Dental materials based on thiourea derivatives capable of overlapping

Abstract

To provide dental materials based on polymerizable thiourea derivatives.SOLUTION: Provided is a radically polymerizable dental material, which includes a combination of a hydroperoxide and a thiourea derivative according to the following Formula (I) as initiator system for the radical polymerization: in which R is absent or is an (n+1)-valent, aromatic, aliphatic, linear or branched C1-C50 hydrocarbon radical, which can be interrupted by one or more than one ether, thioether, ester, amide or urethane groups; PG is a radically polymerizable (meth)acrylate, (meth)acrylamide or vinyl group; and n is 1, 2 or 3.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a radically polymerizable composition having a hydroperoxide-thiourea redox initiator system containing a radically polymerizable thiourea derivative. The composition is particularly suitable as a dental material, for example, as a prosthetic material, cement, adhesive, and composite material for direct filling.

Background Art

[0002] The main fields of use of polymers in the dental field are removable prostheses (e.g., teeth and prosthetic base materials) and fixed prostheses (e.g., veneer materials, crowns or cements), filling materials (e.g., direct or indirect filling composite materials, fixed cements or adhesives) or auxiliary materials (e.g., impression materials). Polymers are usually obtained by radical polymerization of a polymerizable organic matrix, usually a mixture of monomers, an initiator component and a stabilizer.

[0003] Methyl methacrylate (MMA) (prosthetic material), a mixture of functionalized monomers, such as 2-hydroxyethyl methacrylate (HEMA), or an acid group-containing adhesive monomer, such as 10-methacryloyloxydecyl dihydrogen phosphate (MDP), having a dimethacrylate (adhesive) or a mixture containing only dimethacrylate (composite cement and filling composite material), is usually used as a monomer. Commonly used dimethacrylates are 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropyl)phenyl]propane (bis-GMA) and 1,6-bis-[2-methacryloyloxyethoxycarbonylamino]-2,2,4-trimethylhexane (UDMA), which have a high viscosity and result in polymers having very excellent mechanical properties. In particular, triethylene glycol dimethacrylate (TEGDMA), 1,10-decanediol dimethacrylate (D3MA) or bis(3-methacryloyloxymethyl)tricyclo-[5.2.1.02.6]decane (DCP) are used as reactive diluents.

[0004] Methacrylate-based dental materials are cured by radical polymerization, and depending on the area of use, photoinitiators (for photocuring, direct filling composites, and adhesives), thermal initiators (for indirect composites or prosthetic materials), or redox initiator systems (for composite cements) are used. Combinations of photoinitiators and redox initiators are also common, for example, in the case of deep cavity filling materials.

[0005] Redox systems are used especially when there is a risk of incomplete curing, for example, in the case of prosthetic materials because the monomers have low reactivity, or when fixing cements because irradiation is insufficient.

[0006] To ensure sufficient storage stability of the materials, materials based on redox initiators are usually used as so-called two-component systems (2C systems), where the oxidizing agent (peroxide or hydroperoxide) and the reducing agent (amine, sulfinic acid, barbiturate, thiourea, etc.) are incorporated into two separate components. These components are mixed with each other immediately before use. The two components need to be matched so that a homogeneous blend and easy application are possible and a sufficient processing time for dental purposes is achieved. The processing time means the time from the blending of the two components to the start of hardening of the mixed material. On the other hand, the curing time, i.e., the period until the material is completely cured, should not be too long.

[0007] For a long time, redox initiator systems based on mixtures of dibenzoyl peroxide (DBPO) with tertiary aromatic amines, such as N,N - diethanol - p - toluidine (DEPT), N,N - dimethyl - sym. - xylylidene (DMSX) or N,N - diethyl - 3,5 - di - tert. - butylaniline (DABA), have been mainly used in dental composite cements. In DBPO / amine - based redox initiator systems, the processing time and the curing time can be set relatively appropriately in combination with a phenolic inhibitor. A drawback of such DBPO / amine systems is the discoloration caused by the slow oxidation of the amine. Furthermore, radical formation in the case of DBPO / amine - based redox initiator systems is impaired by acids and thus also by acidic monomers, which are commonly used to prepare enamel - dentin adhesives. The amine component is protonated by an acid - base reaction and thereby inactivated.

[0008] The above - mentioned drawbacks can be partly overcome with hydroperoxide redox initiator systems because a tertiary amine is not required as a reducing agent. Furthermore, hydroperoxides are more thermally stable than peroxides. Cumene hydroperoxide, for example, has a half - life temperature T 1 / 2 of 158 °C for 10 hours, while the 10 - hour half - life temperature T 1 / 2 of DBPO is only 73 °C.

[0009] DE2635595C2 discloses a polymerizable dental filling compound containing a substituted thiourea reducing agent in combination with a hydroperoxide oxidizing agent as an initiator system. The material is said to have improved color stability and shelf life, as well as good curing rates.

[0010] EP1693046B1 discloses dental cements and core build - up materials containing a (2 - pyridyl) - 2 - thiourea derivative in combination with a hydroperoxide, where the hydroperoxide group is bonded to a tertiary carbon atom.

[0011] WO2007 / 016508A1 discloses a polymerizable dental composition comprising a thiourea derivative in combination with a hydroperoxide as an initiator system. The composition does not contain monomers having acid groups.

[0012] According to EP1754465B1, the reactivity of the cumene hydroperoxide / acetylthiourea system can be increased by the addition of a soluble copper compound.

[0013] US7,275,932B2 proposes the use of hydroperoxides and thiourea derivatives in combination with an acidic compound as an accelerator. Preferred acidic compounds are acrylates and methacrylates having an acid group such as methacrylic acid.

[0014] EP2233544A1 and EP2258336A1 disclose dental materials comprising hydroperoxides and thiourea derivatives in combination with a vanadium compound as an accelerator.

[0015] WO03 / 057792A2 discloses dental materials comprising polymerizable thiourea derivatives such as allylthiourea, 1-allyl-3-(2-hydroxyethyl)-2-thiourea or 4-oxo-9-thioxo-5-oxa-3,8,10-triazatridec-12-en-1-yl methacrylate as reducing agents. These are for having a lower risk of potential toxicity or narcotic side effects.

[0016] Initiator systems based on hydroperoxides and thiourea derivatives have gained considerable importance in avoiding the drawbacks associated with peroxide / amine systems. The drawback is that many thiourea derivatives have a strong bitter taste (D. Mela, Chem. Senses 14 (1989) 131-135; Lange et al., Chem. Amer. Chem. Soc. 51 (1929) 1911-1914; Qin et al., Talanta 199 (2019) 131-139) which remains prominent even after hardening and causes discomfort to many patients.

Prior Art Documents

Patent Documents

[0017]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Patent Document 6

Patent Document 7

Patent Document 8

Non-Patent Documents

[0018]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Summary of the Invention

Means for Solving the Problems

[0019] The object of the present invention is to provide a dental material that does not have the drawbacks of the state-of-the-art technology. The material should be tasteless, have excellent biocompatibility and excellent curing properties, and have excellent mechanical properties. This specification provides, for example, the following. (Reclaim) (Item 1) A radically polymerizable dental material comprising a combination of a thiourea derivative and a hydroperoxide as an initiator system for radical polymerization, having the following formula (I):

Chemical formula

Mode for Carrying Out the Invention

[0020] As an initiator system for radical polymerization, the following formula (I):

Chemical formula

Chemical formula

[0021] The variables preferably have the following meanings: R is a (n + 1)-valent, aromatic, linear or branched C1-C hydrocarbon radical which can be interrupted by one or more, preferably 1 to 6, particularly preferably 1 to 3 ether, ester, or urethane groups 20 and is a hydrocarbon radical. PG is a radically polymerizable methacrylate or a vinyl group. n is 1 or 2.

[0022] The variables particularly preferably have the following meanings: R is a (n + 1)-valent, aromatic, aliphatic, linear or branched C1-C hydrocarbon radical which can be interrupted by 1 to 6 ether groups or 1 ester or urethane group 20 and is a hydrocarbon radical. PG is a radically polymerizable methacrylate or a vinyl group. n is 1, or R is a phenylene radical, preferably a p-phenylene radical, or a radical having the formula -Ph-CH2-. PG is a vinyl group. n is 1 Here, when R is -Ph-CH2-, the vinyl group is bonded to the phenyl radical (Ph): H2C=CH-Ph-CH2-.

[0023] All the formulas shown in this specification are extended only to those compounds that are compatible with the theory of chemical valence. The indication that a radical is interrupted, for example, by one or more ether groups is to be understood to mean that these groups are inserted into the carbon chain of the radical in each case. Thus, these groups are adjacent to C atoms on both sides and cannot be at the ends. The C1 radical cannot be interrupted. Corresponding to the usual nomenclature, aromatic hydrocarbon radicals also mean these radicals containing aromatic and non-aromatic groups. Preferred aromatic radicals are, for example, -Ph-CH2-.

[0024] The preferred, particularly preferred, and very particularly preferred definitions given for the individual variables can be selected independently of each other in each case. Compounds in which all variables have preferred, particularly preferred, and very particularly preferred definitions are, of course, particularly suitable according to the invention.

[0025] The thiourea derivatives of formula I are not known, but can be prepared using known synthetic methods. For example, polymerizable benzoyl and acetylthiourea derivatives can be prepared by reacting the corresponding polymerizable acid chlorides with thiourea at high temperature. Step 1

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chem.

[0026] The polymerizable thiourea derivative of formula (I) according to the present invention is used in combination with a hydroperoxide.

[0027] A preferred hydroperoxide according to the present invention has the formula R 1 -(OOH) m wherein R 1 is an aliphatic or aromatic hydrocarbon radical and m is 1 or 2. Preferred radicals R 1 are alkyl and aryl groups. The alkyl group can be straight-chain, branched or cyclic. The cyclic alkyl radical can be substituted with an aliphatic alkyl group. An alkyl group having 4 to 10 carbon atoms is preferred. The aryl group can be unsubstituted or substituted with an alkyl group. Preferred aromatic hydrocarbon radicals are benzene radicals substituted with one or two alkyl groups. The aromatic hydrocarbon radical preferably contains 6 to 12 carbon atoms. Particularly preferred hydroperoxides are t-amyl hydroperoxide, 1,1,3,3-tetramethylbutyl hydroperoxide, t-butyl hydroperoxide, t-hexyl hydroperoxide, 2,5-dimethyl-2,5-di(hydroperoxy)hexane, diisopropylbenzene monohydroperoxide, paramethane hydroperoxide, p-isopropylcumene hydroperoxide and mixtures thereof. Cumene hydroperoxide (CHP) is highly particularly preferred.

[0028] Even more preferred are the low-odor CHP derivatives disclosed in European patent application EP3692976A1 of formula II.

Chem.

[0029] The variables preferably have the following meanings: Q 1may be interrupted by one or more O atoms, preferably one O atom, and is substituted by one or more, preferably one, substituents selected from -OH and -OR 2 or is preferably unsubstituted, and is a monovalent or divalent, aliphatic, straight-chain or branched C1-C 10 hydrocarbon radical, where R 2 is an aliphatic, straight-chain or branched C1-C6 hydrocarbon radical, X and Y are independent of each other and in each case absent, -O-, -COO-, or OCONR 4 -, where R 4 is H or a C1-C5 alkyl radical, preferably H, methyl and / or ethyl, and very particularly preferably H, where X and Y are preferably not present simultaneously, Q2 is absent, may be interrupted by one or more O atoms, preferably one or more O atoms, and is substituted by one or more, preferably one, substituents selected from -OH and -OR 5 or may be preferably unsubstituted, and is a straight-chain or branched C1-C 10 alkylene radical, where R 5 is an aliphatic, straight-chain or branched C1-C6 hydrocarbon radical, p is 1 or 2, and here the substitution on the aromatic compound occurs at the 3-position, preferably the 4-position.

[0030] The variables particularly preferably have the following meanings: Q 1 may be interrupted by one O atom and may be substituted by one OH group, and is a monovalent or divalent, aliphatic, straight-chain or branched C1-C5 hydrocarbon radical, X is -COO-, Y is absent, Q 2 is absent or is a straight-chain C1-C3 alkylene radical, p is 1 or 2, and the substitution on the aromatic compound occurs at the 4-position. The variable preferably has the following meaning: Q 1 is a monovalent or divalent, aliphatic, branched, preferably linear C1-C4 hydrocarbon radical, X is -COO-, Y is absent, Q 2 is absent or is a methylene radical, p is 1 or 2, where the substitution on the aromatic compound occurs at the 4-position.

[0031] Preferred hydroperoxide derivatives of formula II according to the invention are

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0032] The hydroperoxide derivatives of formula II exhibit excellent storage stability at room temperature and are particularly suitable as low-odor hydroperoxide components in redox initiator systems for dental compositions. The materials according to the invention may contain one or more hydroperoxides.

[0033] According to a further preferred embodiment, the dental material according to the invention further comprises at least one transition metal compound in addition to at least one hydroperoxide of formula I and at least one thiourea derivative. It has been found that the addition of a transition metal compound results in a material with significantly improved mechanical properties after hardening.

[0034] The preferred transition metal compounds according to the present invention are compounds derived from transition metals having at least two stable oxidation states. Compounds of the elements copper, iron, cobalt, nickel and manganese are particularly preferred. These metals have the following stable oxidation states: Cu(I) / Cu(II), Fe(II) / Fe(III), Co(II) / Co(III), Ni(II) / Ni(III), Mn(II) / Mn(III). Materials containing at least one copper compound are particularly preferred.

[0035] The transition metals are preferably used in the form of their salts. Preferred salts are nitrates, acetates, 2-ethylhexanoates and halides, with chlorides being particularly preferred.

[0036] The transition metals can further advantageously be used in complex form, with complexes with chelating ligands being particularly preferred. Preferred simple ligands for complexing the transition metals are 2-ethylhexanoate and THF. Preferred chelating ligands are 2-(2-aminoethylamino)ethanol, aliphatic amines, particularly preferably 1,1,4,7,10,10-hexamethyltriethylenetetramine (HMTETA), N,N,N´,N´´,N´´-pentamethyldiethylenetriamine (PMDETA), tris[2-(dimethylamino)ethyl]amine (Me6TREN), N,N,N´,N´-tetramethylethylenediamine (TMEDA), 1,4,8,11-tetraaza-1,4,8,11-tetramethylcyclotetradecane (Me4CYCLAM), diethylenetriamine (DETA), triethylenetetramine (TETA) and 1,4,8,11-tetraazacyclotetradecane (CYCLAM); pyridine-containing ligands, particularly preferably N,N,N´,N´-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), N,N-bis(2-pyridylmethyl)amine (BPMA), N,N-bis(2-pyridylmethyl)octylamine (BPMOA), 2,2´-bipyridine and 8-hydroxyquinoline. Highly particularly preferred ligands are acetylacetone, dimethylglyoxime, and 1,10-phenanthroline.

[0037] In the case of an electrically neutral ligand, the charge of the transition metal ion needs to be balanced by a suitable counterion. For this purpose, the above-mentioned ions used to form salts are particularly considered, where acetate and chloride are particularly preferred. Chloride and the complex are characterized by relatively good solubility in the monomers used in the preparation of dental materials.

[0038] Instead of the transition metal complex, a non-complex salt of a transition metal can be used in combination with a complex-forming organic compound, preferably in combination with the above-mentioned chelating compounds, to prepare dental materials. The organic ligand forms a catalytically active complex when mixed with the transition metal salt. The use of such combinations of transition metal salts and organic ligands is preferred.

[0039] Metallic copper, preferably Cu + , iron, preferably Fe 3+ , cobalt, preferably Co 3+ , and nickel, preferably Ni 2+ transition metal compounds are preferred.

[0040] Preferred copper salts are Cu(II) carboxylates (e.g., acetic acid or 2-ethylhexanoic acid), CuCl2, CuBr2, CuI2, particularly preferably CuBr, and very particularly preferably CuCl. Preferred copper complexes are complexes with ligands acetylacetone, phenanthroline (e.g., 1,10-phenanthroline (phen)), aliphatic amines such as 1,1,4,7,10,10-hexamethyltriethylenetetramine (HMTETA), N,N,N´,N´´,N´´-pentamethyldiethylenetriamine (PMDETA), tris[2-(dimethylamino)ethyl]amine (Me6TREN), etc.

[0041] Preferred iron salts are FeCl3, FeBr2 and FeCl2. Preferred iron complexes are the ligands acetylacetone, triphenylphosphine, 4,4'-di(5-nonyl)-2,2'-bipyridine (dNbpy) or 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene (PriIm). The complexes Fe(acac)2 and FeCl2(PPh3)2 are very particularly preferred.

[0042] Preferred nickel salts are NiBr2 and NiCl2, and preferred nickel complexes are nickel acetylacetonate and NiBr2(PPh3)2.

[0043] According to the present invention, copper compounds, copper complexes, in particular mixtures of copper salts and complexing organic ligands are particularly preferred. Salts and complexes of monovalent copper (Cu + ) are very particularly preferred, and copper(I) chloride (CuCl) is most preferred. Compositions containing salts of monovalent copper, in particular CuCl, are characterized by particularly good storage stability.

[0044] The materials according to the invention preferably contain at least one thiourea derivative of formula (I) in an amount of from 0.001 to 5% by weight, particularly preferably from 0.005 to 3.0% by weight, and very particularly preferably from 0.1 to 3.0% by weight.

[0045] The hydroperoxide(s) is preferably used in an amount of from 0.01 to 5% by weight, particularly preferably from 0.05 to 4.0% by weight, and very particularly preferably from 0.1 to 3.0% by weight (total).

[0046] The transition metal compound, where applicable, is preferably used in an amount of from 0.0001 to 1% by weight, preferably from 0.0005 to 0.5% by weight, and particularly preferably from 0.0007 to 0.020% by weight.

[0047] Unless otherwise specified, all percentages in this specification relate to the total mass of the composition.

[0048] In combination with at least one hydroperoxide, the thiourea derivative of formula (I) is particularly suitable for curing radically polymerizable compositions.

[0049] The material according to the invention preferably comprises at least one radically polymerizable monomer. Compositions comprising at least one mono- or polyfunctional (meth)acrylate as the radically polymerizable monomer are particularly preferred. Monofunctional (meth)acrylates mean compounds having one, and polyfunctional (meth)acrylates mean compounds having two or more, preferably 2 to 4 radically polymerizable groups. According to a very particularly preferred embodiment, the composition according to the invention comprises at least one dimethacrylate or a mixture of mono- and dimethacrylates. Materials cured in the oral cavity preferably comprise mono- and / or polyfunctional methacrylates as the radically polymerizable monomer.

[0050] Preferred mono- or polyfunctional (meth)acrylates are methyl, ethyl, 2-hydroxyethyl, butyl, benzyl, tetrahydrofurfuryl or isobornyl (meth)acrylate, p-cumylphenoxyethylene glycol methacrylate (CMP-1E), 2-(2-biphenyloxy)ethyl methacrylate, bisphenol A dimethacrylate, bis-GMA (addition product of methacrylic acid and bisphenol A diglycidyl ether), ethoxylated or propoxylated bisphenol A dimethacrylate, for example 2-[4-(2-methacryloyloxyethoxyethoxy)phenyl]-2-[4-(2-methacryloyloxyethoxy)phenyl]propane) (SR-348c, manufactured by Sartomer, containing three ethoxy groups) and 2,2-bis[4-(2-methacryloxypropoxy)phenyl]propane, UDMA (addition product of 2-hydroxyethyl methacrylate and 2,2,4-trimethylhexamethylene-1,6-diisocyanate), V-380 (addition product of a mixture of 0.7 mol of 2-hydroxyethyl and 0.3 mol of 2-hydroxypropyl methacrylate and 1 mol of α,α,α`,α`-tetramethyl-m-xylylene diisocyanate), di-, tri- or tetraethylene glycol dimethacrylate, trimethylolpropane trimethacrylate, pentaerythritol tetramethacrylate, and glycerol di- or trimethacrylate, 1,4-butanediol dimethacrylate, 1,10-decanediol dimethacrylate (D3MA), bis(methacryloyloxymethyl)tricyclo-[5.2.1.02,6]decane (DCP), polyethylene glycol or polypropylene glycol dimethacrylate, for example, polyethylene glycol 200 dimethacrylate or polyethylene glycol 400 dimethacrylate (PEG200DMA or PEG400DMA) or 1,12-dodecanediol dimethacrylate, or mixtures thereof.

[0051] According to one embodiment, the composition according to the invention preferably further comprises, in addition to the above monomers, one or more acid group-containing radically polymerizable monomers (adhesive monomers). These impart self-adhesive and / or self-etching properties to the material. Thus, acid group-containing monomers are particularly suitable for the preparation of self-adhesive dental materials such as, for example, luting cements.

[0052] Preferred acid group-containing monomers are polymerizable carboxylic acids, phosphonic acids and phosphate esters, and their anhydrides. Preferred carboxylic acids and carboxylic anhydrides are 4-(meth)acryloyloxyethyl trimellitic anhydride, 10-methacryloyloxydecyl malonic acid, N-(2-hydroxy-3-methacryloyloxypropyl)-N-phenylglycine, 4-vinylbenzoic acid. Preferred phosphate esters are 2-methacryloyloxyethyl phenyl hydrogen phosphate, 10-methacryloyloxydecyl dihydrogen phosphate (MDP) and dipentaerythritol pentamethacryloyloxy phosphate. Preferred phosphonic acids are 4-vinylbenzylphosphonic acid, 2-[4-(dihydroxyphosphoryl)-2-oxa-butyl]-acrylic acid, and their amides, for example esters such as 2-[4-(dihydroxyphosphoryl)-2-oxa-butyl]-acrylic acid 2,4,6-trimethylphenyl ester.

[0053] Particularly preferred acid group-containing monomers are 4-vinylbenzylphosphonic acid, 2-[4-(dihydroxyphosphoryl)-2-oxa-butyl]-acrylic acid and their amides, for example esters such as 2-[4-(dihydroxyphosphoryl)-2-oxa-butyl]-acrylic acid 2,4,6-trimethylphenyl ester, (meth)acrylamide dihydrogen phosphates such as 6-methacrylamidohexyl or 1,3-bis(methacrylamido)-propan-2-yl dihydrogen phosphate, and mixtures thereof. These particularly preferred acid group-containing monomers are characterized by high hydrolysis stability.

[0054] In addition to the initiator system according to the present invention, the composition according to the present invention may advantageously further contain an initiator for radical photopolymerization. Such compositions are dual-curable, i.e., they can be cured by both chemistry and light. Preferred photoinitiators are benzophenone, benzoin, and their derivatives, α-diketones, and their derivatives, for example, 9,10-phenanthrenequinone, 1-phenyl-propan-1,2-dione, diacetyl and 4,4`-dichlorobenzyl. Camphorquinone (CQ) and 2,2-dimethoxy-2-phenyl-acetophenone are preferably used in combination with a reducing agent, for example ethyl-4-(dimethylamino)benzoate (EDMAB), or N,N-dimethylaminoethyl methacrylate as an amine.

[0055] According to the present invention, these compositions without amines are preferred. Therefore, Norrish type I photoinitiators are particularly preferred. Norrish type I photoinitiators do not require an amine component.

[0056] Preferred Norrish type I photoinitiators are acyl or bisacylphosphine oxides. Monoacyltrialkylgermanium, diacyl dialkylgermanium and tetraacylgermanium compounds, for example, benzoyltrimethylgermanium, dibenzoyldiethylgermanium, bis(4-methoxybenzoyl)diethylgermanium (Iboserin (registered trademark)), tetrabenzoyl germanium and tetrakis(o-methylbenzoyl)germanium are particularly preferred.

[0057] Furthermore, mixtures of different photoinitiators can be used, for example, in combination with camphorquinone and ethyl 4-dimethylaminobenzoate, bis(4-methoxybenzoyl)diethylgermanium or tetrakis(o-methylbenzoyl)germanium can also be used.

[0058] The dental material according to the present invention may further advantageously contain one or more organic or inorganic fillers. Particulate fillers are preferred. The filler-containing composition is particularly suitable as a dental luting cement or a filling composite material.

[0059] Preferred inorganic fillers are oxides such as SiO2, ZrO2 and TiO2 or mixed oxides of SiO2, ZrO2, ZnO and / or TiO2, nanoparticle or microfine fillers such as pyrogenic silica or precipitated silica, glass powders such as quartz, glass ceramic, borosilicate or radiopaque glass powder, preferably barium or strontium aluminosilicate glass, and radiopaque fillers such as ytterbium trifluoride, tantalum(V) oxide, barium sulfate, or a mixed oxide of SiO2 with ytterbium(III) oxide or tantalum(V) oxide. The dental material according to the present invention may further contain fibrous fillers, nanofibers, whiskers, or mixtures thereof. According to a preferred embodiment, the material according to the present invention does not contain fluoroaluminosilicate glass, calcium aluminosilicate glass, or other fillers that react with organic acids in the sense of an acid-base reaction.

[0060] Preferably, the oxide has a particle size of 0.010 to 15 μm, the nanoparticle or microfine filler has a particle size of 10 to 300 nm, the glass powder has a particle size of 0.01 to 15 μm, preferably 0.2 to 1.5 μm, and the radiopaque filler has a particle size of 0.2 to 5 μm.

[0061] Particularly preferred fillers are a mixed oxide of SiO2 and ZrO2 having a particle size of 10 to 300 nm, a glass powder having a particle size of 0.2 to 1.5 μm, in particular a radiopaque glass powder such as barium or strontium aluminosilicate glass, and a radiopaque filler having a particle size of 0.2 to 5 μm, in particular a mixed oxide of ytterbium trifluoride and / or ytterbium(III) oxide with SiO2.

[0062] Furthermore, the ground prepolymer or pearl polymer (iso filler) is suitable as a filler. These can consist of only organic polymers or can themselves consist of organic polymers filled with inorganic fillers such as radiopaque glass powder(s) and ytterbium trifluoride. The monomers and fillers defined above are suitable for the preparation of ground prepolymers and pearl polymers. The composition for manufacturing a complete denture preferably contains only organic fillers, particularly preferably a ground polymer or pearl polymer based on polymethyl methacrylate (PMMA), and very particularly preferably a pearl polymer based on PMMA as a filler. According to a preferred embodiment, the material according to the present invention does not contain a polymer having an acid group, particularly a polymer having a carboxylic acid group.

[0063] Unless otherwise specified, all particle sizes are weight average particle sizes, where the determination of particle sizes in the range of 0.1 μm to 1000 μm is carried out by static light scattering, preferably using a LA-960 static laser scattering particle size analyzer (Horiba, Japan). In this specification, a laser diode having a wavelength of 655 nm and an LED having a wavelength of 405 nm are used as light sources. By using two light sources with different wavelengths, the entire size distribution of the sample can be measured with only one measurement pass, where the measurement is performed as a wet measurement. For this purpose, an aqueous dispersion of 0.1 - 0.5% of the filler is prepared, and the scattered light thereof is measured in a flow cell. The scattered light analysis for calculating the particle size and particle size distribution is carried out according to the Mie theory according to DIN / ISO13320.

[0064] Particle sizes less than 0.1 μm are preferably determined by dynamic light scattering (DLS). The measurement of particle sizes in the range of 5 nm to 0.1 μm is preferably carried out by dynamic light scattering (DLS) of an aqueous particle dispersion, preferably using a Malvern Zetasiser Nano ZS (Malvern Instruments, Malvern UK) having a He-Ne laser with a wavelength of 633 nm, a scattering angle of 90°, and a temperature of 25°C.

[0065] As the particle size decreases, light scattering decreases. A particle size of less than 0.1 μm can also be determined by SEM or TEM spectroscopy. Transmission electron microscopy (TEM) is preferably carried out at an acceleration voltage of 300 kV using a Philips CM30 TEM. For sample preparation, droplets of the particle dispersion are applied to a 50 Å thick copper grid (mesh size 300) coated with carbon, and then the solvent is evaporated.

[0066] Fillers can be divided into macro-fillers and micro-fillers according to their particle sizes, where fillers with an average particle size of 0.2 - 10 μm are called macro-fillers, and fillers with an average particle size of about 5 - 100 nm are called micro-fillers. Macro-fillers can be obtained, for example, by grinding quartz, radiopaque glass, borosilicate glass, or ceramics, and usually consist of fragmented parts. Micro-fillers such as mixed oxides can be prepared, for example, by hydrolytic co-condensation of metal alkoxides. Fillers with small particle sizes have a greater thickening effect.

[0067] To improve the bond between filler particles and the crosslinked polymer matrix, the filler is preferably surface-modified, particularly preferably by silanization, very particularly preferably by a radically polymerizable silane, especially 3-methacryloyloxypropyltrimethoxysilane. Functionalized acidic phosphates, such as 10-methacryloyloxydecyl dihydrogen phosphate, can also be used for surface modification of non-silicate fillers, such as ZrO2 or TiO2.

[0068] Furthermore, the dental material according to the present invention may contain one or more additional additives, especially stabilizers, colorants, bactericidal active ingredients, fluoride ion-releasing additives, foaming agents, fluorescent brighteners, plasticizers, and / or UV absorbers. The material according to the present invention may also contain one or more organic or inorganic solvents as additives. However, according to a preferred embodiment, the material according to the present invention does not contain water.

[0069] (a) 0.001 to 5.0% by weight, preferably 0.005 to 3.0% by weight, particularly preferably 0.1 to 3.0% by weight of at least one thiourea derivative of formula (I), (b) 0.01 to 5.0% by weight, preferably 0.05 to 4.0% by weight, particularly preferably 0.1 to 3.0% by weight of at least one hydroperoxide, (c) 5 to 95% by weight, preferably 10 to 95% by weight, particularly preferably 10 to 90% by weight of at least one radically polymerizable monomer, (d) 0 to 80% by weight of a filler, and (e) 0.01 to 5% by weight, preferably 0.1 to 3% by weight, particularly preferably 0.1 to 2% by weight of an additive According to the present invention, a dental material containing the above is preferred.

[0070] All amounts in this specification are relative to the total mass of the composition, unless otherwise specified.

[0071] The filling level is adjusted according to the desired use purpose of the material. Preferably, the filled composite has a filler content of 50 to 80% by weight, particularly preferably 70 to 80% by weight, the dental cement has a filler content of 10 to 70% by weight, particularly preferably 60 to 70% by weight, and the prosthesis material preferably has a filler content of 0 to 10% by weight, particularly preferably 0 to 5% by weight.

[0072] (f) 0.0001 to 1% by weight, preferably 0.0005 to 0.5% by weight, particularly preferably 0.0007 to 0.02% by weight of at least one transition metal compound A dental material additionally containing the above is particularly preferred.

[0073] These dental materials consisting of the named components are particularly preferred, where each individual component is preferably selected from the above-mentioned preferred and particularly preferred substances in each case. In all cases, mixtures of several substances, and thus, for example, mixtures of monomers, can also be used as each component.

[0074] The materials according to the invention preferably exist in the form of two separate components, the first component containing a hydroperoxide (catalyst paste) and the second component containing a thiourea derivative (base paste). Since the components preferably have a paste-like consistency, they are also referred to herein as pastes. The compositions of the catalyst paste and the base paste are essentially different in that the catalyst paste contains one or more hydroperoxides and the base paste contains one or more thiourea derivatives.

[0075] The pastes are mixed with each other for use, thereby initiating the hardening reaction. The pastes are preferably blended, so that the catalyst and the base paste can be used in a volume ratio of 1:1. After mixing the pastes, the material has the composition defined above.

[0076] The dental materials according to the invention are characterized in particular by not having a bitter taste after hardening. Furthermore, they have good hardening properties, i.e., they have an advantageous processing time in combination with an advantageous hardening time. Furthermore, after hardening, the materials have mechanical properties comparable to those of materials based on established redox systems, such as, but not limited to, a mixture of acetylthiourea and cumene hydroperoxide (CHP).

[0077] The compositions according to the invention are particularly suitable as dental materials, in particular as dental cements, filling composites and veneer materials, and as materials for the production of prostheses, artificial teeth, inlays, onlays, crowns and bridges. The compositions are mainly suitable for intraoral application by dentists for repairing damaged teeth, i.e., therapeutic applications, such as, for example, as dental cements, filling composites, veneer materials. However, they can also be used non-therapeutically (outside the oral cavity), for example, for the production or repair of dental restorations such as prostheses, artificial teeth, inlays, onlays, crowns, bridges.

[0078] The present invention will be described in more detail below with reference to examples of embodiments.

Example

[0079] Example 1 Synthesis of N-(2-methacryloyloxyhexanoyl)-thiourea

Chemical formula

Chemical formula

[0080] Step 2: tert-Butyl 6-methacryloyloxyhexanoate [Chemical formula] A solution of tert-butyl 6-hydroxyhexanoate (11.15 g, 59.2 mmol), triethylamine (7.18 g, 71.0 mmol) and N,N-dimethylaminopyridine (0.36 g, 3.0 mmol) in toluene (50 ml) was cooled to 0 °C. A solution of methacrylic anhydride (10.95 g, 71.0 mmol) in toluene (10 ml) was added dropwise, and the reaction mixture was stirred at 0 °C for 1 hour and at ambient temperature for 1 hour. The reaction solution was washed with hydrochloric acid (1 N, 3 × 100 ml), sodium hydroxide solution (1 N, 3 × 100 ml), water (2 × 100 ml) and saturated aqueous sodium chloride solution (100 ml), dried over anhydrous sodium sulfate, filtered and concentrated on a rotary evaporator. 14.35 g (56.0 mmol; 95% yield) of a colorless liquid was obtained. 1 1H-NMR (CDCl3, 400 MHz): δ = 6.09 (m, 1H; =CH), 5.54 (m, 1H; =CH), 4.15 (t, 2H; J = 6.5 Hz; O-CH2), 2.23 (t, 2H; J = 7.4 Hz; (C=O)CH2), 1.94 (m, 3H; CH3), 1.74 - 1.60 (m, 4H; CH2), 1.44 (s, 9H; CH3), 1.43 - 1.37 (m, 2H; CH2). 13 13C-NMR (CDCl3, 100.6 MHz): δ = 172.8 (C=O), 167.3 (C=O), 136.4 (=C), 125.1 (=CH2), 79.9 (C), 64.4 (CH2), 35.3 (CH2), 28.2 (CH2), 28.0 (CH3), 25.4 (CH2), 24.6 (CH2), 18.2 (CH3).

[0081] Step 3: 6-Methacryloyloxyhexanoic acid [Chemistry] tert-Butyl 6-methacryloyloxyhexanoate (8.79 g, 34.3 mmol) was dissolved in dichloromethane (100 ml), and trifluoroacetic acid (20 ml) was added. The reaction mixture was stirred at ambient temperature. After 18 hours, the solution was concentrated on a rotary evaporator. The trifluoroacetic acid residue was removed by azeotropic distillation with toluene to give 6.87 g (34.3 mmol; 100% yield) of a slightly yellowish liquid. 1 1H-NMR (CDCl3, 400 MHz): δ = 11.40 (br s, 1H; OH), 6.10 (m, 1H; =CH), 5.56 (m, 1H; =CH), 4.16 (t, 2H; J = 6.5 Hz; O-CH2), 2.39 (t, 2H; J = 7.4 Hz; (C=O)CH2), 1.94 (m, 3H; CH3), 1.76 - 1.66 (m, 4H; CH2), 1.49 - 1.41 (m, 2H; CH2). 13 13C-NMR (CDCl3, 100.6 MHz): δ = 179.7 (C=O), 167.6 (C=O), 136.2 (=C), 125.4 (=CH2), 64.4 (CH2), 33.7 (CH2), 28.1 (CH2), 25.3 (CH2), 24.1 (CH2), 18.1 (CH3).

[0082] Step 4: 6-Methacryloyloxyhexanoyl chloride [Chemistry] Oxalyl chloride (5.15 g, 40.6 mmol) was added dropwise to a solution of 6-methacryloyloxyhexanoic acid (6.77 g, 33.8 mmol) and N,N-dimethylformamide (0.1 ml) in dichloromethane (100 ml). The reaction solution was stirred at ambient temperature for 3 hours and then concentrated on a rotary evaporator. 7.18 g (32.8 mmol; 97% yield) of a yellowish liquid was obtained. 1 1H-NMR (CDCl3, 400 MHz): δ = 6.08 (m, 1H; =CH), 5.56 (m, 1H; =CH), 4.15 (t, 2H; J = 6.5 Hz; O-CH2), 2.93 (t, 2H; J = 7.4 Hz; (C=O)CH2), 1.94 (m, 3H; CH3), 1.80 - 1.68 (m, 4H; CH2), 1.50 - 1.43 (m, 2H; CH2). 13 13C-NMR (CDCl3, 100.6 MHz): δ = 173.4 (C=O), 167.2 (C=O), 136.2 (=C), 125.2 (=CH2), 64.0 (CH2), 46.7 (CH2), 28.0 (CH2), 24.7 (CH2), 24.5 (CH2), 18.1 (CH3).

[0083] Step 5: N-(2-Methacryloyloxyhexanoyl)thiourea [Chemical formula] 6-Methacryloyloxyhexanoyl chloride (7.05 g, 32.2 mmol) was dissolved in toluene (80 ml). Thiourea (2.70 g, 35.5 mmol) was added and the suspension was heated to reflux for 3 hours. After cooling, the suspension was filtered. The filter residue was washed with toluene (100 ml), dried, suspended in water (100 ml), filtered, washed with water (2 × 50 ml), and then dried. The yellowish solid was dissolved in toluene (50 ml) at 60 °C. The solution was cooled to 0 °C and cold filtered. The filter residue was washed with cold toluene (2 × 10 ml) and dried. 1.18 g (4.6 mmol; yield 14%) of a white solid (melting point: 97 °C) was obtained. 11H-NMR (CDCl3, 400 MHz): δ = 9.95 (broad singlet, 1H; NH), 9.61 (broad singlet, 1H; NH), 7.54 (broad singlet, 1H; NH), 6.10 (singlet, 1H; =CH), 5.56 (singlet, 1H; =CH), 4.16 (triplet, 2H; J = 6.5 Hz; O-CH2), 2.41 (triplet, 2H; J = 7.4 Hz; (C=O)CH2), 1.94 (singlet, 3H; CH3), 1.77 - 1.64 (multiplet, 4H; CH2), 1.50 - 1.39 (multiplet, 2H; CH2). 13 13C-NMR (CDCl3, 100.6 MHz): δ = 182.0 (C=S), 173.8 (C=O), 167.5 (C=O), 136.3 (=C), 125.4 (=CH2), 64.2 (CH2), 36.8 (CH2), 28.1 (CH2), 25.3 (CH2), 24.1 (CH2), 18.2 (CH3).

[0084] Example 2 Synthesis of N-(4-vinylbenzoyl)thiourea

Chemical Structure

Chemical Structure

[0085] Step 2: N-(4-Vinylbenzoyl)thiourea

Chem.

[0086] Example 3 N-(2-Methacryloyloxyethoxysuccinoyl)thiourea

Chemical formula

Chemical formula

[0087] Step 2: N-(2-Methacryloyloxyethoxysuccinoyl)thiourea

Chemical Structure

[0088] Example 4 (Comparative Example) Synthesis of 4-oxo-9-thioxo-5-oxa-3,8,10-triazatridec-12-en-1-yl methacrylate

Chemical Structure

[0089] Example 5 Thiourea-based composite cement according to the present invention In each case, the chemically curable composite cement consisting of a base paste and a catalyst paste is prepared from a mixture of dimethacrylate UDMA (an addition product of 2-hydroxyethyl methacrylate and 2,2,4-trimethylhexamethylene-1,6-diisocyanate), bis-GMA (an addition product of methacrylic acid and bisphenol A diglycidyl ether) and 2-(2-biphenyloxy)-ethyl methacrylate (MA-836), as well as the stabilizers MEHQ (hydroquinone monomethyl ether) and TEMPO (2,2,6,6-tetramethylpiperidin-1-yl)oxyl), the filler GM27884 0.7μm sil. (silane-treated glass filler GM G018-056, average particle size 0.7μm, Schott) and the initiator components CHP (cumene hydroperoxide, 80%), copper(II) acetylacetonate (Cu(acac)2), and in each case from a thiourea compound. Table 1: Composition of catalyst paste Cat-1 [Table 1] Table 2: Composition of base paste [Table 2] *) Comparative example

[0090] The catalyst paste Cat-1 was blended with various base pastes at a volume ratio of 1:1, and the processing time of the resulting cement was determined. The processing time (PT) of the paste mixture was determined using a rheometer (Motion Compact Rheometer MCR 302, Anton Paar). For this purpose, the catalyst paste and the base paste were manually blended at a ratio of 1:1 on a mixing block. Next, the material was applied to a mold made of Delrin with a roughened surface of the rheometer. The measuring bob shaft fixed to the spindle with a similarly rough surface compressed the sample, and the storage modulus was determined with a slight rotation. The inflection points were defined in each case at the start of the stable phase and after reaching a specific gradient. Next, the inflection points were connected with a straight line. The measurement point farthest from this straight line was defined as PT. The entire measurement was performed at 28.7 °C in a temperature-controlled chamber. The results are shown in Table 3. Table 3: Processing time (PT) of cement

Table 3

[0091] The flexural strength and flexural modulus of the cement were determined according to the EN ISO-4049 standard (Dentistry - Polymer-based filling, restorative and luting materials). For this purpose, the catalyst paste Cat-1 was blended with various base pastes at a volume ratio of 1:1 in each case, and test pieces according to the standard were prepared from the mixture. These were cured by storing in a heating cabinet at 37 °C for 45 minutes, and the mechanical properties were measured. The results are summarized in Table 4.

[0092] The results demonstrate that after hardening, the composite cement according to the present invention has much better mechanical properties than comparative materials having known polymerizable thiourea derivatives, which are comparable in every respect to the mechanical properties of cements based on the trials and tested initiator systems of CHP using hexanoylthiourea. Table 4: Flexural strength (FS, MPa) and flexural modulus (FM, MPa) of hardened cement

Table 4

Claims

1. A radically polymerizable dental material comprising a combination of a thiourea derivative and a hydroperoxide as an initiator system for radical polymerization, having the following formula (I): 【Chemical 30】 (wherein the variables have the following meanings: R is absent or is a (n+1)-valent, aromatic, aliphatic, straight-chain or branched C hydrocarbon group which may be interrupted by one or more ether, thioether, ester, amide or urethane groups １ ~C ５０ and is a hydrocarbon group, PG is a radically polymerizable (meth)acrylate, (meth)acrylamide or vinyl group, n is 1, 2, or 3) A radically polymerizable dental material, characterized by comprising a thiourea derivative according to the formula.

2. The variable has the following meaning: R is a (n+1)-valent, aromatic, aliphatic, straight-chain or branched C that can be interrupted by one or more ether, ester, or urethane groups １ ~C ３０ hydrocarbon group, PG is a radically polymerizable methacrylate, methacrylamide or vinyl group, n is 1 or 2 The dental material according to claim 1, having.

3. The variable has the following meaning: R is an (n + 1)-valent, aromatic, aliphatic, straight-chain or branched C which can be interrupted by 1 to 6 ether groups, or one ester or urethane group １ ~C ２０ hydrocarbon group, PG is a radically polymerizable methacrylate or vinyl group, n is 1, or R is a phenylene group, PG is a vinyl group, n is 1 The dental material according to claim 2, having.

4. Formula R １ (OOH) ｍ The dental material according to any one of claims 1 to 3, comprising a compound of formula R １ wherein R is an aliphatic or aromatic hydrocarbon group and m is 1 or 2.

5. The dental material according to claim 4, comprising t-amyl hydroperoxide, 1,1,3,3-tetramethylbutyl hydroperoxide, t-butyl hydroperoxide, t-hexyl hydroxyperoxide, 2,5-dimethyl-2,5-di(hydroperoxide)hexane, diisopropylbenzene monohydroperoxide, paramethane hydroperoxide, p-isopropylcumene hydroperoxide, cumene hydroperoxide (CHP) or a mixture thereof.

6. The following formula (II) 【Chemical 31】 (wherein the variables have the following meanings: Q １ which may be interrupted by one or more S and / or O atoms and which is unsubstituted or may be substituted by one or more substituents, and is a p-valent, aromatic, aliphatic, straight-chain or branched C １ -C １４ hydrocarbon group, X and Y are each independently either absent, -O-, -COO-, -CONR ３ -, or -O-CO-NR ４ -, where R ３ and R ４ are each independently H or C １ to C ５ alkyl group, Q ２ either does not exist, may be interrupted by S and / or O atoms, is unsubstituted, or is substituted with -OH, -OR ５ , -Cl and / or -Br, and is an aliphatic, straight-chain or branched C １ ~C １４ alkylene group, where R ５ is an aliphatic, straight-chain or branched C １ ~C １０ hydrocarbon group, Q ３ is C １ to C ３ an alkylene group or does not exist, Here, Q ２ when it does not exist, X and / or Y do not exist, p is 1, 2, 3 or 4, and here The substituents of the aromatic compound occur at the 2, 3, or 4 positions) The dental material according to any one of claims 1 to 5, comprising a hydroperoxide according to the formula.

7. The dental material according to any one of claims 1 to 6, further comprising a transition metal compound.

8. 0.001 to 5% by weight of at least one thiourea derivative of formula (I), 0.01 to 5% by weight of hydroperoxide, Optionally, 0.0001 to 1% by weight of a transition metal compound, The dental material according to any one of claims 1 to 7, all of which are relative values with respect to the total mass of the material.

9. The dental material according to any one of claims 1 to 8, further comprising at least one radically polymerizable monomer.

10. As radically polymerizable monomers, methyl, ethyl, 2-hydroxyethyl, butyl, benzyl, tetrahydrofurfuryl or isobornyl (meth)acrylate, p-cumylphenoxyethylene glycol methacrylate (CMP-1E), 2-(2-biphenyloxy)ethyl methacrylate, bisphenol A dimethacrylate, bis-GMA (an addition product of methacrylic acid and bisphenol A diglycidyl ether), ethoxylated or propoxylated bisphenol A dimethacrylate, 2-[4-(2-methacryloyloxyethoxyethoxy)phenyl]-2-[4-(2-methacryloyloxyethoxy)phenyl]propane) (SR-348c), 2,2-bis[4-(2-methacryloxypropoxy)phenyl]propane, UDMA (an addition product of 2-hydroxyethyl methacrylate and 2,2,4-trimethylhexamethylene-1,6-diisocyanate), V-380 (an addition product of a mixture of 0.7 mol of 2-hydroxyethyl methacrylate and 0.3 mol of 2-hydroxypropyl methacrylate and 1 mol of α,α,α',α'-tetramethyl-m-xylylene diisocyanate), di-, tri- or tetraethylene glycol dimethacrylate, trimethylolpropane trimethacrylate, pentaerythritol tetramethacrylate, glycerol di- and trimethacrylate, 1,4-butanediol dimethacrylate, 1,10-decanediol dimethacrylate (D ３ MA), bis(methacryloyloxymethyl)tricyclo-[5.2.1.02,6]decane (DCP), polyethylene glycol or polypropylene glycol dimethacrylate, polyethylene glycol 200 dimethacrylate, polyethylene glycol 400 dimethacrylate (PEG200DMA or PEG400DMA), 1,12-dodecanediol dimethacrylate or a mixture thereof, the dental material according to claim 9.

11. The dental material according to claim 9 or 10, further comprising at least one acid group-containing radically polymerizable monomer.

12. At least one organic or inorganic filler, nanoparticle or microfine filler, for example, pyrogenic silica or precipitated silica, glass powder, for example, quartz, glass ceramic or radiopaque glass powder, radiopaque filler, for example, ytterbium trifluoride, tantalum(V) oxide, barium sulfate, ytterbium(III) oxide or a mixed oxide of tantalum(V) and SiO ２ The dental material according to any one of claims 1 to 11, further comprising ground prepolymer or pearl polymer.

13. (a) 0.001 to 5.0% by weight of at least one thiourea derivative of formula (I), (b) 0.01 to 5.0% by weight of at least one hydroperoxide, (c) 5 to 95% by weight of at least one radically polymerizable monomer, (d) 0 to 80% by weight of filler(s), and (e) 0.01 to 5% by weight of additive(s), The dental material according to any one of claims 1 to 12, in each case being a relative value with respect to the total mass of the material.

14. The dental material according to claim 13, comprising 50 to 80% by weight (filling composite material) or 10 to 70% by weight (cement) or 0 to 10% by weight of filler (prosthetic material).

15. The dental material according to any one of claims 1 to 14, for therapeutic use.

16. Non-therapeutic use of the dental material according to any one of claims 1 to 14 for the extraoral manufacture or repair of dental restorations such as prostheses, artificial teeth, inlays, onlays, crowns, bridges and complete dentures.

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