Basic core material encapsulated in an inorganic shell suitable for use in biological carrier materials

Abstract

To provide a hardenable dental composition comprising an encapsulated material.SOLUTION: Provided is a composition comprising (e.g. a first part comprising) an encapsulated material comprising a basic core material and an inorganic shell material comprising a metal oxide surrounding the core; and (e.g. a second part comprising) water or an acidic component. Also provided is an encapsulated material suitable for use in a biological carrier material. The material comprises a basic core material and an inorganic shell material comprising a metal oxide surrounding the core.SELECTED DRAWING: None

Description

Background Art

[0001] A variety of cements suitable for use in medical and dental applications have been described. See, for example, U.S. Patent No. 5,154,762 to Mitra et al., International Publication No. 2016 / 005822, and U.S. Patent Application No. 2008 / 0058442.

Summary of the Invention

[0002] In one embodiment, a curable dental composition is described, the curable dental composition comprising a first portion comprising an encapsulated material, the encapsulated material comprising a basic core material and an inorganic shell material comprising a metal oxide surrounding the core, the first portion, and a second portion comprising water or an acidic component.

[0003] In typical embodiments, when the first and second portions are combined, the composition initially has an acidic or neutral pH. The shell is decomposable by water or the acidic component of the second portion. The basic core material releases -OH upon decomposition of the shell, thereby raising the pH.

[0004] In some embodiments, the basic core material is curable, 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 nanoscale particulate filler. In some embodiments, the first and / or second portions comprise a polymerizable material.

[0005] In another embodiment, a composition is described, the composition comprising an encapsulated material comprising a basic core material and an inorganic shell material comprising a metal oxide surrounding the core, and water or an acidic component.

[0006] In another embodiment, an encapsulated material suitable for use in a biocompatible carrier material includes a basic core material and an inorganic shell material including a metal oxide surrounding the core. Curable (e.g., dental) compositions including the encapsulated material are also described. In some embodiments, the curable composition further includes a second filler and / or a polymerizable material as described herein. In some embodiments, the curable or cured composition contacts water or an acidic component (e.g., a biological fluid) during use.

[0007] The curable or hardened (e.g., cured) compositions described herein Various methods of use are also described, including preparing and applying the composition to a tooth or bone structure. In some embodiments, the composition includes a polymerizable material and the method further includes curing the composition by exposing it to a radiation source. The curable or hardened (e.g., cured) composition can provide various technical effects, such as delayed release of the basic core material, increased delay of basicity, promoting remineralization of the tooth or bone structure, and increasing the average ALP activity of dental pulp cells. In some embodiments, the composition is a dental adhesive or cement used to bond a dental article to a tooth structure. In other embodiments, the composition is a dental restorative.

BEST MODE FOR CARRYING OUT THE INVENTION

[0008] Described herein is an encapsulated material. The encapsulated material is suitable for use in a biocompatible carrier material, such as a curable dental composition. The encapsulated material includes a chemically basic core material and an inorganic shell material surrounding the core. The shell material and the thickness of the shell can be selected to enable control and / or delayed release or reaction of the basic core material. In some embodiments, the release of the basic core material is utilized to increase basicity after a long period of time.

[0009] The encapsulated filler contains a basic core material. The basic core material, as well as the material (e.g., compound) in which the core is formed, are generally solid at 25 °C.

[0010] The basic core can be a single particle or a plurality of 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 do not include aggregation and / or agglomeration.

[0011] In some embodiments, the basic core may include a plurality of aggregated particles. "Aggregation" or "aggregating" refers to a strong association between primary particles. For example, the primary particles can be chemically bonded to each other. Decomposing an aggregate into smaller particles (e.g., primary particles) is typically not achieved during the preparation of the core material and its encapsulation such that the aggregated core particles remain as aggregates. Similarly, the term "non-aggregated" refers to a primary particle that does not include a strong association with other primary particles.

[0012] In other embodiments, the basic core may include a plurality of agglomerated particles. As used herein, the term "agglomeration" or "agglomerating" refers to a weak association of primary particles. For example, the primary particles may be held together by charge or polarity. Decomposing an aggregate into smaller particles (e.g., primary particles) can occur during the preparation of the core material and its encapsulation. Similarly, the term "non-agglomerated" refers to a primary particle that does not include a strong association with other primary particles.

[0013] The average (e.g., primary, aggregated, or agglomerated) particle size of the core is typically at least 0.2, 0.5, 1, 2, 3, 4, or 5 micrometers, typically 1 mm or less, 750 micrometers or less, or 500 micrometers or less when measured using, for example, a sedimentation analyzer. In some embodiments, such as in the case of curable dental compositions, the basic core material typically has an average (e.g., primary, aggregated, or agglomerated) particle size of 250, 200, 150, 100, or 50 micrometers or less. Since the shell is typically thin, the encapsulated material also typically falls within the average particle size ranges described above.

[0014] The core material is basic. Chemically basic materials are those that donate electrons, accept protons, and typically provide hydroxyl ions in an aqueous solution.

[0015] The core of the encapsulated material is considered basic if it has or exhibits one or more of the following properties: that they contain a sufficient amount of high pKa components, that they result in a basic pH when added to deionized water (according to the test methods further described in the examples), or that they result in a basic pH when added to an acidic buffer (according to the test methods further described in the examples).

[0016] Basic materials function to react with acids and acidic buffers to cause an increase in pH. The change in pH and the rate of pH change depend on the strength of the basic component, the chemical and physical form of the basic component therein, and the amount of the basic component in the core material.

[0017] In some embodiments, the core of the encapsulated material is strongly basic. The strongly basic material typically comprises and is prepared from a sufficient amount of a strongly basic material (e.g., a 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, and 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 at least 1, 2, or 3 moles of a strongly basic core compound (e.g., CaO) per mole of silica, on a cation molar basis. Similarly, strongly basic aluminates typically contain at least 1, 2, or 3 moles of a strongly basic core compound (e.g., CaO) per mole of alumina, on a cation molar basis.

[0018] In some embodiments, the strongly basic material can be a heterogeneous physical mixture of at least one strongly basic compound and a weakly basic or neutral material. For example, the strongly basic material may 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. One gram of a mixture of 96 wt% silica and 4 wt% sodium hydroxide in one liter of water on a weight percent basis will 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 shell decomposition. Thus, in this embodiment, the basic core material may contain a small amount (e.g., at least 1, 2, or 3 wt% of the strongly basic material) to provide a delayed pH of at least 8.5 or 9 in deionized water (according to the test method 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 the strongly basic material can be at least 5, 6, 7, 8, 9, or 10 wt% of the entire encapsulated material.

[0019] In other embodiments, the core of the encapsulated material is a multi-component crystalline compound containing at least one strongly basic material (e.g., a compound) and other components (such as alkaline earth silicate) and prepared therefrom. In still 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., a compound). The strongly basic material (e.g., a compound) can be distributed homogeneously or heterogeneously within the glass structure. When the core of the encapsulated material is a molten multi-component material such as glass, the concentration of the strongly basic compound (which can be determined by X-ray fluorescence (XRF) or inductively coupled plasma (ICP)) is typically in the range from at least 25, 30, 35, 40, 45, or 50 wt% to over 75 wt% based on the entire basic core material.

[0020] In some preferred embodiments, the core comprises and is prepared from CaO having a pKa of 11.6. CaO can be utilized to provide a source of calcium ions and, in combination, to effect both a delay in the rise of pH. The amount of CaO is typically at least 5, 10, 15, 20, or 25 wt% and can go up to and including more than 75 wt%. The amount of Ca is about 71% of such values.

[0021] Specific examples of strongly basic multi-component core materials containing CaO include Portland cement (reported to contain 60 - 70 wt% CaO), tricalcium silicate (containing about 75 wt% CaO), and bioactive glass such as available from 3M Advanced Material Division (containing about 25 wt% CaO and about 25 wt% Na2O).

[0022] In other embodiments, the core of the encapsulated material is weakly basic. The weakly basic material contains 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, and weakly basic salts such as NaF, calcium acetate, and hydrogen phosphate.

[0023] Alternatively, the weakly basic core material can contain or be prepared from a smaller amount of strongly basic compound. Alone, the weakly basic core material typically cannot provide a sufficient amount of hydroxyl ions to adequately raise the pH of an acidic solution. However, alone, the weakly basic core material can provide a sufficient amount of hydroxyl ions to adequately raise the pH of water. Further, the encapsulated weakly basic core material can be used in combination with an encapsulated strongly basic core material.

[0024] The encapsulated basic material is typically not a reducing agent for a redox curing system. In some preferred curable (e.g., dental or medical) materials, the preferred technical effect is to control the pH such that the composition is acidic for a sufficient time to promote adhesion and then becomes basic to promote remineralization. This change in pH is sufficiently delayed such that it occurs after curing. Encapsulation of the reducing agent would delay the redox curing reaction. Further, since the reducing agent is typically a weak base utilized at relatively low concentrations, the encapsulated reducing agent alone does not bring about the desired increase in pH.

[0025] In a preferred embodiment, 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 in a weak acid solution and / or in a weak base solution. The weak acid solution typically has a pH of less than 7 but greater than 4. The weak base solution typically has a pH of greater than 7 but less than 10. Low solubility means that less than 100 grams (i.e., 10 wt%) per liter dissolves. In some embodiments, less than 50, 25, 5, or 1 gram per liter dissolves. Examples of neutral compounds include silica, zirconia, titania, alumina, and combinations thereof. A pKa greater than 7 is slightly basic, but such basicity is less than that of the weakly basic core material and significantly less than that of the strongly basic core material as described above.

[0026] When the core material comprises only a basic material (e.g., a compound) or a combination of a basic material with a neutral material and is prepared therefrom, the basicity of the core material can be estimated based on the weight of the components. Thus, the core material contains an amount of the basic material (e.g., a compound) as described above.

[0027] However, when the core material further comprises an acidic material (e.g., a compound), it may be more difficult to estimate the basicity. In particular, for embodiments where it is difficult to estimate the basicity of the core material based on its composition or composition analysis, the basicity of the core material or the 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 the encapsulated core material is actually basic.

[0028] For example, fluoroaluminosilicate (FAS) glass is a homogeneous glass structure prepared from about 19 wt% of a strongly basic compound (SrO), with the remainder prepared from neutral (SiO2) 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 thus considered a weakly acidic core material.

[0029] In some embodiments, the basicity of the core material or the encapsulated core material can be determined by the change in pH of a specific amount (0.25 g) of the material in 25 g of deionized water. An unencapsulated core material typically changes 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 hour or 24 hours. For example, referring to Table 10, an unencapsulated (e.g., bioactive glass) core material can bring about a pH of 10 in water within 20 seconds. Since the core material cannot release hydroxyl ions until the inorganic shell material is sufficiently decomposed, e.g., by dissolution, the same encapsulated core material requires a longer time to bring about such a pH change. However, if there is an encapsulated material present that is less than a bulk of a very small portion of unencapsulated material or sample, even in the case of the encapsulated material, a rapid but smaller pH change can occur in DI water.

[0030] In a preferred embodiment, the basicity of the core material or the encapsulated material can be determined by the change in pH of a specific amount (0.25 g) of the material in a buffer solution, or by the change in pH of 10 g of an aqueous potassium hydrogen phthalate buffer (e.g., buffer BDH5018 having a pH of 4) adjusted to a pH of 4.00 with hydrochloric acid and 15 g of deionized water 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 can reach a pH of at least 8.5 or 9. It is understood that a greater amount of hydroxyl ions is required to change an acidic solution to a basic pH compared to deionized water. Thus, this pH change can 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 can take up to 1 hour or 24 hours. Since the core material cannot release hydroxyl ions that react with the acid until the inorganic shell material is sufficiently decomposed, e.g., by dissolution and / or decomposition, the same encapsulated core material requires an even longer time to effect such a pH change. In one embodiment, referring to Table 8, an unencapsulated (e.g., bioactive glass) core material reaches 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 reaches a pH of 8.5 according to the buffer test within 35 minutes and the pH continues to rise after 1 hour.

[0031] A weakly basic core material can result in a small increase in pH when tested according to the buffer test. For example, the pH can rise from 4 to 5. However, a weakly basic core material does not provide an amount of hydroxyl ions sufficient to reach a pH of at least 8.5 or 9 when tested according to the buffer test.

[0032] Thus, an encapsulated basic core material, as described herein, does not initially (i.e., immediately after immersion of the material in water or buffer) change the pH, but the pH rises at various rates depending on the shell and the basic core material.

[0033] In some embodiments, the basic core material is curable or self-curing 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 a large amount 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 curable or self-curing, such a basic core material can be the sole curable material of the curable composition. Thus, the first portion of the composition may contain 100% of the encapsulated basic core material.

[0034] Aqueous medical and dental cements such as those described in U.S. Patent No. 5,154,762 to Mitra et al. typically do not contain a large amount of calcium silicate. Rather, such compositions generally include 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-cure when mixed with water. However, such acid-reactive fillers can be combined with a polyfunctional acid component to provide a curable material.

[0035] In some embodiments, the encapsulated material is an encapsulated (e.g., dental) filler. The encapsulated (e.g., dental) filler can contain a substantial amount of neutral metal oxide having low solubility in water or an acidic solution having a pH of 3 to 4, as described above. Examples of neutral metal oxides include silica, zirconia, titania, and alumina. The amount of neutral metal oxide can range from at least 10, 15, 20, 25, 30 wt% to a maximum of 50, 60, 70, 80, or 90 wt% of the total weight of the basic core material. Encapsulated calcium silicate may also be characterized as a filler due to its silica content.

[0036] The hardenable dental composition or other suitable (e.g., biological) carrier material includes materials that promote remineralization, such as materials that release calcium ions, phosphorus-containing ions (e.g., phosphates), fluoride ions, or combinations thereof. These materials can be present within the core of the encapsulated filler, provided as a second filler such as FAS glass, or provided as a separate component within the hardenable dental composition.

[0037] In some embodiments, the core of the encapsulated (e.g., filler) material preferably includes a material that promotes remineralization, such as a material that releases calcium ions, phosphorus ions, fluoride ions, or combinations thereof. CaO, as described above, can function as both a highly basic material (e.g., compound) and a source of calcium ions. If the basic core material includes a strong basic material that does not release calcium ions, the core may further include another calcium material, such as calcium glycerophosphate.

[0038] In some embodiments, the core of the encapsulated (e.g., dental) filler further includes and is prepared from a material that promotes remineralization by the release of fluoride ions. In other embodiments, the (e.g., dental) composition further includes a second filler that includes a material that promotes remineralization by the release of fluoride ions. The core or the second filler material includes and is prepared from fluoride compounds such as AlF3, Na2AlF3, and mixtures thereof, in an amount in the range of about 5 to 40% by weight. In some embodiments, the amount of AlF3 is in the range of 10 to 30% by weight of the core or the second filler material. In some embodiments, Na2AlF3 is in the range of 2 to 10% by weight of the core or the second filler material.

[0039] In some embodiments, the core of the encapsulated (e.g., dental) filler further comprises a material that promotes remineralization by the release of phosphorus ions. In other embodiments, the (e.g., dental) composition further comprises a second filler that comprises a material that promotes remineralization by the release of fluoride ions. In some embodiments, the core or the second filler material comprises and is prepared from phosphorus compounds such as P2O5, AlPO4, and mixtures thereof in an amount in the range of 2 to 25% by weight. In some embodiments, the amount of P2O5 is in the range of 2 to 15% by weight of the core or the second filler material. In some embodiments, the amount of AlPO4 is in the range of 2 to 10% by weight of the core or the second filler material.

[0040] The basic core can be encapsulated with an inorganic shell containing a metal oxide by any suitable method such as vapor deposition, atomic layer deposition (ALD), sputtering, or evaporation, which are well-known techniques in the art.

[0041] In some embodiments, the method of manufacturing the encapsulating material includes, as described above, preparing basic core particles and encapsulating the basic core particles with an inorganic coating (e.g., a continuous non-particulate) using at least one of the vapor deposition techniques. Examples of vapor deposition methods include chemical vapor deposition (CVD) methods such as atmospheric pressure chemical vapor deposition (APCVD), hydrolytic CVD, and plasma CVD.

[0042] Advantages of the vapor deposition techniques for providing the coating 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 provide a coating consisting of a conformal layer on irregular materials (e.g., powders or porous microparticles).

[0043] ALD and CVD are coating processes involving chemical reactions, and the chemical reactants used are called chemical precursors. That is, these are precursors to the coating material to be formed (e.g., metal oxide coating) (i.e., coating precursors). 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).

[0044] When simple decomposition of the precursor (e.g., thermal decomposition or plasma-enhanced decomposition) is sufficient to form the coating, a single coating precursor can be 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 a coating (e.g., metal oxide coating), at least two coating precursors (e.g., metal oxide precursors) are used. The additional coating precursor is a co-reactant to 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 a coating.

[0045] ALD coatings are generally deposited one monolayer at a time via alternate pulses of chemical precursors (e.g., coating precursors containing at least one metal cation), absorption of a single layer of the precursor, removal of the excess precursor, and pulsing of the co-reactant (e.g., co-reactant to the coating precursor containing at least one metal cation). Thus, these coatings tend to be conformal and uniform. Alternatively, for example, an ALD system can also deposit thicker non-self-limiting coatings, where a significantly larger amount than a single monolayer of each chemical reactant adsorbs onto the substrate during each pulse or cycle, resulting in a much larger amount of coating deposition.

[0046] CVD coatings can involve similar chemical reactions, but both precursors are typically supplied simultaneously and continuously. The uniformity can be improved by continuously mixing the powder being coated.

[0047] An effective coating method for producing the encapsulated materials described herein is atmospheric pressure CVD (APCVD). APCVD can be carried out with simple equipment such as glass products. In some embodiments, a hydrolysis reaction is used to form a (e.g., continuous) metal oxide coating at a temperature in the range from room temperature (about 22 °C) to about 180 °C.

[0048] Exemplary precursors for ALD and CVD processes include 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 having mixed alkyl, halide, hydride, alkoxy, and other groups, and other volatile metal organic compounds, and coating precursors containing at least one metal cation (e.g., metal oxide precursors). 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-metal coating materials are deposited using chemical reactions between coating precursors and co-reactant substances for the coating precursors (e.g., a metal nitride coating is deposited using a metal nitride precursor containing at least one metal cation and a co-reactant substance for the metal nitride precursor).

[0049] 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 comprises at least 50, 60, 70, 80, 90, or 100 weight % of a single metal oxide or combinations thereof. Exemplary metal oxides can include forms such as hydroxides and oxyhydroxides, and forms that include mixed anions (e.g., in addition to oxides, halides, hydroxyls, minor amounts of alkyl or carboxylates, etc.). The shell material is primarily an inorganic material having a carbon content of 20, 10, 5, or 1 weight % or less. Further, the encapsulated basic material can also have a carbon content of 20, 10, 5, or 1 weight % or less. The shell material may further include metal nitrides, metal sulfides, metal oxysulfides, and metal oxynitrides. The coating can be amorphous, crystalline, or a mixed single-phase or multi-phase, and can contain one or more cations and one or more anions. In some embodiments, the coating is amorphous alumina that contains some hydroxyls or bound water, or does not contain them.

[0050] The shell material may be a weakly basic material. However, the basicity of the shell material is not sufficient (as subsequently described) to cause the desired pH change, particularly according to the buffer test or disk buffer test described above.

[0051] In some embodiments, encapsulating the basic particles with a continuous coating is performed via an APCVD coating process, where an alumina-based coating is provided using trimethylaluminum (TMA) and water. The precursors can be introduced into the reaction chamber by flowing a carrier gas through bubblers of each liquid precursor. Generally, as typical in CVD processes, the carrier gas with each component is delivered simultaneously and continuously 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 each, independently, at least 50 or 100 cm 3 / min to 1000, 1500, or 2000 cm 3 / min. The water flow rate is typically higher than the TMA flow rate by a factor in the range of 2 to 10 times or more. In some embodiments, the flow of any precursor can be started or maintained individually during a period when the flow of the other precursor is absent. In some embodiments, the flow of the precursors can be changed or adjusted one or more times throughout the process.

[0052] In some embodiments, the ratio of a co-reactant (e.g., water) to a coating precursor containing at least one metal cation (e.g., TMA) is higher initially than after the process. In other embodiments, the ratio of a co-reactant (e.g., water) to a coating precursor containing at least one metal cation is lower initially than after the process. In some embodiments, the composite particles are exposed to only the co-reactant (e.g., water) for an initial period before being exposed to a coating precursor containing at least one metal cation. In some embodiments, the composite particles are exposed to only a coating precursor containing at least one metal cation before exposure to a second reactant (e.g., the co-reactant to the coating precursor). In some embodiments, different flow conditions are maintained in the range from at least 5 minutes (or in other embodiments, at least 10, 15, 20, 30, 45, 60, or 90 minutes) up to 150 minutes.

[0053] 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.

[0054] 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 thickness of the shell can range up to 250, 500, 750, or 1000 nm (1 micrometer). In some embodiments, for example in the case of an encapsulated dental filling, the thickness of the shell typically ranges up to 100, 150, or 200 nm.

[0055] On a weight-% basis, the shell material is typically at least 0.1, 0.2, 0.3, 0.4, or 0.5 weight-% of the total encapsulated material. The amount of shell material on a weight-% basis can range up to 15 or 20 weight-% of the total encapsulated material, but more typically is 10, 9, 8, 7, 6, or 5 weight-% or less.

[0056] In preferred embodiments, the shell material and the thickness of the shell can be selected to enable control and / or delayed release or reaction of the basic core material.

[0057] In preferred embodiments, the shell is initially impermeable (i.e., materials from the composition and the core material cannot interact by simple diffusion through the shell). Interaction occurs after the shell has been changed by interaction with other materials (e.g., decomposition, corrosion, or dissolution). The composition (e.g., a two-component composition) can be designed to include a component such as water or an acid that decomposes the shell. In other embodiments, decomposition of the shell can occur by coming into 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 retained within soft tissue surrounding a tooth or bone).

[0058] Referring to Tables 4-7 of the following examples, in one embodiment, the unencapsulated (e.g., Portland cement or tricalcium silicate) basic material results in 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, the encapsulated (e.g., Portland cement or tricalcium silicate) basic material does not result in a basic pH (e.g., at least 8.5, 9, 9.5, 10, or 10.5) in 2, 3, 4, 5, 6, 7, 8, 9, or 10 minutes according to the aforementioned buffer test. In some embodiments, the encapsulated (e.g., Portland cement) basic material does not result in a basic pH (e.g., at least 8.5, 9, 9.5, 10, or 10.5) in 15, 20, 25, 30, 35, 40, or 45 minutes. In some embodiments, the encapsulated (e.g., Portland cement) basic material does not result in a basic pH (e.g., at least 8.5, 9, 9.5, 10, or 10.5) in 100, 200, or 300 minutes.

[0059] Referring to Table 8 of the following examples, in another embodiment, the unencapsulated (e.g., bioactive glass) basic material results in a basic pH (e.g., at least 8.5, 9, 9.5, 10, or 10.5) within 5 minutes when subjected to the aforementioned buffer test. However, the encapsulated (e.g., bioactive glass) basic material does not result in a basic pH (e.g., at least 8.5, 9, 9.5, 10, or 10.5) in 30 - 40 minutes according to the aforementioned buffer test.

[0060] Referring to Table 9 of the following examples, in another embodiment, a non-encapsulated (e.g., Portland cement) basic material provides a basic pH of 11.5 within 20 seconds when tested in deionized water. However, an encapsulated (e.g., Portland cement) basic material provides a basic pH of at least 8.5 within 20 seconds when tested in deionized water. Referring to Table 10 of the following examples, in another embodiment, a non-encapsulated (e.g., bioactive glass) basic material provides a basic pH of 10.5 within 20 seconds when tested in deionized water. However, an encapsulated (e.g., bioactive glass) basic material provides a basic pH of at least 9.8 within 20 seconds. Thus, the change in pH of an acidic (e.g., buffer) solution can occur at a significantly slower rate than in deionized water.

[0061] In a preferred embodiment, the delayed release or reaction of the basic core material is utilized to increase the basicity of a (e.g., biological) carrier material such as a curable dental material, typically at a later time point such as after curing, after application to a tooth or bone structure. A non-encapsulated basic material can cause an undesirably large (and even more undesirable rapid) increase in pH. The same encapsulated basic material causes the desired increase in pH but can cause it at a later time.

[0062] The basicity of a (e.g., biological) carrier material such as a curable (e.g., dental) composition containing an encapsulated basic material is determined by the pH of a hardened (i.e., cured) material disk (height 3.1 mm × 1.3 It can be evaluated by measuring the pH change (in mm). PBS buffer can be prepared by dissolving 8 g of NaCl, 0.2 g of KCl, 1.44 g of Na2HPO4, and 0.24 g of KH2PO4 in 800 ml of distilled H2O, adjusting the pH to 7.4 with HCl, adjusting the volume to 1 L with additional distilled water, and sterilizing by autoclaving. This test will hereinafter be referred to as the "disc buffer test" in this specification.

[0063] A representative two-component curable (e.g., dental) composition that can be used for the purpose of evaluating an encapsulated (e.g., dental) basic material includes a first part described below and a second part containing the encapsulated basic material. The first and second parts are combined (at a weight ratio of 1:1) and radiation-cured as described in more detail in the examples. In one embodiment, the second part includes 65% by weight of the encapsulated basic material described herein, 33.7 parts of hydroxyethyl methacrylate (HEMA), and 1% by weight of fumed silica. In another embodiment, the second part includes 33.7 parts of hydroxyethyl methacrylate (HEMA), 16.25 - 65% by weight (e.g., 32.5% by weight) of the encapsulated basic material described herein, 0 - 32.5% by weight of FAS glass, and 1% by weight of fumed silica.

[0064] [Table 1]

[0065] In some embodiments, the concentration of the encapsulated basic material is typically in the range of at least 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, or 65 wt% to a maximum of 100% of the second part of the curable (e.g., dental) composition. The whole of the curable (e.g., dental composition) contains half of such a concentration of the encapsulated basic material. Thus, the concentration of the encapsulated basic material is typically in the range of 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 wt% to a maximum of 50% by weight of the whole curable (e.g., dental) composition. A formulation having 16.25 wt% bioactive glass in the second part (8 wt% in total) showed limiting performance, but it is speculated that increasing the concentration of highly basic materials (CaO, Na2O) of the bioactive glass can result in a delay in the rise to a pH of at least 8.5 or 9.

[0066] Referring to Tables 12-22 of the following examples, in one embodiment, the unencapsulated basic material brings about 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 containing more than 16.25 wt% of the encapsulated basic material.

[0067] The curable (e.g., dental) composition is typically acidic (pH 1, 2, 3, 4, 5, or 6) before curing by containing an acidic component for a time sufficient to provide good adhesion to bone or tooth structure. This period can vary to some extent, being acidic initially (immediately after immersion of the curable or cured composition in water or buffer) and typically acidic for at least 30 seconds, 1, 2, 3, 4, or 5 minutes. In other embodiments, the curable or cured (e.g., dental) composition is initially neutral (pH 7-7.5) and becomes basic (e.g., at least 8, 8.5, 9, 9.5, 10, 10.5 or 11) after various periods in the range of 1 hour to 1 day, and in some embodiments after various periods in the range of up to 2, 3, 4, 5, 6, or 7 days or more.

[0068] In some embodiments, a curable (e.g., dental) composition can be characterized as a cement having multiple curing modes. In some embodiments, the cement cures through a first mechanism via an ionic reaction between an acid and an acid-reactive filler (e.g., FAS glass). The reaction of the encapsulated basic (e.g., filler) material is delayed as described above and thus typically does not interfere with the curing reaction. The cement also cures through a second mechanism via photoinitiated free radical crosslinking of ethylenically unsaturated components. Optionally, the cement cures through a third mechanism via redox-initiated free radical crosslinking of ethylenically unsaturated components.

[0069] Such cements are typically formulated into two parts, with the first part typically being a powder or liquid part containing an encapsulated basic filler and an acid-reactive (e.g., FAS-glass) filler for curing. The second part is typically an aqueous liquid part containing an acidic polymer and water. Optionally, the encapsulated filler can be designed to provide controlled curing and then continuously increase the pH.

[0070] Optionally, the cement may contain a water-soluble reducing agent and a water-soluble oxidizing agent in separate parts. If the reducing agent is present in the liquid part, then the oxidizing agent is typically present in the powder part, and vice versa. Suitable reducing agents include ascorbic acid, sulfinic acid, barbituric acid and its derivatives, cobalt(II) chloride, iron chloride, iron sulfate, hydrazine, hydroxylamine (depending on the choice of oxidizing agent), oxalic acid, thiourea, and salts of dithionate or sulfite anions. Suitable oxidizing agents are the same as those described above.

[0071] The amounts of the reducing agent and the oxidizing agent are sufficient to provide the desired degree of polymerization of the ethylenically unsaturated component. The amount of the reducing agent typically ranges from at least 0.01 or 0.02 to a maximum of 5, 6, 7, 8, 9, or 10 wt% based on the total weight (including water) of the non-set cement composition. The amount of the oxidizing agent typically ranges from at least 0.01 or 0.02 to a maximum of 5, 6, 7, 8, 9, or 10 wt% based on the total weight (including water) of the non-set cement composition.

[0072] The reducing agent or the oxidizing agent can be encapsulated with a polymer as described in U.S. Patent No. 5,154,762 to Mitra et al. When a curable (e.g., dental) composition cures through redox-initiated free radical cross-linking of the ethylenically unsaturated component, the composition contains a sufficient amount of the oxidizing agent for the cross-linking reaction that is not encapsulated within an inorganic shell containing a metal oxide. The curable (e.g., dental) composition may also contain an oxidizing agent encapsulated within an inorganic shell containing a metal oxide for the purpose of raising the pH over a period of time.

[0073] The cement is not limited to two-component powder-liquid compositions. For example, one-component anhydrous formulations can be prepared. These are sold in dry form and can be prepared for use by adding water. Also, two-component paste-paste formulations can be prepared by adding a suitable polymerizable liquid (e.g., 2-hydroxyethyl methacrylate, or "HEMA") that does not react with the filler to an encapsulated basic and / or additional acid-reactive (e.g., FAS glass) filler to obtain a first paste. The above-mentioned acidic polymer is combined with a suitable filler (e.g., quartz) that does not react with the acidic polymer to obtain a second paste. The two pastes are stirred together to be prepared for use.

[0074] The cement contains water during use. The water may be present in the composition sold or may be added immediately before use. The water may be distilled water, deionized water, or plain water It may be water. The amount of water is generally an amount sufficient to provide suitable handling and mixing characteristics and to permit ion transport in the filler-acid reaction. The amount of water is typically at least 1, 2, 3, 4, or 5% and typically 20 or 25% or less of the total weight of the cement (i.e., the combination of the first and second parts and any added water).

[0075] The cement is typically ion-curable, i.e., it can react by an ion reaction to produce a cured mass. The ion reaction mainly occurs between acid groups on the polymer and an acid-reactive (e.g., FAS glass) filler.

[0076] In some embodiments, the 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 wt% to a maximum of about 50, 55, or 60 wt% of the first part of the two-component composition. Since the first part typically corresponds to half of the total curable (e.g., dental) composition, the total concentration of acid-reactive (FAS) glass is half of the concentration just described. In addition to its involvement in the ion reaction, FAS glass releases phosphate and fluoride ions, which are known to promote remineralization.

[0077] In some embodiments, the concentration of the acid-reactive (FAS) glass is higher 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 higher than the concentration of the acid-reactive (FAS) glass. In some embodiments, the weight ratio of the encapsulated basic filler to the unencapsulated acid-reactive (FAS) glass is typically at least 1:1 or greater than 1:1, e.g., 1.5:1, 2:1, 2.5:1, or 3:1 to a maximum of 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1 in the second part of the two-component composition.

[0078] The cement may further include at least one ethylenically unsaturated moiety. The ethylenically unsaturated moiety may be present as a separate component (e.g., as an acrylate-functional monomer or a methacrylate-functional monomer), or may be present as a group on another component such as an acidic polymer.

[0079] The ethylenically unsaturated group is typically a (e.g., terminal) free-radical polymerizable group, such as (meth)acrylic, e.g., (meth)acrylamide (H2C=CHCON- and H2C=CH(CH3)CON-), and (meth)acrylate (CH2CHCOO- and CH2C(CH3)COO-). Other ethylenically unsaturated polymerizable groups include vinyl (H2C=C-), such as vinyl ether (H2C=CHO-). The ethylenically unsaturated terminal polymerizable group is preferably a (meth)acrylate group, particularly in the case of a composition cured by exposure to actinic radiation (e.g., UV or blue light). Further, the methacrylate-functional group is typically more preferred than the acrylate-functional group in dental curable compositions.

[0080] 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 weights) dimethacrylate, urethane methacrylate, acrylamide, methacrylamide, methylene bis-acrylamide or methacrylamide, with diacetone acrylamide and methacrylamide being preferred. Optionally, 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.

[0081] The second part contains 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 polyacrylic acid or a phosphorus-containing acid.

[0082] In some embodiments, the acid component is an acidic polymer. Suitable acidic polymers include those listed in column 2, lines 62 to column 3, line 6 of U.S. Patent No. 4,209,434. Preferred acidic polymers include homopolymers and copolymers of alkene acids such as acrylic acid, itaconic acid, and maleic acid.

[0083] In some embodiments, the acidic polymer can be characterized as a photocurable ionomer, i.e., a polymer having pendant ionic groups capable of a curing reaction and pendant free radical polymerizable groups that can be polymerized, i.e., cured, upon exposure of the resulting mixture to radiation energy.

[0084] For example, as described in U.S. Patent No. 5,130,347, the photocurable ionomer has the general formula: B(X) m (Y) n having wherein 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 more, n is a number having an average value of 1 or more.

[0085] Preferably, the backbone chain B is an oligomeric or polymeric backbone chain of carbon-carbon bonds and optionally contains 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.

[0086] Preferred X groups are acidic groups, with carboxyl groups being particularly preferred.

[0087] Suitable Y groups include, but are not limited to, polymerizable ethylenically unsaturated groups and polymerizable epoxy groups. Ethylenically unsaturated groups, particularly those that can be polymerized by a free radical mechanism, are preferred, examples of which are substituted and unsubstituted acrylates, methacrylates, alkenes, and acrylamides.

[0088] The X and Y groups can be attached to the backbone chain B directly or using any non-interfering organic linking group such as substituted or unsubstituted alkyl, alkoxyalkyl, aryl, aryloxyalkyl, alkoxyaryl, aralkyl, or alkaryl groups.

[0089] 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 are conveniently prepared by reacting a polyalkenoic acid (e.g., a polymer of the 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 of free radical polymerizability (e.g., a (meth)acrylate group) bonded to the ionomer by an amide bond. The molecular weight of the resulting photocurable ionomer is typically from about 1000 to about 100,000 g / mol.

[0090] (e.g., photocurable ionomer) acidic polymers typically have a (weight average) molecular weight in the range of at least 5000 g / mol to a maximum of about 100,000 g / mol when measured using 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.

[0091] The concentration of acidic components such as photocurable ionomers is typically at least 5, 6, 7, 8, 9, or 10 wt%, typically 30, 25, 20, or 15 wt% or less in the first part of the two-component composition. Since the first part typically corresponds to only half of the total curable (e.g., dental) composition, the total concentration of acidic components such as photocurable ionomers is approximately half of the concentrations just described.

[0092] In some embodiments, the acid component is a curable component in the form of an ethylenically unsaturated compound having an acid and / or acid precursor functional group. Examples of acid precursor functional groups include anhydrides, acid halides, and pyrophosphates. Examples of 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%, less than 5 wt%, or less than 1 wt%) or no ethylenically unsaturated compounds having carboxylic acid functional groups when the composition contains a radiopaque filler including a basic surface such as in the case of zirconia.

[0093] Examples of ethylenically unsaturated compounds having acid functional groups 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)acryloyloxyethyl) phosphate, ((meth)acryloyloxypropyl) phosphate, bis((meth)acryloyloxypropyl) phosphate, bis((meth)acryloyloxy)propyloxy phosphate, (meth)acryloyloxyhexyl phosphate, bis((meth)acryloyloxyhexyl) phosphate (e.g., MHP), (meth)acryloyloxyoctyl phosphate, bis((meth)acryloyloxyoctyl) phosphate, (meth)acryloyloxydecyl phosphate, bis((meth)acryloyloxydecyl) phosphate, and caprolactone methacrylate phosphate.

[0094] In some embodiments, the (e.g., dental) composition further comprises another (i.e., a second) filler in addition to the encapsulated fillers described herein. The second filler typically does not contain a (e.g., strong) basic core material as described herein. The second filler typically contains a neutral metal oxide having low solubility as described above. The second filler may also be weakly basic or weakly acidic.

[0095] In some embodiments, the second filler is an acid-reactive (FAS glass) filler as described above.

[0096] In some embodiments, the other filler comprises (e.g., inorganic metal oxide) nanoparticles. Such nanoparticles, or in other words "nanoscopic fillers", can be used as viscosity and thixotropy modifiers. Such nanoparticles can also contribute in part to the mechanical properties of the dental curable composition. Such nanoparticles also contribute to the refractive index of the polymerizable resin due to their size.

[0097] In some embodiments, the inorganic oxide nanoparticles have a primary particle size of 100 nm or less. The primary particle size typically refers to the size of discrete non-aggregated particles. In other less general embodiments, the nanoparticles may be aggregates of two or more (e.g., fused or covalently bonded) particles, and such aggregates have a particle size of 100 nm or less. The average particle size can be determined by cutting a thin sample of the cured dental composition and measuring the particle sizes of about 50 to 100 particles using a transmission electron micrograph at a magnification of 300,000 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.

[0098] The dental composition optionally further comprises nanoparticles having a relatively low refractive index (e.g., inorganic metal oxides), such as silica. Inclusion of the low refractive index nanoparticles can reduce the refractive index of the polymerizable resin. Suitable silica nanoparticles are commercially available under the trade name NALCO COLLOIDAL SILICAS from Ecolab (St. Paul, MN). For example, preferred silica particles can be obtained by using NALCO products 1034A, 1040, 1042, 1050, 1060, 2327, and 2329.

[0099] The silica nanoparticles are preferably produced from an aqueous colloidal dispersion of silica (i.e., a sol or aquasol). Colloidal silica is typically present in the silica sol at a concentration of about 1 to 50 weight percent. Commercially available colloidal silica sols having different colloidal sizes can be used; see Surface & Colloid Science, Vol. 6, ed. Matijevic, E., Wiley Interscience, 1973. Preferred silica sols for use in the production of the filler are dispersions of amorphous silica in an aqueous medium (e.g., Nalco colloidal silica from Ecolab), and those having a low sodium concentration and capable of being acidified by mixing with a suitable acid (e.g., Ludox colloidal silica from E.I. Dupont de Nemours & Co., or Nalco 2326 from Ecolab).

[0100] In some embodiments, the dental composition comprises at least 0.5, 1, 1.5, or 2 weight percent of low refractive index (e.g., silica) nanoparticles. The amount of low refractive index (e.g., silica) nanoparticles is typically 30, 25, 20, 15, or 5 weight percent or less of the dental composition. In other embodiments, the dental composition comprises less than 1, 0.5, 0.25, 0.1, or 0.005 weight percent of low refractive index (e.g., silica) nanoparticles or substantially no low refractive index (e.g., silica) nanoparticles.

[0101] 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 ratio 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 to 1, 1.2 to 1, 1.3 to 1, 1.4 to 1, 1.5 to 1, 1.6 to 1, 1.7 to 1, 1.8 to 1, 1.9 to 1, or 2 to 1. In some embodiments, the weight ratio 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 to 1, 2.2 to 1, 2.3 to 1, or 2.4 to 1. In some embodiments, the weight ratio or volume ratio of the high refractive index (e.g., zirconia) nanoparticles to the low refractive index (e.g., silica) nanoparticles is 100 to 1, 75 to 1, 50 to 1, 25 to 1, 10 to 1, or 5 to 1 or less.

[0102] Some suitable low refractive index (e.g., silica) nanoparticles and high refractive index (e.g., zirconia) nanoparticles are disclosed in U.S. Patent Nos. 6,387,981 (Zhang et al.) and 6,572,693 (Wu et al.), and PCT International Publications 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. Patent Nos. 7,090,721 (Craig et al.), 7,090,722 (Budd et al.), 7,156,911 (Kangas et al.), U.S. Patent No. 7,241,437 (Davidson et al.), and U.S. Patent No. 7,649,029 (Kolb et al.).

[0103] The dental compositions described herein preferably contain a recognizable amount of an inorganic metal oxide filler. The nature of the filler used in dental applications is typically ceramic.

[0104] The filler can be selected from one or more of a wide range of materials suitable for incorporation into compositions for dental use, such as fillers currently used in dental composites and dental articles (such as crowns). The filler is generally non-toxic and suitable for use in the oral cavity. The filler 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.

[0105] To increase radiopacity, it is common to include components such as YbF3 up to about 5 wt%. In some embodiments, the radiopacity of the cured dental composition is that of at least 3 mm of aluminum.

[0106] The nature of the filler can be either particulate or fibrous. Particulate fillers can generally be defined as having a length-to-width ratio or aspect ratio of 20:1 or less, more typically 10:1 or less. Fibers can be defined as having an aspect ratio greater than 20:1, or more typically greater than 100:1. The shape of the particles can vary over a range from spherical to elliptical, or more planar, such as flakes or disks. The macroscopic properties can be highly dependent on the shape of the filler particles, particularly the uniformity of the shape.

[0107] The dental compositions described herein include inorganic metal oxide filler materials that are larger in size than nanoparticles. As described previously, nanoparticles are typically discrete, non-aggregated particles having a particle size of 100 nm or less. In contrast, the inorganic metal oxide filler is a particulate or fibrous material having at least one dimension greater than 100 nm, such as at least 150 nm or at least 200 nm. In the case of particulate fillers, the average particle size of the non-aggregated discrete particles or aggregated particles is at least 200 nm. The inorganic metal oxide filler is very effective for improving the wear properties after curing.

[0108] In some embodiments, the filler may include a crosslinked organic material that is insoluble in the polymerizable resin and may optionally be filled with an inorganic filler. Examples of suitable organic filler particles include filled or unfilled ground polycarbonate, polyepoxide, poly(meth)acrylate, and the like.

[0109] In some embodiments, the dental compositions described herein include non-acid reactive fillers such as quartz, fumed silica, non-glass microparticles of the type described in U.S. Patent No. 4,503,169 (Randklev), and nanocluster fillers, e.g., those described in U.S. Patent No. 6,730,156 (Windisch et al.), U.S. Patent No. 6,572,693 (Wu et al.), and U.S. Patent No. 8,722,759 (Craig).

[0110] In some embodiments, the filler includes nanoclusters, i.e., a group of two or more particles joined by intermolecular forces sufficient to agglomerate the particles, which are relatively weak even when dispersed in the curable resin, in the form of nanoparticles. Preferred nanoclusters can include lightly agglomerated, substantially amorphous clusters of non-heavy metal oxides (e.g., silica) particles and heavy metal oxides (i.e., having an atomic number greater than 28) such as zirconia. Zirconia may be crystalline or amorphous. In some embodiments, 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 the lightly agglomerated nanoclusters typically becomes quite large.

[0111] 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-component dental composition, the filler comprising the neutral metal oxide is present in a substantial amount in the first or second liquid-containing portion. In some embodiments, the neutral or non-reactive filler is present in either or both of the acidic and non-acidic portions, while the acid-reactive filler (e.g., FAS glass) and / or the encapsulated basic core is present in the non-acidic portion and reacts with the acidic portion after mixing.

[0112] In some embodiments, the first portion of the curable (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 a maximum of 30, 35, or 40 wt%. The total curable (e.g., dental) composition comprises approximately half of such a concentration of the second filler comprising a neutral metal oxide, such as a zirconia / silica nanocluster filler.

[0113] In some embodiments, the second filler may also be encapsulated with a shell material comprising a metal oxide as described in U.S. Patent No. 7,396,862.

[0114] Mixtures of fillers can also be used.

[0115] In an exemplary embodiment, the second filler may include a surface treatment to enhance the bond between the nanoparticles, the inorganic oxide filler, and the resin. Various surface treatments are described in the art and include, for example, organometallic coupling agents and carboxylic acids such as those described in U.S. Patent No. 8,647,510 (Davidson et al.). The encapsulated basic material may also optionally include a surface treatment.

[0116] Suitable copolymerizable organometallic compounds have the general formula: CH2=C(CH3) m Si(OR) n or CH2=C(CH3) m C=OOASi(OR)n [wherein, 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] may be included. The organometallic coupling agent may be functionalized with reactive curable groups such as acrylates, methacrylates, vinyl groups and the like. Preferred coupling agents include gamma-methacryloxypropyltrimethoxysilane, gamma-mercaptopropyltriethoxysilane, gamma-aminopropyltrimethoxysilane, and the like.

[0117] In some embodiments, combinations of surface modifiers may be useful, and at least one of these agents has a functional group 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 polyethers, alkyls, hydroxyalkyls, hydroxyaryls, or aminoalkyl-functional silanes.

[0118] Surface modification can be carried out either following mixing with the monomer or at any time after mixing. Typically, it is preferred to combine the organosilane surface treatment compound with the nanoparticles before incorporation into the resin. The required amount of the surface modifier depends on several factors such as particle size, type of particles, molecular weight of the modifier, and type of the modifier. Generally, it is preferred to attach a substantially monolayer of the modifier to the surface of the particles.

[0119] Various ethylenically unsaturated monomers can be utilized in the dental composition. The ethylenically unsaturated monomer of the dental composition is typically a liquid that is stable at about 25°C, which means that the monomer does not substantially polymerize, crystallize, or otherwise cure 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 monomer typically does not change (e.g., increase) by more than 10% of the initial viscosity.

[0120] In particular, in the case of dental restorative compositions, the 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 higher. The inclusion of sulfur atoms and / or the presence of one or more aromatic moieties can increase the refractive index (compared to monomers of the same molecular weight that do not contain such substituents).

[0121] The curable (e.g., dental) components of the curable composition can include a wide range of "other" ethylenically unsaturated compounds (with or without acid functionality), epoxy-functional (meth)acrylate resins, vinyl ethers, and the like.

[0122] (E.g., photopolymerizable) dental compositions 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 esters, methacrylic esters, hydroxy-functional acrylic esters, hydroxy-functional methacrylic esters, and combinations thereof.

[0123] Examples of such free radical 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, tetrahydrofurfuryl (meth)acrylate, bis[1-(2-acryloxy)]-p-ethoxyphenyldimethylmethane, bis[1-(3-acryloxy-2-hydroxy)]-p-propoxyphenyldimethylmethane, ethoxylated bisphenol A di(meth)acrylate, and tris-hydroxyethyl-isocyanurate tri(meth)acrylate; (meth)acrylamides (i.e., acrylamide and methacrylamide), such as (meth)acrylamide, methylenebis-(meth)acrylamide, and diacetone (meth)acrylamide; urethane (meth)acrylate; bis-(meth)acrylate 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)acrylate. If desired, it is possible to use a mixture of two or more free radical polymerizable compounds.

[0124] A curable (e.g., dental) composition may contain a monomer having a hydroxyl group and an ethylenically unsaturated group within 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-methacryloxypropoxy)phenyl]propane (bisGMA). Suitable ethylenically unsaturated compounds are available from a wide range of commercial suppliers, such as Sigma-Aldrich, St. Louis, etc.

[0125] In some embodiments, the first part of a two-component curable (e.g., dental) composition contains 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, 30 wt% to up to about 35, 40, 45, or 50 wt% of the first part of the two-component composition. Since the first part corresponds to only half of the total curable (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 concentrations just described.

[0126] The compositions described herein (e.g., dental) may include one or more curable components in the form of ethylenically unsaturated compounds having acid functional groups. Such components contain an acidic group and an ethylenically unsaturated group within a single molecule. When present, this polymerizable component optionally includes an ethylenically unsaturated compound having an acid functional group. Preferably, the acid functional group includes 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 ethylenically unsaturated compounds having acid functional groups.

[0127] As used herein, ethylenically unsaturated compounds having acid functional groups are intended to include monomers, oligomers, and polymers having ethylenic unsaturation and acid and / or acid precursor functional groups. Examples of acid precursor functional groups include anhydrides, acid halides, and pyrophosphates. Examples of acid functional groups can include carboxylic acid functional groups, phosphoric acid functional groups, phosphonic acid functional groups, sulfonic acid functional groups, or combinations thereof.

[0128] Examples of the ethylenically unsaturated compound 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)acryloyloxyethyl) phosphate, ((meth)acryloyloxypropyl) phosphate, bis((meth)acryloyloxypropyl) phosphate, bis((meth)acryloyloxy)propyloxy phosphate, (meth)acryloyloxyhexyl phosphate, bis((meth)acryloyloxyhexyl) phosphate, (meth)acryloyloxyoctyl phosphate, bis((meth)acryloyloxyoctyl) phosphate, (meth)acryloyloxydecyl phosphate, bis((meth)acryloyloxydecyl) phosphate, caprolactone methacrylate phosphate, di- or tri-methacrylate of citric acid, 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, which can be used as a constituent. Also, it is possible to use monomers, oligomers, and polymers such as unsaturated carbonic acids (e.g., (meth)acrylic acid), aromatic (meth)acrylated acids (e.g., methacrylated trimellitic acid), and their anhydrides.

[0129] The dental composition may contain an ethylenically unsaturated compound having an acid functional group having at least one P-OH moiety. Such a composition is self-adhesive and non-aqueous. For example, such a composition is a first compound containing at least one (meth)acryloxy group and at least one -O-P(O)(OH) x group, where x = 1 or 2, and at least one -O-P(O)(OH) xA first compound in which the base and at least one (meth)acryloxy group are linked together by a C1-C4 hydrocarbon group; at least one (meth)acryloxy group and at least one -O-P(O)(OH) x A second compound containing a group, wherein x = 1 or 2, and at least one -O-P(O)(OH) x A second compound in which the group and at least one (meth)acryloxy group are linked together by a C5-C12 hydrocarbon group; an ethylenically unsaturated compound having no acid functional group; an initiator system; and a filler may be included.

[0130] 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 the polymerizable composition (and to prevent separation therefrom). 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.

[0131] In some embodiments, the mixture of monomers is photopolymerizable, and the composition contains a photoinitiator (i.e., a photoinitiator system) that initiates the polymerization (or curing) of the composition when irradiated with actinic radiation. Such a photopolymerizable composition may be free-radical polymerizable. The photoinitiator typically has an effective wavelength range of from about 250 nm to about 800 nm. Suitable photoinitiators (i.e., photoinitiator systems comprising one or more compounds) for polymerizing free-radical photopolymerizable compositions include two-component and three-component systems. A typical three-component photoinitiator includes an iodonium salt, a photosensitizer, and an electron donor compound, as described in U.S. Patent No. 5,545,676 (Palazzotto et al.). Examples of 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 in the range of from about 300 nm to about 800 nm (preferably from 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.

[0132] Other suitable photoinitiators for polymerizing free-radical photopolymerizable compositions typically include the class of phosphine oxides having an effective wavelength range of from about 380 nm to about 1200 nm. Preferred phosphine oxide free-radical initiators having an effective wavelength range of from about 380 nm to about 450 nm are acyl and bisacylphosphine oxides.

[0133] Commercially available phosphine oxide photoinitiators that can initiate free radical reactions when irradiated in the wavelength range of approximately 380 to approximately 450 nm include bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide (IRGACURE 819 (Ciba Specialty Chemicals (Tarrytown, N.Y.))), bis(2,6-dimethoxybenzoyl)-(2,4,4-trimethylpentyl)phosphine oxide (CGI 403 (Ciba Specialty Chemicals)), 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)), 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, N.C.))).

[0134] A tertiary amine may be used in combination with an acylphosphine oxide. 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 from about 0.1 weight percent to about 5.0 weight percent, based on the total weight of the composition. In some embodiments, the dental curable composition may be irradiated with ultraviolet (UV) light or blue light. In this embodiment, suitable photoinitiators include those available under the trade names IRGACURE and DAROCUR from Ciba Speciality Chemical Corp., Tarrytown, N.Y., 1-hydroxycyclohexyl phenyl ketone (IRGACURE 184), 2,2-dimethoxy-1,2-diphenylethane-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 907), and 2-hydroxy-2-methyl-1-phenylpropan-1-one (DAROCUR 1173).

[0135] The photopolymerizable composition is typically prepared by admixing the various components of the composition. In embodiments where the photopolymerizable composition does not cure in the presence of air, the photoinitiator is combined under "safe light" conditions (i.e., conditions that do not cause premature curing of the composition). When preparing the mixture, a suitable inert solvent may be used, if desired. Examples of suitable solvents include acetone and dichloromethane.

[0136] Curing occurs by exposing the composition to a radiation source, preferably a visible light source. It is convenient to use a light source that emits actinic light in the range of 250 nm to 800 nm (especially blue light with a wavelength of 380 nm to 520 nm), such as a quartz halogen lamp, tungsten halogen lamp, mercury arc, carbon arc, low, medium, and high pressure mercury lamps, plasma arc, light emitting diode, and laser. Generally, a useful light source has an intensity in the range of 0.200 to 6000 mW / cm 2 2. An intensity of 1000 mW / cm for 20 seconds can generally bring about the desired curing. Various conventional lights can be used to cure such compositions. 2

[0137] Optionally, the composition may contain a solvent (such as alcohol (e.g., propanol, ethanol), ketone (e.g., acetone, methyl ethyl ketone), ester (e.g., ethyl acetate), other non-aqueous solvents (e.g., dimethylformamide, dimethylacetamide, dimethyl sulfoxide, 1-methyl-2-pyrrolidinone)), and water. In some embodiments, a dental composition (e.g., a one-component dental composition) typically contains water in an amount of 5 wt% or less of the total dental composition.

[0138] If desired, the composition can contain additives such as indicators, dyes such as photofading dyes, pigments, inhibitors, accelerators, viscosity modifiers, wetting agents, buffers, radical and cationic stabilizers (e.g., BHT), and other similar components that will be apparent to those skilled in the art.

[0139] ​In addition, a medicine or other therapeutic substance can be optionally added to the dental composition. Examples include, but are not limited to, fluoride sources, whitening agents, anti-caries agents (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 regulators, thixotropic agents, polyols, anti-inflammatory agents, antibacterial agents (in addition to antibacterial lipid components), antifungal agents, xerostomia treatment agents, desensitizing agents, and the like, which are types often used in dental compositions. Combinations of any of the above additives may be used. A person skilled in the art can select any of such additives and select the amount thereof without undue experimentation to achieve the desired result.

[0140] As is known in the art, the curable dental composition can be used to treat oral surfaces such as teeth. In some embodiments, the composition can be hardened by curing after the dental composition is applied. For example, when a dental curable composition is used as a restorative material such as tooth filling, this method generally includes applying the curable composition to an oral surface (e.g., a cavity) and curing the composition. In some embodiments, a dental adhesive may be applied before applying the curable dental restorative material described herein. Also, the dental adhesive is typically hardened by curing simultaneously with the curing of the highly filled dental restorative composition. The method of treating an oral surface can include preparing a dental article and adhering the dental article to the oral (e.g., tooth) surface.

[0141] In one embodiment, the cured dental composition can be used for pulp capping. In this embodiment, the cell proliferation of dental pulp stem cells in contact with the cured dental composition (e.g., the same molded disk used in the buffer disk test) was evaluated in the manner described in more detail in the examples. The average cell proliferation was at least 75% of the control (where there was no disk of the cured dental composition). In some embodiments, the average cell proliferation was at least 80, 85, or 90% of the control. The average alkaline phosphatase (ALP) activity also increased as compared to the control. In some embodiments, the average ALP activity ranged from at least 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0 mU / mL to a maximum of 1.1 or 1.2 mU / mL or more.

[0142] In another embodiment, the cured dental composition can be used as an adhesive. The cured dental composition can exhibit an adhesiveness 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 adhesiveness can range up to a maximum of 20 MPa or more.

[0143] As used herein, "dental composition" refers to a material containing a filler that can adhere or bond to the oral surface. Dental curable compositions can be used to bond dental articles to tooth structures, to form coatings (e.g., sealants or varnishes) on tooth surfaces, to be placed directly in the oral cavity and used as restoratives that cure in situ, or alternatively, to be used to fabricate prostheses that are adhesively bonded in the oral cavity outside the oral cavity.

[0144] Examples of sclerosing dental compositions include adhesives (e.g., dental and / or orthodontic adhesives), cements (e.g., two-component cements), primers (e.g., orthodontic primers), liners (applied to the base of a cavity to reduce tooth hypersensitivity), root repair and pulp capping, coatings such as sealants (e.g., for pits and fissures), and varnishes; as well as resin restoratives such as tooth fillings (also called direct composites), and articles for crowns, bridges, and dental implants. Also, highly filled dental compositions are used for mill blanks, from which crowns can be milled. Composites are highly filled pastes designed to be suitable for filling substantial defects in the 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, and the like, or act as filling materials themselves when applied and cured as a layer. Dental cements are also used to permanently bond dental restoration articles such as crowns, bridges, or orthodontic appliances to the tooth surface or implant abutment.

[0145] As used herein, "dental article" refers to an article capable of adhering (e.g., bonding) to a tooth structure or dental implant. Examples of dental articles include crowns, bridges, veneers, inlays, onlays, fillings, orthodontic devices and appliances.

[0146] "Orthodontic device" refers to any device intended to be bonded to a tooth structure and includes, but is not limited to, orthodontic brackets, buccal tubes, lingual retainers, orthodontic bands, mouth openers, buttons, and cleats. The device has a base for receiving an adhesive, which base may be a flange made of metal, plastic, ceramic, or a combination thereof. Alternatively, the base may be a custom base formed from a cured adhesive layer (i.e., a single or multi-layer adhesive).

[0147] "Oral surface" refers to a soft or hard surface in the oral environment. Hard surfaces typically include, for example, tooth structures such as natural and artificial tooth surfaces, bone, and the like.

[0148] "Hardenable" and "curable" describe materials or compositions that can be hardened (e.g., polymerized or crosslinked) by heating to induce polymerization and / or crosslinking; by irradiating with 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 carried out, for example, by combining and mixing two or more components to form a homogeneous composition. Alternatively, two or more components can be prepared as separate layers and these layers can be intermixed (e.g., spontaneously or by application of shear stress) at the interface to initiate polymerization.

[0149] "Hardened" refers to a cured (e.g., polymerized or crosslinked) material or composition.

[0150] "Hardening agent" refers to something that initiates the hardening of a resin. Examples of hardening agents can include, for example, polymerization initiator systems, photoinitiator systems, thermal initiator systems, and / or redox initiator systems.

[0151] "(Meth)acrylate" is an abbreviated expression that refers to acrylate, methacrylate, or a combination thereof, "(meth)acrylic acid" is an abbreviated expression that refers to acrylic acid, methacrylic acid, or a combination thereof, and "(meth)acryl" is an abbreviated expression that refers to acryl, methacryl, or a combination thereof.

[0152] ​As used herein, the terms "a", "an", "the", "at least one", and "one or more" are used interchangeably.

[0153] Also, in this specification, the description of a numerical range by endpoints includes all numbers included within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, 5, etc.).

Examples

[0154] Materials Hydroxyethyl methacrylate (HEMA) was obtained from Evonik Industries, Sarasota, FL. Ethyl 4-dimethylaminobenzoate (EDMAB) was obtained from Sigma-Aldrich Corporation, St. Louis, MO. Camphorquinone (CPQ) was obtained from Sigma-Aldrich. 2,6-Di-tert-butyl-4-methylphenol (BHT) was obtained from PMC Specialties Incorporated, Cincinnati, OH. Fumed silica R812S was obtained from Degussa-Huls Corporation, Parsippany, NJ. Calcium glycerophosphate was obtained from Spectrum Laboratory Products, Gardena, CA. Ytterbium fluoride (YbF3) was obtained from Treibacher Industrie Incorporated, Toronto, Canada. Buffer BDH5018 (aqueous potassium hydrogen phthalate buffer adjusted to a pH of 4.00 with hydrochloric acid at 25°C) obtained from VWR International, Radnor, PA. The VBP polymer was made by reacting a PAA:ITA copolymer with sufficient 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. Patent No. 5,130,347 (Mitra). The PAA:ITA copolymer was made from a 4:1 molar ratio of acrylic acid:itaconic acid prepared according to Example 3 of U.S. Patent No. 5,130,347. The Zr / Si nanocluster filler is a silane-treated zirconia / silica nanocluster filler prepared essentially as described in U.S. Patent No. 6,730,156 [Preparation Example A (lines 51 - 64) and Example B (column 25, line 65 - column 26, line 40)]. Portland cement: White Portland cement (Federal White Type 1, ASTM designation C150) was purchased from Federal White Cement, Woodstock, Ontario, Canada. The main 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 (excluding trace components of magnesium oxide, potassium sulfate, and sodium sulfate) contains a significant amount of strong base (CaO). Portland cement typically contains about 61% - 69% CaO, about 18% - 24% SiO2, about 2% - 6% Al2O3, about 1% - 6% Fe2O3, and about 0.5% - 5% MgO. Bioactive glass [45S5] was prepared using the following composition: SiO2 (45 wt%), Na2O (24.5 wt%), CaO (24.5 wt%), P2O5 (6 wt%). Bioactive glass is a strongly basic material. It is homogeneous with two strongly basic components (Na2O and CaO) which are 49 wt% of the total composition. Tricalcium silicate (3CaO·SiO2) powder was prepared by the sol-gel method. 0.5 mol of Si(OC2H5)4 (tetraethyl orthosilicate, TEOS), 200 mL of a solution of water and nitric acid as a catalyst were combined under continuous stirring. Then, 1.5 mol of Ca(NO3)2·4H2O was added to the solution. The solution was heated to 60 °C and maintained until gelation occurred. Then, the gel was dried at 200 °C and calcined at 1500 °C for 6 hours. Tricalcium silicate is a strongly basic homogeneous compound having about 74 wt% of a strongly basic component (CaO). Fluoroaluminosilicate (FAS) glass was prepared essentially as described in Example 1 of U.S. Patent No. 5,154,762. Powder components of SiO2 (34.6 wt%), AlF3 (21.5 wt%), SrO (18.7 wt%), Al2O3 (9.4 wt%), AlPO4 (6.5 wt%), Na2AlF6 (5.6 wt%), P2O5 (3.7 wt%) were mixed and melted in an arc furnace at 1350 - 1450 °C, and roller quenched in an amorphous single-phase FAS glass. Then, the glass was ball milled to obtain a milled product having a surface area of 2.6 m 2 / g (measured according to the Brunauer-Emmett-Teller (BET) method).

[0155] Calculation Using the following formulas 1 - 6, the shell thickness, the weight percentage of the core material, and the weight percentage of the shell material for the encapsulated materials prepared by the processes described in Examples 1 - 5 were calculated. In the calculation, the total surface area of the core material was determined by representing the particles of the core material powder as spheres (surface area = 4π(d / 2) 2 , volume = (4 / 3)(π)(d / 2) 3 ). Formula 1: [Number] ST em (cm) = the shell thickness of the encapsulated material. V mo (cm 3 ) = the volume of the metal oxide prepared by the APCVD process. SA c(cm 2 ) = Total surface area of the core material powder. Equation 2:

Number

Number

Number

Number

[0156] For the encapsulated material with tricalcium silicate core, the core particles had additional porosity that affected the measured apparent surface area. For the encapsulated material with tricalcium silicate, the effective surface area of the core and the thickness of the shell coating were estimated using an indirect method. The encapsulated material with tricalcium silicate and the encapsulated material with Portland cement (with the same shell material) that had approximately the same time as the time required to change the pH of the buffer from 4 to 9 (following the procedure of Examples 6 - 9) were estimated to have the same shell thickness. Therefore, the shell thickness of the encapsulated material with tricalcium silicate was based on the value calculated for the corresponding encapsulated material with Portland cement.

[0157] Example 1. Encapsulated material with 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 frit funnel tube (2 cm in diameter and 18 cm in height). The reactor had an inlet tube extending from below the frit routed parallel to the reactor body and an extended top region above the frit, enabling the desired reactor height and attachments for the precursor injector tube and the exhaust outlet. The temperature was controlled at 180 °C using an oil bath. Nitrogen carrier gas was used in a standard bubbler configuration for the liquid precursor. The bubbler was maintained at an ambient temperature of approximately 22 °C. The flow rate through the trimethylaluminum (TMA) bubbler was in the range of 100 - 330 cm 3 / min. The flow rate through the water bubbler was in the range of (250 - 1250 cm 3 / min). The total coating time was in the range of 20 - 100 minutes. Encapsulated materials A - J were prepared by varying the following parameters: the amount of bioactive glass added, the particle size of the bioactive glass powder, the TMA flow rate, the water flow rate, and the 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 in diameter and 30 cm in 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 above 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 a 5 mm media to obtain a particle size of 10 microns before adding it to the reactor. The average particle size of each milled powder was measured using a Model LA950 Laser Particle Size Analyzer (Horiba Scientific, Edison, NJ) with water.

[0158] Table 1a reports the calculated shell thickness (nanometers), core weight %, and shell weight % for encapsulated materials A - J.

[0159]

Table 2

[0160]

Table 3

[0161] Example 2. Encapsulated Material with 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 frit funnel tube (4 cm in diameter, 30 cm in height). The reactor had an inlet tube extending from below the frit routed parallel to the reactor body and an extended top region above the frit, allowing for the desired reactor height and attachments for the precursor injector tube and exhaust outlet. The temperature was controlled at 180 °C using an oil bath. Nitrogen carrier gas was used in a standard bubbler configuration for the liquid precursor. The bubbler was maintained at an ambient temperature of about 22 °C. The flow rate through the trimethylaluminum (TMA) bubbler was 500 cm 3 / min. The flow rate through the water bubbler was 1750 cm 3 / min. The total coating time was 40 min. Table 2 lists the average particle size of the tricalcium silicate powder added to the reactor and other encapsulation parameters. Following the coating procedure, the resulting encapsulated materials were individually sieved to collect the encapsulated materials with a particle size less than 38 microns. These sieved encapsulated materials were designated as encapsulated materials K and L.

[0162] Table 2a reports the calculated shell thickness (nanometers), core weight %, and shell weight % for the encapsulated materials K - L.

[0163]

Table 4

[0164]

Table 5

[0165] Example 3. Encapsulated Materials with 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 frit funnel tube (4 cm in diameter and 30 cm in height). The reactor had an inlet tube extending from below the frit routed parallel to the reactor body and an extended top region above the frit, enabling the desired reactor height and attachments for the precursor injector tube and exhaust outlet. The temperature was controlled at 180 °C using an oil bath. Nitrogen carrier gas was used in a standard bubbler configuration for the liquid precursor. The bubbler was maintained at an ambient temperature of about 22 °C. The flow rate through the trimethylaluminum (TMA) bubbler ranged from 240 - 1000 cm 3 / min. The flow rate through the water bubbler ranged from (610 - 2500 cm 3 / min). The total coating time ranged from 10 - 105 minutes. Encapsulated materials M - U were prepared by varying the following parameters: the amount of Portland cement added, the particle size of the Portland cement powder, the TMA flow rate, the water flow rate, and the coating time. Table 3 lists the encapsulation parameters for the encapsulated materials M - U.

[0166] For the 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) when measured using a Coulter Counter Multisizer 3 (Beckman Coulter Company, Brea, CA).

[0167] For the encapsulated materials N - S, prior to addition to the reactor, fine particles were removed from the Portland cement sample by air classification using an AVEKA CCE centrifugal air classifier model 100 (AVEKA CCE LLC, Cottage Grove, MN). Parameters were selected to obtain a coarse material with a yield of 56% and provided a sample having an average particle size of 24.4 microns (D10 - D90 range of 13.8 - 38.4 microns) when measured using a Coulter Counter Multisizer 3 (Beckman Coulter Company).

[0168] For the encapsulated materials T - U, prior to addition to the reactor, fine and coarse particles were removed from the Portland cement sample using an AVEKA CCE centrifugal air classifier model 100. In the first step, approximately 24% of the coarse portion of the initial sample was removed, and then in the second step, approximately 25% of the fine portion was removed from the remaining sample. The resulting Portland cement powder had an average particle size of 19.6 microns (D10 - D90 range of 9.4 - 31.5 microns) when measured using a Coulter Counter Multisizer 3 (Beckman Coulter Company).

[0169] Table 3a reports the calculated shell thickness (nanometers), core weight %, and shell weight % for the encapsulated materials M - U.

[0170] [Table 6]

[0171]

Table 7

[0172] Example 4. Encapsulated Material with Portland Cement Core and 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. Before filling the reactor, fine particles were removed from the Portland cement sample using the air classification procedure described for the 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) when measured using a Coulter Counter Multisizer 3 (Beckman Coulter Company). The reactor was a glass frit funnel tube (4 cm in diameter, 30 cm in height). The reactor had an inlet tube extending from below the frit routed parallel to the body of the reactor and an extended top region above the frit, allowing for the desired reactor height and attachments for the precursor injector tube and exhaust outlet. The temperature was controlled at 180 °C using an oil bath. Nitrogen carrier gas was used in a standard bubbler configuration for the liquid precursor. The bubbler was maintained at an ambient temperature of about 22 °C. The flow rate through the titanium tetrachloride bubbler was 1000 cm 3 / min. The flow rate through the water bubbler was 1000 cm 3 / min. The total coating time was 57 minutes.

[0173] Example 5. Encapsulated Material with Portland Cement Core and Silicon Dioxide Shell Portland cement was encapsulated with a silicon dioxide-based material using the atmospheric pressure chemical vapor deposition method (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. Before filling the reactor, fine particles were removed from the Portland cement sample using the air classification procedure described for the 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) when measured using a Coulter Counter Multisizer 3 (Beckman Coulter Company). The reactor was a glass frit funnel tube (4 cm in diameter, 30 cm in height). The reactor had an inlet tube extending from below the frit routed parallel to the body of the reactor and an extended top region above the frit, enabling 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 in a standard bubbler configuration for the liquid precursor. The bubbler was maintained at an ambient temperature of approximately 22 °C. The flow rate through the silicon tetrachloride bubbler was 60 cm 3 / min. The flow rate through the water bubbler was 1300 cm 3 / min. The total coating time was 58 minutes.

[0174] Table 3b reports the calculated values of shell thickness (nanometers), core weight %, and shell weight % for the encapsulated materials of Examples 4 and 5.

[0175]

Table 8

[0176] Example 6. To each of four glass vials, 15 g of deionized water and 10 g of a pH 4 buffer solution (buffer BDH5018, VWR International) were filled, and the solution in the vial was stirred. Unencapsulated Portland cement (0.25 g, particle size of 24.4 microns) 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 was continued in the vial, and the pH of each solution was measured over 8 - 10 minutes using a Mettler Toledo M300 pH Meter (Mettler Toledo Corporation, Columbus, OH). The thickness of the shell of the encapsulated material was corrected by changing the coating time to a longer coating time to produce a thicker shell. The shell of encapsulated material O became approximately 4.25 times thicker than the shell of encapsulated material Q. The results are presented in Table 4, indicating that the encapsulated material brought about a delayed reaction with the basic core material or a delayed release of the basic core material.

[0177]

Table 9

[0178] Example 7. To each of two glass vials, 15 g of deionized water and 10 g of a pH 4 buffer solution (buffer BDH5018, VWR International) were filled, and the solution in the vial was stirred. The material encapsulated with titanium dioxide of Example 4 (0.25 g) was added to the first vial. The material encapsulated with silicon dioxide of Example 5 (0.25 g) was added to the second vial. Stirring was continued in the vial, and the pH of each solution was measured over 45 minutes using a Mettler Toledo M300 pH Meter (Mettler Toledo Corporation). The results are shown in Table 5, indicating that the encapsulated material brought about a delayed reaction with the basic core material or a delayed release of the basic core material.

[0179]

Table 10

[0180] Example 8. Each of three glass vials was filled with 15 g of deionized water and 10 g of a pH 4 buffer solution (buffer BDH5018, VWR International), and the solution in the vial was 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 was continued in the vials, and the pH of each solution was measured over 12 minutes using a Mettler Toledo M300 pH Meter (Mettler Toledo Corporation). The results are shown in Table 6, indicating that the encapsulated material resulted in a delayed reaction with the basic core material or a delayed release of the basic core material.

[0181]

Table 11

[0182] Example 9. Each of the four glass vials was filled with 15 g of deionized water and 10 g of a pH 4 buffer solution (buffer BDH5018, VWR International), and the solution in the vial was stirred. The encapsulated material O (0.25 g) was added to the first vial. The encapsulated material P (0.25 g) was added to the second vial. The encapsulated material Q (0.25 g) was added to the third vial. The encapsulated material R (0.25 g) was added to the fourth vial. Stirring was 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, indicating that the delayed release of the basic core material depends on the thickness of the shell. The thickness of the shell of the encapsulated material was modified by changing the coating time to a longer coating time to produce a thicker shell. The thickness of the aluminum oxide shell of the encapsulated materials O to R decreased gradually as follows: shell thickness: encapsulated material O > encapsulated material P > encapsulated material Q > encapsulated material R. The relative shell thicknesses of the encapsulated materials O to R were approximately 8.5:4.5:2:1 (Table 7).

[0183]

Table 12

[0184] Example 10. To each of two glass vials, 15 g of deionized water and 10 g of a pH 4 buffer solution (buffer BDH5018, VWR International) were filled, and the solution in the vial was stirred. Unencapsulated bioactive glass (0.25 g, with a particle size of 38 - 45 microns) was added to the first vial. Encapsulated material J (0.25 g) was added to the second vial. Stirring was continued in the vial, and using a Mettler Toledo M300 pH Meter (Mettler Toledo Corporation), the pH of each solution was measured over 60 minutes. The results are shown in Table 8, indicating that the encapsulated material brought about a delayed reaction with the basic core material or a delayed release of the basic core material.

[0185]

Table 13

[0186] Example 11. Each of two glass vials was filled with 25 g of deionized water. Unencapsulated Portland cement (0.25 g, with a particle size of 24.4 microns) was added to the first vial. Encapsulated material P (0.25 g) was added to the second vial. The contents were stirred, and using a Mettler Toledo M300 pH Meter (Mettler Toledo Corporation), the pH of each solution was measured over 5 minutes. The results are shown in Table 9, indicating that the encapsulated material brought about a delayed reaction or release with the basic core material.

[0187]

Table 14

[0188] Example 12. Each of the two glass vials was filled with 25 g of deionized water. Unencapsulated bioactive glass (0.25 g, with a particle size of 38.45 microns) 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 3 minutes using a Mettler Toledo M300 pH Meter (Mettler Toledo Corporation). The results are shown in Table 10, indicating that the encapsulated material resulted in a delayed reaction with the basic core material or a delayed release of the basic core material.

[0189]

Table 15

[0190] Example 13 (Comparative Example). A glass vial was filled with 25 g of deionized water, and 0.25 g of unencapsulated FAS glass (0.25 g) was added to the vial. The contents were stirred, and the pH of the solution was measured over 3 minutes using a Mettler Toledo M300 pH Meter (Mettler Toledo Corporation). The results are shown in Table 11.

[0191]

Table 16

[0192] Example 14. Dental composition containing an encapsulated material of bioactive glass Dental compositions 1 - 6 (DC - 1 to DC - 6) were prepared using pastes B1 - B6 as the first part of the composition and a paste selected from paste A as the second part of the composition.

[0193] The composition of Paste A is reported in Table 12 (each component is reported in wt%). Paste A was prepared in bulk. BHT and CPQ were added to a mixing cup containing HEMA. The filled cup was placed on 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 was continued. The CGP, Zr / Si nanocluster filler, and ytterbium fluoride component were combined to form a homogeneous mixture, which was then added to the cup. Mixing was continued until the mixture was homogeneous. The resulting paste was stored at 4 °C when not in use.

[0194] The compositions of Pastes B1 - B4 and Paste BA are reported in Table 13 (each component is reported in wt%). 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. Next, the EDMAB\HEMA mixture was 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.

[0195] The compositions of Pastes B5 and B6 are reported in Table 14, and the pastes were prepared according to the above general method for Pastes B1 - B4.

[0196] Regarding dental composition 1, paste B1 was the first part of the composition. The paste A of DC-1 and paste B1 (1:1 by weight) were combined on a mixing pad and stirred until homogeneous (mixed for about 10 - 30 seconds). The pH of the resulting paste was immediately measured using an ORION PERPHECT ROSS pH Micro Electrode (catalog number 8220BNWP, Thermo Fisher Scientific Company, Waltham, PA). The pH measurement value 30 seconds after inserting the probe into the paste was recorded. The recorded pH was 4.3. A Teflon disk mold (diameter 3.1 mm and height 1.3 mm) was immediately filled with the paste, and then the paste was cured for 20 seconds on each side of the mold using an ELIPAR S10 curing light (3M Oral Care, Maplewood, MN). The resulting molded disk was immediately removed from the mold and placed into a 2 mL plastic centrifuge tube containing 1.5 mL of GIBCO phosphate buffered saline (PBS) solution (1×, pH 7.4) (Thermo Fisher Scientific). The disk was completely immersed in the PBS solution. The tube was capped and stored at room temperature.

[0197] Regarding dental composition 2 (DC-2), paste B2 replaced paste B1 as the first part of the composition. A molded disk was prepared using DC-2 following the procedure described for DC-1. The pH of the paste measured immediately before filling the mold was 3.8.

[0198] Regarding dental composition 3 (DC-3), paste B3 replaced paste B1 as the first part of the composition. A molded disk was prepared using DC-3 following the procedure described for dental composition 1. The pH of the paste measured immediately before filling the mold was 3.7.

[0199] For dental composition 4 (DC-4), paste B4 replaced paste B1 as the first part of the composition. According to the procedure described for DC-1, a formed disk was prepared using DC-4. The pH of the paste measured immediately before filling the mold was 3.6.

[0200] For dental composition 5 (DC-5), paste B5 replaced paste B1 as the first part of the composition. According to the procedure described for DC-1, a formed disk was prepared using DC-5. The pH of the paste measured immediately before filling the mold was 4.9.

[0201] For dental composition 6 (DC-6), paste B6 replaced paste B1 as the first part of the composition. According to the procedure described for DC-1, a formed disk was prepared using DC-6. The pH of the paste measured immediately before filling the mold was 3.8.

[0202] 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 the encapsulated material. According to the procedure described for DC-1, a formed disk was prepared using comparative DC-A. The pH of the paste measured immediately before filling the mold was 3.6.

[0203] For each immersion disk, the pH of the PBS solution was periodically measured over 364 hours using an ORION PERPHECT ROSS pH Micro Electrode (catalog number 8220BNWP, Thermo Fisher). The sample was gently shaken before each measurement. The pH profiles of the PBS solution are reported in Tables 15 and 16. The pH measurement recorded at "0 hours" was performed immediately after immersing the disk in the PBS solution.

[0204] In Table 15, the concentration (wt%) of the encapsulated material H incorporated into the dental composition decreased from DC-1 to DC-4 compared to Comparative DC-A which did not contain the encapsulated material H (i.e., the concentration of the incorporated encapsulated material was DC-1 > DC-2 > DC-3 > DC-4 > Comparative DC-A). In Table 16, the shell thickness of the encapsulated material in dental compositions DC-1, DC-5, and DC-6 was varied such that DC-6 contained the encapsulated material with the thickest shell and DC-5 contained the encapsulated material with the thinnest shell.

[0205]

Table 17

[0206]

Table 18

[0207]

Table 19

[0208]

Table 20

[0209]

Table 21

[0210] Example 15. Dental Composition Containing Encapsulated Material of Portland Cement Dental compositions (DC-7 to DC-11) were prepared using pastes B7 to B11 as the first part of the composition and a paste selected from paste A as the second part of the composition.

[0211] Paste A was prepared as reported in Example 14.

[0212] Report the compositions of pastes B7 - B9 in Table 17 (each component is reported in wt%). Pastes B7 - B9 were prepared by adding and mixing EDMAB into a flask containing HEMA. In a separate beaker, FAS glass, encapsulated material P (from Table 3), and fumed silica were mixed to form a homogeneous mixture. Next, the EDMAB / HEMA mixture was 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.

[0213] Report the composition of paste B10 in Table 18. Paste B10 was prepared according to the general method described above for pastes B7 - B9, except that the encapsulated material P was replaced with the encapsulated material of Example 4 (titanium dioxide encapsulated Portland cement).

[0214] Report the composition of paste B11 in Table 19. Paste B11 was prepared according to the general method described above for pastes B7 - B9, except that the encapsulated material P was replaced with the encapsulated material of Example 5 (silicon dioxide encapsulated Portland cement).

[0215] For dental composition 7 (DC - 7), paste B7 was the first part of the composition. Paste A and paste B7 of DC - 7 (1:1 by weight) were combined on a mixing pad and stirred until homogeneous (mixed for about 10 - 30 seconds). The pH of the resulting paste was measured with an ORION Measurement was immediately performed using a PERPHECT ROSS pH Micro Electrode (Catalog No. 8220BNWP, Thermo Fisher Scientific Company). The pH measurement value 30 seconds after inserting the probe into the paste was recorded. The recorded pH was 3.5. A Teflon disk mold (diameter 3.1 mm and height 1.3 mm) was immediately filled with the paste, and then the paste was cured for 20 seconds on each side of the mold using an ELIPAR S10 curing light (3M Oral Care, Maplewood, MN). The obtained molded disk was immediately taken out of the mold and placed into a 2 mL plastic centrifuge tube containing 1.5 mL of GIBCO phosphate buffered saline (PBS) solution (1×, pH 7.4) (Thermo Fisher Scientific). The disk was completely immersed in the PBS solution. The tube was capped and stored at room temperature.

[0216] For dental composition 8 (DC-8), paste B8 replaced paste B7 as the first part of the composition. A molded disk was prepared using DC-8 following the procedure described for DC-7. The pH of the paste measured immediately before filling the mold was 3.5.

[0217] For dental composition 9 (DC-9), paste B9 replaced paste B7 as the first part of the composition. A molded disk was prepared using DC-9 following the procedure described for DC-7. The pH of the paste measured immediately before filling the mold was 3.6.

[0218] For dental composition 10 (DC-10), paste B10 replaced paste B7 as the first part of the composition. A molded disk was prepared using DC-10 following the procedure described for DC-7. The pH of the paste measured immediately before filling the mold was 3.3.

[0219] For the dental composition 11 (DC-11), paste B11 replaced paste B7 as the first part of the composition. A molded disk was prepared using DC-11 according to the procedure described for DC-7. The pH of the paste measured immediately before filling the mold was 3.3.

[0220] For each immersion disk, the pH of the PBS solution was periodically measured over 333 or 646 hours using an ORION PERPHECT ROSS pH Micro Electrode (catalog number 8220BNWP, Thermo Fisher). The sample was gently shaken before each measurement. The pH profiles of the PBS solution are reported in Tables 20 and 21. The pH measurement recorded at "0 hours" was performed immediately after immersion of the disk in the PBS solution.

[0221] In Table 20, dental compositions with 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.

[0222] [Table 22]

[0223] [Table 23]

[0224] [Table 24]

[0225] [Table 25]

[0226] [Table 26]

[0227] Example 16. Dental composition containing a material encapsulated with tricalcium silicate According to the procedure reported in Example 14, a molded disk was prepared using the dental composition DC-12. 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 stirred paste measured immediately before filling the mold was 3.7. The pH of the PBS solution surrounding the disk was measured periodically over 790 hours according to the procedure described in Example 14, and the results were reported in Table 23. The pH measurement recorded at "0 hours" was performed immediately after immersion of the disk in the PBS solution.

[0228] [Table 27]

[0229] [Table 28]

[0230] Example 17. Cell proliferation of dental pulp stem cells contacted with a dental composition containing an encapsulated bioactive glass Dental compositions 1 to 4 and molded disks (diameter 3.1 mm and height 1.3 mm) of comparative dental composition A were prepared using the general mixing and curing procedures for preparing the molded disks described in Example 14. Individual disks were also prepared from a commercially available dental base / liner product (Comparative Example X) and a commercially available pulp cap / liner product (Comparative Example Y). The disks were placed continuously in a 70% ethanol bath for 20 minutes and individually sterilized by rinsing with PBS (3 times), and then incubated overnight in dental pulp stem cell (DPSC) basal medium (Lonza Group LTD., Basel, Switzerland) (37 °C, 5% CO2, 98% relative humidity). Human dental pulp stem cells (DPSC, Lonza Group LTD.) were seeded at 20,000 cells / mL per well in a COSTAR 48-well cell culture plate (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.

[0231] 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) together with an MTT colorimetric assay kit (Invitrogen Corporation, Carlsbad, CA). In Table 24, the average OD540 (n = 6) for DPSC samples contacted with dental compositions 1 to 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 is recorded.

[0232]

Table 29

[0233] Cell proliferation of dental pulp stem cells contacted with a dental composition containing encapsulated Portland cement or encapsulated tricalcium silicate Molding disks (3.1 mm in diameter and 1.3 mm in 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. As described in Example 17, a control (well seeded with DPSCs but without the addition of a molding disk) was also prepared. In Table 25, the average OD540 (n = 4) for DPSC samples contacted with dental compositions 8, 10, 11, 12 (containing an encapsulated material having a Portland cement or tricalcium silicate core with different shell coatings), comparative dental composition A (not containing an encapsulated material), comparative examples X and Y, and the control are recorded.

[0234]

Table 30

[0235] Example 19. ALP activity of dental pulp stem cells contacted with a dental composition Dental compositions 1-4, Comparative dental composition A, Comparative Example X, and Comparative Example Y molding disks (diameter 3.1 mm and height 1.3 mm) were prepared using the general mixing and curing procedures for preparing the molding disks described in Example 14. The disks were individually sterilized by continuously placing them in a 70% ethanol bath for 20 minutes and rinsing them with PBS (3 times), and then incubated overnight in dental pulp stem cell (DPSC) basal medium (Lonza Group LTD.) (at 37 °C, 5% CO2, 98% relative humidity). Human dental pulp cells (DPSC, Lonza Group LTD.) were seeded at 20,000 cells / mL per well in a COSTAR 48-well cell culture plate (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, human dental pulp stem cells were seeded in additional wells, but no molding disks were added to any of these wells.

[0236] On day 7, the DPSC cells were harvested, and the cell lysates of 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. In Table 26, the average ALP concentrations (n = 2) for DPSC samples contacted with dental compositions 1-4 (containing various concentrations of encapsulated bioactive glass materials), Comparative dental composition A (not containing an encapsulated material), Comparative Examples X and Y, and the control are recorded in mU / mL.

[0237]

Table 31

[0238] Example 20. ALP Activity of Dental Pulp Stem Cells Contacted with Dental Compositions Formed disks (diameter 3.1 mm and height 1.3 mm) 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. As described in Example 19, a control (well seeded with DPSCs but without the addition of formed disks) was also prepared. In Table 27, the average ALP concentrations (n = 1 - 3) for dental compositions 8, 10, 11, 12 (containing encapsulated materials with Portland cement or tricalcium silicate cores with different shell coatings), comparative dental composition A (not containing encapsulated materials), comparative examples X and Y, and DPSC samples contacted with the control are recorded in mU / mL.

[0239]

Table 32

[0240] Example 21. Encapsulated materials having a calcium hydroxide core or a mixed-phase calcium silicate core Calcium hydroxide (CH) powder was obtained from Jost Chemical (St. Louis, MO, product number: 2242). The material was passed through a 25-micron sieve.

[0241] Mixed-phase calcium silicate (MPCS) was prepared by mixing 14.1 wt% SiO2, 50.3 wt% CaCO3, 34.7 wt% H2O, and 0.8 wt% BYK-W9012. The wetting and dispersing additive of BYK-W9012 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 ground using a mortar and pestle to obtain a powder having an average particle size of 11.35 microns measured by laser diffraction.

[0242] 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 that the reactor was heated with a heating tape), and the powder amounts and flow rates were reported in Table 28.

[0243]

Table 33

[0244] Example 22. pH Buffer Test of Encapsulated Materials The test described in Example 6 was performed on both unencapsulated CH and MPCS, and encapsulated CH and MPCS sampled from the batches described in Table 28. The pH of the buffer solution just before powder addition was 4.1 for all four samples. The results are shown in Table 29, indicating that the encapsulated materials resulted in a delayed reaction with the basic core material or a delayed release of the basic core material.

[0245]

Table 34

[0246] 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. An aluminum oxide coating was deposited by self-limiting surface reactions on the target particle material using a flow-through atomic layer deposition (FTALD) reactor incorporating a sequential four-step process (precursor A, purge, precursor B, purge).

[0247] The sequential four-step process consisted of the following sequence: (1) a precursor A (i.e., trimethylaluminum (TMA)) pulse, (2) an N2 purge, (3) a precursor B (i.e., ozone @ 20% pulse), and (4) an N2 purge. The time and pressure of the TMA precursor pulse were set at 1.125 seconds at a pressure of 1 - 3 torr inside the reactor. The time and pressure of the ozone precursor pulse were set at 1.000 seconds at a pressure of 1 - 4 torr inside the reactor. The purge time was in the range of 100 - 120 seconds per half cycle. The four-step sequence is referred to herein as 1 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.

[0248] The internal sample chamber consisted of a 34 mm frit tube with one end closed and the other open end fitted with a fitting (VCR8 fitting). The fitting was then attached to a precursor delivery system that allowed various gases to be added inside the frit tube and exhausted through the walls of the frit tube.

[0249] The precursor delivery system was designed using a rotary union such that the frit tube (sample chamber) rotated independently of the rest of the reactor system. The frit 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 precursors during the deposition process.

[0250] During the deposition process, the tube containing the particles was rotated, thereby lifting the particles along the walls of the tube and allowing them to free fall to the bottom of the tube. During free fall, the particles were sequentially exposed to various precursors and purge steps as the gas flowing into the open end of the frit tube was exhausted through the walls. A vibration motor that provided additional agitation to maintain free flow of the particles during the deposition process was also attached to the reactor assembly. All gases were heated to 80 °C so that the gas flow did not cool the sample.

[0251] To ensure that a sufficient amount of the precursor was supplied to the reactor, the filling of the precursor was monitored using a residual gas analyzer (obtained under the trade name "SRS RESIDUAL GAS ANALYZER" from Stanford Research Systems, Inc., Sunnyvale, CA).

[0252] The obtained encapsulated powder was measured for pH change using the procedure described in Example 6. The results are reported in Table 30.

[0253]

Table 35

[0254] Example 24. Measurement of the adhesive strength of dental composition 8 (DC-8) and comparative dental composition A (DC-A) applied to the dentin surface. Bovine incisors (10) were separately embedded in resin packs (one tooth per pack) with a diameter of 25 mm and a height of 10 - 20 mm. Each obtained pack was ground with 120 - grit sandpaper to expose the dentin layer of the tooth, and then polished with 320 - grit sandpaper. All experiments were carried out indoors at a constant temperature of 75 °C, a humidity of 50%, and using light filtered at 450 nm. Each tooth surface was blotted to remove excess water, and a 5 - mm - diameter circle of exposed dentin was framed 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 site, wiped off to a uniform height with the mask using a spatula, and then cured for 20 seconds using ELIPAR S10 LED curing light (3M Company). Next, using a disposable applicator, SCOTCHBOND Universal Adhesive (3M Company) was applied to the cured surface for 20 seconds. This site was dried with a gentle air flow for 5 seconds and then photocured for 10 seconds using ELIPAR S10 LED curing light. A Teflon mask with a 5 - mm - diameter hole lined with gelatin and a depth of 2 - 5 mm was aligned with the tape mask and fixed with a metal clip. Then, the hole was filled with FILTEK Z250 dental composite resin (3M Company) and photocured for 20 seconds using ELIPAR S10 LED curing light to fabricate a peg. Next, the tooth sample was placed in a chamber (37 °C and 95% humidity) for 0.5 hour. The metal clip was removed from the tooth sample, and each sample 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 fixed to 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 in length. The wire was looped over the FILTEK Z250 peg and fixed in the same plane as the tooth / resin surface. Then, to determine the adhesion of the cured dental composition DC - 8 to the tooth, tension was applied until failure (i.e., the assembly was broken from the tooth surface or the tooth was broken).

[0255] The 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) determined for Dental Compositions DC-A and DC-8 are reported in Table 31.

[0256]

Table 36

[0257] 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 three times for 1 minute at 3000 rpm in a FlackTek DAC 150 FVZ speed mixer. A Teflon disk mold (3.1 mm in diameter and 1.3 mm in height) was 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 formed disk 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 (1×, pH 7.4) (Thermo Fisher Scientific). The disk was completely immersed in the PBS solution. The tube was capped and stored at room temperature. The disks from Dental Composition B functioned as a control (containing no encapsulated material).

[0258] 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. Formed disks were prepared using DC-13 following the procedure described for DC-B.

[0259] Dental Composition C (DC-C) was prepared by combining 3 g of unencapsulated Portland cement with 1 g of DC-B. The mixture was mixed three times for 1 minute at 3000 rpm. Molded disks were prepared with DC-C following the procedure described for DC-B. The disk from Dental Composition C served as a control (containing unencapsulated Portland cement).

[0260] For each immersed disk, the pH of the PBS solution was measured periodically over a period of 90.4 hours using an ORION PERPHECT ROSS pH Micro Electrode (catalog number 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 disk in the PBS solution.

[0261] [Table 37]

Claims

**Claim 1** A curable dental composition comprising: a first part containing an encapsulated material, said encapsulated material comprising a basic core material and an inorganic shell material surrounding said core and containing a metal oxide; a second part containing water or an acidic component; **Claim 2** The dental composition according to claim 1, wherein when said first and second parts are combined, the composition initially has an acidic or neutral pH. **Claim 3** The dental composition according to claim 1 or 2, wherein said shell is decomposable by said second part. **Claim 4** The dental composition according to any one of claims 1 to 3, wherein said basic core material releases -OH upon decomposition of said shell. **Claim 5** The dental composition according to any one of claims 1 to 4, wherein said basic core material comprises a component having a pKa in the range of 8 to 14. **Claim 6** The dental composition according to any one of claims 1 to 5, wherein said basic core material comprises a component having a pKa in the range of 11 to 14. **Claim 7** The dental composition according to any one of claims 1 to 6, wherein said basic core material comprises a material that releases calcium ions. **Claim 8** The dental composition according to any one of claims 1 to 7, wherein said basic core material comprises at least 25, 30, 35, 40, or 45% by weight of a component having a pKa in the range of 11 to 14. **Claim 9** The dental composition according to any one of claims 1 to 8, wherein said shell is a continuous film having a thickness of less than 500 nm. **Claim 10** The dental composition according to any one of claims 1 to 9, wherein said inorganic shell material is less basic than said basic core material. **Claim 11** The dental composition according to any one of claims 1 to 10, wherein said inorganic shell material comprises a metal oxide having a pKa of 6 to 8. **Claim 12** The dental composition according to any one of claims 1 to 11, wherein when 0.25 grams of said encapsulated material is combined with 25 g of deionized water, a pH of at least 8.5 or 9 is obtained within 24 hours. **Claim 13** The dental composition according to any one of claims 1 to 12, wherein when 0.25 grams of said encapsulated material is combined with a solution of 15 g of deionized water and 10 g of an 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.

14. The dental composition according to any one of claims 1 to 13, wherein the basic core material is curable.

15. The dental composition according to claim 14, wherein the basic core material contains calcium silicate.

16. The dental composition according to any one of claims 1 to 15, wherein the basic core material is a dental filling material containing a neutral metal oxide having low solubility in the second portion.

17. The dental composition according to any one of claims 1 to 16, wherein the curable dental composition contains a material that promotes remineralization by releasing calcium ions, phosphorus ions, fluoride ions, or a combination thereof.

18. The dental composition according to any one of claims 1 to 16, further comprising at least one second filler.

19. The dental composition according to claim 18, wherein the second filler contains a nano-scale particulate filler.

20. The dental composition according to claim 19, wherein the second filler contains zirconia, silica, or a mixture thereof.

21. The dental composition according to any one of claims 19 to 20, wherein the second filler contains a nanocluster filler.

22. The dental composition according to any one of claims 1 to 21, wherein the first and / or second portion contains a polymerizable material.

23. The dental composition according to claim 22, wherein the polymerizable material contains a hydroxy-functional (meth)acrylate monomer, an acidic polymer, or a combination thereof.

24. The dental composition according to any one of claims 1 to 23, wherein the cured dental composition provides a pH of at least 8.5 or 9 within 500 hours according to the disk buffering test.

25. The dental composition according to any one of claims 1 to 24, wherein the average cell proliferation of dental pulp cells is at least 75% of the control sample when in contact with the cured dental composition.

26. The dental composition according to any one of claims 1 to 25, wherein the average ALP activity of dental pulp cells increases when in contact with the cured dental composition.

27. A composition, a first portion containing an encapsulated material, wherein the encapsulated material contains a basic core material and an inorganic shell material containing a metal oxide surrounding the core, the first portion, and a second portion containing water or an acidic component.

28. A composition, An encapsulated material comprising a basic core material and an inorganic shell material comprising a metal oxide surrounding the core, and Water or an acidic component, a composition comprising.

29. The composition according to claim 27 or 28, further characterized by any one or a combination of claims 2 to 26.

30. An encapsulated material suitable for use as a biocompatible carrier material, the encapsulated material comprising a basic core material and an inorganic shell material comprising a metal oxide surrounding the core.

31. The encapsulated material according to claim 30, further characterized by any one or a combination of claims 4 to 16.

32. The encapsulated core material according to claim 30 or 31, wherein the composition is curable or self-curing when mixed with water.

33. A curable composition comprising the encapsulated material according to any one of claims 30 to 32.

34. The curable dental composition according to claim 33, which is a dental or medical composition.

35. The curable composition according to any one of claims 30 to 34, further comprising a second filler and / or a polymerizable material according to any one or a combination of claims 18 to 23.

36. The curable composition according to any one of claims 32 to 35, which is in contact with water or an acidic component during use.

37. The curable composition according to claim 36, wherein the water or acidic component is a biological fluid.

38. A method of delaying the release of a basic core material, comprising: Preparing the composition according to any one of claims 1 to 37, and Applying the composition to a tooth or bone structure, a method comprising.

39. A method of effecting a basic delay increase, comprising: Preparing the composition according to any one of claims 1 to 37, and Applying the composition to a tooth or bone structure, a method comprising.

40. A method of promoting remineralization, comprising: Preparing the composition according to any one of claims 1 to 37, wherein the basic core further comprises a material that promotes remineralization, preparing, and Applying the composition to a tooth or bone structure, a method comprising.

41. The method according to claim 40, wherein the material that promotes remineralization releases calcium ions, phosphorus-containing ions, fluoride ions, or a combination thereof.

42. A method of increasing the average ALP activity of dental pulp cells, comprising: Preparing a composition according to any one of claims 1 to 35, wherein the basic core further comprises a material that promotes remineralization, and applying the composition to a tooth or bone structure, a method comprising.

43. A composition according to any one of claims 1 to 37 for use in applying to a tooth or bone structure, the composition being resulting in a delayed release of the basic core material, resulting in a delayed increase in basicity, promoting remineralization, increasing the average ALP activity of dental pulp cells, or a combination thereof, a composition.

44. A method of using a composition, comprising preparing a composition according to any one of claims 1 to 37, and applying the composition to a tooth or bone structure, a method comprising.

45. The method according to claim 44, wherein the composition comprises a polymerizable material and the method further comprises curing the composition by exposing it to a radiation source.

46. The method according to claim 44 or 45, wherein the composition results in a delayed release of the basic core material.

47. The method according to any one of claims 44 to 46, wherein the composition results in a delayed increase in basicity.

48. The method according to any one of claims 44 to 47, wherein the composition promotes remineralization of a tooth or bone structure.

49. The method according to any one of claims 44 to 48, wherein the composition increases the average ALP activity of dental pulp cells.

50. The method according to any one of claims 44 to 49, wherein the composition is a dental adhesive or cement used for bonding a dental article to a tooth structure.

51. The method according to any one of claims 44 to 49, wherein the composition is a dental restorative.

52. A method for producing an encapsulated material, comprising preparing a basic core material, and encapsulating the basic core material with an inorganic shell material containing a metal oxide by at least one vapor deposition technique, a production method.

53. The production method according to claim 52, comprising atomic layer deposition or atmospheric pressure chemical vapor deposition.

54. The production method according to claim 52 or 53, wherein the shell material and the thickness of the shell are selected to enable a delayed release of the basic core material.

55. The production method according to claim 52 or 53, wherein the encapsulated material results in an increase in pH after a longer duration than the same material without encapsulation.

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