Composition for fast-curing thermosetting resins containing amines, thiols and unsaturated molecules

Abstract

The present invention relates to a composition comprising two triazine-trione (TATO)-based compounds containing at least one thiol group and at least one unsaturated carbon-carbon bond, the composition further comprising an amine group or compound and a Type I photoinitiator. The composition can be used to treat teeth and bones.

Description

[Technical Field]

[0001] The present invention relates to a composition that can be used as a light-curing resin for bone fracture fixation or dental repair. The composition provides fast curing properties and good mechanical properties. The present invention can be used in a variety of applications and can be provided as a kit. [Background technology]

[0002] Fast-curing resin-based materials have become popular in dentistry due to their durability and versatility—they can be formed into natural shapes and hardened within seconds. Historically, methacrylate monomers have been used in these types of resins, but they suffer from several drawbacks, such as insufficient conversion of functional groups and vitrification, which leads to leaching of unreacted monomers. Thiol-ene and thiol-yne resins polymerized via stepwise radical polymerization have been proposed as an alternative to methacrylate-based resins because their stepwise reaction leads to higher monomer conversion. Highly crosslinked thiol-ene and thiol-yne materials have demonstrated great potential for use in light-curing resin-based materials, such as dental or bone adhesives and composites. Typically, the thiol compounds used are based on 3-mercaptopropionic acid or thioglycolic acid, because the presence of an ester in the vicinity of these thiols reduces the stability of the SH bond, allowing for the facile formation of radicals, which leads to high reactivity in radical reactions of carbon-carbon double or triple bonds. However, these esters also induce water absorption, making the material water-sensitive and susceptible to hydrolysis, which reduces its properties for dental fillings or bone fixation. Furthermore, water absorption by these esters can lubricate highly crosslinked materials sufficiently to lower their glass transition temperature below the physiological temperature of 37°C, making them unusable for filling and fixation in internal structures. To create more durable materials, compounds without esters have been used. However, alkylthiols (without nearby esters) are less reactive in radical reactions, slowing the reaction rate and potentially leading to reduced crosslinking and softening of the material for both radical thiol-ene and thiol-yne polymerizations, since the formation of thiyl radicals is crucial for both initiation and propagation of polymerization.

[0003] Catalysts or accelerators can be used to increase the reaction rate, thereby allowing for a reduction in initiator concentration. Reducing the photoinitiator concentration not only improves the potential cure depth but also reduces the amount of initiator residue that can leach from the material and cause toxicity. Amines are frequently used in base-catalyzed thiol-ene reactions, which proceed via Michael addition. However, when using Type I radical photoinitiator versions of thiol-ene or thiol-yne reactions, amines have been found to be poor catalysts for rapid resin reaction to hard materials. The use of amines in photoinitiated thiol-ene and thiol-yne reactions has been shown to significantly slow the reaction and has not shown any benefit to the rapid cure of resin-based materials. Furthermore, amines are commonly used as coinitiators for Type II photoinitiator systems, where the amine acts via electron / proton transfer with the excited Type II photoinitiator. However, it is well known in the art that amines are not required in thiol-ene systems because the thiol can act as a coinitiator by itself. Indeed, the addition of amines has been shown to decrease the reaction rate and final conversion in radical thiol-ene reactions. This effect has been demonstrated particularly for Type I photoinitiators, where no coinitiator, such as an amine, is involved in the photoinduced radical formation.

[0004] PCT / EP2017 / 077350 and PCT / EP2018 / 079289 disclose amine-containing photoinitiator compositions of aqueous thiol-ene and thiol-yne solutions, including TATATO, TMTATO, 1,3,5-tri(prop-2-yn-1-yl)-1,3,5-triazine-2,4,6-trione (TPYTATO), and 1,3,5-tri(hex-5-yn-1-yl)-1,3,5-triazine-2,4,6-trione (THYTATO), where the amine-containing compounds also contain phosphonic acid moieties, and such compounds could be used only in minimal amounts so as not to interfere with the adhesive properties highly associated with good polymerization. The presence of the amine showed no effect, as adhesion interference did not change whether the phosphonic acid compound contained an amine or not.

[0005] Materials based on fast-setting resins of thiol-ene and thiol-yne materials with high mechanical durability and low water sensitivity are needed to enable the development of the area into functional commercial products for dental and fracture repair. Summary of the Invention

[0006] The object of the present invention is to overcome the drawbacks of the prior art. The resin composition of the present invention allows for fast-curing materials with high strength in moist environments such as bone and dental restorations without the problem of monomer leakage. The new resin is essential for the introduction of light-curing thiol-ene or thiol-yne resins in bone and dental restorations, and also moves away from the use of methacrylate resins and bisphenol A derivatives, which are known to be potentially harmful.

[0007] The present invention uses photoinitiated thiol-ene or thiol-yne coupling polymerizations that reach instantaneous cure only upon addition of a photoinitiator and amine catalyst. In addition to leveraging the high conversion of thiol-ene and thiol-yne polymerizations, the present invention also has the advantage of curing in seconds while maintaining a strong material in the wet state, a characteristic not previously demonstrated and enabling its use in clinical settings.

[0008] In a first aspect, the present invention relates to a composition according to claim 1.

[0009] In a second aspect, the present invention relates to a kit comprising at least two suitable containers, the first container of the kit containing a compound having the following general structure: [ka] wherein R1 is a C1-C10 alkyl group having at least one thiol group, and a second container of the kit contains a first compound having the following structure: [ka] wherein R2 is a C1-C10 alkyl group having at least one unsaturated carbon-carbon double or triple bond, and optionally at least one of the first or second containers further comprises a third compound, wherein the first compound, the second compound and / or any third compound comprises at least one amine group; The optional third compound has the structure: [ka] wherein at least one of R3, R4 and R5 preferably contains at least one unsaturated carbon-carbon double or triple bond or thiol; At least one of the first container, the second container, or the optional third container contains a photoinitiator, and optionally a stabilizer, and optionally a filler.

[0010] All embodiments described herein relate to all aspects unless otherwise stated, and all embodiments can be combined unless otherwise stated. [Brief explanation of the drawings]

[0011] [Figure 1] Illustrated are structures of molecules suitable as the first compound in the resin composition: a) 1,3,5-tris(3-mercaptopropyl)-1,3,5-triazinane-2,4,6-trione (TMTATO); b) 1,3,5-tris(2,3-dimercaptopropyl)-1,3,5-triazinane-2,4,6-trione (TDMTATO); c) 1,3,5-tris(3-mercapto-2-methylpropyl)-1,3,5-triazinane-2,4,6-trione (TMMTATO). [Figure 2]Illustrated are structures of molecules suitable as the second compound in the resin composition: a) 1,3,5-triallyl-1,3,5-triazinane-2,4,6-trione (TATATO); b) 1,3,5-tri(prop-2-yn-1-yl)-1,3,5-triazinane-2,4,6-trione (TPYTATO); c) 1,3,5-tri(hex-5-yn-1-yl)-1,3,5-triazinane-2,4,6-trione (THYTATO). [Figure 3] Illustrated are structures of molecules suitable as the third compound in the resin: a) N-(3-(dimethylamino)propyl)methacrylamide (DMAPMA); b) 2-(dimethylamino)ethyl methacrylate (DMAEMA); c) 3-(allyloxy)-2-((allyloxy)methyl)-N-(3-(dimethylamino)propyl)-2-methylpropanamide (BADMPAPA); d) 2-(dimethylamino)ethyl 3-(allyloxy)-2-((allyloxy)methyl)-2-methylpropanoate (BADMEAPA); e) 2-(2,2-bis((allyloxy)methyl)butoxy)-N,N-dimethylethan-1-amine; f) 3-dimethylamino-1-propyne; g) 1-dimethylamino-2-pentyne; h) triethylamine; i) 1,1,4,7,10,10-hexamethyltriethylenetetramine. [Figure 4] The structures of suitable photoinitiators are illustrated: a) diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO); b) ethyl (2,4,6-trimethylbenzoyl)phenylphosphinate; c) (diethylgermanediyl)bis((4-methoxyphenyl)methanone) (Ivocerin®). [Figure 5] A table of resin compositions is shown. [Figure 6a] Mechanical properties: Flexural modulus. [Figure 6b] Mechanical properties: Flexural strength of resins using different irradiation and curing times. [Figure 6c] Mechanical properties: Indicates the flexural modulus of the resin after 5 seconds of irradiation. [Figure 6d]Mechanical properties: The flexural modulus and flexural strength (values ​​in %) of the modified resins relative to their references after 5 seconds of irradiation are given. [Figure 7] 1 shows the effect of water absorption on storage modulus with increasing temperature from dynamic mechanical analysis. [Figure 8a] The cytotoxicity of the appropriate monomers is shown. [Figure 8b] Figure 2 shows the cytotoxicity of cured resin 2.2 sterilized with either 2-propanol or UV light. [Figure 9] Flexural modulus and flexural strength of different cured resins from three-point bending tests are shown. [Figure 10] The maximum load of the fracture fixation model is shown. [Figure 11] Representative cyclic loading data for a fracture fixation model is shown. DETAILED DESCRIPTION OF THE INVENTION

[0012] The present inventors have shown that amine catalysts can enhance the cure rate for thiol-ene and thiol-yne compositions via photoinitiated radicals using Type I photoinitiators. Rapid cure is required for these types of resin-based materials to reach clinical use. The present invention relates to the development of fiber-reinforced adhesive patches (FRAPs), a novel concept for adhesive fixation of fractures that may provide new and innovative ways to treat fractures and bone defects in a variety of applications. FRAP is further described in International Publication No. 2011 / 048077, and the present invention can be used with the FRAP methodology. The present invention also relates to thiol-ene and thiol-yne dental restorative materials, which can be used with adhesion-enhancing primers described in PCT / EP2017 / 077350 and PCT / EP2018 / 079289.

[0013] Type I photoinitiators work by cleavage of the original photoinitiator into two radical fragments. Irradiation with UV light leads to homolytic bond cleavage and the generation of two highly reactive radical species. These radicals then initiate polymerization.

[0014] Until now, problems with the cure and durability of thiol-ene and thiol-yne resin-based materials have prevented their use in clinical settings for bone and tooth repair. However, the present inventors have developed a new, fast-curing, photoinitiated resin composition that can solve these significant problems. This resin-based material has several application areas, such as tooth filling and tooth restoration. It also enables the transfer of resin-based materials to fracture procedures, such as FRAP, where current methacrylate-based dental materials are not suitable from a toxicological standpoint.

[0015] This concept is based on years of research into material use and performance. Mechanical testing immediately after curing and 24 hours after curing demonstrates significant improvements in the compositions of the present invention compared to common compositions described in the literature. The compositions have proven useful in ex vivo fracture fixation and animal trials involving femur fractures in rats. The compositions have also been used for the first ex vivo tooth repair with promising results.

[0016] The advantages of the composition of the present invention are that it cures quickly, exhibits negligible monomer leakage, and provides higher strength and reproducibility (low standard deviation).

[0017] composition The compositions according to the present invention comprise a first compound, a second compound, and optionally a third compound. The first compound has the following general structure: [ka] wherein R1 is a C1-C10 alkyl group having at least one thiol group, and the second compound has the following structure: [ka] wherein R2 is a C1-C10 alkyl group having at least one unsaturated carbon-carbon double or triple bond, and optionally a third compound. At least one of the first compound, the second compound, or the optional third compound contains at least one amine group. The structures of the first and second compounds may be described as being triazine-trione (TATO)-based. The composition preferably further comprises a Type I photoinitiator selected from peroxide, nitrile, phosphine oxide, and germanium-based photoinitiators, and optionally a stabilizer. In a preferred embodiment, the composition is placed in a light-protected or shielded container to avoid premature activation of the photoinitiator.

[0018] Furthermore, in one embodiment, one of the first compound, the second compound, and the optional third compound comprises at least one amine group. In one embodiment, preferably, the third compound comprises at least one amine group, and more preferably, the third compound comprises at least one amine group and at least one carbon-carbon double or triple bond or thiol. The composition further comprises a photoinitiator and, optionally, a stabilizer.

[0019] The addition of amine-containing molecules to thiol-ene or thiol-yne compositions containing a first compound and a second compound has been found to be a key factor in increasing the cure rate of the compositions from hours to seconds using photoinitiated polymerization. This increase in cure rate was surprising because the current view of amines in radical thiol-ene and thiol-yne reactions is that they slow the reaction rate. Another surprising effect is that the amine group does not act to a significant extent as an initiator, and therefore, there is little prepolymerization via Michael addition, which can lead to premature cure and unusable mixtures. Thus, unexpectedly fast-curing yet stable compositions are presented herein that can be used as photoinitiated resins for several hours after mixing without inducing significant prepolymerization, enabling their use in clinical settings.

[0020] The first compound can be any suitable thiol compound according to structure (1). The first compound can contain one, two, or three thiol groups. In one embodiment, the first compound contains at least two, or preferably at least three, thiol groups. In one preferred embodiment, the first compound is selected from TMTATO, 1,3,5-tris(2,3-dimercaptopropyl)-1,3,5-triazinane-2,4,6-trione (TDMTATO), or 1,3,5-tris(3-mercapto-2-methylpropyl)-1,3,5-triazinane-2,4,6-trione (TMMTATO). In another embodiment, the first compound is preferably TMTATO. In one embodiment, the amount of the first compound is 20 to 90% by weight, preferably 30 to 80% by weight, or more preferably 40 to 60% by weight of the total amount of the first compound, the second compound, and any third compound. Without being bound by theory, it is believed that these amounts result in a thermoset resin with improved properties.

[0021] The second compound can be any suitable unsaturated compound. The second compound can contain at least three unsaturated carbon-carbon double or triple bonds. In one embodiment, the second compound contains an allyl group, or a terminal or non-terminal double bond or a terminal or non-terminal triple bond. Non-limiting examples of suitable second compounds are disclosed in Figure 2. In one embodiment, the second compound is selected from 1,3,5-triallyl-1,3,5-triazinane-2,4,6-trione (TATATO), 1,3,5-tri(prop-2-yn-1-yl)-1,3,5-triazinane-2,4,6-trione (TPYTATO), or 1,3,5-tri(hex-5-yn-1-yl)-1,3,5-triazinane-2,4,6-trione (THYTATO). In another embodiment, the second compound is TATATO. In one embodiment, the amount of the second compound is 10 to 80% by weight, preferably 10 to 60% by weight, or more preferably 10 to 50% by weight of the total amount of the first compound, the second compound, and any third compound.

[0022] In yet another embodiment, the amount of the first compound is 20 to 90 wt %, preferably 30 to 80 wt %, or more preferably 40 to 60 wt % of the total amount of the first compound, the second compound, and any third compound, and the amount of the second compound is 10 to 80 wt %, preferably 10 to 60 wt %, or more preferably 10 to 50 wt % of the total amount of the first compound, the second compound, and any third compound.

[0023] The optional third compound can be any suitable amine-containing compound. In one embodiment, the optional third compound has the following general structure: [ka] wherein at least one of R3, R4, and R5 preferably contains at least one unsaturated carbon-carbon double or triple bond or thiol. Each of R3, R4, and R5 can be any suitable substituent, preferably hydrogen, or an alkyl, alkylene, alkoxy, alkyl ester, alkyl ether, methacryl group, alkylamide, methacrylamide, or the corresponding conjugate acid. In a preferred embodiment, R3 is a double bond-containing group such as a vinyl group, acrylate, methacrylate group, or methacrylamide group, or a group containing at least one unsaturated carbon-carbon double or triple bond or thiol, such as a triple bond or thiol, and R4 and R5 can be any suitable substituent, preferably hydrogen, or an alkyl, alkylene, alkoxy, alkyl ester, alkyl ether, methacryl group, alkylamide, or methacrylamide. In a preferred embodiment, the R3, R4, and R5 groups are selected so that the pKa of the third compound, or its conjugate acid, is greater than 3, preferably greater than 6, more preferably greater than 10, and more preferably between 8 and 13. In another embodiment, none of R3, R4, and R5 is a trivalent phosphorus-containing group, such as a phosphonic acid group. Such groups make the compound acidic, which is believed to be a disadvantage in certain applications. The third compound acts as a catalyst, and an advantage of using catalysts containing double, triple bonds, or thiols is that they can be incorporated into the formed polymer or thermoset, thereby reducing the possibility of catalyst leakage.In one embodiment, the optional third compound is selected from N-(3-(dimethylamino)propyl)methacrylamide (DMAPMA), 2-(dimethylamino)ethyl methacrylate (DMAEMA), 3-(allyloxy)-2-((allyloxy)methyl)-N-(3-(dimethylamino)propyl)-2-methylpropanamide (BADMPAPA), 2-(dimethylamino)ethyl 3-(allyloxy)-2-((allyloxy)methyl)-2-methylpropanoate (BADMEAPA), 2-(2,2-bis((allyloxy)methyl)butoxy)-N,N-dimethylethan-1-amine, 3-dimethylamino-1-propyne, 1-dimethylamino-2-pentyne, triethylamine, and 1,1,4,7,10,10-hexamethyltriethylenetetramine. In another embodiment, the third compound is DMAPMA. In another embodiment, the third compound is BADMPAPA. In one embodiment, the amount of the optional third compound is 0.1 to 50% by weight, preferably 0.5 to 30% by weight, and more preferably 1 to 10% by weight of the total amount of the first compound, the second compound, and the optional third compound.

[0024] In one embodiment, the molar amount of amine groups relative to thiol groups in the composition is between 0.1 and 200 mol %, such as 0.1 and 50 mol %, or 0.1 and 20 mol %, or 0.1 and 5 mol %.

[0025] In yet another embodiment, the amount of the first compound is 20-90 wt %, preferably 30-80 wt %, or more preferably 40-60 wt % of the total amount of the first compound, the second compound, and any third compound, and the amount of the second compound is 10-80 wt %, preferably 10-60 wt %, or more preferably 10-50 wt % of the total amount of the first compound, the second compound, and any third compound, and wherein the molar amount of amine groups relative to thiol groups in the composition is between 0.1-200 mol %, such as 0.1-50 mol %, or 0.1-20 mol %, or 0.1-5 mol %.

[0026] In one embodiment, the functionality ratio between thiol groups and unsaturated groups such as double or triple bonds in the composition is between 1.10:1 and 1:1.10, or more preferably between 1.05:1 and 1:1.05, or more preferably between 1.01:1 and 1:1.01, where a thiol group counts as 1 functionality, a double bond counts as 1 functionality, and a triple bond counts as 2 functionality.

[0027] In yet another embodiment, the amount of the first compound is 20-90 wt %, preferably 30-80 wt %, or more preferably 40-60 wt % of the total amount of the first compound, the second compound, and any third compound, and the amount of the second compound is 10-80 wt %, preferably 10-60 wt %, or more preferably 10-50 wt % of the total amount of the first compound, the second compound, and any third compound, wherein the functionality ratio between thiol groups and unsaturated groups such as double or triple bonds in the composition is between 1.10:1 and 1:1.10, or more preferably between 1.05:1 and 1:1.05, or more preferably between 1.01:1 and 1:1.01.

[0028] Any suitable Type I photoinitiator may be used. The initiator is preferably a peroxide, nitrile, phosphine oxide, or germanium-based initiator that is sensitive to radiation to generate reactive species. In one embodiment, the photoinitiator is selected from diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO), ethyl(2,4,6-trimethylbenzoyl)phenylphosphinate (TPO-L), and bis(4-methoxybenzoyl)diethyl-germanium (Ivocerin). The amount of photoinitiator may be 0.05 to 5% by weight, such as 0.1 to 2% by weight, of the total weight of the composition.

[0029] In yet another embodiment, the amount of the first compound is 20 to 90 wt %, preferably 30 to 80 wt %, or more preferably 40 to 60 wt % of the total amount of the first compound, the second compound, and any third compound, and the amount of the second compound is 10 to 80 wt %, preferably 10 to 60 wt %, or more preferably 10 to 50 wt % of the total amount of the first compound, the second compound, and any third compound, and the amount of the photoinitiator may be 0.05 to 5 wt %, such as 0.1 to 2 wt %, of the total amount of the composition.

[0030] Any suitable stabilizer may be used. The stabilizer is preferably selected from, but not limited to, phenols, quinones, or phosphorus compounds. In one embodiment, the stabilizer is catechol or a catechol derivative. In one embodiment, the amount of the stabilizer is 0.05 to 5% by weight, preferably 0.5 to 3% by weight, of the total amount of the composition.

[0031] Fillers can be added to the resin mixture to improve the rheological properties of the resin composition and the mechanical properties of the cured material, particularly when used for bone fixation or dental restoration. The filler can be any suitable filler. Fillers can include, but are not limited to, ceramics, such as metal phosphates, metal sulfates, and oxide forms, or polymers, or metals. In a preferred embodiment, the additive is glass or hydroxyapatite particles, preferably hydroxyapatite particles. Fillers can be in the form of, but are not limited to, crystals, spheres, rods, flakes, fibers, or heterogeneous particles. In one embodiment, the filler is functionalized to contain one or more carbon-carbon double or triple bonds and / or one or more thiol groups.

[0032] The composition may contain any suitable solvent, but preferably the composition is essentially or completely free of solvent. In one embodiment, the composition contains less than 5% by weight, preferably less than 1% by weight, of solvent. In one embodiment, the composition preferably contains less than 5% by weight, more preferably less than 1% by weight, of water.

[0033] Purpose The present invention can be used, for example, as a resin-based material for treating hard tissues such as bones and teeth. The composition can be used in combination with a primer, adhesive, fiber sheet, screw, or plate for fracture fixation or tooth repair. The composition can be applied to the site, formed into the desired shape, and then hardened into a hard, strong material using a light source.

[0034] kit The present invention further relates to a kit for providing and applying a resin composition, the kit comprising at least two suitable containers, a first container and a second container, and optionally a third container, wherein one first container contains a resin having the general structure (triazine-trione (TATO)): [ka] wherein R1 is a C1-C10 alkyl group having at least one thiol group. The second container contains a first compound having the structure: [ka] wherein R2 is a C1-C10 alkyl group having at least one unsaturated carbon-carbon double or triple bond. At least one of the first container, the second container, or any third container may further comprise an optional third compound, wherein at least one of the first compound, the second compound, and / or any third compound comprises at least one amine group. The optional third compound may have the structure: [ka] wherein at least one of R3, R4 and R5 preferably contains at least one unsaturated carbon-carbon double or triple bond or thiol.

[0035] At least one of the containers contains a photoinitiator, and optionally at least one of the containers of the kit contains a stabilizer and optionally a filler. In one embodiment, the first container further contains an optional third compound. In another embodiment, the second container further contains an optional third compound. In one embodiment, the filler is in the third container, and the third container preferably does not contain the first compound, the second compound, and any third compound. [Example]

[0036] Example 1 Figure 5 shows an example of the compounds in the resin mixture, using equimolar amounts of thiol and unsaturated functional groups, 75 μmol / g amine and 16 μmol / g initiator, and a filler content of 56 wt %, unless otherwise noted. The components were added to a vial and mixed with a spatula at room temperature and ambient air conditions. The initiator was added in the dark, and the vial was always protected from light with aluminum foil.

[0037] Example 2 Bending deflection test: Rectangular beams measuring 35 x 5 x 1 mm were prepared by spreading different resin compositions according to the present invention onto silicone molds and cured with a Bluephase 20i (Ivoclar Vivadent) lamp for 5, 10, or 20 seconds using light with a wavelength of 385-500 nm and a light intensity of 2000 mW / cm per unit area. The beams were mounted in a three-point bending setup on a universal tensile tester immediately after curing or 24 hours after curing. A support span of 30 mm and a crosshead speed of 5 mm / min were used. Results are shown in Figure 6.

[0038] Key conclusions: The addition of an amine catalyst allows for high-performance materials immediately after polymerization, whereas the absence of an amine catalyst requires longer cure times. Tests with Type I photoinitiators showed that adding an amine as a catalyst improved mechanical durability. Adding an amine in combination with Irgacure 819 provided an improvement equivalent to doubling the amount of initiator. Tests with Type II initiator camphorquinone showed that despite optimal light wavelengths, the initiator failed to function well under the conditions used and was not a suitable initiator for these types of materials. Additionally, the amount of amine used in this test, along with camphorquinone, significantly reduced mechanical performance.

[0039] Example 3 Glass transition analysis: Dynamic mechanical analysis was performed on different resin compositions according to the invention on a TA Instruments (New Castle, DE, USA) DMA Q800 in tension mode using a material geometry of 1.5 x 6.5 x 2.5 mm. The temperature was gradually increased from 20 °C up to 110 °C or 140 °C, depending on the material requirements, at a heating rate of 10 °C / min to reach the rubber plate. A strain of 0.1% was induced at a frequency of 1 Hz. The results are shown in Figure 7.

[0040] Key conclusion: The ester-free TATO material with amine catalyst exhibits a high glass transition temperature (T) that remains well above 50°C. g ), and the mechanical properties will not be significantly different in a physiological environment compared to the laboratory environment of the tests performed. The ester-based TATO material exhibits an initial T of approximately 30°C upon water absorption. g and would be softer in a physiological environment compared to the laboratory environment of the tests performed.

[0041] Example 4 The cytotoxicity of the compounds was evaluated by an in vitro cell viability test. RAW 264.7 cells were maintained in DMEM medium containing 10% FBS and 100 U of penicillin-streptomycin solution. The cells were washed, harvested with trypsin, transferred to a 96-well plate at a density of 5,000 cells / well, and incubated for 24 hours before use. Components were dissolved in DMSO and diluted in DMEM to prepare working media with final concentrations of 1 μM, 10 μM, and 100 μM. The old DMEM was removed from the cells and replaced with the above fresh working medium, followed by an additional 24 hours of incubation. The AlamarBlue test was then performed according to the general instructions. Data were acquired using an Infinite® M200 plate reader (Tecan, Switzerland) with a fluorescence model ex / em wavelength of 560 / 590 nm. Data were acquired using i-control™ software. In all cases, six replicate wells were set up for each sample, and PBS-treated cells served as a negative control. Each test was repeated three times. Additionally, a dissolution test was performed to evaluate the in vitro toxicity of the crosslinked Material 2.2. The material was sterilized with 2-propanol or UV light for 3 hours. The sample was then incubated in complete DMEM medium at a concentration of 10 mg / ml for 24 hours to allow potential compounds to leach out. The test medium was then transferred to a 96-well plate (Raw 264.7, 5000 cells / well) at 100 μl per well and incubated for an additional 72 hours. The MTT test was applied to assess viability, and data were acquired using an Infinite® M200 plate reader (Tecan, Switzerland) at 570 nm. Three parallel sections were prepared for each sample to obtain the leached medium for each cell line. Six parallel wells per section of material were used in the MTT assay. The results are shown in Figure 8.

[0042] Key conclusions: RAW 264.7 cells were highly resistant to the compounds tested and the cross-linked material 2.2 did not leach out compounds that caused toxic effects on RAW 264.7 cells.

[0043] Example 5 Bending deflection test: A rectangular beam measuring 35 x 5 x 1 mm was prepared by spreading the resin composition of the present invention onto a silicone mold and cured for 20 seconds with a Bluephase 20i lamp (Ivoclar Vivadent) using light with a wavelength of 385-500 nm and a light intensity of 2000 mW / cm2 per unit area. After 24 hours of curing, the beam was mounted in a three-point bending setup on a universal tensile tester. A support span of 30 mm and a crosshead speed of 5 mm / min were used. Results are shown in Figure 9.

[0044] The key conclusion: Stiff and strong materials can be made from the tested resins.

[0045] Example 6 The second and fifth metacarpal bones were excised from pigs' feet obtained from a butcher shop. The metacarpal bones were cleaned free of soft tissue, and the transverse fracture was incised into bone fragments. Two screws were placed on each side of the fracture. The screws were screwed in halfway, and Resin 2.2 was applied around the screws and across the entire fracture. The screws were then fully screwed in, and the adhesive was cured using a light-emitting diode (LED) polymerization lamp (Bluephase® 20i) for light-curing dental materials, with a wavelength of 385–515 nm and an intensity of 2000–2200 mW / cm2, with dominant wavelengths of 470 nm and 400 nm. The total exposure time was 1 cm. 2The test was performed for 10 seconds per cycle. The screws were then covered with Resin 2.2 and a fiber mesh, which was then cured under light. Finally, a thin layer of adhesive was applied and then cured. Three-point bending tests were performed using an Instron 5566 instrument manufactured by Instron Korea LLC. The load was measured using a 10 kN load cell, and a continuous displacement of 5 mm / min was used. A preload of 1 N and a span length between the lower supports of 3 cm were used. For fatigue testing, a 500 N load cell was used, and a cyclic force of 10 N to 70 N was applied at a crosshead speed of 25 mm / min. A preload of 10 N and a preload rate of 5 mm / min were used. Kirschner wire (K-wire) and LCP Compact Hand Locking tension plate 1.5 were used as reference fixtures. Measurements were performed at 23°C and 50% relative humidity. The specimens were kept as moist as possible before being placed in the machine. Data were collected using Bluehill software, and the results are shown in Figures 10 and 11.

[0046] Key conclusions: Resin 2.2 exhibits high strength when used as a fixator in a finger fracture model.

Claims

1. A composition comprising a first compound, a second compound, and a third compound, wherein the first compound has the general structure according to (1): 【Chemical 1】 wherein each R1 is independently a C1-C10 alkyl group and at least one R1 comprises at least one thiol group, and the first compound is selected from 1,3,5-tris(3-mercaptopropyl)-1,3,5-triazinane-2,4,6-trione (TMTATO), 1,3,5-tris(2,3-dimercaptopropyl)-1,3,5-triazinane-2,4,6-trione (TDMTATO), or 1,3,5-tris(3-mercapto-2-methylpropyl)-1,3,5-triazinane-2,4,6-trione (TMMTATO); and the second compound has the general structure according to (2): 【Chemistry 2】 wherein each R2 is independently a C1-C10 alkyl group and at least one R2 contains at least one unsaturated carbon-carbon double or triple bond, and the second compound is selected from 1,3,5-triallyl-1,3,5-triazinane-2,4,6-trione (TATATO), 1,3,5-tri(prop-2-yn-1-yl)-1,3,5-triazinane-2,4,6-trione (TPYTATO), or 1,3,5-tri(hex-5-yn-1-yl)-1,3,5-triazinane-2,4,6-trione (THYTATO); at least one of the first compound, the second compound, or the third compound comprises at least one amine group; the third compound is an amine-containing compound selected from N-(3-(dimethylamino)propyl)methacrylamide (DMAPMA), 2-(dimethylamino)ethyl methacrylate (DMAEMA), 3-(allyloxy)-2-((allyloxy)methyl)-N-(3-(dimethylamino)propyl)-2-methylpropanamide (BADMPAPA), 2-(dimethylamino)ethyl 3-(allyloxy)-2-((allyloxy)methyl)-2-methylpropanoate (BADMEAPA), 2-(2,2-bis((allyloxy)methyl)butoxy)-N,N-dimethylethan-1-amine, 3-dimethylamino-1-propyne, or 1-dimethylamino-2-pentyne; the composition further comprises a Type I photoinitiator and optionally a stabilizer; and A composition wherein the Type I photoinitiator is selected from a peroxide, a nitrile, a phosphine oxide, or a germanium-based photoinitiator.

2. The composition of claim 1 , wherein the first compound is TMTATO.

3. 3. The composition of claim 1 or 2, wherein the third compound is selected from N-(3-(dimethylamino)propyl)methacrylamide (DMAPMA) or 3-(allyloxy)-2-((allyloxy)methyl)-N-(3-(dimethylamino)propyl)-2-methylpropanamide (BADMAPA).

4. 4. The composition according to claim 1, wherein the amount of the first compound is 20 to 90% by weight, preferably 30 to 80% by weight, or more preferably 40 to 60% by weight of the total amount of the first compound, the second compound, and the third compound.

5. 5. The composition according to claim 1, wherein the amount of the second compound is 10 to 80% by weight, preferably 10 to 60% by weight, or more preferably 10 to 50% by weight of the total amount of the first compound, the second compound, and the third compound.

6. 6. The composition according to any one of claims 1 to 5, wherein the amount of the third compound is 0.1 to 50 wt %, preferably 0.1 to 30 wt %, or more preferably 0.1 to 10 wt % of the total amount of the first compound, the second compound, and the third compound.

7. The composition of any one of claims 1 to 6, wherein the third compound has a pKa greater than 3, preferably greater than 6, more preferably between 8 and 13.

8. The composition according to any one of claims 1 to 7, wherein the composition comprises a stabilizer, the stabilizer being preferably a phenolic compound, a quinone compound or a phosphorus compound.

9. A composition according to any one of claims 1 to 8, wherein the amount of stabilizer is from 0.05 to 5% by weight, preferably from 0.5 to 3% by weight.

10. The composition of any one of claims 1 to 9, wherein the composition comprises a filler.

11. The composition according to any one of claims 1 to 10, wherein the amount of filler is from 20 to 90% by weight, preferably from 25 to 80% by weight, or more preferably from 40 to 75% by weight.

12. The composition of any one of claims 1 to 11, wherein the composition is essentially free or completely free of solvent.

13. 13. The composition according to any one of claims 1 to 12, wherein the functionality ratio between thiol groups and unsaturated groups, such as double or triple bonds, in the composition is between 1.10:1 and 1:1.10, preferably between 1.05:1 and 1:1.05, more preferably between 1.01:1 and 1:1.

01.

14. 14. The composition according to any one of claims 1 to 13, wherein the molar amount of amine groups relative to thiol groups in the composition is between 0.1 and 100 mol %, preferably between 0.1 and 50 mol %, or between 0.1 and 20 mol %, or more preferably between 0.1 and 5 mol %.

15. A kit comprising at least two suitable containers, wherein a first container of the kit contains a compound having the following general structure: 【Chemistry 3】 wherein R1 is a C1-C10 alkyl group having at least one thiol group, and said first compound is selected from 1,3,5-tris(3-mercaptopropyl)-1,3,5-triazinane-2,4,6-trione (TMTATO), 1,3,5-tris(2,3-dimercaptopropyl)-1,3,5-triazinane-2,4,6-trione (TDMTATO), or 1,3,5-tris(3-mercapto-2-methylpropyl)-1,3,5-triazinane-2,4,6-trione (TMMTATO); and a second container of the kit has the following structure: 【Chemistry 4】 wherein R2 is a C1-C10 alkyl group having at least one unsaturated carbon-carbon double or triple bond, and said second compound is selected from 1,3,5-triallyl-1,3,5-triazinane-2,4,6-trione (TATATO), 1,3,5-tri(prop-2-yn-1-yl)-1,3,5-triazinane-2,4,6-trione (TPYTATO), or 1,3,5-tri(hex-5-yn-1-yl)-1,3,5-triazinane-2,4,6-trione (THYTATO), and at least one of said first container, said second container, or any third container further comprises a third compound, and at least one of said first compound, said second compound, and said third compound comprises at least one amine group; the third compound is an amine-containing compound selected from N-(3-(dimethylamino)propyl)methacrylamide (DMAPMA), 2-(dimethylamino)ethyl methacrylate (DMAEMA), 3-(allyloxy)-2-((allyloxy)methyl)-N-(3-(dimethylamino)propyl)-2-methylpropanamide (BADMPAPA), 2-(dimethylamino)ethyl 3-(allyloxy)-2-((allyloxy)methyl)-2-methylpropanoate (BADMEAPA), 2-(2,2-bis((allyloxy)methyl)butoxy)-N,N-dimethylethan-1-amine, 3-dimethylamino-1-propyne, or 1-dimethylamino-2-pentyne; At least one of the first container, the second container, or the optional third container comprises a Type I photoinitiator, and optionally a stabilizer, and optionally a filler; and wherein the Type I photoinitiator is selected from a peroxide, a nitrile, a phosphine oxide, or a germanium-based photoinitiator.

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