NIELSEN, Mette Skovgaard (Parkvej 19 D, Taastrup, DK-2630, DK)
VAN LELIEVELD, Alexander (Engelstedsgade 32 2, Copenhagen Ø, DK-2100, DK)
NIELSEN, Mette Skovgaard (Parkvej 19 D, Taastrup, DK-2630, DK)
| CLAIMS 1. A dental filling material comprising one or more fillers and a polymerizable resin base, wherein said one or more fillers comprise metastable zirconia particles in the tetragonal and/or cubic crystalline phase with less than 30 % (v/v) in the monoclinic phase, said zirconia particles having surface functionalities of the formula: -Zr-O-Zr-O-C(=O)-X-C(R1)(R2)(R3) wherein X is selected from -O-, -NH- and -S-; R1 and R2 are independently selected from hydrogen, optionally substituted Ci-30-alkyl, a (meth)acrylate moiety, a (meth)acrylate-Ci-i2- alkyl moiety, optionally substituted C2-3o-alkenyl, optionally substituted C5-30-alkadienyl, and optionally substituted C8-3o-alkatrienyl, or when X is -NH-, R1 and R2 may together designate =0; and R3 is selected from hydrogen, Ci-6-alkyl, hydroxy and halogen. 2. The dental filling material according to claim 1, wherein said zirconia particles having surface functionalities of the formula: -Zr-O-Zr-O-CC=O)-X-CH(R1R2) wherein X is selected from -O-, -NH- and -S-; and R1 and R2 are independently selected from hydrogen, optionally substituted Ci-30-alkyl, optionally substituted C2-3o-alkenyl, optionally substituted C5-30-alkadienyl, and optionally substituted C8-3o-alkatrienyl, or when X is -NH-, R1 and R2 may together designate =0. 3. A dental filling material comprising one or more fillers and a polymerizable resin base, wherein said one or more fillers comprise metastable zirconia particles in the tetragonal and/or cubic crystalline phase with less than 30 % (v/v) in the monoclinic phase, said zirconia particles being prepared by a process comprising the sequential steps of: a) preparation of an amorphous powder of zirconia; b) calcination of the amorphous powder of zirconia at a temperature in the range of 400-600 0C so as to obtain metastable zirconia particles in the tetragonal and/or cubic crystalline phase with less than 30 % (v/v) in the monoclinic phase; c) treatment of the metastable zirconia particles with a compound of the formula H-X-CCF^XF^XR^wherein X is selected from -0-, -NH- and -S-; R1 and R2 are independently selected from hydrogen, optionally substituted Ci-30-alkyl, a (meth)acrylate moiety, a (meth)acrylate-Ci-i2-alkyl moiety, optionally substituted C2-3o-alkenyl, optionally substituted C5-30-alkadienyl, and optionally substituted C8-3o-alkatrienyl, or when X is -NH-, R1 and R2 may together designate =0; and R3 is selected from hydrogen, Ci-6-alkyl, hydroxy and halogen. 4. The dental filling material according to any of the preceding claims, wherein the average crystal size is in the range of 5-12 nm, such as 6-10 nm, in particular 6-9 nm or 6-8 nm. 5. The dental filling material according to any one of the preceding claims, wherein the zirconia particles have a BET surface area of 10-250 m2/g. 6. The dental filling material according to any one of the preceding claims, wherein the zirconia particles have an average crystal size in the range of 5-12 nm and a BET surface area of in the range of 10-250 m2/g. 7. The dental filling material according to any one of the preceding claims, wherein the improvement, "T", in the required amount of water (trigger molecule) is at least 30 %, when compared to a native sample metastable zirconia, and determined according to the method described herein ("Determination of water adsorption") with reference to the formula: T=(IOO %*((tu-tm)/tu)). 8. The dental filling material according to any one of the preceding claims, consisting of: 40-85 % by weight of the one or more fillers including the metastable zirconia; 15-60 % by weight of the a polymerizable resin base; 0-25 % by weight of additives; and 0-4 % by weight of solvents and/or water. 9. The dental filling material according to any one of the preceding claims, wherein X is -O-; and R1 and R2 are independently selected from hydrogen and optionally substituted Ci-i2-alkyl and optionally substituted Ci-i2-alkenyl. 10. The dental filling material according to claim 9, wherein the surface functionality is derived from H-X-CH(R1R2), which is selected from methanol and 2-propanol. 11. The dental filling material according to any one of the claims 1-8, wherein X is selected from -O- and -S-; and R1 and R2 are independently selected from hydrogen, optionally substituted Ci-30-alkyl, a (meth)acrylate moiety, a (meth)acrylate-Ci.i2-alkyl moiety, optionally substituted C2-30-alkenyl, optionally substituted C5-3o-alkadienyl, and optionally substituted C8-30-alkatrienyl, with the proviso that at least one of R1 and R2 are selected from a (meth)acrylate moiety and a (meth)acrylate-Ci-i2-alkyl moiety. 12. A method of controlling the volumetric shrinkage of a dental filling material upon curing, comprising the step of: (a) providing a dental filling comprising one or more fillers and a polymerizable resin base, wherein said one or more fillers comprise metastable zirconia particles in the tetragonal and/or cubic crystalline phase with less than 30 % (v/v) in the monoclinic phase, said zirconia particles having surface functionalities of the formula: -Zr-O-Zr-O-C(=O)-X-C(R1)(R2)(R3) wherein X is selected from -O-, -NH- and -S-; R1 and R2 are independently selected from hydrogen, optionally substituted Ci-30-alkyl, a (meth)acrylate moiety, a (methJacrylate-Ci-iz- alkyl moiety, optionally substituted C2.30-alkenyl, optionally substituted C5_3O-alkadienyl, and optionally substituted C8-3o-alkatrienyl, or when X is -NH-, R1 and R2 may together designate =0; and R3 is selected from hydrogen, C1-6-alkyl, hydroxy and halogen; (b) allowing the resin base to polymerize and cure, and allowing the metastable zirconia particles to undergo a martensitic transformation from a first metastable phase to a second stable phase. 13. The method according to claim 12, wherein the triggering of the metastable zirconia particles in order to facilitate the martensitic transformation takes place simultaneous and subsequent to the curing by means of water diffusion into the dental filling material. 14. A dental filling material as defined in any one of the claims 1-11 for use in medicine, in particular in dentistry. |
FIELD OF THE INVENTION
The present invention relates to the field of dental materials, in particular dental materials in which shrinkage of the resin base upon polymerization is countered by volumetric expansion of zirconia particles.
BACKGROUND OF THE INVENTION
The applicant's earlier PCT application No. WO 2005/099652 Al discloses a composite material exhibiting a low or even negligible volumetric shrinkage upon curing, or even a small expansion {e.g. up to 0.5 %), in particular composite materials in the form of dental filling materials, as well as a method of controlling volumetric shrinkage of a composite material upon curing. According to WO 2005/099652 Al, a volume stable composite material for dental use can, e.g., be obtained by the use of metastable zirconia particles.
The phase transformation of such metastable zirconia can be induced by trigger molecules such as H 2 O, HF, HCI, HBr and NH 3 (see in particular WO 2007/104312) The mechanism behind the initiation of phase transformation of zirconia is believed to be cleavage of Zr-O-Zr bridges with the use of trigger molecules. In the case where the amount of trigger molecules is limited, the generated amount of trigger molecules becomes the rate determining step of phase transformation. In other words the generation of trigger molecules limits the phase transformation in effect limiting the possible degree of phase transformation within a given period of time. This is the case where zirconia is encapsulated in a solid material where the diffusion is slow. Such a case can be illustrated by dental filling materials, where the filler is metastable zirconia and the resin material has been cured. The diffusion is very slow in a polymeric material (like dental filling materials) below its glass transition temperature. When such a material is subject to trigger molecules, e.g. water present in the mouth, triggering molecules (water) will be limited by diffusion, and phase transformation will be relatively slow. Another example is the system, where the triggering molecules is provided by photoactive molecules {e.g. a triazine), which upon light exposure liberates Cl radicals. The Cl radicals will then be used in the polymerization reaction with the monomers in the resin or will abstract a hydrogen atom and provide HCI to the surface of zirconia. When the resin cures, the diffusion will again be reduced in the dental filling material and the radicals will be subject to the "cage effect". Both the reaction with other monomers and the caging effect limits the amount of HCI available for the initiation of phase transformation on the surface of the metastable zirconia particles.
It is therefore very important to find ways of minimizing the amount of trigger molecules necessary to initiate a phase transformation.
Since the initiation of metastable zirconia is initiated on the surface of zirconia, a key element of making metastable zirconia is a high surface area. To ensure that the zirconia will not sinter (to much) in the calcination process, the surface should be covered with an organic surfactant (e.g. ethanol). The surfactants will be burned off during the calcination step and provide CO 2 to the zirconia surface. Some of species that are formed include bicarbonate, covalent bound carbonates, ionic carbonates and carboxylates illustrated below (commonly referred to as "carbonyl species" and broadly described as carbonates).
Zr /^°\ X Zr / 0 X + ZVr 0 X X Z r
Such species react with trigger molecules like water and HCI and will thereby "consume" at least some of the trigger molecules intended for initiation of the phase transformation.
In some embodiments, it is a great advantage to minimize the effects of carbonyl species.
In other embodiments, it may be an advantage that at least some of the trigger molecules are "consumed" by the carbonyl species so that the rate of phase transformation is reduced.
In view of the above, it is one object of the invention to provide dental filling materials wherein the degree of phase transformation and the rate at which the phase transformation takes place can be refined.
BRIEF DESCRIPTION OF THE INVENTION
In view of the objective mentioned above, the present invention provides a dental filling material comprising one or more fillers and a polymerizable resin base, wherein said one or more fillers comprise metastable zirconia particles in the tetragonal and/or cubic crystalline phase with less than 30 % (v/v) in the monoclinic phase, said zirconia particles having surface functionalities of the formula:
-Zr-O-Zr-O-C(=O)-X-C(R 1 )(R 2 )(R 3 )
wherein X is selected from -O-, -NH- and -S-; R 1 and R 2 are independently selected from hydrogen, optionally substituted Ci- 30 -alkyl, a (meth)acrylate moiety, a (meth)acrylate-Ci-i 2 - alkyl moiety, optionally substituted C 2 - 3 o-alkenyl, optionally substituted C 5 - 30 -alkadienyl, and optionally substituted C 8 - 3 o-alkatrienyl, or when X is -NH-, R 1 and R 2 may together designate =0; and R 3 is selected from hydrogen, Ci- 6 -alkyl, hydroxy and halogen.
The invention further provides, a dental filling material comprising one or more fillers and a polymerizable resin base, wherein said one or more fillers comprise metastable zirconia particles in the tetragonal and/or cubic crystalline phase with less than 30 % (v/v) in the monoclinic phase, said zirconia particles being prepared by a process comprising the sequential steps of:
a) preparation of an amorphous powder of zirconia;
b) calcination of the amorphous powder of zirconia at a temperature in the range of 400-600 0 C so as to obtain metastable zirconia particles in the tetragonal and/or cubic crystalline phase with less than 30 % (v/v) in the monoclinic phase;
c) treatment of the metastable zirconia particles with a compound of the formula H-X- C(R 1 XR 2 XR 3 ),
wherein X is selected from -O-, -NH- and -S-; R 1 and R 2 are independently selected from hydrogen, optionally substituted Ci- 30 -alkyl, a (meth)acrylate moiety, a (meth)acrylate-Ci-i 2 - alkyl moiety, optionally substituted C 2 - 3 o-alkenyl, optionally substituted C 5 - 30 -alkadienyl, and optionally substituted C 8 - 3 o-alkatrienyl, or when X is -NH-, R 1 and R 2 may together designate =0; and R 3 is selected from hydrogen, Ci- 6 -alkyl, hydroxy and halogen.
Moreover, the present invention provides a method of controlling the volumetric shrinkage of a dental filling material upon curing, comprising the step of:
(a) providing a dental filling comprising one or more fillers and a polymerizable resin base, wherein said one or more fillers comprise metastable zirconia particles in the tetragonal and/or cubic crystalline phase with less than 30 % (v/v) in the monoclinic phase, said zirconia particles having surface functionalities of the formula:
-Zr-O-Zr-O-C(=O)-X-C(R 1 )(R 2 )(R 3 )
wherein X is selected from -O-, -NH- and -S-; R 1 and R 2 are independently selected from hydrogen, optionally substituted Ci- 30 -alkyl, a (meth)acrylate moiety, a (meth)acrylate-Ci-i 2 - alkyl moiety, optionally substituted C 2 - 3 o-alkenyl, optionally substituted C 5 - 30 -alkadienyl, and optionally substituted C 8 - 3 o-alkatrienyl, or when X is -NH-, R 1 and R 2 may together designate =0; and R 3 is selected from hydrogen, Ci- 6 -alkyl, hydroxy and halogen;
(b) allowing the resin base to polymerize and cure, and allowing the metastable zirconia particles to undergo a martensitic transformation from a first metastable phase to a second stable phase. Still further, the present invention provides a dental filling material as defined herein for use in medicine, in particular in dentistry.
DETAILED DESCRIPTION OF THE INVENTION
It is known (see e.g. Bell et al, J. Catal., 204, 330 (2001) that absorbed carbonates can react with methanol and form methyl carbonate. In this way the carbonate is less prone to react with the triggering molecules as described above.
This reaction is not limited to methanol alone, in fact other substances capable of making an addition to the carbonates without providing chemical groups that can react with the trigger molecules are believed to be suitable. Two important groups include alcohols and thiols. A criterion for these appears to be that the alcohol and thiol groups are available for reaction, thus not engaged in intramolecular bonding. A further criterion for these substances appears to be that they are not blocking the reactive sites for initiating the phase transformation on zirconia. These sites are believed to be Zr-O-Zr bonds with vicinal hydroxyl groups on the zirconium atom (see figure below).
Based on the observations made by the present inventors, it has been found that the rate of phase transformation of dental filling materials comprising metastable zirconia intended for phase transformation can be more accurately controlled, and, in particular, the "consumption" of trigger molecules can be suppressed, by modification of the "carbonates" present at the surface of the zirconia particles.
Hence, one aspect of the present invention relates to a dental filling material comprising one or more fillers and a polymerizable resin base, wherein said one or more fillers comprise metastable zirconia particles in the tetragonal and/or cubic crystalline phase with less than 30 % (v/v) in the monoclinic phase, said zirconia particles having surface functionalities of the formula:
-Zr-O-Zr-O-C(=O)-X-C(R 1 )(R 2 )(R 3 )
wherein X is selected from -O-, -NH- and -S-; R 1 and R 2 are independently selected from hydrogen, optionally substituted Ci- 30 -alkyl, a (meth)acrylate moiety, a (meth)acrylate-Ci-i 2 - alkyl moiety, optionally substituted C 2 - 3 o-alkenyl, optionally substituted C 5 - 30 -alkadienyl, and optionally substituted C 8 - 3 o-alkatrienyl, or when X is -NH-, R 1 and R 2 may together designate =0; and R 3 is selected from hydrogen, Ci- 6 -alkyl, hydroxy and halogen.
Another aspect of the present invention relates to a dental filling material comprising one or more fillers and a polymerizable resin base, wherein said one or more fillers comprise metastable zirconia particles in the tetragonal and/or cubic crystalline phase with less than 30 % (v/v) in the monoclinic phase (preferably less than 25 % (v/v), such as less than 20 % (v/v), in particular less than 15 % (v/v), such as less than 10 % (v/v), more preferable virtually none, are in the monoclinic phase), said zirconia particles being prepared by a process comprising the sequential steps of:
a) preparation of an amorphous powder of zirconia;
b) calcination of the amorphous powder of zirconia at a temperature in the range of 400-600 0 C so as to obtain metastable zirconia particles in the tetragonal and/or cubic crystalline phase with less than 30 % (v/v) in the monoclinic phase;
c) treatment of the metastable zirconia particles with a compound of the formula H-X- C(R 1 XR 2 XR 3 ),
wherein X is selected from -O-, -NH- and -S-; R 1 and R 2 are independently selected from hydrogen, optionally substituted Ci- 30 -alkyl, a (meth)acrylate moiety, a (meth)acrylate-Ci-i 2 - alkyl moiety, optionally substituted C 2 - 3 o-alkenyl, optionally substituted C 5 - 30 -alkadienyl, and optionally substituted C 8 - 3 o-alkatrienyl, or when X is -NH-, R 1 and R 2 may together designate =0; and R 3 is selected from hydrogen, Ci- 6 -alkyl, hydroxy and halogen.
These and other characteristics of the invention will be explained in the following. Dental filling material
The present invention relates to dental filling material comprising one or more fillers including metastable zirconia and a polymerizable resin base.
It is well known that many resin bases used in dentistry exhibit volumetric shrinkage upon curing thereof. Thus, a particular feature of the present invention is the presence of zirconia particles that will reduce or eliminate the volumetric shrinkage caused by the polymerizable resin base, or even counteract this volumetric shrinkage to such an extent that the dental filling material exhibits a net volumetric expansion upon curing of the polymeric resin base.
Thus, in a preferred embodiment of the dental filling material, the resin base, upon polymerization and in the absence of any compensating effect from the one or more zirconia particles, causes a volumetric shrinkage (ΔV r e S ι n ) of the dental filling material of at least 0.50 %, and wherein said dental filling material, upon polymerization of said resin base and upon phase transformation of said zirconia particles, exhibits a total volumetric shrinkage (ΔV to t a ι) of at least 0.25 %-point less than the uncompensated volumetric shrinkage (ΔV resιn ) caused by the resin base. More particularly, the volumetric shrinkage (ΔV resιn ) is at least 1.00 %, such as at least 1.50 %, and the total volumetric shrinkage (ΔV to t a ι) is at least 0.50 %-point less, such as at least 1.00 %-point less than the uncompensated volumetric shrinkage.
The dental filling material typically comprises 5-95 %, or 10-90 %, by weight of the one or more fillers (including zirconia particles) and 5-95 %, or 10-90 %, by weight of the polymerizable resin base, in particular 30-95 %, or 30-90 %, by weight of the one or more fillers and 5-70 %, or 10-70 %, by weight of the polymerizable resin base.
Filler/Filler ingredient
In view of the above, it is apparent that the one or more fillers, and in particular the surface- modified metastable zirconia particles, are important constituents of the dental filling material.
Fillers are frequently used in connection with polymeric materials in order to provide desirable mechanical properties of such materials, e.g. abrasion resistance, opacity, colour, radiopacity, hardness, compressive strength, compressive modulus, flexural strength, flexural modulus, etc. Such fillers may be selected from one or more of a wide variety of materials, e.g. those that are suitable for the use in dental and/or orthodontic dental filling materials.
Fillers can be inorganic materials or cross-linked organic materials that are insoluble in the resin component of the composition. Cross-linked organic materials may as such be filled with an inorganic filler. The filler should - in particular for dental uses - be nontoxic and suitable for use in the mouth. The filler can be radiopaque or radiolucent. The filler typically is substantially insoluble in water.
The term "filler" is to be understood in the normal sense, and fillers conventionally used in dental filling materials in combination with polymer are also useful in the present context. The polymerizable resin base (see further below) can be said to constitute the "continuous" phase wherein the filler is dispersed.
Some examples of suitable inorganic fillers are naturally occurring or synthetic materials including, but not limited to: quartz; nitrides {e.g. silicon nitride); glasses derived from, for example, Zr, Sr, Ce, Sb, Sn, Ba, Zn, and Al; feldspar; borosilicate glass; kaolin; talc; titania; low Mohs hardness fillers such as those described in U.S. Pat. No. 4,695,251 (Randklev); and silica particles {e.g. submicron pyrogenic silicas such as those available under the trade designations AEROSIL, including "OX 50," "130," "150" and "200" silicas from Degussa AG, Hanau, Germany and CAB-O-SIL M5 silica from Cabot Corp., Tuscola, III.). Examples of suitable organic filler particles include filled or unfilled pulverized polycarbonates, polyepoxides, and the like.
Other illustrative examples of fillers are barium sulfate (BaSO 4 ), calcium carbonate (CaCO 3 ), magnesium hydroxide (Mg(OH) 2 ), quartz (SiO 2 ), titanium dioxide (TiO 2 ), zirconia (ZrO 2 ), alumina (AI 2 O 3 ), lantania (La 2 O 3 ), amorphous silica, silica-zirconia, silica-titania, barium oxide (BaO), barium magnesium aluminosilicate glass, barium aluminoborosilicate glass (BAG), barium-, strontium- or zirconium-containing glass, milled glass, fine YF 3 Or YbF 5 particles, glass fibres, metal alloys, etc. Metal oxides, e.g. titanium dioxide (TiO 2 ) and zirconia (ZrO 2 ), alumina (AI 2 O 3 ), lantania (La 2 O 3 ), constitute a particularly useful group of fillers for use in the dental filling materials of the present invention.
In one interesting embodiment, at least 5 %, e.g. at least 10 %, or even at least 20 %, by weight of the one or more fillers are glass particles. It is believed that inclusion of glass particles may further improve the optical (and thereby aesthetic) properties of the dental filling material by making it more transparent. The weight content of the one or more filler materials in the dental filling material is typically in the range of 5-95 %, or 10-90 %, such as 30-95 %, such as 40-95 %, e.g. 60-95 %. It should be understood that a combination of two or more fillers may be desirable, just as the particle size distribution of the filler(s) may be fairly broad in order to allow a dense packing of the filler and thereby facilitate incorporation of a high amount of fillers in the dental filling material. Typically, dental filling materials have a distribution of one or more sizes of fine particles plus nanofillers (5-15 %). This distribution permits more efficient packing, whereby the smaller particles fill the spaces between the large particles. This allows for filler content, e.g., as high as 77-87 % by weight. An example of a one size distribution filler would be 0.4 μm structural micro-filler, with the distribution as follows: 10 % by weight of the filler particles have a mean particle size of less than 0.28 μm; 50 % by weight of the filler particles have a mean particle size of less than 0.44 μm; 90 % by weight of the filler particles have a mean particle size of less than 0.66 μm.
Typically, the particle size of the filler(s) is in the range of 0.01-50 μm, such as in the range of 0.02-25 μm.
In some embodiments, the particle size of the filler(s) is/are in the range of 0.2-20 μm with some very fine particles of about 0.04 μm. As an example, fairly large filler particles may be used in combination with amorphous silica in order to allow for a dense packing of the fillers.
The term "particle size" is intended to mean the shortest dimension of the particulate material in question. In the event of spherical particles, the diameter is the "particle size", whereas the width is the "particle size" for a fiber- or needle-shaped particulate material. It should of course be understood that an important feature of such particles is the actual crystal size in that the crystal size (and not the particle size) will be determinative for the preferred crystal phase under given conditions (see also further below).
For aesthetic reasons, it is preferred to include a certain amount of nanofillers in the dental filling material. As used herein the term "nanofiller" refers to filler particles having a size of at the most 100 nm (nanometers). As used herein for a spherical particle, "size" refers to the diameter of the particle. As used herein for a non-spherical particle, "size" refers to the longest dimension of the particle.
This being said, the weight ratio between (i) the nanofillers and (ii) fraction of the one or more fillers not being said nanofillers appears to play a certain role, and is typically in the range of 10:90 to 100:0, preferably 10:90 to 40:60, in particular 10:90 to 30:70. In some embodiments, particularly useful fillers are zirconia, amorphous silica, milled barium-, strontium- or zirconium-containing glass, milled acid-etchable glass, fine YF 3 Or YbF 5 particles, glass fibres, etc.
The zirconia particles typically constitute(s) 20-100 % of the total weight of the one or more fillers, e.g. 30-100 %, such as 40-100 % or 50-100 %.
When calculated on the basis of the total weight of the dental filling material, the zirconia particles typically constitute(s) 15-95 % of the total weight of the dental filling material, e.g. 25-95 %, such as 30-95 %, more specifically 60-95 %.
In the present context, the term "metastable first phase" means that the zirconia particles existing in such as phase has a free energy that is higher than the free energy of the second phase, and that an activation barrier (F*) must be overcome before transformation from the first phase (high energy state) to the second phase (low energy state) can proceed. Thus, the phase transformation does not proceed spontaneously. It should be understood that the "system" in which the zirconia particles is metastable is the dental filling material including all its constituents, i.e. the dental filling material before curing.
The phase transformation is martensitic, which by definition means that the crystal structure of the zirconia particles needs no extra atoms to undergo the transformation. Thus, the transformation can be very fast, almost instantaneous.
The expression "free energy" refers to the sum of free energies from the particle bulk, the particle surface and strain contributions. For most practical purposes, only the free energies from the particle bulk and the particle surface need to be considered.
Thus, when considering potential zirconia particles, it is relevant to take into consideration the two main requirements:
A first requirement for the zirconia particles is that the second crystalline phase thereof, within the selected particle size range, is "stable" under "standard" conditions, i.e. standard pressure (101.3 kPa) and at least one temperature in the range of 10-50 0 C, i.e. corresponding to the conditions under which the product is used.
A second requirement for the zirconia particles is that a metastable first crystalline phase of the zirconia particles can exist under the same "standard" conditions. The expression "stable" refers to a phase which does not transform spontaneously under the conditions required for transforming the zirconia particles from the first metastable phase. Thus, the "stable" phase need not always be the phase with the "globally" lowest free energy, but it often will be.
Zirconia can exist in three major crystalline phases: the tetragonal phase, the cubic phase and the monoclinic phase. The specific volume (density 1 ) of the three phases is 0.16, 0.16 and 0.17 cm 3 /g, respectively. Thus, the monoclinic (the second phase) and one of the former two phases (the first phase) have a volume ratio of 1.045 and 1.046, respectively. The tetragonal and the cubic phases have higher bulk energy than the monoclinic phase at the standard conditions.
The surface energy of the tetragonal phase of zirconia is lower than the one of the monoclinic phase at standard temperature and pressure, which results in stable tetragonal (pure) zirconia crystals at room temperature. The crystals must be small (typically with an average crystal size of 5-12 nm) for the difference of surface energy to compete with difference of in bulk energy of the tetragonal and monoclinic phase.
In the present context, the metastable zirconia particles are present in the tetragonal and/or cubic crystalline phase with less than 30 % (v/v) in the monoclinic phase, i.e. of the bulk of material (the particles) less than 30 % (v/v) represent monoclinic phase crystals which are not capable of exhibiting a volumetric expansion. Preferably, less than 25 % (v/v), such as less than 20 % (v/v), in particular less than 15 % (v/v), such as less than 10 % (v/v), preferably virtually none, are in the monoclinic phase.
For zirconia in the metastable tetragonal or cubic crystalline phase, the particle size is preferably in the range of 5-2000 nm, though it is believed that the presence of particles of a mean particle size in the range of 20-120 nm and in a range of 500-1000 nm {i.e. a bimodal particle size distribution), provides the best balance between optical and structural properties.
It is further possible to include dopants, although not currently preferred. The rationale and consideration behind the use of dopants are, e.g., discussed in WO 2007/104312.
In its native form, the metastable zirconia particles comprise zirconia in the tetragonal and cubic crystalline phases, possibly with a small amount of the material in the monoclinic phase (i.e. in the phase corresponding to already phase-transformed material). The highest degree of phase transformation in a dental material (e.g. provoked by water (gas) diffusing into the dental material) corresponds to the degree of phase transformation possible in a moist environment (i.e. at 100 % humidity (100 % water (gas)). With reference to the examples given herein, it appears that this "highest degree of phase transformation" by the action of water (gas) is approx. 60 %. In order to obtain an even higher degree of phase transformation, the sample may be placed in water (liquid), whereby the degree of phase transformation typically will be close to 100 %. The difference in the degree of phase transformation between the use of water (gas) and water (liquid) as the trigger molecule is believed to be caused by the difference in "activity".
Polymehzable resin base
Another important constituent of the dental filling material is the polymerizable resin base.
The term "polymerizable resin base" is intended to mean a composition of a constituent or a mixture of constituents such as monomer, dimers, oligomers, prepolymers, etc. that can undergo polymerization so as to form a polymer or polymer network. By polymer is typically meant an organic polymer. The resin base is typically classified according to the major monomer constituents.
The weight content of the polymerizable resin base in the dental filling material is typically in the range of 5-95 %, or 5-90 %, e.g. 5-70 %, such as 5-60 %, e.g. 5-40 %.
Virtually any polymerizable resin base can be used within the present context. Polymerizable resin bases of particular interest are, of course, such that upon curing will cause a volumetric shrinkage of the dental filling material when used without a compensating filler ingredient.
The term "curing" is intended to mean the polymerisation and hardening of the resin base.
One class of preferred hardenable resins are materials having free radically active functional groups and include monomers, oligomers, and polymers having one or more ethylenically unsaturated groups. Alternatively, the hardenable resin can be a material from the class of resins that include cationically active functional groups. In another alternative, a mixture of hardenable resins that include both cationically curable and free radically curable resins may be used for the dental materials of the invention. In a still further alternative, the hardenable resin is a condensation-curing resin base, i.e. one where the polymer is formed by condensation polymerisation.
In the class of hardenable resins having free radically active functional groups, suitable materials for use in the invention contain at least one ethylenically unsaturated bond, and are capable of undergoing addition polymerization. Such free radically polymerizable materials include mono-, di- or poly- acrylates and methacrylates such as methyl acrylate, methyl methacrylate, ethyl acrylate, isopropyl methacrylate, n-hexyl acrylate, stearyl acrylate, allyl acrylate, glycerol diacrylate, glycerol triacrylate, ethyleneglycol diacrylate, diethyleneglycol diacrylate, triethyleneglycol dimethacrylate, 1,3-propanediol diacrylate, 1,3-propanediol dimethacrylate, trimethylolpropane triacrylate, 1,2,4-butanetriol trimethacrylate, 1,4- cyclohexanediol diacrylate, pentaerythritol triacrylate, pentaerythritol tetraacrylate, pentaerythritol tetramethacrylate, sorbitol hexacrylate, the diglycidyl methacrylate of bis- phenol A ("Bis-GMA"), bis[l-(2-acryloxy)]-p-ethoxyphenyldimethylmethane, bis[l-(3- acryloxy-2-hydroxy)]-p-propoxyphenyldimethylmethane, 2,2-bis(4-(2- Methacryloxyethoxy)phenylpropane (Bis-EMA), and trishydroxyethyl-isocyanurate trimethacrylate; the bis-acrylates and bis-methacrylates of polyethylene glycols of molecular weight 200-500, copolymerizable mixtures of acrylated monomers such as those in U.S. Pat. No. 4,652,274, and acrylated oligomers such as those of U.S. Pat. No. 4,642,126; and vinyl compounds such as styrene, diallyl phthalate, divinyl succinate, divinyladipate and divinylphthalate. Mixtures of two or more of these free radically polymerizable materials can be used if desired.
An alternative class of hardenable resins useful in the dental materials of the invention may include cationically active functional groups. Materials having cationically active functional groups include cationically polymerizable epoxy resins, vinyl ethers, oxetanes, spiro- orthocarbonates, spiro-orthoesters, and the like.
Preferred materials having cationically active functional groups are epoxy resins. Such materials are organic compounds having an oxirane ring which is polymerizable by ring opening. These materials include monomeric epoxy compounds and epoxides of the polymeric type and can be aliphatic, cycloaliphatic, aromatic or heterocyclic. These materials generally have, on the average, at least 1 polymerizable epoxy group per molecule, preferably at least about 1.5 and more preferably at least about 2 polymerizable epoxy groups per molecule. The polymeric epoxides include linear polymers having terminal epoxy groups (e.g. a diglycidyl ether of a polyoxyalkylene glycol), polymers having skeletal oxirane units (e.g. polybutadiene polyepoxide), and polymers having pendent epoxy groups (e.g. a glycidyl methacrylate polymer or copolymer). The epoxides may be pure compounds or may be mixtures of compounds containing one, two, or more epoxy groups per molecule. The "average" number of epoxy groups per molecule is determined by dividing the total number of epoxy groups in the epoxy-containing material by the total number of epoxy-containing molecules present. These epoxy-containing materials may vary from low molecular weight monomelic materials to high molecular weight polymers and may vary greatly in the nature of their backbone and substituent groups. Illustrative of permissible substituent groups include halogens, ester groups, ethers, sulfonate groups, siloxane groups, nitro groups, phosphate groups, and the like. The molecular weight of the epoxy-containing materials may vary from about 58 to about 100,000 or more.
Useful epoxy-containing materials include those which contain cyclohexane oxide groups such as epoxycyclohexanecarboxylates, typified by 3,4-epoxycyclohexylmethyl-3,4- epoxycyclohexanecarboxylates, 4-epoxy-2-meth ylcyclohexylmethyl-3,4-epoxy-2- methylcyclohexane carboxylate, and bis(3,4-epoxy-6-methylcyclohexylmethyl)adipate. For a more detailed list of useful epoxides of this nature, reference is made to the U.S. Pat. No. 3,117,099, which is hereby incorporated herein by reference.
Particularly interesting resin bases that are useful for dental applications are those based on compounds selected from the group consisting of methacrylic acid (MA), methylmethacrylate (MMA), 2-hydroxyethyl-methacrylate (HEMA), triethyleneglycol dimethacrylate (TEGDMA), bisphenol-A-glycidyl dimethacrylate (BisGMA), bisphenol-A-ethyl dimethacrylate (BisEMA), bisphenol-A-propyl dimethacrylate (BisPMA), urethane-dimethacrylate (UDMA), and HEMA condensed with butanetetracarboxylic acid (TCB), as well as those based on combinations of the above-mentioned compounds. Such resin bases are, e.g., disclosed and discussed in US 6,572,693. A particularly useful combination of compounds is TEGDMA and BisGMA, see, e.g., US 3,066,112.
Other constituents of the dental filling material
The dental filling material may comprise other constituents which provide beneficial rheological, cosmetic, etc. properties. Examples of such other constituents are dyes, flavorants polymerisation initiators and co-initiators, stabilizers, fluoride releasing materials, sizing agents, antimicrobial ingredients.
Thus, the resin base may include initiators and co-initiators, and illustrative examples of such compounds, particularly for use in dental applications, are benzoylperoxide (BPO), camphorquinone (CPQ), phenylpropanedione (PPD) and N,N-di(2-hydroxyethyl)-p-toluidine (DEPT), N,N-dimethyl-p-aminobenzoic acid ethyl ester (DABE).
Shading can be achieved by using a number of color pigments. These include metal oxides, which provide the wide variety of colors of the dental filling material; for example, oxides of iron can act as a yellow, red to brown pigment, copper as a green pigment, titanium as a yellowish-brown pigment, and cobalt imparts a blue color.
Fluorescence is more subtle optical properties that further enhance the natural-looking, lifelike appearance or "vitality" of the tooth. Fluorescence is defined as the emission of electromagnetic radiation that is caused by the flow of some form of energy into the emitting body, which ceases abruptly when the excitation ceases. In natural teeth, components of the enamel, including hydroxyapatite, fluorescence under long wavelength ultraviolet light, emitting a white visible light. This phenomenon is subtle in natural daylight but still adds further to the vitality of the tooth. In contrast, under certain lighting conditions, the lack of fluorescence in a restorative material may become alarming. Under "black light" conditions, such as that often used in discotheque-type night clubs, if a restoration does not fluoresce, the contrast between the tooth and restoration may be so great that the tooth may actually appear to be missing. Fluorescence can, e.g., be achieved by adding an anthracene-like molecule.
The weight content of other constituents in the dental filling material is typically in the range of 0-10 %, such as 0-5 %, e.g. 0-4 % or 1-5 %.
The dental filling material may further comprise one or more water- or acid-releasing agent which typically constitute 0.01-5 % by weight, e.g. 0.1-1 % by weight, of the dental filling material. Examples of such constituents are disclosed in the applicant's earlier WO 2007/104312.
Preferably, the dental filling material is substantially solvent free and water free. By the term "substantially solvent free and water free" is meant that the dental filling material comprises less than 1 %, such as less than 0.5 % or less than 150 ppm, by weight of solvents and/or water.
In order to avoid premature curing of the polymerizable resin base, it may be advantageous to prepare and store the dental filling material as a two-component material intended for mixing immediately prior to use.
Definitions
In the present context, the term "Ci- 30 -alkyl" is intended to mean a linear, cyclic or branched hydrocarbon group having 1 to 30 carbon atoms, such as methyl, ethyl, propyl, /so-propyl, pentyl, cyclopentyl, hexyl, cyclohexyl, decyl, dodecyl, etc. The term "Ci- 6 -alkyl" is intended to mean a linear, cyclic or branched hydrocarbon group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, /so-propyl, pentyl, cyclopentyl, hexyl, cyclohexyl.
Similarly, the term "C 2 - 3 o-alkenyl" is intended to cover linear, cyclic or branched hydrocarbon groups having 2 to 30 carbon atoms and comprising one unsaturated bond. Examples of alkenyl groups are vinyl, allyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, heptadecaenyl, etc. In line herewith, the terms "C 5 - 3 o-alkadienyl" and "C 8 - 3 o-alkatrienyl" are intended to cover linear, cyclic or branched hydrocarbon groups having 5 to 30 carbon atoms, or 8-30 carbon atoms, respectively, and comprising two unsaturated bonds, or three unsaturated bonds, respectively.
In the present context, i.e. in connection with the terms "alkyl", "alkenyl", "alkadienyl", "alkatrienyl" and the like, the term "optionally substituted" is intended to mean that the group in question may be substituted one or several times, preferably 1-3 times, with group(s) selected from hydroxy (which when bound to an unsaturated carbon atom may be present in the tautomeric keto form), Ci- 6 -alkoxy {i.e. Ci- 6 -alkyl-oxy), C 2 - 6 -alkenyloxy, oxo (forming a keto or aldehyde functionality), amino, mono- and di(Ci- 6 -alkyl)amino, carbamoyl, mono- and di(Ci- 6 -alkyl)aminocarbonyl, cyano, where any alkyl, alkoxy, and the like, representing substituents may be substituted with hydroxy, Ci- 6 -alkoxy, amino, mono- and di(Ci- 6 -alkyl)amino, Ci- 6 -alkylcarbonylamino, or Ci- 6 -alkylaminocarbonyl.
Typically, the substituents are selected from hydroxy, Ci- 6 -alkoxy {i.e. Ci- 6 -alkyl-oxy), C 2 - 6 - alkenyloxy, and oxo.
The term "a (meth)acrylate moiety" and the like is intended to mean a group derived from an acrylate- or methacrylate-containing compound by abstraction of a hydrogen atom. In the present context, the (meth)acrylate moiety is preferably intended to be involved in a polymerization process upon polymerization of the resin base. Hence, the (meth)acrylate moiety may be derived from the types of (meth)acrylates which suitably are used as constituents of the resin base, e.g. mono-, di- or poly- acrylates and methacrylates such as methyl acrylate, methyl methacrylate, ethyl acrylate, isopropyl methacrylate, n-hexyl acrylate, stearyl acrylate, allyl acrylate, glycerol diacrylate, glycerol triacrylate, ethyleneglycol diacrylate, diethyleneglycol diacrylate, triethyleneglycol dimethacrylate, 1,3- propanediol diacrylate, 1,3-propanediol dimethacrylate, trimethylolpropane triacrylate, 1,2,4- butanetriol trimethacrylate, 1,4-cyclohexanediol diacrylate, pentaerythritol triacrylate, pentaerythritol tetraacrylate, pentaerythritol tetramethacrylate, sorbitol hexacrylate, the diglycidyl methacrylate of bis-phenol A ("Bis-GMA"), bis[l-(2-acryloxy)]-p- ethoxyphenyldimethylmethane, bis[l-(3-acryloxy-2-hydroxy)]-p- propoxyphenyldimethylmethane, and trishydroxyethyl-isocyanurate trimethacrylate; and the bis-acrylates and bis-methacrylates of polyethylene glycols of molecular weight 200-500.
As illustrative examples, the (meth)acrylate moiety may be of any one of the formulae:
CH 2 =CH-C(=O)-O~, CH 2 =C(CH 3 )-C(=O)-O~,
CH 2 =C(~)-C(=O)-O-(C 1 - 5 -alkyl), ~CH=CH-C(=O)-O-(Ci -6 -alkyl), ~CH=C(CH 3 )-C(=O)-O-(C 1 - 5 -alkyl), CH 2 =CH-C(=O)-O-(Ci- 5 -alkylene)~, CH 2 =C(CH 3 )-C(=O)-O-(C 1 - 5 -alkylene)~, CH 2 =C(CH 2 (~))-C(=O)-O-(Ci -6 -alkyl), etc. (where "~" designates the bond to which the moiety is attached)
The term "alkylene" means the biradical corresponding to "alkyl".
The terms "halogen" and "halo" include fluoro, chloro, bromo, and iodo.
Moreover, it should be understood that the compounds may be present as enantiomers or diastereomers. The present invention encompasses each and every of such possible enantiomers and diastereomers as well as racemates and mixtures enriched with respect to one or the possible enantiomers or diastereomers.
Embodiments
In order to obtain zirconia particles that could undergo a fast phase transformation, a large surface area, e.g. 10-250 m 2 /g or even better 50-200 m 2 /g, of the particles is preferred.
As mentioned above, the average crystal size of the zirconia is preferably in the range of 5- 12 nm, such as 6-10 nm, in particular 6-9 nm or 6-8 nm. "Crystals" refers to crystal domains with a homogeneous crystal lattice.
In a currently interesting embodiment, the zirconia particles have an average crystal size in the range of 5-12 nm and a BET surface area of in the range of 10-250 m 2 /g.
As also mentioned above, the average particle size is typically in the range of 50-2000 nm, such as in the range of 50-1000 nm, in particular 100-600 nm. Furthermore, it is believed that the zirconia particles advantageously may have a certain porosity in order to allow for a rapid transformation (as described herein). Thus, the average pore size of the particles is preferably in the range of 1-50 nm.
With respect to the porosity, it is believed that zirconia particles having a porosity in the range of 0.1-20 %, such as 0.2-10 %, are particularly interesting.
The dental filling material according to any one of the preceding claims, wherein the improvement, "T", (in fact a reduction) in the required amount of water (trigger molecule) is at least 30 %, such as at least 50 %, preferably at least 70 %, and in particular at least 90 %, when compared to a native sample metastable zirconia, and determined according to the method described herein ("Determination of water adsorption") with reference to the formula:
T=(IOO %*((tu-tm)/tu)).
In one interesting embodiment, the dental filling material described herein, consists of:
40-85 % by weight of the one or more fillers including the metastable zirconia; 15-60 % by weight of the a polymerizable resin base;
0-25 % by weight, such as 0-5 % by weight of additives; and 0-4 % by weight of solvents and/or water.
With respect to the type of surface functionalities of the formula -Zr-O-Zr-O-C(=O)-X- CH(R 1 R 2 ) and the corresponding compounds used to introduce the surface functionalities, it is in one embodiment preferred that X is selected from -O-, -NH- and -S-; and R 1 and R 2 are independently selected from hydrogen, optionally substituted Ci- 30 -alkyl, optionally substituted C 2 - 3 o-alkenyl, optionally substituted C 5 - 3 o-alkadienyl, and optionally substituted C 8 - 3 o-alkatrienyl, or when X is -NH-, R 1 and R 2 may together designate =0.
In one variant hereof, X is -O-; and R 1 and R 2 are independently selected from hydrogen and optionally substituted Ci-i 2 -alkyl and optionally substituted Ci-i 2 -alkenyl. More particular, the surface functionality is derived from a molecule H-X-CH(R 1 R 2 ), which is selected from methanol (H-O-CH 3 ) and 2-propanol (CH 3 -CHOH-CH 3 ).
In another interesting variant hereof, X is -NH-; and R 1 and R 2 are independently selected from hydrogen and optionally substituted Ci-i 2 -alkyl and optionally substituted Ci_i 2 -alkenyl, or R 1 and R 2 together designate =0. More particular, the surface functionality is derived from a molecule H-NH-CH(R 1 R 2 ), which is formamide (NH 2 C(=O)).
In another embodiment, the surface functionality is selected from methanol, ethanol, iso- propanol, n-propanol, n-butanol, iso-butanol, iso-octanol, 1,5-pentanediol, octane thiol, and acetamide.
Within the various embodiments described herein, the intra-molecular distance between the X-group in the surface functionality and any heteroatoms included in R 1 and/or R 2 should preferably be at least 3 carbon atoms, in particular at least 4 carbon atoms.
In the currently most preferred embodiments, R 1 and R 2 do not include any heteroatoms.
In some variant of the before-mentioned embodiments, R 3 is selected from hydrogen and Ci- 6 -alkyl.
The before-mentioned surface functionalities are particularly interesting with respect to blocking the carbonyl species on the surface of the zirconia particles.
In another highly interesting embodiment, which of course may be combined with the foregoing, the surface functionalities are blocking the carbonyl species, but are on the other hand capable of being involved in the polymerization process upon polymerization of the resin base.
Hence, in this embodiment, and with respect to the type of surface functionalities of the formula -Zr-O-Zr-O-C(=O)-X-CH(R 1 R 2 ) and the corresponding compounds used to introduce the surface functionalities, X is selected from -O- and -S-; and R 1 and R 2 are independently selected from hydrogen, optionally substituted Ci- 30 -alkyl, a (meth)acrylate moiety, a (meth)acrylate-Ci-i 2 -alkyl moiety, optionally substituted C 2 - 3 o-alkenyl, optionally substituted C 5 - 30 -alkadienyl, and optionally substituted C 8 - 3 o-alkatrienyl, with the proviso that at least one of R 1 and R 2 are selected from a (meth)acrylate moiety and a (meth)acrylate-Ci-i 2 -alkyl moiety. In one variant hereof, X is -O-; and R 1 and R 2 are independently selected from hydrogen, optionally substituted Ci-i 2 -alkyl, a (meth)acrylate moiety, a (meth)acrylate-Ci-i 2 - alkyl moiety, optionally substituted C 2 _i 2 -alkenyl, and optionally substituted C 5 -i 2 -alkadienyl, with the proviso that at least one of R 1 and R 2 are selected from a (meth)acrylate moiety and a (meth)acrylate-Ci-i 2 -alkyl moiety. In some interesting variants hereof, R 3 is selected from hydrogen and Ci- 6 -alkyl. Examples of acrylate molecules which may be used to prepare corresponding surface functionalities of the type including (meth)acrylate moieties and (meth)acrylate-Ci-i 2 -alkyl moieties are the following :
In a further interesting embodiment, which of course may be combined with the foregoing embodiments, the surface functionalities are blocking the carbonyl species, but are at the same time capable of releasing -OH, halogen ions or radicals, or other trigger molecules or species. A detailed description of the concept of trigger molecules is disclosed in WO 2007/104312. Such hydroxyl, halogen ions and radicals may either react with hydrogens in the monomer matrix of the resin base under formation of trigger molecules, or may as such act as trigger molecules. It is envisaged that such compounds {e.g. those specifically disclosed in WO 2007/104312) which are capable of releasing trigger molecules can be incorporated as corresponding surface functionalities on the zirconia particles, i.e. as described above.
Hence, in one variant hereof, R 3 is selected from hydroxy and halogen. In other variants, R 1 and R 2 are independently selected from hydrogen, optionally substituted Ci- 30 -alkyl, optionally substituted C 2 - 3 o-alkenyl, optionally substituted C 5 - 30 -alkadienyl, and optionally substituted C 8 - 3 o-alkatrienyl, of which at least one is substituted with hydroxy and/or halogen.
In another embodiment, the surface functionality may be a photo-active moiety {e.g. a triazine moiety), which upon light exposure liberates hydroxyl or halogen radicals. The radicals will then be involved in the polymerization reaction with the monomers of the resin base or will abstract a hydrogen atom and provide trigger molecules to the surface of zirconia.
Use of the dental filling materials
The present invention further provides the dental filling material as defined herein for use in medicine, in particular in dentistry.
The dental filling materials may be used and are cured essentially as conventional dental filling materials of the same type, except for the fact that the martensitic transformation should be controlled along with the curing of the resin base, i.e. at least in part by the chemical trigger(s), or afterwards by the diffusion of water into the dental filling material.
Generally, it is believed that the martensitic transformation can be activated either by physical means (e.g. application of mechanical pressure, tension, ultrasound, Roentgen irradiation, microwaves, longitudinal waves, electromagnetic irradiation such as light, near infrared irradiation, heating, etc.) or by chemical means (e.g. modification of the surface free energy by contacting the surface of the zirconia particles with a chemical, e.g. a constituent of the dental filling material or an additive such as water). Hence, it should be understood that the martensitic transformation may be further triggered by physical means, although it is believed that the chemical means (i.e. a trigger molecule) will contribute significantly, or even completely, to the triggering of the martensitic transformation of the zirconia particles.
It should be understood that the martensitic transformation of the zirconia particles preferably shall take place with the curing (polymerization and hardening) of the resin base. However, since the crystals are small, the expansion due to phase transformation will not cause deterioration of the mechanical properties of the cured compound. Therefore, transformation triggered by slow mechanisms, e.g., diffusion of water into the cured compound upon curing and subsequent to curing is the currently preferred mechanism of triggering the phase transformation. Triggering the transformation before the curing is undesired since the volume compensating effect will be less or lost depending on how much is transformed before curing is initiated.
Method of the invention
In view of the above, the present invention also provides a method of controlling the volumetric shrinkage of a dental filling material upon curing, comprising the step of: (a) providing a dental filling comprising one or more fillers and a polymerizable resin base, wherein said one or more fillers comprise metastable zirconia particles in the tetragonal and/or cubic crystalline phase with less than 30 % (v/v) in the monoclinic phase, said zirconia particles having surface functionalities of the formula:
-Zr-O-Zr-O-C(=O)-X-C(R 1 )(R 2 )(R 3 )
wherein X is selected from -O-, -NH- and -S-; R 1 and R 2 are independently selected from hydrogen, optionally substituted Ci- 30 -alkyl, a (meth)acrylate moiety, a (meth)acrylate-Ci-i 2 - alkyl moiety, optionally substituted C 2 - 3 o-alkenyl, optionally substituted C 5 - 30 -alkadienyl, and optionally substituted C 8 - 3 o-alkatrienyl, or when X is -NH-, R 1 and R 2 may together designate =0; and R 3 is selected from hydrogen, Ci- 6 -alkyl, hydroxy and halogen;
(b) allowing the resin base to polymerize and cure, and allowing the metastable zirconia particles to undergo a martensitic transformation from a first metastable phase to a second stable phase.
Various embodiments of the meanings of the substituents X, R 1 , R 2 and R 3 are as described further above.
Preferably, the zirconia particles should be triggered to undergo the martensitic transformation either simultaneous with the curing or subsequent to the curing in order to fully benefit from the volumetric expansion of the zirconia particles.
In one currently preferred embodiment, the triggering of the metastable zirconia particles in order to facilitate the martensitic transformation takes place simultaneous and subsequent to the curing by means of water diffusion into the dental filling material.
In another embodiment, the martensitic transformation of the zirconia particles is initiated by exposure of the surface of the zirconia particles to a chemical trigger. In this instance, the martensitic transformation is preferably triggered simultaneously with or after the curing is initiated, but before the curing is completed.
More specifically, the present invention further provides a method of reconstructing a tooth, comprising the step of
(a) preparing a cavity in the tooth; (b) filing said cavity with a dental filling material as defined above; and
(c) allowing the resin base of the dental filling material to polymerize and cure, and allowing the zirconia particles of the dental filling material to undergo a martensitic transformation from a first metastable phase to a second stable phase.
The above-defined method for the reconstruction of a tooth may generally comprise further steps obvious to the person skilled in the art of dentistry.
EXPERIMENTALS
General procedure
Metastable zirconia is prepared according to the following general procedure:
1. Precipitation of amorphous zirconia
Reaction: ZrOCI 2 + 2 NH 3 ■ * ZrO(OH) 2 + 2 NH 4 CI
A solution of 0.5 M ZrOCI 2 and an aqueous solution of 5 M NH 3 is prepared. The two solutions are added together at a rate of approx. 2.8 times as much by volume 5 M NH 3 as 0.5 M ZrOCI 2 in this way the pH is kept at a constant level of 10 at room temperature and with stirring. A precipitate is thereby formed.
2. Washing
The precipitate is filtered and washed with water at room temperature in a basket centrifuge in order to exclude chlorine and ammonium ions. Completion of the washing procedure is detected with lack of any AgCI precipitate (white) after treatment of the washing water with a 0.5 M AgNO 3 .
3. Conditioning
The washed precipitate is suspended in water and refluxed for 10 hours.
4. Washing The precipitate is then filtered and washed with water again as in step 2.
5. Alcohol Treatment
The precipitate is treated with a suitable alcohol {e.g. ethanol or iso-propanol) using an azeotropic distillation principle to remove water from the amorphous zirconia to a content of less than 1 % of the distillate. (The distillate was checked with a zirconium(IV) butoxide, 80 wt% solution in 1-butanol. A white precipitate in this test indicated that the water content was lower than 0.7 % in the distillate.)
6. Drying
The powder is dried at 60 0 C for 2 days.
7. Calcination
The amorphous powder is calcinated at 450 0 C for approx. IVi hour under a dry air flow.
8. Surface modification
Under an inert atmosphere, the tetragonal zirconia is treated 8 h with dry methanol (or another compound as specified herein) and filtered off and left drying overnight under an inert atmosphere.
Analysis
Determination of types of carbonyl species
IR: The adsorption of CO 2 on zirconia has been widely studied (especially by Teichner et al : D. Bianchi, T. Chafik, M. Khalfallah and S. J. Teichner; Appl. Catal., 105 (1993) 223). The kind of species formed on the surface of zirconia is very dependent on the process condition like, temperature, amount of CO 2 and the surface of zirconia. However by following the synthesis steps above the most common species are: ionic carbonate CO 3 2' : 1444 cm "1 , bidented bicarbonate HCO 3 " : 1598 cm "1 , bidented covalent surface carbonate "CO 3 ": 1558 and 1325 cm "1 and ionic carboxylate CO 2 " : 1423 cm "1 . The intensities of the ionic carbonate and carboxylate are the same, creating a double peak in the IR spectrum. The bidentate covalent surface carbonates are shoulders to the double peak and the bicarbonate is a small peak and only a shoulder to the bidentate covalent surface carbonate peak.
All of these carbonates can react with methanol and form methyl carbonates. Methyl carbonates give rise to an IR spectrum with three significant peaks at: 1600, 1474 and 1370 cm "1 . The formation of a substituted carbonate can therefore be observed in IR as a change of the carbonate peaks into the substituted species peaks. The above standing peaks are all designated to the C-O (or C=O) vibration as these are the most intensity strong peak and are by far the easiest way of recognising a change in carbonates on the surface of zirconia.
Determination of water adsorption
The amount of water adsorped on the zirconia surface at a given partial pressure can be determined using an "autosorbtion" machine, e.g. a Quantachrome XT autosorb 1 analyser. The degree of water adsorption can be used to determine the amount of trigger molecules (water) necessary to phase transform zirconia. In fact, an autosorbtion study can be used to study the amount needed to phase transform zirconia.
A sample of zirconia is kept at 0 0 C (ice bath) during the experiment. In order to avoid premature phase transformation it is necessary to use a seal that only opens in the autosorbtion machine. This way the sample can be kept under an inert atmosphere or vacuum until the measurement starts and again after the sample is removed from the machine.
1) The zirconia (metastable) sample is evacuated to the relative pressure, P, being of 0.01 x P 0 ; Po being the ambient pressure, i.e. 1 atm.
2) The sample is then titrated with water in gaseous form by the procedure of finding a relative pressure and then noting the amount of water necessary to get this pressure.
3) at a given end-point (a given P/ Po) the sample re-evacuated and taken to a glove-box.
4) The sample is then mixed in a dental resin (see Example 1) which is cured by blue light, e.g. Bluephase.
5) The degree of phase transformation is determined by the use of X-ray diffraction (XRD). 6) The point where the zirconia does not phase transform more upon added water moisture can be found. This point is found by comparing the degree of phase transformation for a series of samples as a function of water moisture added. This point can be used to compare unmodified zirconia and modified zirconia, and thereby the effect of the compound used for the surface modification.
The water adsorption for a sample of surface-modified zirconia can be compared with a sample of unmodified zirconia so as to determine the improvement {i.e. reduction) in the amount of water (trigger molecule) needed in order to provoke the same phase transformation as would be obtainable when the sample was place in a chamber with 100 % humidity at room temperature (25 0 C).
Improvement of amount of trigger molecules to phase transform the modified zirconia relative to the unmodified zirconia, (T), is calculated as:
T=(IOO %*((tu-tm)/tu))
wherein tu= mL/g adsorbed water moisture needed to trigger the phase transformation of unmodified zirconia, and wherein tm=mL/g adsorbed water moisture needed to trigger the phase transformation of modified zirconia.
In this way the minimum of amount of trigger molecules needed to induce a phase transformation corresponding to that obtainable at 100 % humidity can be determined. The effect of surface modifying the zirconia surface is lowering the amount of trigger molecules needed to phase transform the zirconia. This can be described in ml_ gaseous water per gram zirconia. The effect can also be described as relative to the amount needed to phase transform the unmodified zirconia at a given partial pressure.
To find the extent to which an uncharacterised sample of zirconia is surface modified, several analysis methods can be used of which two are outlined below.
1) The zirconia particles (suspected of being surface modified metastable zirconia) in an uncured dental material can be isolated by dissolving the resin with a suitable solvent e.g. acetone. The surface modification for a sample can be removed by vacuum and heating. To remove any surface modification, the sample can be heated to 450 0 C under a flow of dry air. The autosorption analysis can show if the trigger amount (water adsorption) is more for the sample than for the native sample (i.e. the isolated sample before the heating and vacuum treatment). This method only reveals if there were a surface modification and whether it is removed. If there are different kinds of filler particles it can not be determined on which particles the surface modification is present. However the autosorption study can be complemented with IR and surface sensitive analysis method like XPS.
2) The particles from the dental material can be isolated by dissolving the resin in a suitable solvent e.g. acetone. A sample of the particles can then be modified with methanol by suspending them in the solvent for 8 hours and dried overnight. The autosorption analysis can then be used to determine the trigger amount necessary to phase transform the particles before and after modification to determine if the modification had an effect. If not this indicates that the particles were surface modified before they were exposed to methanol. Further determination can be complemented with IR and surface sensitive analysis method like XPS to see whether the zirconia were initially modified.
Determination of the degree of phase transformation
The metastable zirconia particles prepared represent tetragonal and/or cubic crystalline phase zirconia. After complete martensitic phase transformation, the zirconia particles are present in the monoclinic crystalline phase. It is important to understand that "metastability" of zirconia particles is not just a result of the particles being in the tetragonal and/or cubic crystalline phase. Hence, a number of other factors also play an important role, e.g. the crystal size, the surface structure, the surface functionalities {i.e. amount of reactive sites), etc.
Within the present context, the metastable zirconia particles representing tetragonal and/or cubic crystalline phase zirconia with not representation of monoclinic crystalline phase zirconia are defined as being 0 % phase transformed. Correspondingly, stable zirconia particles representing monoclinic crystalline phase zirconia with no representation of tetragonal and/or cubic crystalline phase zirconia are defined as being 100 % phase transformed.
The degree of phase transformation is expressed as the volume ratio of zirconia in the monoclinic phase and is determined by means of X-ray diffraction (XRD).
The phase transformation is measured by means of powder XRD of a sample of the resin+zirconia material. The volume fraction of monoclinic zirconia (V m ) can be determined from the following relationships:
X m = (I m (l l l) + I m (l l-l))/( Im(I I l) + Im(I l- I) + It(I I l)) V m =1.311 X m /(l + 0.311X m )
where I m (lll) and I m (ll-1) are the line intensities of the (111) and (11-1) peaks for monoclinic phase zirconia and It(Hl) is the sum of the intensities of the (111) peaks for tetragonal phase zirconia and cubic phase zirconia.
Determination of the average crystal size
The average crystal size (x) can be found using Scherrers expression:
x=K λ/(B cosθ),
where K is a equipment dependent constant typically between 0.89 and 1, λ is the wavelength of x-rays, θ is the center angle of the peak and B is the width of the peak at half peak height.
Example 1
A solution of 0.5 M ZrOCI 2 was prepared from ZrOCI 2 8H 2 O and water. The amorphous zirconia ZrO x (OH) 4 . 2x was precipitated with a 5 M NH 3 aqueous solution at a constant pH of 10. To keep the pH constant at 10 the two solutions were added together at a rate of 2.8 times as much 5 M NH 3 as 0.5 M ZrOCI 2 8H 2 O. 92 ml. 0.5 M ZrOCI 2 and 258 ml. 5 M NH 3 solution were used. The suspension was then filtered and washed on a basket centrifuge until a negative chlorine test was obtained (with 960 ml_ water). The filter cake was then suspended in 300 ml_ water and refluxed for 10 h. The suspension was allowed to cool and was then filtered. The filter cake was washed with 200 ml_ water and suspended in 300 ml_ dry iso-propanol and was dried using a azeotropic distillation principle. The drying was done with a rotorvapor and 1200 ml_ iso-propanol. The distillate was checked with a zirconium(IV) butoxide, 80 wt% solution in 1-butanol. A white precipitate in this test indicated that the water content was lower than 0.7 % in the distillate. The amorphous was then dried in an oven at 60 0 C for 2 days. The powder was then calcined in a tube oven at 450 0 C with a dry air flow of 20 mL/min; the dew-point was -43.2°C. The following handling and preparation of analysis was done in a glove-box in inert atmosphere.
The average crystal size was about 8 nm and the BET area of the particles was 150 m 2 /g. The "native" particles represented metastable zirconia particles in the tetragonal and/or cubic crystalline phase with less than 5 % (v/v) in the monoclinic phase.
An IR spectrum of the calcined and dried sample was obtained by pressing a pellet with the diameter of 30 mg zirconia and placing it between two CaF 2 windows in an airtight holder.
The IR showed ionic Carbonate CO 3 2" : 1444 cm "1 , bidented covalent surface carbonate "CO 3 ": 1558 and 1325 cm "1 and ionic carboxylate CO 2 " : 1423 cm "1 .
A sample of 0.123 g zirconia was run on Quantachrome XT autosorb 1 analyser. The analysis showed that at a relative pressure of 0.15 P/Po, 17 mL/g water was adsorbed. The sample was then re-evacuated and mixed with 0.2 g of a dental resin (containing : 35.5 % (w/w) BisGMA, 44 % (w/w) UDMA, 19.5 % (w/w) TEGDMA. 0.5 % (w/w) camphorquinone (CQ), 0.5 % (w/w) N,N-dimethyl-p-aminobenzoic acid ethylester (DABE)).
The curing was initiated by light from a curing device at max intensity 1100 mW/cm 2 (Bluephase from Ivoclar Vivadent). The material was cured for a period of 2 min. The cured sample was then analysed with XRD. The degree of phase transformation was 60 %.
A sample of 1 g zirconia (calcined and dried; see above) was suspended in dry methanol for 8 h. The suspension was filtered and left to dry in the filter overnight under an inert atmosphere. An IR spectrum was obtained by pressing a pellet with the diameter of 30 mg modified zirconia and placing it between two CaF 2 windows in an airtight holder, all done in a glove-box with inert atmosphere. The IR showed three significant peaks at: 1600, 1474 and 1370 cm "1 . The formation of methyl carbonate could therefore be observed in IR.
A sample of 0.118 g zirconia was run on Quantachrome XT autosorb 1 analyser. The analysis showed that at a relative pressure of 0.15 P/P o , 3.6 mL/g water was adsorbed. The sample was then re-evacuated and mixed with 0.2 g of a dental resin (containing : 35.5 % (w/w) BisGMA, 44 % (w/w) UDMA, 19.5 % (w/w) TEGDMA. 0.5 % (w/w) camphorquinone (CQ), 0.5 % (w/w) N,N-dimethyl-p-aminobenzoic acid ethylester (DABE)).
The material was cured for a period of 2 min as above. The cured sample was then analysed with XRD. The degree of phase transformation was 60 %.
This shows that the modified zirconia only needed
(100 %-100 %*(17 mL/g - 3.6 mL/g)/17 mL/g) = 20 % of the amount of trigger molecules to obtain the same partial pressure, indicating that far less trigger molecules are needed to phase transform the modified zirconia.
Example 2
Modified and unmodified zirconia were prepared as in Example 1. Sample of modified and unmodified zirconia, respectively, were each mixed with 0.2 g of a dental resin (35.5 % (w/w) BisGMA, 44 % (w/w) UDMA, 19.5 % (w/w) TEGDMA. 0.5 % (w/w) camphorquinone (CQ), 0.5 % (w/w) N,N-dimethyl-p-aminobenzoic acid ethylester (DABE)), and the resin was cured.
The two samples were put in water at 37°C and taken out for measurements with XRD to observe the phase transformation as a function of time.
After two days, the sample with the modified zirconia was phase transformed to an extent of 57 %, no further phase transformation was observed after prolonged storage. The unmodified zirconia was phase transformed to an extent of 25 % after 3 days and to 40 % after 21 days. No further study of this sample was conducted.
Example 3
A test dental filling material was prepared by mixing 200 mg of the methanol modified zirconia particles (prepared as in Example 1) and 500 mg of a polymer resin system (36 % (w/w) BisGMA, 43 % (w/w) UDMA, 19.35 % (w/w) TEGDMA. 0.5 % (w/w) camphorquinone (CQ), 0.5 % (w/w) N,N-dimethyl-p-aminobenzoic acid ethylester (DABE), 0.05 % (w/w)) with 100 mg of the trigger molecule 2-(4-methoxystyryl)-4,6-bis(trichloromethyl)-l,3,5-triazine.
The phase transformation was initiated by light from a curing device at max intensity 1100 mW/cm 2 (Bluephase from Ivoclar Vivadent), simultaneously with the curing of resin. After 2 min, 15 % of the zirconia particles were phase transformed. After 30 min, 53 % of the zirconia particles were phase transformed.
Example 4
A test dental filling material was prepared by mixing 200 mg of the non-modified zirconia particles (prepared as in Example 1, but without methanol treatment) and 500 mg of a polymer resin system (36 % (w/w) BisGMA, 43 % (w/w) UDMA, 19.35 % (w/w) TEGDMA. 0.5 % (w/w) camphorquinone (CQ), 0.5 % (w/w) N,N-dimethyl-p-aminobenzoic acid ethylester (DABE), 0.05 % (w/w)) with 100 mg of the trigger molecule 2-(4-methoxystyryl)-4,6- bis(trichloromethyl)-l,3,5-triazine.
The phase transformation was initiated by light from a curing device at max intensity 1100 mW/cm 2 (Bluephase from Ivoclar Vivadent), simultaneously with the curing of resin.
After 2 h of light exposure very little phase transformation was detected. Apparently, the trigger species derived from the triazine was almost completely "consumed" by the "carbonates" present at the surface of the zirconia particles.
Example 5
A test dental filling material was prepared by mixing 200 mg of the zirconia particles
(prepared as in Example 1) and 500 mg of a polymer resin system (36 % (w/w) BisGMA, 43 % (w/w) UDMA, 19.35 % (w/w) TEGDMA. 0.5 % (w/w) camphorquinone (CQ), 0.5 % (w/w) N,N-dimethyl-p-aminobenzoic acid ethylester (DABE)) with 100 mg of the trigger molecule 2- (4-methoxystyryl)-4,6-bis(trichloromethyl)-l,3,5-triazine.
Beforehand, the resin system was mixed with 1 mmol of dry methanol. The phase transformation was initiated by light from a curing device at max intensity 1100 mW/cm 2 (Bluephase from Ivoclar Vivadent), simultaneously with the curing of resin. After 30 min, 45 % of the zirconia particles were phase transformed.
Example 6
Samples were prepared and tested using the same methods as described in Example 5, but substituting methanol with different other chemical substances (1 mmol) as described in the table below.
It has been shown (experimentally) that the substances used for the addition reaction on the carbonates are blocking the reactive groups if the substance is able to make a bond to hydroxylic groups by making a bidentate bond as a bridge over the hydroxylic groups. It is believed that the Zr-O-Zr bond is protected by the bridge. In order to avoid bridge bonding the substances can be monodentate (only able to bind with one group) or the bonding groups should be far away far each other. The distance between the binding groups can be determined by intervals of C-bonds in the substance. Ethylene glycol and 1,3 propanediol are blocking the phase transformation, whereas 1,4 butanediol is blocking the phase transformation to some extend and 1,5 butanediol is not. The distance between the bonding groups should be more than 3 carbon bonds and even better more than 4 carbon bonds.
Example 7
20 g zirconia, 16 g commercial methacrylate monomer for dental use, 1 g 3-(acryloyloxy)-2- hydroxy-propyl methacrylate 60 ml anhydrous acetonitrile were dispersed with a high speed dissolver for 20 min. 20 ml acetonitrile was added, due to evaporation and the mixture was dispersed of 5 min longer. The mixture was transferred to an airtight chamber and ultrasonicated 45 min with a 1000 w transducer at 100 % amplitude. The acetonitrile was evaporated under vacuum and camphorquinone and N,N-dimethyl-p-aminobenzoic acid ethylester (DABE) and the resin was cured. The sample was stored in water at 37 °C. After three days, the sample was phase transformed to an extent of 61 % (determined with XRD).