide surrounding the core; and a second part comprising a composition having a viscosity of 6500 cps or less and including a liquid material. 3. A hardenable dental composition comprising: The present invention also includes a one-part composition comprising a composition including a liquid material and an encapsulated material, wherein the encapsulated material includes a basic core material and an inorganic shell material including a metal oxide surrounding the core, and the one-part composition is viscous at 23°C and a shear rate of 100 s using a Brookfield viscometer and a Type A T-bar spindle. -1 or has a viscosity of less than 25,000 cps when measured at or having a viscosity of more than 40,000 cps; Hardenable dental composition. 4. A first part comprising an encapsulated material, the encapsulated material comprising a basic core material and an inorganic shell material comprising a metal oxide surrounding the core; a non-aqueous second portion; and Redox curing system, 1. A two-part hardenable dental composition comprising: 5. The two-part hardenable dental composition of embodiment 4, wherein the second part comprises a polymerizable resin. 6. A first part comprising an encapsulated material and a reducing agent, the encapsulated material comprising a basic core material and an inorganic shell material comprising a metal oxide surrounding the core; a second part comprising an oxidizing agent selected from the group consisting of peroxide compounds, persulfate compounds, perborate compounds, and perchlorate compounds. 7. The dental composition of embodiment 1, 2, 4, or 6, wherein upon combining the first and second parts, the composition initially has an acidic or neutral pH. 8. The dental composition of embodiments 1-7, wherein the shell is degradable by the second portion. 9. The dental composition of embodiments 1-8, wherein the basic core material releases -OH upon decomposition of the shell. 10. The dental composition of embodiments 1-9, wherein the basic core material comprises a component having a pKa in the range of 8-14. 11. The dental composition of any one of embodiments 1-10, wherein the basic core material comprises a component having a pKa in the range of 11-14. 12. The dental composition of embodiments 1-11, wherein the basic core material comprises a material that releases calcium ions. 13. The dental composition of any one of embodiments 1-12, wherein the basic core material comprises at least 25, 30, 35, 40, or 45 wt. % of components having a pKa in the range of 11-14. 14. The dental composition of embodiments 1-13, wherein the shell is a continuous film having a thickness of less than 500 nm. 15. The dental composition of embodiments 1-14, wherein the inorganic shell material is less basic than the basic core material. 16. The dental composition of claims 1-15, wherein the inorganic shell material comprises a metal oxide having a pKa of 6-8. 17. The dental composition of any one of embodiments 1-16, wherein 0.25 grams of the encapsulated material when combined with 25 g of deionized water results in a pH of at least 8.5 or 9 within 24 hours. 18. The dental composition of any one of embodiments 1-17, wherein when 0.25 grams of the encapsulated material is combined with a solution of 15 g of deionized water and 10 g of aqueous potassium hydrogen phthalate buffer solution adjusted to a pH of 4.00 with hydrochloric acid at 25° C., a pH of at least 8.5 or 9 is obtained within 24 hours. 19. The dental composition of embodiments 1-18, wherein the basic core material is hardenable. 20. The dental composition of embodiment 19, wherein the basic core material comprises calcium silicate. 21. The dental composition of embodiments 1-20, wherein the basic core material is a dental filler comprising a neutral metal oxide having low solubility in the second portion. 22. The dental composition of embodiments 1-21, wherein the hardenable dental composition comprises a material that promotes remineralization through the release of calcium ions, phosphorus ions, fluoride ions, or a combination thereof. 23. The dental composition of embodiments 1-21, wherein the composition further comprises at least one second filler. 24. The dental composition of embodiment 23, wherein the second filler comprises a nanoscopic particulate filler. 25. The dental composition of embodiment 24, wherein the second filler comprises zirconia, silica, or a mixture thereof. 26. The dental composition of embodiments 24 and 25, wherein the second filler comprises a nanocluster filler. 27. The dental composition of any one of embodiments 1-26, wherein the liquid material of the first and / or second parts comprises water, an acid, a polymerizable resin, or a combination thereof. 28. The dental composition of embodiment 27, wherein the polymerizable material comprises a hydroxy-functional (meth)acrylate monomer, an acidic polymer, or a combination thereof. 29. The dental composition of embodiments 1-28, wherein the hardened dental composition provides a pH of at least 8.5 or 9 within 500 hours according to a disc buffer test. 30. The dental composition of embodiments 1-29, wherein the average cell proliferation of dental pulp cells when in contact with the hardened dental composition is at least 75% of that of a control sample. 31. The dental composition of embodiments 1-30, wherein the mean alkaline phosphatase (ALP) activity of dental pulp cells increases when in contact with the hardened dental composition. 32. An encapsulated material suitable for use in a biocarrier material, the encapsulated material comprising a basic core material and an inorganic shell material comprising a metal oxide surrounding the core. 33. The encapsulated material of embodiment 32, wherein the encapsulated material is further characterized by any one of claims 9 to 21 or a combination thereof. 34. The encapsulated core material of embodiments 32-33, wherein the composition is hardenable or self-hardening when mixed with water. 35. A curable composition comprising an encapsulated material for use in a biocarrier material, the curable composition comprising a basic core material and an inorganic shell material comprising a metal oxide surrounding the core, characterized by the curable composition according to claims 1 to 6. 36. The hardenable dental composition of embodiment 35, wherein the composition is a dental or medical composition. 37. The curable composition of any one of embodiments 32-36, wherein the curable composition further comprises a second filler and / or polymerizable material according to any one of claims 23-28 or a combination thereof. 38. The curable composition of any one of embodiments 34 to 37, which is contacted with water or an acidic component during use. 39. The hardenable composition of embodiment 38, wherein the water or acidic component is a biological fluid. 40. A method for delaying the release of a basic core material, comprising: Providing a composition according to any one of embodiments 1 to 39; applying the composition to the tooth or bone structure. 41. A method for providing a delayed increase in basicity, comprising: Providing a composition according to any one of embodiments 1 to 39; applying the composition to the tooth or bone structure. 42. A method for promoting remineralization, comprising: Providing the dental composition of any one of embodiments 1 to 39, wherein the basic core further comprises a material that promotes remineralization by release of calcium ions, phosphorus-containing ions, fluoride ions, or a combination thereof; applying the composition to the tooth or bone structure. 43. The method of embodiment 40, wherein the remineralization-promoting material releases calcium ions, phosphorus-containing ions, fluoride ions, or a combination thereof. 44. A method for increasing the mean alkaline phosphatase (ALP) activity of dental pulp cells, comprising: providing a composition according to any one of embodiments 1 to 37, wherein the basic core further comprises a material that promotes remineralization; applying the composition to the tooth or bone structure. 45. A composition for use in applying to teeth or bone structures, the composition comprising: provide delayed release of the basic core material; provide a delayed increase in basicity, Promotes remineralization, Increase the average alkaline phosphatase (ALP) activity of dental pulp cells, or a combination thereof. 46. ​​A method of using a composition, comprising: Providing a composition according to any one of embodiments 1 to 39; applying the composition to the tooth or bone structure. 47. The method of embodiment 46, wherein the composition comprises a polymerizable material, and the method further comprises curing the composition by exposing it to a radiation source. 48. The method of embodiments 46-47, wherein the composition provides delayed release of the basic core material. 49. The method of embodiments 46-48, wherein the composition provides a delayed increase in basicity. 50. The method of embodiments 46-49, wherein the composition promotes remineralization of tooth or bone structure. 51. The method of embodiments 46-50, wherein the composition increases the mean alkaline phosphatase (ALP) activity of dental pulp cells. 52. The method of embodiments 46-51, wherein the composition is a dental adhesive or cement used to bond a dental article to a tooth structure. 53. The method of embodiments 46-51, wherein the composition is a dental restorative. 54. A dispensing device containing a curable composition, the curable composition comprising: A dispensing device comprising a liquid material and an encapsulated material, the encapsulated material comprising a basic core material and an inorganic shell material comprising a metal oxide surrounding the core. 55. The dispensing device of embodiment 54, wherein the liquid material comprises a polymerizable resin. 56. The dispensing device of embodiment 54 or 55, wherein the composition has a viscosity in the range of 200 cps to 100,000 cps at 23°C. 57. The device is A cartridge and a nozzle at one end of the cartridge, the nozzle having an outlet; a plunger at the opposite end of the cartridge for dispensing the curable composition from the cartridge; A dispensing device according to embodiments 54 to 56, comprising: 58. The dispensing device of embodiment 57, wherein the curable composition is a two-component composition and the cartridge has two chambers. 59. The dispensing device of embodiments 54 to 58, wherein the dispensing device is a syringe device. 60. The cartridge is first and second chambers; a dispensing nozzle at one end of the cartridge, the dispensing nozzle comprising a static mixer and an outlet; 60. The dispensing device of embodiments 54 to 59, comprising a plunger at an opposite end of the cartridge, the plunger comprising two rods, one end of the rods sealing the first and second portions of the composition in the chamber, and the opposite ends of the plunger rods connected. 61. The dispensing device of embodiments 57-60, wherein the cartridge has a volume of 5, 4.5, 4, 3.5, 3, or 2.5 cc or less. 62. The dispensing device of embodiments 58 to 61, wherein the first chamber and the second chamber have a volume ratio of approximately 1:1. 63. The dispensing device of embodiments 57-62, wherein the dispensing nozzle has a volume of 0.25, 0.20, 0.15, 0.10, or 0.05 cc or less. 64. The dispensing device of embodiments 57 to 62, wherein the outlet has a diameter of 1.5 or 1 mm or less. 65. The dispensing device of embodiments 57-64, wherein the composition has a viscosity of 5,000 cps or less at 23°C. 66. A kit comprising: a hardenable composition comprising a composition including a liquid material and an encapsulated material, wherein the encapsulated material comprises a basic core material and an inorganic shell material comprising a metal oxide surrounding the core; and a dispensing device. 67. The kit of embodiment 66, wherein the dispensing device is pre-filled with the hardenable composition. 68. The kit of claims 66 and 67, wherein the kit further comprises instructions. 69. The kit of embodiments 66 to 68, wherein the dispensing device is according to claims 54 to 65. 70. The method of any one of embodiments 46 to 53, wherein a dispensing device of any one of claims 54 to 65 and / or a kit of any one of claims 66 to 69 is utilized to provide the composition of any one of claims 7 to 39. [Example]

[0224] material Hydroxyethyl methacrylate (HEMA) was obtained from Evonik Industries (Sarasota, FL).

[0225] Ethyl 4-dimethylaminobenzoate (EDMAB) was obtained from Sigma-Aldrich Corporation (St. Louis, MO).

[0226] Camphorquinone (CPQ), benzoyl peroxide-LUPEROX A75 (BPO), 2-(4-dimethylamino)phenyl)ethanol (DMAPE), triethylene glycol dimethacrylate (TEGDMA), and bisphenol A glyceroate dimethacrylate (BisGMA) were obtained from Sigma-Aldrich.

[0227] 2,6-Di-tert-butyl-4-methylphenol (BHT) was obtained from PMC Specialties Incorporated (Cincinnati, Ohio).

[0228] Fumed silica (AEROSIL R972) was obtained from Evonik Corporation (Piscataway, NJ).

[0229] Fumed silica R812S was obtained from Degussa-Huls Corporation (Parsippany, NJ).

[0230] Calcium glycerophosphate was obtained from Spectrum Laboratory Products (Gardena, CA).

[0231] Ytterbium fluoride (YbF3) was obtained from Treibacher Industrie Incorporated (Toronto, Canada).

[0232] Buffer BDH5018 (aqueous potassium hydrogen phthalate buffer adjusted to a pH of 4.00 with hydrochloric acid at 25° C.) was obtained from VWR International (Radnor, PA).

[0233] The VBP polymer was made by reacting a PAA:ITA copolymer with enough IEM (2-isocyanatoethyl methacrylate) to convert 16 mole percent of the acid groups of the copolymer to pendant methacrylate groups, according to the dry polymer preparation of Example 11 of U.S. Pat. No. 5,130,347 (Mitra).

[0234] The PAA:ITA copolymer was made from a 4:1 molar ratio of acrylic acid:itaconic acid prepared according to Example 3 of US Pat. No. 5,130,347.

[0235] The Zr / Si nanocluster filler was a silane-treated zirconia / silica nanocluster filler prepared essentially as described in U.S. Pat. No. 6,730,156 [Preparation Example A (lines 51-64) and Example B (column 25, line 65 to column 26, line 40)].

[0236] Portland cement: White Portland cement (Federal White Type 1, ASTM designation C150) was purchased from Federal White Cement (Woodstock, Ontario, Canada). The major components of the composition reported by the manufacturer are tricalcium silicate (3CaO-SiO2), dicalcium silicate (2CaO-SiO2), tricalcium aluminate (3CaO-Al2O3), tetracalcium aluminoferrite (4CaO-Al2O3-Fe2O3), magnesium oxide, calcium oxide, potassium sulfate, and sodium sulfate. Portland cement is a strongly basic material containing multiple components. Each major component (except for minor components of magnesium oxide, potassium sulfate, and sodium sulfate) contains a significant amount of strong base (CaO). Portland cement typically contains about 61% to 69% CaO, about 18% to 24% SiO2, about 2% to 6% Al2O3, about 1% to 6% Fe2O3, and about 0.5% to 5% MgO.

[0237] Bioactive glass [45S5] was prepared with the following composition: SiO (45 wt%), NaO (24.5 wt%), CaO (24.5 wt%), and PO (6 wt%). Bioactive glass is a strongly basic material. It is homogeneous, with two strongly basic components (NaO and CaO) totaling 49 wt% of the composition.

[0238] Tricalcium silicate (3CaOSiO2) powder was prepared by the sol-gel method. A solution of 0.5 mol Si(OC2H5)4 (tetraethyl orthosilicate, TEOS), 200 mL of water as a catalyst, and nitric acid was combined under continuous stirring. Then, 1.5 mol Ca(NO3)2-4H2O was added to the solution. The solution was heated to 60°C and maintained until gelation occurred. The gel was then dried at 200°C and calcined at 1500°C for 6 hours. Tricalcium silicate is a strongly basic, homogeneous compound with approximately 74% by weight of the strong base component (CaO).

[0239] Fluoroaluminosilicate (FAS) glass was prepared essentially as described in Example 1 of U.S. Patent No. 5,154,762. The powder components SiO (34.6 wt%), AlF (21.5 wt%), SrO (18.7 wt%), AlO (9.4 wt%), AlPO (6.5 wt%), NaAlF (5.6 wt%), and P0 (3.7 wt%) were mixed, melted in an arc furnace at 1350-1450°C, and roller-quenched to form an amorphous single-phase FAS glass. The glass was then ball-milled to a 2.6 mm diameter. 2 A ground product was obtained with a surface area of ​​1 / g (measured according to the Brunauer-Emmett-Teller (BET) method).

[0240] BisEMA-6 refers to ethoxylated (6 moles of ethylene oxide) bisphenol A dimethacrylate available as "CD541" from Sartomer Co., Inc. (Exton, PA), which is further described in U.S. Pat. No. 6,030,606.

[0241] BZT refers to 2-(2'-hydroxy-5'-methacryloxyethylphenyl)-2H-benzotriazole, CAS Registry Number 96478-09-0, available as "TINUVIN® 796" from Ciba, Inc. (Tarrytown, NY), and also available from Sigma-Aldrich Corp. (St. Louis, MO).

[0242] DPIHFP or DPIPF6 refers to diphenyliodonium hexafluorophosphate, CAS Registry Number 58109-40-3, available from Johnson Matthey, Alfa Aesar Division (Ward Hill, MA).

[0243] ENMAP refers to ethyl N-methyl-N-phenyl-3-aminopropionate (also known as N-methyl-N-phenyl-beta-alanine ethyl ester), CAS Registry Number 2003-76-1, which can be prepared by known methods such as those described by Adamson et al., JCSOA9; J. Chem. Soc.; 1949; spl. 144-152, and is also available from Johnson Matthey, Alfa Aesar Division (Ward Hill, MA).

[0244] IRGACURE 819 refers to bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide photoinitiator, CAS Registry Number 162881-26-7, available from Ciba Specialty Chemicals Corp. (Tarrytown, NY) and also from Sigma-Aldrich Corp. (St. Louis, MO).

[0245] PEG600 DM refers to poly(ethylene glycol) dimethacrylate with an average molecular weight of approximately 600, available from Sartomer Co., Inc. (Exton, PA).

[0246] UDMA refers to diurethane dimethacrylate, CAS Registry Number 72869-86-4, available from Rohm America LLC (Piscataway, NJ) under the trade designation "ROHAMERE 6661-0," also available from Dajac Laboratories (Trevose, PA).

[0247] S / T silica / zirconia nanocluster refers to a silane-treated silica-zirconia nanocluster filler prepared essentially as described in U.S. Pat. No. 6,730,156, column 25, lines 50-63 (Preparatory Example A) and column 25, lines 64 to column 26, line 40 (Preparatory Example B), but with minor modifications, including adjusting the pH to about 8.8 with NH4OH (instead of 3-3.3 with trifluoroacetic acid), performing the silanization in 1-methoxy-2-propanol (instead of water), and gap drying (instead of spray drying) to obtain the S / T silica / zirconia cluster.

[0248] S / T 20 nm silica nanoparticles refers to silane-treated silica nanoparticle fillers having a nominal particle size of approximately 20 nanometers, prepared essentially as described in U.S. Pat. No. 6,572,693, column 21, lines 63-67 (Nano-sized particle fillers, Type 2).

[0249] S / T nanozirconia nanoparticles refer to silane-treated zirconia nanoparticle fillers, which can be prepared from zirconia sol, generally as described in U.S. Pat. No. 8,647,510, column 36, line 61 to column 37, line 16 (Example 11A-IER). The zirconia sol is added to an equal weight of 1-methoxy-2-propanol containing 3-methacryloxypropyltrimethoxysilane (1.1 mmol of 3-methacryloxypropyltrimethoxysilane per gram of nanozirconia to be surface-treated). The mixture is heated to approximately 85°C with stirring for 3 hours. The mixture is cooled to 35°C, the pH is adjusted to approximately 9.5 with NH4OH, and the mixture is reheated to approximately 85°C with stirring for 4 hours. The resulting S / T nanozirconia is isolated by removing the solvent via gap drying. S / T nanozirconia can also be prepared as described in U.S. Pat. No. 7,649,029, column 19, line 39 to column 20, line 41 (Filler I), except that 3-methacryloxypropyltrimethoxysilane is replaced with a blend of Silquest A-174 and A-1230, and the solvent may be removed by gap drying.

[0250] calculation The following equations 1-6 were used to calculate the shell thickness, weight percent of core material, and weight percent of shell material for the encapsulated materials prepared by the processes described in Examples 1-5, 26, and 28-29. In the calculations, the total surface area of ​​the core material was calculated by assuming the core material powder particles as spheres (surface area = 4π(d / 2) 2 , volume = (4 / 3)(π)(d / 2) 3 ) was measured.

[0251] Formula 1:

number

[0252] Formula 2:

number

[0253] Formula 3:

number

[0254] Formula 4:

number

number

[0255] For encapsulated materials with a tricalcium silicate core, the core particle had additional porosity, which affected the apparent surface area measurement. For tricalcium silicate encapsulated materials, an indirect method was used to estimate the effective surface area of ​​the core and the thickness of the shell coating. It was estimated that tricalcium silicate encapsulated materials and Portland cement encapsulated materials (with the same shell material) with approximately the same time required to change the pH of the buffer solution from 4 to 9 (following the procedures in Examples 6-9) would have the same shell thickness. Therefore, the shell thickness of the tricalcium silicate encapsulated materials was based on the value calculated for the corresponding Portland cement encapsulated materials.

[0256] measurement Viscosity measurements were taken using a Brookfield DV-I+ viscometer with a HELIPATH stand and a Type AT bar spindle (AMETEK Brookfield, Middleboro, MA) at 23°C and a shear rate of 100 s -1Test results were taken when the viscosity reading stabilized (typically within 0.5 to 2 minutes). Viscosity is reported in centipoise (cP).

[0257] Example 1. Encapsulated material with a bioactive glass core Bioactive glass (BG) powder was encapsulated with an aluminum oxide (AO)-based material using atmospheric pressure chemical vapor deposition (APCVD). The bioactive glass was coated by reacting trimethylaluminum (obtained from Strem Chemicals, Newburyport, MA, and dispensed from a stainless steel bubbler) with water vapor in a fluidized-bed reactor. The reactor was a glass-fritted funnel tube (2 cm diameter, 18 cm height). The reactor had an inlet tube extending from below the frit routed parallel to the body of the reactor and an extended top area above the frit to allow for the desired reactor height and attachment for the precursor injector tube and exhaust outlet. Temperature was controlled at 180 °C using an oil bath. Nitrogen carrier gas was used in a standard bubbler configuration for liquid precursors. The bubbler was maintained at an ambient temperature of approximately 22 °C. The flow rate through the trimethylaluminum (TMA) bubbler was 100–330 cm. 3 The flow rate through the water bubbler ranged from 250 to 1250 cm / min. 3The coating time ranged from 20 to 100 minutes. Encapsulated materials A–J were prepared by varying the following parameters: amount of bioactive glass added, particle size of the bioactive glass powder, TMA flow rate, water flow rate, and coating time. Table 1 lists the encapsulation parameters for encapsulated materials A–J. For encapsulated materials G–J, a larger reactor was used (4 cm diameter, 30 cm height). For encapsulated materials A–C and G–J, the particle size of the bioactive glass powder was selected by passing the powder through a 45-micron sieve and collecting it on a 38-micron sieve before adding it to the reactor. For encapsulated materials D–F, the bioactive glass powder was milled using a ball mill with 5 mm media to obtain a particle size of 10 microns before adding it to the reactor. The average particle size of each powder after milling was measured using a Model LA950 Laser Particle Size Analyzer (Horiba Scientific, Edison, NJ) with water.

[0258] Table 1a reports the calculated shell thickness (in nanometers), weight percent of core, and weight percent of shell for each encapsulated material AJ.

[0259] [Table 2]

[0260] [Table 3]

[0261] Example 2. Encapsulated material with a tricalcium silicate core Tricalcium silicate (TCS) was encapsulated with an aluminum oxide-based material using atmospheric pressure chemical vapor deposition (APCVD). Tricalcium silicate powder (30 g) was coated by reacting trimethylaluminum (obtained from Strem Chemicals and dispensed from a stainless steel bubbler) with water vapor in a fluidized-bed reactor. The reactor was a glass-fritted funnel tube (4 cm diameter, 30 cm height). The reactor had an inlet tube extending from below the frit routed parallel to the body of the reactor and an extended top area above the frit to allow for the desired reactor height and attachment for the precursor injector tube and exhaust outlet. Temperature was controlled at 180 °C using an oil bath. Nitrogen carrier gas was used in a standard bubbler configuration for liquid precursors. The bubbler was maintained at an ambient temperature of approximately 22 °C. The flow rate through the trimethylaluminum (TMA) bubbler was 500 cm. 3 The flow rate through the water bubbler was 1750 cm 3 / min. The total coating time was 40 minutes. Table 2 lists the average particle size and other encapsulation parameters of the tricalcium silicate powder added to the reactor. Following the coating procedure, the resulting encapsulated materials were individually sieved to collect encapsulated materials having particle sizes less than 38 microns. These sieved encapsulated materials were designated as encapsulated materials K and L.

[0262] Table 2a reports the calculated shell thickness (nanometers), weight percent core, and weight percent shell for each encapsulated material K-L.

[0263] [Table 4]

[0264] [Table 5]

[0265] Example 3. Encapsulated material with a Portland cement core Portland cement (PC) was encapsulated with an aluminum oxide-based material using atmospheric pressure chemical vapor deposition (APCVD). Portland cement powder was coated by reacting trimethylaluminum (obtained from Strem Chemicals and dispensed from a stainless steel bubbler) with water vapor in a fluidized-bed reactor. The reactor was a glass-fritted funnel tube (4 cm diameter, 30 cm height). The reactor had an inlet tube extending from below the frit routed parallel to the body of the reactor and an extended top area above the frit to allow for the desired reactor height and attachment for the precursor injector tube and exhaust outlet. Temperature was controlled at 180 °C using an oil bath. Nitrogen carrier gas was used in a standard bubbler configuration for liquid precursors. The bubbler was maintained at an ambient temperature of approximately 22 °C. The flow rate through the trimethylaluminum (TMA) bubbler ranged from 240 to 1000 cm. 3 The flow rate through the water bubbler ranged from 610 to 2500 cm / min. 3 / min). The total coating time ranged from 10 to 105 minutes. Encapsulated materials M to U were prepared by varying the following parameters: amount of Portland cement added, particle size of Portland cement powder, TMA flow rate, water flow rate, and coating time. Table 3 lists the encapsulation parameters for encapsulated materials M to U.

[0266] For encapsulated material M, the Portland cement powder added to the reactor was used as received and had an average particle size of 17.1 microns (D10-D90 range of 6.0-33.5 microns) as measured using a Coulter Counter Multisizer 3 (Beckman Coulter Company, Brea, CA).

[0267] For encapsulated materials N through S, fine particles were removed from the Portland cement samples by air classification using an AVEKA CCE Centrifugal Air Classifier Model 100 (AVEKA CCE LLC, Cottage Grove, MN) before addition to the reactor. Parameters were selected to obtain a 56% yield of crude material, providing samples with an average particle size of 24.4 microns (D10-D90 range of 13.8-38.4 microns) as measured using a Coulter Counter Multisizer 3 (Beckman Coulter Company).

[0268] For encapsulated materials T through U, fine and coarse particles were removed from the Portland cement samples prior to addition to the reactor using an AVEKA CCE Model 100 centrifugal air classifier. In a first pass, a total of approximately 24% of the initial sample's coarse fraction was removed, followed by a second pass, which removed approximately 25% of the fine fraction from the remaining sample. The resulting Portland cement powder had a mean particle size of 19.6 microns (D10-D90 range of 9.4-31.5 microns) as measured using a Coulter Counter Multisizer 3 (Beckman Coulter Company).

[0269] Table 3a reports the calculated shell thickness (in nanometers), weight percent of core, and weight percent of shell for each encapsulated material M through U.

[0270] [Table 6]

[0271] [Table 7]

[0272] Example 4. Encapsulated Material with a Portland Cement Core and a Titanium Dioxide Shell. Portland cement was encapsulated with a titanium dioxide-based material using atmospheric pressure chemical vapor deposition (APCVD). Portland cement powder (50 g) was coated by reacting titanium tetrachloride (obtained from Strem Chemicals and dispensed from a stainless steel bubbler) with water vapor in a fluidized-bed reactor. Prior to loading into the reactor, fine particles were removed from the Portland cement sample using the air classification procedure described for Encapsulated Materials N-S in Example 3. The average particle size of the resulting powder was 24.4 microns (D10-D90 range of 13.8-38.4 microns), as measured using a Coulter Counter Multisizer 3 (Beckman Coulter Company). The reactor was a glass-fritted funnel tube (4 cm diameter, 30 cm height). The reactor had an inlet tube extending from below the frit routed parallel to the body of the reactor and an extended top area above the frit to allow for the desired reactor height and fittings for the precursor injector tube and exhaust outlet. The temperature was controlled at 180°C using an oil bath. Nitrogen carrier gas was used with a standard bubbler configuration for liquid precursors. The bubbler was maintained at an ambient temperature of approximately 22°C. The flow rate through the titanium tetrachloride bubbler was 1000 cm. 3 The flow rate through the water bubbler was 1000 cm 3 / min. The total coating time was 57 min.

[0273] Example 5. Encapsulated material with a Portland cement core and a silicon dioxide shell Portland cement was encapsulated with a silicon dioxide-based material using atmospheric pressure chemical vapor deposition (APCVD). Portland cement powder (50 g) was coated by reacting silicon tetrachloride (obtained from Strem Chemicals and dispensed from a stainless steel bubbler) with water vapor in a fluidized-bed reactor. Prior to loading into the reactor, fine particles were removed from the Portland cement sample using the air classification procedure described for encapsulated materials N-S in Example 3. The average particle size of the resulting powder was 24.4 microns (D10-D90 range of 13.8-38.4 microns), as measured using a Coulter Counter Multisizer 3 (Beckman Coulter Company). The reactor was a glass-fritted funnel tube (4 cm diameter, 30 cm height). The reactor had an inlet tube extending from below the frit routed parallel to the body of the reactor and an extended top area above the frit to allow for the desired reactor height and fittings for the precursor injector tube and exhaust outlet. The temperature was controlled at 180°C using an oil bath. Nitrogen carrier gas was used with a standard bubbler configuration for liquid precursors. The bubbler was maintained at an ambient temperature of approximately 22°C. The flow rate through the silicon tetrachloride bubbler was 60 cm 3 The flow rate through the water bubbler was 1300 cm 3 / min. The total coating time was 58 min.

[0274] Table 3b reports the calculated shell thickness (nanometers), weight percent of core, and weight percent of shell for the encapsulated materials of Examples 4 and 5.

[0275] [Table 8]

[0276] Example 6 Four glass vials were each filled with 15 g of deionized water and 10 g of pH 4 buffer solution (Buffer BDH5018, VWR International), and the solutions were stirred. Unencapsulated Portland cement (0.25 g, 24.4 micron particle size) was added to the first vial. Unencapsulated FAS glass (0.25 g) was added to the second vial. Encapsulated material O (0.25 g) was added to the third vial. Encapsulated material Q (0.25 g) was added to the fourth vial. Stirring continued in the vials, and the pH of each solution was measured over 8–10 min using a Mettler Toledo M300 pH Meter (Mettler Toledo Corporation, Columbus, OH). Shell thickness of the encapsulated materials was modified by changing the coating time to a longer coating time to produce a thicker shell. The shell of encapsulated material O was approximately 4.25 times thicker than the shell of encapsulated material Q. The results are presented in Table 4 and show that the encapsulated materials resulted in a delayed reaction with or delayed release of the basic core material.

[0277] [Table 9]

[0278] Example 7 Two glass vials were each filled with 15 g of deionized water and 10 g of a pH 4 buffer solution (Buffer BDH5018, VWR International), and the solutions in the vials were stirred. 0.25 g of the titanium dioxide encapsulated material from Example 4 was added to the first vial. 0.25 g of the silicon dioxide encapsulated material from Example 5 was added to the second vial. Stirring continued in the vials, and the pH of each solution was measured over a 45-minute period using a Mettler Toledo M300 pH Meter (Mettler Toledo Corporation). The results are shown in Table 5 and indicate that the encapsulated material resulted in a delayed reaction with or delayed release of the basic core material.

[0279] [Table 10]

[0280] Example 8 Three glass vials were each filled with 15 g of deionized water and 10 g of pH 4 buffer solution (Buffer BDH5018, VWR International), and the solutions in the vials were stirred. Unencapsulated tricalcium silicate (0.25 g) was added to the first vial. Encapsulated material K (0.25 g) was added to the second vial. Encapsulated material L (0.25 g) was added to the third vial. Stirring continued in the vials, and the pH of each solution was measured over a 12-minute period using a Mettler Toledo M300 pH Meter (Mettler Toledo Corporation). The results are shown in Table 6 and indicate that the encapsulated material resulted in a delayed reaction with or delayed release of the basic core material.

[0281] [Table 11]

[0282] Example 9. Four glass vials were each filled with 15 g of deionized water and 10 g of pH 4 buffer solution (Buffer BDH5018, VWR International), and the solutions in the vials were stirred. Encapsulated material O (0.25 g) was added to the first vial. Encapsulated material P (0.25 g) was added to the second vial. Encapsulated material Q (0.25 g) was added to the third vial. Encapsulated material R (0.25 g) was added to the fourth vial. Stirring continued in the vials, and the pH of each solution was measured using a Mettler Toledo M300 pH Meter (Mettler Toledo Corporation). The time at which each solution reached pH 9 was recorded. The results are shown in Table 7 and demonstrate the dependence of the delayed release of the basic core material on shell thickness. The shell thickness of the encapsulated material was modified by changing the coating time to a longer coating time, producing a thicker shell. The thickness of the aluminum oxide shell of encapsulated materials O through R progressively decreased as follows: Shell thickness: encapsulated material O > encapsulated material P > encapsulated material Q > encapsulated material R. The relative shell thickness of encapsulated materials O through R was approximately 8.5:4.5:2:1 (Table 7).

[0283] [Table 12]

[0284] Example 10. Two glass vials were each filled with 15 g of deionized water and 10 g of pH 4 buffer solution (Buffer BDH5018, VWR International), and the solutions in the vials were stirred. Unencapsulated bioactive glass (0.25 g, 38-45 micron particle size) was added to the first vial. Encapsulated Material J (0.25 g) was added to the second vial. Stirring continued in the vials, and the pH of each solution was measured over a 60-minute period using a Mettler Toledo M300 pH Meter (Mettler Toledo Corporation). The results are shown in Table 8 and indicate that the encapsulated material resulted in delayed reaction with or delayed release of the basic core material.

[0285] [Table 13]

[0286] Example 11 Two glass vials were each filled with 25 g of deionized water. Unencapsulated Portland cement (0.25 g, 24.4 micron particle size) was added to the first vial. Encapsulated material P (0.25 g) was added to the second vial. The contents were stirred, and the pH of each solution was measured over a 5-minute period using a Mettler Toledo M300 pH Meter (Mettler Toledo Corporation). The results are shown in Table 9 and indicate that the encapsulated material resulted in a delayed reaction or delayed release of the basic core material.

[0287] [Table 14]

[0288] Example 12 Two glass vials were each filled with 25 g of deionized water. Unencapsulated bioactive glass (0.25 g, 38.45 micron particle size) was added to the first vial. Encapsulated Material J (0.25 g) was added to the second vial. The contents were stirred, and the pH of each solution was measured over a 3-minute period using a Mettler Toledo M300 pH Meter (Mettler Toledo Corporation). The results are shown in Table 10 and indicate that the encapsulated material resulted in a delayed reaction with or delayed release of the basic core material.

[0289] [Table 15]

[0290] Example 13 (Comparative Example). A glass vial was filled with 25 g of deionized water and 0.25 g of unsealed FAS glass (0.25 g) was added to the vial. The contents were stirred and the pH of the solution was measured over a 3-minute period using a Mettler Toledo M300 pH Meter (Mettler Toledo Corporation). The results are reported in Table 11.

[0291] [Table 16]

[0292] Example 14. Dental compositions containing bioactive glass encapsulated materials Dental Compositions 1 to 6 (DC-1 to DC-6) were prepared using a paste selected from Pastes B1 to B6 as a first part of the composition and Paste A as a second part of the composition.

[0293] The composition of Paste A is reported in Table 12 (each component is reported as a weight percent). Paste A was prepared in bulk. BHT and CPQ were added to a mixing cup containing HEMA. The filled cup was placed in a FlackTek SPEEDMIXER (FlackTek Incorporated, Landrum, SC), and the contents were mixed at 2500 rpm until a homogeneous mixture was obtained. Next, a mixture of VBP in water was added to the cup, and mixing continued. The CGP, Zr / Si nanocluster filler, and ytterbium fluoride components were combined to form a homogeneous mixture, and this mixture was then added to the cup. Mixing continued until the mixture was homogeneous. The resulting paste was stored at 4°C when not in use.

[0294] The compositions of Pastes B1-B4 and Paste BA are reported in Table 13 (each component is reported in weight percent). Pastes B1-B4 and Paste BA were prepared by adding EDMAB to a flask containing HEMA and mixing. In a separate beaker, FAS glass, encapsulated material H (from Table 1), and fumed silica were mixed to form a homogeneous mixture. The EDMAB\HEMA mixture was then added to the mixture in the beaker, and the contents were stirred until homogeneous. The beaker was covered, and the pastes were used within 24 hours of preparation.

[0295] The compositions of Pastes B5 and B6 are reported in Table 14 and the pastes were prepared according to the general method described above for Pastes B1 to B4.

[0296] For Dental Composition 1, Paste B1 was the first part of the composition. Paste A and Paste B1 from DC-1 (1:1 weight ratio) were combined on a mixing plate and mixed with a spatula until homogenous (approximately 10-30 seconds of mixing). The pH of the resulting paste was immediately measured using an ORION PERPHECT ROSS pH Micro Electrode (Cat. No. 8220BNWP, Thermo Fisher Scientific Company, Waltham, PA). The pH reading was recorded 30 seconds after the probe was inserted into the paste. The recorded pH was 4.3. Teflon disk molds (3.1 mm diameter and 1.3 mm height) were immediately filled with the paste, and the paste was then cured for 20 seconds on each side of the mold using an ELIPAR S10 curing light (3M Oral Care, Maplewood, MN). The resulting molded disc was immediately removed from the mold and placed in a 2 mL plastic centrifuge tube containing 1.5 mL of GIBCO phosphate-buffered saline (PBS) solution (1X, pH 7.4) (Thermo Fisher Scientific). The disc was completely immersed in the PBS solution. The tube was capped and stored at room temperature.

[0297] For dental composition 2 (DC-2), paste B2 replaced paste B1 as the first part of the composition. DC-2 was used to prepare molded discs according to the procedure described for DC-1. The pH of the paste measured immediately before filling the mold was 3.8.

[0298] For Dental Composition 3 (DC-3), Paste B3 replaced Paste B1 as the first part of the composition. Molded discs were prepared using DC-3 according to the procedure described for Dental Composition 1. The pH of the paste was measured to be 3.7 immediately before filling the mold.

[0299] For dental composition 4 (DC-4), paste B4 replaced paste B1 as the first part of the composition. DC-4 was used to prepare molded discs according to the procedure described for DC-1. The pH of the paste measured immediately before filling the mold was 3.6.

[0300] For dental composition 5 (DC-5), paste B5 replaced paste B1 as the first part of the composition. DC-5 was used to prepare molded discs according to the procedure described for DC-1. The pH of the paste measured immediately before filling the mold was 4.9.

[0301] For dental composition 6 (DC-6), paste B6 replaced paste B1 as the first part of the composition. DC-6 was used to prepare molded discs according to the procedure described for DC-1. The pH of the paste measured immediately before filling the mold was 3.8.

[0302] For Comparative Dental Composition A (Comparative DC-A), Paste BA replaced Paste B1 as the first part of the composition. Paste BA did not contain any encapsulated material. Comparative DC-A was used to prepare molded discs according to the procedure described for DC-1. The pH of the paste measured immediately before filling the mold was 3.6.

[0303] For each of the immersed discs, the pH of the PBS solution was measured periodically over a 364-hour period using an ORION PERPHECT ROSS pH Micro Electrode (catalog number 8220BNWP, Thermo Fisher Scientific). The samples were gently shaken before each measurement. The pH profiles of the PBS solutions are reported in Tables 15 and 16. The pH measurement recorded at "0 hours" was taken immediately after immersion of the discs in the PBS solution.

[0304] In Table 15, the concentration (wt %) of encapsulated material H incorporated into the dental compositions decreased from DC-1 to DC-4 (i.e., the concentration of incorporated encapsulated material was DC-1 > DC-2 > ​​DC-3 > DC-4 > Comparative DC-A), with Comparative DC-A not containing encapsulated material H. In Table 16, the shell thickness of the encapsulated material in dental compositions DC-1, DC-5, and DC-6 was varied, with DC-6 containing the encapsulated material with the thickest shell and DC-5 containing the encapsulated material with the thinnest shell.

[0305] [Table 17]

[0306] [Table 18]

[0307] [Table 19]

[0308] [Table 20]

[0309] [Table 21]

[0310] Example 15. Dental composition containing encapsulated Portland cement material Dental compositions (DC-7 to DC-11) were prepared using a paste selected from Pastes B7 to B11 as a first part of the composition and Paste A as a second part of the composition.

[0311] Paste A was prepared as reported in Example 14.

[0312] The compositions of Pastes B7-B9 are reported in Table 17 (each component is reported in weight percent). Pastes B7-B9 were prepared by adding EDMAB to a flask containing HEMA and mixing. In a separate beaker, FAS glass, encapsulated material P (from Table 3), and fumed silica were mixed to form a homogeneous mixture. The EDMAB\HEMA mixture was then added to the mixture in the beaker, and the contents were stirred until homogeneous. The beaker was covered, and the pastes were used within 24 hours of preparation.

[0313] The composition of Paste B10 is reported in Table 18. Paste B10 was prepared according to the general method described above for Pastes B7 to B9, except that encapsulated material P was replaced with the encapsulated material of Example 4 (titanium dioxide encapsulated Portland cement).

[0314] The composition of Paste B11 is reported in Table 19. Paste B11 was prepared according to the general method described above for Pastes B7 to B9, except that encapsulated material P was replaced with the encapsulated material of Example 5 (silicon dioxide encapsulated Portland cement).

[0315] For Dental Composition 7 (DC-7), Paste B7 was the first part of the composition. Paste A and Paste B7 (1:1 by weight) of DC-7 were combined on a mixing plate and mixed with a spatula until homogenous (approximately 10-30 seconds of mixing). The pH of the resulting paste was immediately measured using an ORION PERPHECT ROSS pH Micro Electrode (Cat. No. 8220BNWP, Thermo Fisher Scientific Company). The pH reading was recorded 30 seconds after the probe was inserted into the paste. The recorded pH was 3.5. A Teflon disk mold (3.1 mm diameter and 1.3 mm height) was immediately filled with the paste, and the paste was then cured for 20 seconds on each side of the mold using an ELIPAR S10 curing light (3M Oral Care, Maplewood, MN). The resulting molded disc was immediately removed from the mold and placed in a 2 mL plastic centrifuge tube containing 1.5 mL of GIBCO phosphate-buffered saline (PBS) solution (1X, pH 7.4) (Thermo Fisher Scientific). The disc was completely immersed in the PBS solution. The tube was capped and stored at room temperature.

[0316] For dental composition 8 (DC-8), paste B8 replaced paste B7 as the first part of the composition. DC-8 was used to prepare molded discs according to the procedure described for DC-7. The pH of the paste was measured to be 3.5 immediately before filling the mold.

[0317] For dental composition 9 (DC-9), paste B9 replaced paste B7 as the first part of the composition. DC-9 was used to prepare molded discs according to the procedure described for DC-7. The pH of the paste measured immediately before filling the mold was 3.6.

[0318] For dental composition 10 (DC-10), paste B10 replaced paste B7 as the first part of the composition. DC-10 was used to prepare molded discs according to the procedure described for DC-7. The pH of the paste measured immediately before filling the mold was 3.3.

[0319] For dental composition 11 (DC-11), paste B11 replaced paste B7 as the first part of the composition. DC-11 was used to prepare molded discs according to the procedure described for DC-7. The pH of the paste measured immediately before filling the mold was 3.3.

[0320] For each of the immersed discs, the pH of the PBS solution was measured periodically over a period of 333 or 646 hours using an ORION PERPHECT ROSS pH Micro Electrode (catalog number 8220BNWP, Thermo Fisher Scientific). The samples were gently shaken before each measurement. The pH profiles of the PBS solutions are reported in Tables 20 and 21. The pH measurement recorded at "0 hours" was taken immediately after immersion of the discs in the PBS solution.

[0321] In Table 20, dental compositions having various concentrations of incorporated encapsulated material P were evaluated. DC-7 contained approximately twice the amount of encapsulated material P (by weight %) as DC-9. Comparative DC-A did not contain encapsulated material P.

[0322] [Table 22]

[0323] [Table 23]

[0324] [Table 24]

[0325] [Table 25]

[0326] [Table 26]

[0327] Example 16. Dental composition containing an encapsulated material of tricalcium silicate Dental composition DC-12 was used to prepare molded discs according to the procedure reported in Example 14. DC-12 was prepared using Paste B12 (composition in Table 22) as the first part of the composition and Paste A as the second part of the composition. The pH of the paste, stirred with a spatula just before filling the mold, was measured to be 3.7. The pH of the PBS solution surrounding the disc was measured periodically over 790 hours according to the procedure described in Example 14, and the results are reported in Table 23. The pH measurement recorded at "0 time" was taken immediately after immersion of the disc in the PBS solution.

[0328] [Table 27]

[0329] [Table 28]

[0330] Example 17. Cell proliferation of dental pulp stem cells in contact with dental compositions containing encapsulated bioactive glass Molded discs (3.1 mm in diameter and 1.3 mm in height) of dental compositions 1-4 and comparative dental composition A were prepared using the general mixing and curing procedure for preparing molded discs described in Example 14. Individual discs were also prepared from a commercially available dental base / liner product (Comparative Example X) and a commercially available dental pulp cap / liner product (Comparative Example Y). The discs were individually sterilized by sequentially placing them in a 70% ethanol bath for 20 minutes and rinsing with PBS (three times), then incubated overnight at 37°C, 5% CO2, and 98% relative humidity in dental pulp stem cell (DPSC) basal medium (Lonza Group LTD., Basel, Switzerland). Human dental pulp stem cells (DPSCs, Lonza Group LTD.) were seeded at 20,000 cells / mL per well in COSTAR 48-well cell culture plates (Corning Incorporated, Corning, NY) containing DPSC basal medium. Each well was loaded with a disk, and the cells were cultured for 7 days (37°C, 5% CO2, 98% relative humidity). As a control, additional wells were seeded with human dental pulp stem cells, but no molded disks were added to any of these wells.

[0331] On day 7, the DPSC samples were evaluated for cell proliferation using absorbance measurements taken at 540 nm using a microplate reader (Tecan Group LTD., Mannedorf, Switzerland) with an MTT colorimetric assay kit (Invitrogen Corporation, Carlsbad, CA). Table 24 reports the average OD540 (n=6) for DPSC samples contacted with Dental Compositions 1-4 (containing various concentrations of encapsulated bioactive glass material), Comparative Dental Composition A (containing no encapsulated material), Comparative Examples X and Y, and the control.

[0332] [Table 29]

[0333] Example 18. Cell proliferation of dental pulp stem cells in contact with dental compositions containing encapsulated Portland cement or encapsulated tricalcium silicate Molded discs (3.1 mm diameter and 1.3 mm height) of dental compositions 8, 10, 11, 12, comparative dental composition A, comparative example X, and comparative example Y were prepared and tested for cell proliferation according to the procedure described in Example 17. Controls (wells seeded with DPSCs but no molded discs added) were also prepared as described in Example 17. Table 25 reports the average OD540 (n=4) for DPSC samples contacted with dental compositions 8, 10, 11, 12 (containing encapsulated materials having a Portland cement or tricalcium silicate core with different shell coatings), comparative dental composition A (no encapsulated material), comparative examples X and Y, and the control.

[0334] [Table 30]

[0335] Example 19. ALP activity of dental pulp stem cells contacted with dental compositions Molded discs (3.1 mm diameter and 1.3 mm height) of Dental Compositions 1-4, Comparative Dental Composition A, Comparative Example X, and Comparative Example Y were prepared using the general mixing and curing procedure for preparing molded discs described in Example 14. The discs were individually sterilized by sequentially placing them in a 70% ethanol bath for 20 minutes and rinsing with PBS (three times), then incubated overnight (at 37°C, 5% CO2, and 98% relative humidity) in dental pulp stem cell (DPSC) basal medium (Lonza Group LTD.). Human dental pulp cells (DPSCs, Lonza Group LTD.) were seeded at 20,000 cells / mL per well in COSTAR 48-well cell culture plates (Corning Incorporated, Corning, NY) containing DPSC basal medium. A disc was loaded into each well, and the cells were cultured for 7 days (at 37°C, 5% CO2, and 98% relative humidity). As a control, additional wells were seeded with human dental pulp stem cells, but no molded discs were added to any of these wells.

[0336] On day 7, DPSC cells were harvested, and cell lysates from each sample were analyzed for alkaline phosphatase (ALP) activity using a human ALP ELISA kit (BioVision Incorporated, San Francisco, CA) according to the manufacturer's instructions. Table 26 reports the mean ALP concentrations (n=2) in mU / mL for DPSC samples contacted with Dental Compositions 1-4 (containing various concentrations of encapsulated bioactive glass material), Comparative Dental Composition A (containing no encapsulated material), Comparative Examples X and Y, and the control.

[0337] [Table 31]

[0338] Example 20. ALP activity of dental pulp stem cells contacted with dental compositions Molded discs (3.1 mm diameter and 1.3 mm height) of dental compositions 8, 10, 11, 12, comparative dental composition A, comparative example X, and comparative example Y were prepared and tested for ALP activity according to the procedure described in Example 19. Controls (wells seeded with DPSCs but no molded discs added) were also prepared as described in Example 19. Table 27 reports the average ALP concentrations (n=1-3) in mU / mL for DPSC samples contacted with dental compositions 8, 10, 11, 12 (containing encapsulated material having a Portland cement or tricalcium silicate core with different shell coatings), comparative dental composition A (no encapsulated material), comparative examples X and Y, and the control.

[0339] [Table 32]

[0340] Example 21. Encapsulated materials with calcium hydroxide cores or mixed-phase calcium silicate cores Calcium hydroxide (CH) powder was obtained from Jost Chemical (St. Louis, MO, Product Number: 2242). The material was passed through a 25 micron sieve.

[0341] Mixed-phase calcium silicate (MPCS) was prepared by mixing 14.1 wt% SiO, 50.3 wt% CaCO, 34.7 wt% HO, and 0.8 wt% BYK-W9012. The BYK-W9012 wetting and dispersing additive was obtained from BYK-Chemie GmbH (Wesel, Germany). After mixing, the resulting slurry was dried at 100°C for 12 hours and then sintered at 1500°C for 2 hours. The resulting particles were crushed using a mortar and pestle to obtain a powder with an average particle size of 11.35 microns as measured by laser diffraction.

[0342] Calcium hydroxide (CH) and mixed phase calcium silicate (MPCS) were each encapsulated with aluminum oxide using the APCVD process and apparatus described in Example 2, except the reactor was heated with heating tape, and the powder amounts and flow rates are reported in Table 28.

[0343] [Table 33]

[0344] Example 22. pH buffer testing of encapsulated materials The testing described in Example 6 was performed on both unencapsulated CH and MPCS, as well as encapsulated CH and MPCS sampled from the batches described in Table 28. The pH of the buffer solution immediately prior to powder addition was 4.1 for all four samples. The results are shown in Table 29 and indicate that the encapsulated material resulted in a delayed reaction with or delayed release of the basic core material.

[0345] [Table 34]

[0346] Example 23. Portland cement core encapsulated using atomic layer deposition (ALD) Portland cement powder (5 g) was microencapsulated using the atomic layer deposition (ALD) process. A flow-through atomic layer deposition (ALD) reactor incorporating a sequential four-step process (precursor A, purge, precursor B, purge) was used to deposit an aluminum oxide coating via a self-limiting surface reaction on the target particulate material.

[0347] The sequential four-step process consisted of the following sequence: (1) precursor A (i.e., trimethylaluminum (TMA)) pulse, (2) N2 purge, (3) precursor B (i.e., ozone @ 20% pulse), and (4) N2 purge. The TMA precursor pulse time and pressure were set for 1.125 seconds at a pressure of 1 to 3 Torr inside the reactor. The ozone precursor pulse time and pressure were set for 1.000 seconds at a pressure of 1 to 4 Torr inside the reactor. The purge time ranged from 100 to 120 seconds per half cycle. The four-step sequence is referred to herein as one ALD cycle. A 5-g sample of Portland cement was processed using a total of 200 ALD cycles at a process temperature of 150 °C.

[0348] The internal sample chamber consisted of a 34 mm fritted tube closed at one end and fitted with a fitting (VCR8 fitting) at the other open end. The fitting was then attached to a precursor delivery system that allowed various gases to be added to the inside of the fritted tube and vented through the wall of the fritted tube.

[0349] The precursor delivery system was designed with a rotary union so that the fritted tube (sample chamber) rotated independently of the rest of the reactor system. The fritted tube attached to the precursor delivery system was then placed inside a temperature control sleeve or tube used to control the temperature of the particles and precursor during the deposition process.

[0350] During the deposition process, the tube containing the particles was rotated, causing the particles to rise along the tube wall and fall freely to the bottom of the tube. During the free fall, the particles were sequentially exposed to various precursors and purge steps as gases flowed into the open end of the fritted tube and exited through the wall. A vibration motor was also attached to the reactor assembly to provide additional agitation to maintain free-flowing particles during the deposition process. All gases were heated to 80°C to prevent the gas flow from cooling the sample.

[0351] To ensure that a sufficient amount of precursor was delivered to the reactor, the precursor charge was monitored using a residual gas analyzer (obtained under the trade designation "SRS RESIDUAL GAS ANALYZER" from Stanford Research Systems, Inc., Sunnyvale, CA).

[0352] The resulting encapsulated powder was measured for pH change using the procedure described in Example 6. The results are reported in Table 30.

[0353] [Table 35]

[0354] Example 24. Adhesion measurements of Dental Composition 8 (DC-8) and Comparative Dental Composition A (DC-A) applied to dentin surfaces. Ten bovine incisors were individually embedded in resin pucks (one tooth per puck) measuring 25 mm in diameter and 10–20 mm in height. Each resulting puck was scraped with 120-grit sandpaper to expose the dentin layer of the tooth, then polished with 320-grit sandpaper. All experiments were performed indoors at a constant temperature of 75°C, 50% humidity, and 450 nm filtered light. Each tooth surface was blotted to remove excess water, and a 5 mm diameter circle of exposed dentin was outlined using 3M 201+ masking tape (3M Company, Maplewood, MN) as a mask. DC-8 (prepared as described in Example 15) was applied to cover the exposed dentin area, wiped evenly with a spatula, and then cured for 20 seconds using an ELIPAR S10 LED curing light (3M Company). SCOTCHBOND Universal Adhesive (3M Company) was then applied to the cured surface using a disposable applicator for 20 seconds. The area was allowed to dry with a gentle airflow for 5 seconds and then light-cured with an ELIPAR S10 LED curing light for 10 seconds. A Teflon® mask with a 5 mm diameter hole, 2-5 mm deep and lined with gelatin, was aligned with the tape mask and secured in place with a metal clip. The hole was then filled with FILTEK Z250 dental composite resin (3M Company) and light-cured with an ELIPAR S10 LED curing light for 20 seconds to create the peg. The tooth specimens were then placed in a chamber (37°C, 95% humidity) for 0.5 hours. The metal clips were removed from the tooth specimens, and each specimen was immersed in deionized water at 37°C for 24 hours. After 24 hours, the gelatin was dissolved and the Teflon® mask was removed. The resin pack was secured in a circular grip fixture on the upper arm of an Instron 5944 (Instron Corporation, Norwood, MA). The lower fixture had a wire loop approximately 90 mm long. The wire was looped over a FILTEK Z250 peg and secured flush with the tooth / resin surface. Tension was then applied until failure (i.e., the assembly broke from the tooth surface or the tooth broke) to measure the adhesion of the hardened dental composition DC-8 to the tooth.

[0355] This procedure was repeated using Comparative Dental Composition A (DC-A prepared as in Example 14) instead of DC-8. The average (n=10) adhesion values ​​(MPa) measured for dental compositions DC-A and DC-8 are reported in Table 31.

[0356] [Table 36]

[0357] Example 25. Dental composition (DC-13) Dental Composition B (DC-B) was prepared by adding 120 mg of IRGACURE 819 (a photoinitiator obtained from BASF Corporation, Wyandotte, MI) to 40 g of SR 603 (a polyethylene glycol (400) dimethacrylate obtained from Sartomer Americas, Exton, PA). The mixture was mixed in a FlackTek DAC 150 FVZ speed mixer at 3000 rpm for 1 minute, a total of three times. Teflon® disk molds (3.1 mm diameter, 1.3 mm height) were immediately filled with DC-B and then cured for 20 seconds on each side of the mold using an Elipar™ DeepCure-S LED curing light (3M Company). The resulting molded disks were immediately removed from the molds and placed in 2 mL plastic centrifuge tubes containing 1.5 mL of GIBCO phosphate-buffered saline (PBS) solution (1x, pH 7.4) (Thermo Fisher Scientific). The discs were completely immersed in the PBS solution. The tubes were capped and stored at room temperature. The discs from Dental Composition B served as a control (no encapsulated material).

[0358] Dental Composition 13 (DC-13) was prepared by combining 3 g of encapsulated material P with 1 g of DC-B. This mixture was mixed three times for 1 minute at 3000 rpm. The viscosity of DC-13 was 31066 cP (at 23°C and a shear rate of 100 s). -1, using a Type F T-bar spindle).

[0359] Molded discs were prepared using DC-13 according to the procedure described for DC-B.

[0360] Dental Composition C (DC-C) was prepared by combining 3 g of unencapsulated Portland cement with 1 g of DC-B. This mixture was mixed three times for 1 minute at 3000 rpm. Molded discs were prepared with DC-C according to the procedure described for DC-B. The disc from Dental Composition C served as a control (containing unencapsulated Portland cement).

[0361] For each of the immersed discs, the pH of the PBS solution was measured periodically over a period of 90.4 hours using an ORION PERPHECT ROSS pH Micro Electrode (Cat. No. 8220BNWP, Thermo Fisher). Each sample was gently shaken before each measurement. The pH profile of the PBS solution is reported in Table 32. The pH measurement recorded at "0 hours" was taken immediately after immersion of the discs in the PBS solution.

[0362] [Table 37]

[0363] Example 26. Encapsulated Material V (PC Core and AO Shell) Portland cement (PC) was encapsulated with an aluminum oxide (AO)-based material using atmospheric pressure chemical vapor deposition (APCVD). Portland cement powder was coated by reacting trimethylaluminum (obtained from Strem Chemicals and dispensed from a stainless steel bubbler) with water vapor in a fluidized-bed reactor. The reactor was a glass-fritted funnel tube (12 cm diameter, 30 cm height). The reactor had an inlet tube extending from below the frit routed parallel to the body of the reactor and an extended top area above the frit to allow for the desired reactor height and attachment for the precursor injector tube and exhaust outlet. Temperature was controlled at 180 °C using an oil bath. Nitrogen carrier gas was used in a standard bubbler configuration for liquid precursors. The bubbler was maintained at ambient temperature of approximately 2 °C. The flow rate through the trimethylaluminum (TMA) bubbler was 1000 cm. 3 The flow rate through the water bubbler was 2500 cm 3 / min. The total coating time was 214 minutes. The amount of Portland cement added to the reactor was 370 g, and the particle size of the Portland cement powder was 20 microns.

[0364] Encapsulated material V was calculated to have a shell thickness of 50 nm. The weight percent (wt%) calculation resulted in 98.7 wt% core material and 1.3 wt% shell material.

[0365] Example 27. Dental composition (DC-14) The composition of Paste A1 is reported in Table 33 (each component is reported as a weight percent). Paste A1 was prepared in bulk. BHT, CPQ, and LUPEROX A75 benzoyl peroxide (Sigma Aldrich Corporation) were added to a mixing cup containing HEMA. The filled cup was placed in a FlackTek SPEEDMIXER, and the contents were mixed at 2500 rpm until a homogeneous mixture was obtained. Next, a mixture of VBP in water was added to the cup, and mixing continued. The CGP, Zr / Si nanocluster filler, and ytterbium fluoride components were combined to form a homogeneous mixture, and this mixture was then added to the cup. Mixing continued until the mixture was homogeneous. The resulting paste was stored at 4°C when not in use.

[0366] The composition of Paste B13 is reported in Table 34 (each component is reported as a weight percent). Paste B13 was prepared by adding EDMAB and 2-(4-dimethylamino)phenyl)ethanol (DMAPE) to a flask containing HEMA and mixing. In a separate beaker, FAS glass, encapsulated material V, and fumed silica were mixed to form a homogeneous mixture. The EDMAB\DMAPE\HEMA mixture was then added to the mixture in the beaker, and the contents were stirred until homogeneous. The beaker was covered, and the paste was used within 24 hours of preparation.

[0367] Paste A1 (0.25 g) and Paste B13 (0.25 g) were combined on a mixing plate and mixed with a spatula until homogeneous (mixing for 20 seconds). The mixture was piled with a spatula into a mound approximately 1.5 cm in diameter and 3 mm high at its highest point. 30 seconds after the start of mixing, the composition was placed in a heating oven (37°C) and checked for hardening by pricking with the tip of a spatula every 20 to 30 seconds. After 75 seconds in the oven, the composition had hardened.

[0368] [Table 38]

[0369] [Table 39]

[0370] Example 28. Encapsulated Material 1 (PC Core and AO Shell) Portland cement (PC) was encapsulated with an aluminum oxide (AO)-based material using atmospheric pressure chemical vapor deposition (APCVD). Portland cement powder was coated by reacting trimethylaluminum (obtained from Strem Chemicals and dispensed from a stainless steel bubbler) with water vapor in a fluidized-bed reactor. The reactor was a glass-fritted funnel tube (12 cm diameter, 30 cm height). The reactor had an inlet tube extending from below the frit routed parallel to the body of the reactor and an extended top area above the frit to allow for the desired reactor height and attachment for the precursor injector tube and exhaust outlet. Temperature was controlled at 180 °C using an oil bath. Nitrogen carrier gas was used in a standard bubbler configuration for liquid precursors. The bubbler was maintained at an ambient temperature of approximately 22 °C. The flow rate through the trimethylaluminum (TMA) bubbler was 1773 cm. 3 The flow rate through the water bubbler was 5307 cm 3 / min. The total coating time was 120 min. The amount of Portland cement added to the reactor was 800 g, and the particle size of the Portland cement powder was 20 microns.

[0371] Before adding to the reactor, fine and coarse particles were removed from the Portland cement sample using an AVEKA CCE Centrifugal Air Classifier Model 100. In a first pass, a total of approximately 24% of the coarse fraction of the initial sample was removed, and then in a second pass, approximately 25% of the fine fraction was removed from the remaining sample. The resulting Portland cement powder had an average particle size of 20 microns as measured using a Coulter Counter Multisizer 3 (Beckman Coulter Company).

[0372] Encapsulated Material 1 was calculated to have a shell thickness of 46 nm. The weight percent (wt%) calculation resulted in 98.8 wt% core material and 1.2 wt% shell material.

[0373] Example 29. Encapsulated Material 2 (PC Core and AO Shell) Portland cement (PC) was encapsulated with an aluminum oxide (AO)-based material using atmospheric pressure chemical vapor deposition (APCVD). Portland cement powder was coated by reacting trimethylaluminum (obtained from Strem Chemicals and dispensed from a stainless steel bubbler) with water vapor in a fluidized-bed reactor. The reactor was a glass-fritted funnel tube (12 cm diameter, 30 cm height). The reactor had an inlet tube extending from below the frit routed parallel to the body of the reactor and an extended top area above the frit to allow for the desired reactor height and attachment for the precursor injector tube and exhaust outlet. Temperature was controlled at 180 °C using an oil bath. Nitrogen carrier gas was used in a standard bubbler configuration for liquid precursors. The bubbler was maintained at an ambient temperature of approximately 22 °C. The flow rate through the trimethylaluminum (TMA) bubbler was 2670 cm. 3 The flow rate through the water bubbler was 8032 cm 3 / min. The total coating time was 190 minutes. The amount of Portland cement added to the reactor was 1500 g, and the particle size of the Portland cement powder was 20 microns.

[0374] Before adding to the reactor, fine and coarse particles were removed from the Portland cement sample using an AVEKA CCE Centrifugal Air Classifier Model 100. In a first pass, a total of approximately 24% of the coarse fraction of the initial sample was removed, and then in a second pass, approximately 25% of the fine fraction was removed from the remaining sample. The resulting Portland cement powder had an average particle size of 20 microns as measured using a Coulter Counter Multisizer 3 (Beckman Coulter Company).

[0375] Encapsulated Material 2 was calculated to have a shell thickness of 58 nm. The weight percent (wt%) calculation resulted in 98.5 wt% core material and 1.5 wt% shell material.

[0376] Example 30. The composition of Paste AA-1 is reported in Table 35 (each component is reported as a weight percent). Paste AA-1 was prepared in bulk. BisGMA and TEGDMA were combined (1:1 weight ratio) and mixed until homogeneous. In a mixing cup, the BisGMA / TEGDMA mixture was mixed with BPO and CPQ. The filled cup was placed in a FlackTek SPEEDMIXER (FlackTek Incorporated, Landrum, SC) and the contents were mixed at 2400 rpm until a homogeneous mixture was obtained. Fumed silica (AEROSIL R972) was added to the cup. The cup was placed in the FlackTek SPEEDMIXER and the contents were mixed at 2400 rpm until a homogeneous mixture of Paste AA-1 was obtained. The viscosity of Paste AA-1 was 1130 ± 9 cP (at 23°C and a shear rate of 100 s -1 ) was.

[0377] The composition of Paste BB-1 is reported in Table 36 (each component is reported as a weight percent). BisGMA and TEGDMA were combined (1:1 weight ratio) and mixed until homogeneous. In a mixing cup, the BisGMA / TEGDMA mixture was mixed with DMAPE and BHT. The filled cup was placed in a FlackTek SPEEDMIXER and the contents were mixed at 2400 rpm until a homogeneous mixture was obtained. Fumed silica (AEROSIL R972) was added to the cup. The cup was placed in a FlackTek SPEEDMIXER and the contents were mixed at 2400 rpm until a homogeneous mixture was obtained. Encapsulated Material 1 was added to the cup. The cup was placed in a FlackTek SPEEDMIXER and the contents were mixed at 2400 rpm until a homogeneous mixture of Paste BB-1 was obtained. The viscosity of Paste BB-1 was 1450 ± 12 cP (at 23°C and a shear rate of 100 s -1 ) was.

[0378] [Table 40]

[0379] [Table 41]

[0380] Example 31. The composition of Paste BB-2 is reported in Table 37 (each component is reported as a weight percent). BisGMA and TEGDMA were combined (1:1 weight ratio) and mixed until homogeneous. In a mixing cup, the BisGMA / TEGDMA mixture was mixed with DMAPE and BHT. The filled cup was placed in a FlackTek SPEEDMIXER and the contents were mixed at 2400 rpm until a homogeneous mixture was obtained. Fumed silica (AEROSIL R972) was added to the cup. The cup was placed in a FlackTek SPEEDMIXER and the contents were mixed at 2400 rpm until a homogeneous mixture was obtained. Encapsulated Material 2 was added to the cup. The cup was placed in a FlackTek SPEEDMIXER and the contents were mixed at 2400 rpm until a homogeneous mixture of Paste BB-1 was obtained.

[0381] Pastes AA-1 and BB-2 were equilibrated in a chamber at 37° C. and then mixed on a mixing plate in an approximately 1:1 volume ratio. The resulting (e.g., sealant) composition cured after 2 minutes.

[0382] When AA-1 and BB-2 were mixed in a 1:1 volume ratio on a mixing board at room temperature conditions (approximately 23° C.) without the use of a curing light (dark cure), the sample did not cure after 2 minutes.

[0383] Alternatively, pastes AA-1 and BB-2 may be mixed in Elipar at room temperature (approximately 23°C). TM The resulting (e.g., sealant) composition was cured after 10 seconds of exposure to light using a DeepCure-S LED curing light (3M Oral Care, Maplewood, MN) in a 1:1 volume ratio on a mixing board.

[0384] [Table 42]

[0385] Example 32. The composition of Paste AA-2 is reported in Table 38 (each component is reported as a weight percent). Paste AA-2 was prepared in bulk. BisGMA and TEGDMA were combined (1:1 weight ratio) and mixed until homogeneous. In a mixing cup, the BisGMA / TEGDMA mixture was mixed with BPO and CPQ. The filled cup was placed in a FlackTek SPEEDMIXER, and the contents were mixed at 2400 rpm until a homogeneous mixture was obtained. Fumed silica (AEROSIL R972) was added to the cup. The cup was placed in a FlackTek SPEEDMIXER, and the contents were mixed at 2400 rpm until a homogeneous mixture of Paste AA-2 was obtained.

[0386] The composition of Paste BB-3 is reported in Table 39 (each component is reported as a weight percent). BisGMA and TEGDMA were combined (1:1 weight ratio) and mixed until homogeneous. In a mixing cup, the BisGMA / TEGDMA mixture was mixed with DMAPE and BHT. The filled cup was placed in a FlackTek SPEEDMIXER and the contents were mixed at 2400 rpm until a homogeneous mixture was obtained. Fumed silica (AEROSIL R972) was added to the cup. The cup was placed in a FlackTek SPEEDMIXER and the contents were mixed at 2400 rpm until a homogeneous mixture was obtained. Encapsulated Material 2 was added to the cup. The cup was placed in a FlackTek SPEEDMIXER and the contents were mixed at 2400 rpm until a homogeneous mixture of Paste BB-2 was obtained.

[0387] Pastes AA-2 and BB-3 were mixed in a 1:1 volume ratio on a mixing board at room temperature (approximately 23° C.) without the use of a curing light (dark cure). The resulting sealant composition cured within 1 minute.

[0388] Alternatively, pastes AA-2 and BB-3 were mixed in Elipar at room temperature (approximately 23°C). TM The sealant compositions were mixed at a 1:1 volume ratio on a mixing board using a DeepCure-S LED curing light (3M Oral Care) and cured immediately. The resulting sealant compositions cured after 10 seconds of exposure to light.

[0389] [Table 43]

[0390] [Table 44]

[0391] Example 33. A two-chamber syringe device equipped with a dispensing nozzle and static mixer as shown in Figures 1 to 4 was used. The dimensions of the syringe device were: cartridge length = 73.8 mm, cartridge outer diameter = 8.4 mm, volume of each chamber = 1 mL, total volume of the dispensing nozzle = 0.03 mL, diameter of the dispensing nozzle outlet orifice = 0.85 mm, nozzle tip length = 9 mm, and nozzle tip internal angle = 120°. The static mixer shown in Figure 4 was inserted into the cannula portion of the dispensing nozzle. The total length of the series of mixing paddles was 15 mm. Each of the two chambers had an approximately D-shaped cross section, and the D shapes were oriented mirror-image to each other.

[0392] One chamber of the syringe was partially filled (2 / 3 by volume) with Paste AA-2. The second chamber was partially filled (2 / 3 by volume) with Paste BB-3. By depressing the plunger, the pre-filled syringe dispensed a 1:1 volume ratio of Paste AA-2 and Paste BB-3 into the dispensing nozzle. A typodont model of the upper dental arch in a human mouth was used, with deep fissures on each tooth. A thin coating of the sealant composition was applied to the surfaces of 10 teeth of the model using the syringe device. Upon application, the sealant composition was observed to penetrate into the fissures. The total time to apply the sealant composition to the 10 teeth was approximately 45 seconds. The sealant composition hardened approximately 45 seconds after application to the teeth.

[0393] Example 34. The two-chamber syringe apparatus described in Example 6 was used. One chamber of the syringe was partially filled with Paste AA-1 (2 / 3 by volume). The second chamber was partially filled with Paste BB-1 (2 / 3 by volume). By depressing the plunger, the filled syringe dispensed a 1:1 volume ratio of Paste AA-1 and Paste BB-1 into the dispensing nozzle. Using the syringe apparatus, a Teflon® disk mold (3.1 mm diameter, 1.3 mm height) was filled with the paste. The paste was then cured using an ELIPAR S10 curing light (3M Oral Care) on each side of the mold for 20 seconds. The resulting molded disk was immediately removed from the mold and placed in a 2 mL plastic centrifuge tube containing 0.5 mL of a buffer solution prepared by mixing 15 g of deionized water and 10 g of pH 4 buffer solution (Buffer BDH5018, VWR International). The disk was completely immersed in the buffer solution. The tubes were capped and stored at room temperature.

[0394] The pH of the buffer solution was measured using an ORION PERPHECT ROSS pH Micro Electrode (Cat. No. 8220BNWP, Thermo Fisher Scientific Company, Waltham, PA). The sample was gently shaken before each measurement. pH measurements were taken immediately after immersion of the disk in the buffer solution ("0 hours" in the table), and after 15 and 39 hours of immersion.

[0395] Comparative molded discs were prepared and tested according to the described procedure (Table 40), with the only change being that paste BB-1 was replaced with paste BB-C1, which did not contain encapsulated material 1. The pH profile is reported in Table 41.

[0396] [Table 45]

[0397] Example 35 (comparative example). The same procedures and tests were then carried out as described in Example 6, except that Encapsulated Material 1 in Paste BB-1 was replaced with an equal amount of unencapsulated Portland cement (wt%=10%), with the only change being that Paste BB-1 did not contain Encapsulated Material 2. The pH profile is reported in Table 6.

[0398] [Table 46]

[0399] Example 36. The composition of Paste BB-4 is reported in Table 42 (each component is reported as a weight percent). BisGMA and TEGDMA can be mixed (1:1 weight ratio) by stirring until homogeneous. In a mixing cup, the BisGMA / TEGDMA mixture is mixed with the DMAPE and BHT. The filled cup is placed in a FlackTek SPEEDMIXER and the contents are mixed at approximately 2400 rpm until a homogeneous mixture is obtained. Fumed silica (AEROSIL R972) is added to the cup. The cup is placed in a FlackTeK SPEEDMIXER and the contents are mixed at approximately 2400 rpm until a homogeneous mixture is obtained. Encapsulated Material 1 is added to the cup. The cup is placed in a FlackTeK SPEEDMIXER and the contents are mixed at approximately 2400 rpm until a homogeneous mixture of Paste BB-4 is obtained.

[0400] Pastes AA-1 and BB-4 are mixed on a mixing board in an approximately 1:1 volume ratio to provide the resulting sealant composition.

[0401] Example 37. The composition of Paste BB-5 is reported in Table 42 (each component is reported as a weight percent). BisGMA and TEGDMA can be mixed (1:1 weight ratio) by stirring until homogeneous. In a mixing cup, the BisGMA / TEGDMA mixture is mixed with the DMAPE and BHT. The filled cup is placed in a FlackTek SPEEDMIXER and the contents are mixed at approximately 2400 rpm until a homogeneous mixture is obtained. Fumed silica (AEROSIL R972) is added to the cup. The cup is placed in a FlackTeK SPEEDMIXER and the contents are mixed at approximately 2400 rpm until a homogeneous mixture is obtained. Encapsulated Material 1 is added to the cup. The cup is placed in a FlackTeK SPEEDMIXER and the contents are mixed at approximately 2400 rpm until a homogeneous mixture of Paste BB-5 is obtained.

[0402] Pastes AA-1 and BB-5 are mixed on a mixing board in an approximately 1:1 volume ratio to provide the resulting sealant composition.

[0403] Example 38. The composition of Paste BB-6 is reported in Table 42 (each component is reported as a weight percent). BisGMA and TEGDMA can be mixed (1:1 weight ratio) by stirring until homogeneous. In a mixing cup, the BisGMA / TEGDMA mixture is mixed with the DMAPE and BHT. The filled cup is placed in a FlackTek SPEEDMIXER and the contents are mixed at approximately 2400 rpm until a homogeneous mixture is obtained. Fumed silica (AEROSIL R972) is added to the cup. The cup is placed in a FlackTeK SPEEDMIXER and the contents are mixed at approximately 2400 rpm until a homogeneous mixture is obtained. Encapsulated Material 1 is added to the cup. The cup is placed in a FlackTeK SPEEDMIXER and the contents are mixed at approximately 2400 rpm until a homogeneous mixture of Paste BB-6 is obtained.

[0404] Pastes AA-1 and BB-6 are mixed on a mixing board in an approximately 1:1 volume ratio to provide the resulting sealant composition.

[0405] Example 39. The composition of Paste BB-7 is reported in Table 42 (each component is reported as a weight percent). BisGMA and TEGDMA can be mixed (1:1 weight ratio) by stirring until homogeneous. In a mixing cup, the BisGMA / TEGDMA mixture is mixed with the DMAPE and BHT. The filled cup is placed in a FlackTek SPEEDMIXER and the contents are mixed at approximately 2400 rpm until a homogeneous mixture is obtained. Fumed silica (AEROSIL R972) is added to the cup. The cup is placed in a FlackTeK SPEEDMIXER and the contents are mixed at approximately 2400 rpm until a homogeneous mixture is obtained. Encapsulated Material 1 is added to the cup. The cup is placed in a FlackTeK SPEEDMIXER and the contents are mixed at approximately 2400 rpm until a homogeneous mixture of Paste BB-7 is obtained.

[0406] Pastes AA-1 and BB-7 are mixed on a mixing board in an approximately 1:1 volume ratio to provide the resulting sealant composition.

[0407] Example 40. The composition of Paste BB-8 is reported in Table 42 (each component is reported as a weight percent). BisGMA and TEGDMA can be mixed (1:1 weight ratio) by stirring until homogeneous. In a mixing cup, the BisGMA / TEGDMA mixture is mixed with the DMAPE and BHT. The filled cup is placed in a FlackTek SPEEDMIXER and the contents are mixed at approximately 2400 rpm until a homogeneous mixture is obtained. Fumed silica (AEROSIL R972) is added to the cup. The cup is placed in a FlackTeK SPEEDMIXER and the contents are mixed at approximately 2400 rpm until a homogeneous mixture is obtained. Encapsulated Material 1 is added to the cup. The cup is placed in a FlackTeK SPEEDMIXER and the contents are mixed at approximately 2400 rpm until a homogeneous mixture of Paste BB-8 is obtained.

[0408] Pastes AA-1 and BB-8 are mixed on a mixing board in an approximately 1:1 volume ratio to provide the resulting sealant composition.

[0409] Example 41. The composition of Paste BB-9 is reported in Table 42 (each component is reported as a weight percent). BisGMA and TEGDMA can be mixed (1:1 weight ratio) by stirring until homogeneous. In a mixing cup, the BisGMA / TEGDMA mixture is mixed with the DMAPE and BHT. The filled cup is placed in a FlackTek SPEEDMIXER and the contents are mixed at approximately 2400 rpm until a homogeneous mixture is obtained. Fumed silica (AEROSIL R972) is added to the cup. The cup is placed in a FlackTeK SPEEDMIXER and the contents are mixed at approximately 2400 rpm until a homogeneous mixture is obtained. Encapsulated Material 1 is added to the cup. The cup is placed in a FlackTeK SPEEDMIXER and the contents are mixed at approximately 2400 rpm until a homogeneous mixture of Paste BB-9 is obtained.

[0410] Pastes AA-1 and BB-9 are mixed on a mixing board in an approximately 1:1 volume ratio to provide the resulting sealant composition.

[0411] [Table 47]

[0412] Example 42. Resin A can be prepared by mixing the ingredients in Table 43 at 45°C until all ingredients are homogeneously mixed. Resin A is mixed with S\T nanozirconia nanoparticles, S / T 20 nm silica nanoparticles, ST silica / zirconia nanoclusters, and the amounts (wt%) of Encapsulated Material 1 shown in Table 44 to form homogeneous dental compositions with various amounts of Encapsulated Material 1 (16.8 to 67.2 wt%). The dental compositions are shown in Table 44 as Example 42-1, Example 42-2, Example 42-3, and Example 42-4.

[0413] [Table 48]

[0414] [Table 49]

Claims

1. 1. A two-part hardenable dental composition comprising: a first part comprising a composition including a liquid material and an encapsulated material, the encapsulated material including a basic core material and an inorganic shell material including a metal oxide surrounding the core; a second portion comprising a composition comprising a liquid material; The first portion composition has a first viscosity, the second portion composition has a second viscosity, and the difference between the first viscosity and the second viscosity is measured using a Brookfield viscometer and a Type A T-bar spindle at 23° C. at a shear rate of 100 s －１ is no more than 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20, 15, or 10% of the higher viscosity composition when measured at the first part or the second part, or a combination thereof, is curable; A two-part hardenable dental composition.

2. 1. A hardenable dental composition comprising: The present invention relates to a one-part composition comprising a liquid material and an encapsulated material, the encapsulated material comprising a basic core material and an inorganic shell material comprising a metal oxide surrounding the core, the one-part composition being viscous at 23°C and a shear rate of 100 s using a Brookfield viscometer and a Type A T-bar spindle. －１ or has a viscosity of less than 25,000 cps when measured at Or has a viscosity of more than 40,000 cps; Hardenable dental composition.

3. a first portion including an encapsulated material, the encapsulated material including a basic core material and an inorganic shell material including a metal oxide surrounding the core; a non-aqueous second portion; and Redox curing system The two-part hardenable dental composition of claim 1 , comprising:

4. a first part comprising an encapsulated material and a reducing agent, the encapsulated material comprising a basic core material and an inorganic shell material comprising a metal oxide surrounding the core; a second part comprising an oxidizing agent selected from the group consisting of peroxide compounds, persulfate compounds, perborate compounds, and perchlorate compounds; The two-part hardenable dental composition of claim 1 , comprising:

5. The dental composition of claim 1 , wherein the shell is degradable by the second portion.

6. The dental composition of claim 1 , wherein the basic core material comprises a component having a pKa in the range of 8-14.

7. The dental composition of claim 1 , wherein the basic core material comprises a material that releases calcium ions.

8. The dental composition of claim 1 , wherein the shell is a continuous film having an average thickness of less than 500 nm.

9. The dental composition of claim 1 , wherein the basic core material comprises a dental filler comprising a neutral metal oxide.

10. The dental composition of claim 9 , further comprising a second filler that is a nanoscopic filler material, the second filler comprising zirconia, silica, or a mixture thereof.

11. The dental composition of claim 1 , wherein the liquid material of the first part or the second part comprises water, an acidic polymerizable material, or a combination thereof, and the second part comprises a first filler.

12. The composition comprises: provide delayed release of the basic core material; provide a delayed increase in basicity, or a combination thereof.

13. A dispensing device containing the two-part hardenable dental composition of claim 1.

14. The dispensing device of claim 13 , wherein the liquid material comprises a polymerizable resin.

15. The device comprises: A cartridge and a nozzle at one end of the cartridge, the nozzle having an outlet; a plunger at an opposite end of the cartridge for dispensing the curable composition from the cartridge; The dispensing device of claim 13, comprising:

16. The dispensing device of claim 15 , wherein the cartridge has two chambers.

17. The dispensing device of claim 13 , wherein the dispensing device is a syringe device.

18. The cartridge comprises first and second chambers, a dispensing nozzle at one end of the cartridge with a static mixer and an outlet, and a plunger at an opposite end of the cartridge, the plunger comprising two rods, one end of the rods sealing the first and second portions of the composition in the first and second chambers and the opposite ends of the plunger rods connected The dispensing device according to claim 15.

19. 20. The dispensing device of claim 18, wherein the outlet has a diameter of 1.5, or 1 mm or less.

20. A dispensing device containing the one-part hardenable dental composition of claim 2.

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