Dental materials based on oligomers or polymers obtained by ring-opening metathesis polymerization

The present invention relates to dental compositions which contain oligomers or polymers which are obtained by ring-opening metathesis polymerization.

In polymerizable dental materials, mainly ethylenically unsaturated monomers, preferably methacrylate and acrylate monomers, have been used to date. The 2,2-bis [4,1-phenyleneoxy (2-hydroxy-3,1-propanediyl) methacrylic acid ester] propylidene (bis-GMA) [US Pat. No. 3,066,112] described by Bowen is used particularly frequently . Mixtures of this methacrylate with triethylene glycol dimethacrylate (TEGDMA) are still used today as the standard formulation for dental plastic direct filling materials. The curing of such compositions is based on a radical polymerization reaction which is started by appropriately activated radical-forming initiators. The problem here is the disadvantageous polymerization shrinkage that occurs during the polymerization. When used as a filling material, for example, this can lead to the formation of discoloration on the edge of the cavity of the tooth or even to the formation of marginal gaps with a subsequent risk of secondary caries.

In addition to these radical polymerizing systems, two-component systems are also used as dental filling and fastening materials, which consist of a cement reaction between a reactive filler and a liquid that reacts with this filler. Examples of these are the phosphate, silicate, carboxylate [DE-B-1 617 688] and glass ionomer cements [DE-A-2 101889]. A general overview of this area can be found, for example, in AD Wilson; Chemical Society Reviews (1978), 7, (2), 265-296 or in D. Welker, A. Rzanny, R. Göbel; Dental Magazin (1997), 2, 64-76. Compared to the free-radically polymerizing dental materials, these cement materials have the major disadvantage that their mechanical properties such as compressive and flexural strengths are significantly poorer. The reason for this in the case of glass ionomer cements is, among other things, a very high flexibility of the polycarboxylic acid in the liquid.

The object of the present invention is to provide dental materials which contain oligomers or polymers which lead to better mechanical values ​​in the case of cement systems.

The task is solved by providing masses that contain:<ul id="ul0001" list-style="none" compact="compact"><li>(a) 10 to 60% by weight, based on (a) + (b) + (d), monomers, oligomers and / or polymers,</li><li>(b) 40 to 85% by weight, based on (a) + (b) + (d), fillers,</li><li>(c) 0.05 to 2.0% by weight, based on (a), of at least one initiator or an initiator system, and</li><li>(d) 0 to 30% by weight, in particular 5 to 30% by weight, based on (a) + (b) + (d), customary auxiliaries, including pigments, radiopaque additives and / or thixotropy aids,</li></ul> characterized in that 5 to 100 wt .-% of component (a) oligomers or polymers of the general formula<chemistry id="chem0001" num="0001"><img file="EP0904767B1_D0001.tif" /></chemistry> or.<chemistry id="chem0002" num="0002"><img file="EP0904767B1_D0002.tif" /></chemistry> are in which mean:<ul id="ul0002" list-style="none" compact="compact"><li>X is CH₂, NH, O or S,</li><li>m a value from 10 to 20,000,</li><li>n a value from 10 to 20,000,</li></ul> R¹ equal to -CHR⁴-CHR⁵-, <chemistry id="chem0003" num="0003"><img file="EP0904767B1_D0003.tif" /></chemistry> C.₂-C₁₀Alkylene, or C₆-C₁₅-o-arylene which by alkyl, OH, NH₂, C (O) OR⁶, C (O) NHR⁶, PO₃H, SO₃H, Cl, Br or F can be substituted, R1 'equals -CHR⁴-CHR⁵-, <chemistry id="chem0004" num="0004"><img file="EP0904767B1_D0004.tif" /></chemistry> R², R³, R⁴, R⁵ equal to H, C₁-C₁₅-Alkyl, C (O) OR⁶, C (O) NHR⁶, PO₃H, SO₃H, OH and R⁶ is H or a linear, branched or cyclic C₁-C₃₀-Alkyl- or -Arylrest, which may contain 0-10 O or N atoms and 0 to 5 carbonyl groups and is saturated or unsaturated, with the proviso that these compounds contain groups which lead to a hardening of the masses by a cement reaction .

Oligomers or polymers of general formulas I and II can be obtained by ring-opening metathesis polymerization (ROMP). Ring-opening metathesis polymerization is known from the literature and has also been used industrially for some years [Comprehensive Polymer Sci .; 4, 109-142]. Uses of these oligomers or polymers obtained by ROMP for dental applications are not known.

It has surprisingly been found in the context of this invention that compounds of the general formulas (I) and (II) are well suited for dental purposes and lead to compositions with special properties. With cement systems you get better mechanical values. This applies both when the compounds of the formulas (I) and (II) alone and when they are present as a mixture in the dental compositions.

Compound (III) with m = 1000-3000<chemistry id="chem0005" num="0005"><img file="EP0904767B1_D0005.tif" /></chemistry> is an ethylenically unsaturated oligomer or polymer which can be used in the disclosed dental compositions either alone or in combination with other ethylenically unsaturated monomers. Preferred ethylenically unsaturated co-monomers are acrylates or methacrylates. Particularly preferred ethylenically unsaturated co-monomers are bis-GMA, TEGDMA, bis- (hydroxymethyl) tricyclo [5.2.1.0^2,6] -decandiacrlyl acid esters and 2,2-bis [4,1-phenyleneoxy (3,1-propanediyl) methacrylic acid esters] -propylidene.

Further preferred compounds can be found in the formulas (IV) - (VIII) (with m = 1000-3000):<chemistry id="chem0006" num="0006"><img file="EP0904767B1_D0006.tif" /></chemistry><chemistry id="chem0007" num="0007"><img file="EP0904767B1_D0007.tif" /></chemistry><chemistry id="chem0008" num="0008"><img file="EP0904767B1_D0008.tif" /></chemistry>

The synthesis of the compounds (III) - (VII) is carried out in each case by a ROMP of corresponding norbornene derivatives, which in turn are obtained by the Diels-Alder reaction. A general description of these reaction sequences can be found, for example, in "Comprehensive organometallic Chemistry II: a review of the literature 1982-1994", Elsevier 1995, pages 1209-1232. The compound (VIII) can, according to the information from A. Demonceau et al. in Macromolecules (1997), 30 pages 3127 to 3136.

Radical-forming catalysts according to component (c) for curing these ethylenically unsaturated monomers, oligomers and polymers can be substances which can be activated by UV or visible light, such as, for example, benzoin alkyl ethers, benzil ketals, acylphosphine oxides or aliphatic and aromatic 1,2-diketone compounds, for example Camphorquinone, wherein the light polymerization can be accelerated in a manner known per se by adding activators, such as tertiary amines or organic phosphites.

Suitable initiator systems for triggering the radical polymerization via a redox mechanism are, for example, the systems peroxide / amine or peroxide / barbituric acid derivatives and the like. The like. When using such initiator systems, it is expedient to keep an initiator (eg peroxide) and a catalyst component (eg amine) separately available. The two components are then mixed homogeneously with one another shortly before their use.<chemistry id="chem0009" num="0009"><img file="EP0904767B1_D0009.tif" /></chemistry>

In accordance with component (c), cation formers are used for curing epoxy-functionalized monomers, oligomers or polymers. Acid formers such as Lewis or Broensted acids or compounds which release those acids which initiate the cationic polymerization, for example BF, can be used as cation formers₃ or its ethereal adducts (BF₃* THF, BF₃* Et₂O, etc.), AlCl₃, FeCl₃, HPF₆, HAsF₆, HSbF₆, HBF₄ or substances that trigger the polymerization after exposure to UV or visible light or by heat and / or pressure, such as (eta-6-cumene) (eta-5-cyclopentadienyl) iron hexafluorophosphate, (eta-6-cumene) ( eta-5-cyclopentadienyl) iron tetrafluoroborate, (eta-6-cumene) (eta-5-cyclopentadienyl) iron hexafluoroantimonate, substituted diaryliodonium salts and triarylsulfonium salts. Peroxy compounds of the perester, diacyl peroxide, peroxydicarbonate and hydroperoxide type can be used as accelerators. Hydroperoxides are preferably used; cumene hydroperoxide in approximately 70-90% solution in cumene is used as a particularly preferred accelerator. The ratio of photoinitiator to cumene hydroperoxide can be varied within wide limits from 1: 0.001 to 1:10, but preferably a ratio of 1: 0.1 to 1: 6 and particularly preferably from 1: 0.5 to 1: 4 is used . The use of complexing agents such as oxalic acid, 8-hydroxyquinoline, ethylenediaminetetraacetic acid and aromatic polyhydroxy compounds is also possible. Bases, typically tertiary amines, can be added as retarders.

Suitable fillers which can be used in conjunction with the ethylenically unsaturated or epoxy-functionalized oligomers or polymers are generally inorganic fillers. Examples include quartz, ground glasses, silica gels and pyrogenic silicas or their granules. X-ray opaque fillers are preferably used, at least in part. On the one hand, these can be X-ray opaque glasses, i.e. glasses which, for example Contain strontium, barium or lanthanum, or a part of the packing consists of an X-ray opaque additive, such as yttrium trifluoride, strontium hexafluorozirconate or fluorides of the rare earth metals. For better incorporation into the polymer matrix, it is advantageous to hydrophobize the inorganic fillers. Typical hydrophobizing agents are silanes, for example trimethoxymethacryloyloxypropylsilane, or trimethoxyglycidylsilane. The fillers preferably have an average grain size distribution of &lt;20 μm and in particular &lt;5 μm and an upper grain size limit of 150, preferably 70 μm and in particular 25 μm. Mixtures of 5-25% by weight of fillers with an average particle size of 0.02-0.06 µm and 65-85% by weight of fillers with an average particle size of 1-5 µm are particularly preferably used.

Compounds of the general formulas (I) and (II) which set by means of a cement reaction preferably contain free carboxyl groups. To date, polycarboxylic acids have been used, for example, for so-called glass ionomer cements, which are based on acrylic acid, methacrylic acid, maleic acid, fumaric acid or itaconic acid as monomers. A disadvantage of cements which set with such polycarboxylic acids is that they have only very poor flexural strength values ​​in comparison to other dental filling materials. One reason for this is seen in the high flexibility of the polycarboxylic acid chains, which do not lead to sufficient rigidity of the cured material. Attempts to increase the carboxyl group density per monomer unit usually lead to polymers which are no longer sufficiently water-soluble for use in a cement system.

ROMP can be used to produce 5,6-carboxyl-substituted norbornenes from polymeric acids known from the literature, which have a CC double bond and a saturated five-membered ring in their polymer chain according to formulas (I) and (II). These polymer acids have a molecular weight per carbonyl group of 105-107 g / mol and, surprisingly, despite their significantly lower carboxyl group density, are very readily water-soluble compared to conventional polymer acids. In addition, these polymer acids obtained by ROMP bind with acid-soluble glass powders with the formation of cement. In addition, these acids offer the possibility of being modified further by subsequent reactions. For example, the chain length of these molecules can be adapted to the respective application requirement by oxidative cleavage according to the following scheme.<chemistry id="chem0010" num="0010"><img file="EP0904767B1_D0010.tif" /></chemistry>

Particularly preferred compounds that can be used in cements are shown in the formulas (XIV) to (XXIV) (with m = 1000 to 3000):<chemistry id="chem0011" num="0011"><img file="EP0904767B1_D0011.tif" /></chemistry><chemistry id="chem0012" num="0012"><img file="EP0904767B1_D0012.tif" /></chemistry><chemistry id="chem0013" num="0013"><img file="EP0904767B1_D0013.tif" /></chemistry><chemistry id="chem0014" num="0014"><img file="EP0904767B1_D0014.tif" /></chemistry><chemistry id="chem0015" num="0015"><img file="EP0904767B1_D0015.tif" /></chemistry><chemistry id="chem0016" num="0016"><img file="EP0904767B1_D0016.tif" /></chemistry>

The compound (XIV) can, according to the information from A. Demonceau et al. in Macromolecules (1997), 30 pages 3127 to 3136. The synthesis of compounds (XV) to (XXIV) can again be carried out from the corresponding precursors as described in "Comprehensive organometallic Chemistry II: a review of the literature 1982-1994", Elsevier 1995, pages 1209-1232.

For use in dental materials, the polymer acids described here can be introduced either alone or in combination with known acids which have already been used for cements. Such acids are described by way of example in DE-A-2 101 889.

Conventional silicate cement powders such as are also described in DE-A-2 101 889 can be used as the acid-soluble powder according to component (b). However, the use of calcium aluminum fluorosilicate glass powders, which are described in DE-A-2 061 513, is particularly advantageous. Suitable silicate cement powders are also given in "Chemical Society Reviews" (1978), 7 (2), 265-296.

The dental cements are usually applied in the form of a two-component system which consists of a liquid and a powdery component. According to one embodiment i) of the invention, the oligomer or polymer acids according to the invention can be part of the mixing liquid and, according to another embodiment ii) part of the powder component:

In the first-mentioned case (i), the mixing liquid consists of an aqueous solution of the above-defined oligomer or polymer acids and of conventional polymer acids and, if appropriate, customary additives. The acidic monomers are generally present in the aqueous solution in a concentration of at least 20%, usually 30 to 60% by weight, in particular 40 to 50% by weight, if the cement system is intended as dental filling cement. Even lower concentrations are advantageous for cement and prosthetic purposes. The aqueous solutions should have viscosities of at least 0.5 poise, but at most 300 poise. A preferred viscosity range is between 2 and 200, in particular between 5 and 100 poise (at 25 ° C.).

It is customary to distribute dental cements in so-called shake capsules. In these, liquid and powder are provided in two separate chambers and combined and mixed mechanically immediately before use. This predosing can also be applied to the dental materials according to the invention.

According to a further advantageous embodiment (ii) of the invention, the mixing component of the dental cements, ie the oligomer or polymer acids according to component (a), is part of the powder mixture and is present as a premix of glass powder and acid-functional oligomers or polymers. The mixing component can then simply be mixed with water, optionally with the usual additives.

Flowing transitions are possible between the two embodiments i) and ii): for example, half of the liquid and the powdery mixing component can be added to the oligomer and polymer acids, for example.

In embodiment ii), too, it can be expedient to provide and distribute them predisposed in shaking capsules. It can also be particularly advantageous to compress the powder mixture into a tablet.

In addition to the use in dental cements, the compounds XIV to XXIV can also be used as an adhesive agent in so-called bonding compositions. These are either unfilled (0% by weight of component (b)) or low (5 to 30% by weight of component (b)).

Suitable auxiliaries according to component (d) can be, for example, stabilizers, pigments or diluents customarily used in the dental field. In the case of the cement-setting systems, both the powder and the liquid component can be chelated, preferably tartaric acid, in order to improve the hardening characteristics [see. DE-A-2 319 715].

The dental materials according to the invention are suitable for the production of filling materials, fastening cements, inlays, onlays, veneers, provisional crown and bridge materials, dental materials and impression materials.

The invention is to be explained in more detail below by examples.

<b>Examples</b>

<b>example 1</b>

: Synthesis and oxidative degradation of poly-7-oxabicyclo- [2.2.1] -hept-5-en-2,3-dicarboxylic acid

30th g Exo-7-oxabicyclo [2.2.1] -hept-5-en-2,3-dicarboxylic acid anhydride are combined with a solution of K₂[RuCl₅] * xH₂O in 105 g of water heated to 60 ° C with stirring. After about 45 minutes, a clear, highly viscous solution is formed. This is heated to 90 ° C. and a total of 10.0 g of 30% hydrogen peroxide solution are added dropwise within one hour. The solution is then evaporated to dryness and diluted to about 50% with water.

<b>Example 2</b>

: Production of a glass ionomer cement with polymer acids according to the invention

200 mg of the aqueous solution from Example 1 are mixed with 200 mg of an aqueous polycarboxylic acid solution (CHELON-FIL liquid, ESPE, Seefeld). This mixture is spatulated onto a paste with 1.2 g of reactive glass powder (CHELON-FIL powder, from ESPE, Seefeld). To determine the compressive and flexural strength values, the freshly mixed cement is placed in the corresponding test specimen molds and remains there until the end of setting (approx. 5 minutes). The test specimens are then removed from the mold and measured on a Zwick universal testing machine in accordance with the ISO standard 4049 or the ISO standard 9917. The results of the material test are shown in Table 1.

<b>Reference example 1</b>

: Production of a one-component, free-radically polymerizing dental filling material

30 g of exo-7-oxabicyclo [2.2.1] -hept-5-en-2,3-dicarboxylic acid anhydride are dissolved in 23.5 g of hydroxyethylene methacrylate (HEMA) and stirred for 10 hours. Then a solution of 105 g of water and K₂[RuCl₅] * xH₂O (c = 140mg / ml) and heated to 60 ° C with stirring. After about 45 minutes, a clear, highly viscous solution is formed, which is dried under high vacuum for several hours. The viscous residue is then diluted with 10 g of triethylene glycol dimethacrylate (TEGDMA). 10 g of this mixture are mixed with 10 g of bis (hydroxymethyl) tricyclo [5.2.1.0^2,6] -decanediacrylic acid ester and 0.07 g camphorquinone mixed and then kneaded with 0.5 g highly disperse silicon dioxide (Aerosil OX50, Degussa) and 79.5 g finely ground quartz powder to form a homogeneous paste. To determine the compressive and flexural strength values, the paste is introduced into the corresponding test specimen shapes and exposed in accordance with the specifications of ISO standard 4049 and ISO standard 9917. The volume shrinkage is determined by linometer measurement. The results of the material test are shown in Table 2.

<b>Reference example 2</b>

: Production of a one-component, cationically polymerizing dental filling material

10th g of the polymer obtained from monomer 9 of the literature citation A. Demonceau, AW Stumpf, E. Saive, AF Noels; Macromolecules (1997), 30 3127-3136, which is available from ROMP, is mixed with 10 g of 3,4-epoxycyclohexylmethyl-3 ', 4'-epoxycyclohexylcarboxylate, 0.8 g of ferrocenium hexafluoroantimonate and 0.9 g of cumene hydroperoxide and then mixed with 0. 5 g of highly disperse silicon dioxide (Aerosil OX50, from Degussa) and 79.5 g of finely ground quartz powder kneaded into a homogeneous paste. To determine the compressive and flexural strength values, the paste is introduced into the corresponding test specimen shapes and exposed in accordance with the specifications of ISO standard 4049 and ISO standard 9917. The volume shrinkage is determined by linometer measurement. The results of the material test are shown in Table 3.<tables id="tabl0001" num="0001"><table frame="all"><title>Table 1</title><tgroup cols="3" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="52.50mm" /><colspec colnum="2" colname="col2" colwidth="52.50mm" /><colspec colnum="3" colname="col3" colwidth="52.50mm" /><thead valign="top"><row><entry namest="col1" nameend="col3" align="center">Mechanical properties of the glass ionomer cement according to the invention in comparison to a known glass ionomer cement</entry></row><row><entry namest="col1" nameend="col1" /><entry namest="col2" nameend="col2" align="center">Example 2</entry><entry namest="col3" nameend="col3" align="center">Ketac-Fil (ESPE, Seefeld)</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Compressive strength [MPa]^a)</entry><entry namest="col2" nameend="col2" align="center">157</entry><entry namest="col3" nameend="col3" align="center">165</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Flexural strength [MPa]^b)</entry><entry namest="col2" nameend="col2" align="center">52</entry><entry namest="col3" nameend="col3" align="center">35</entry></row></tbody></tgroup><tgroup cols="3" colsep="0" rowsep="0"><colspec colnum="1" colname="col1" colwidth="52.50mm" /><colspec colnum="2" colname="col2" colwidth="52.50mm" /><colspec colnum="3" colname="col3" colwidth="52.50mm" /><tbody valign="top"><row><entry namest="col1" nameend="col3" align="justify">a) Measured according to ISO standard 4049</entry></row><row><entry namest="col1" nameend="col3" align="justify">b) Measured according to ISO standard 9917</entry></row></tbody></tgroup></table></tables><tables id="tabl0002" num="0002"><table frame="all"><title>Table 2</title><tgroup cols="3" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="52.50mm" /><colspec colnum="2" colname="col2" colwidth="52.50mm" /><colspec colnum="3" colname="col3" colwidth="52.50mm" /><thead valign="top"><row><entry namest="col1" nameend="col3" align="center">Mechanical properties of the dental mass according to reference example 1 in comparison to a known composite filling material</entry></row><row><entry namest="col1" nameend="col1" /><entry namest="col2" nameend="col2" align="center">Example 3</entry><entry namest="col3" nameend="col3" align="center">Pertac II (ESPE, Seefeld)</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Compressive strength [Mpa]^a)</entry><entry namest="col2" nameend="col2" align="char" char=",">412</entry><entry namest="col3" nameend="col3" align="char" char=",">420</entry></row><row><entry namest="col1" nameend="col1" align="left">Flexural strength [MPa]^a)</entry><entry namest="col2" nameend="col2" align="char" char=",">98</entry><entry namest="col3" nameend="col3" align="char" char=",">110</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Volume shrinkage [%]^c)</entry><entry namest="col2" nameend="col2" align="char" char=",">1,6</entry><entry namest="col3" nameend="col3" align="char" char=",">2,3</entry></row></tbody></tgroup><tgroup cols="3" colsep="0" rowsep="0"><colspec colnum="1" colname="col1" colwidth="52.50mm" /><colspec colnum="2" colname="col2" colwidth="52.50mm" /><colspec colnum="3" colname="col3" colwidth="52.50mm" /><tbody valign="top"><row><entry namest="col1" nameend="col3" align="justify">a) Measured according to ISO standard 4049</entry></row><row><entry namest="col1" nameend="col3" align="justify">c) Measured with ACTA linometer (AJ de Gee, AJ Feilzer, CL Davidson; Dent Mat (1993), 9, 11-14)</entry></row></tbody></tgroup></table></tables><tables id="tabl0003" num="0003"><table frame="all"><title>Table 3</title><tgroup cols="3" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="52.50mm" /><colspec colnum="2" colname="col2" colwidth="52.50mm" /><colspec colnum="3" colname="col3" colwidth="52.50mm" /><thead valign="top"><row><entry namest="col1" nameend="col3" align="center">Mechanical properties of the dental mass according to reference example 2 in comparison to a known composite filling material</entry></row><row><entry namest="col1" nameend="col1" /><entry namest="col2" nameend="col2" align="center">Example 4</entry><entry namest="col3" nameend="col3" align="center">Pertac II (ESPE, Seefeld)</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Compressive strength [Mpa]^a)</entry><entry namest="col2" nameend="col2" align="char" char=",">390</entry><entry namest="col3" nameend="col3" align="char" char=",">420</entry></row><row><entry namest="col1" nameend="col1" align="left">Flexural strength [MPa]^a)</entry><entry namest="col2" nameend="col2" align="char" char=",">90</entry><entry namest="col3" nameend="col3" align="char" char=",">110</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Volume shrinkage [%]^c)</entry><entry namest="col2" nameend="col2" align="char" char=",">1,4</entry><entry namest="col3" nameend="col3" align="char" char=",">2,3</entry></row></tbody></tgroup><tgroup cols="3" colsep="0" rowsep="0"><colspec colnum="1" colname="col1" colwidth="52.50mm" /><colspec colnum="2" colname="col2" colwidth="52.50mm" /><colspec colnum="3" colname="col3" colwidth="52.50mm" /><tbody valign="top"><row><entry namest="col1" nameend="col3" align="justify">a) Measured according to ISO standard 4049 b) Measured according to ISO standard 9917</entry></row><row><entry namest="col1" nameend="col3" align="justify">c) Measured with ACTA linometer (AJ de Gee, AJ Feilzer, CL Davidson; Dent Mat (1993), 9, 11-14)</entry></row></tbody></tgroup></table></tables>