Betulinol-based triepoxy monomer, composite resin thereof and preparation method of betulinol-based triepoxy monomer

Abstract

The invention belongs to the technical field of dental restoration material preparation, and particularly relates to a betulinol-based epoxy monomer, composite resin thereof and a preparation method. According to the preparation method of the betulinol-based tricyclic epoxy monomer, the betulinol tricyclic oxidized monomer is prepared through esterification and epoxidation reaction, the reaction condition is mild, the product purity is high, the monomer is used for preparing a composite resin matrix through photocuring, the compatibility is excellent, and the betulinol-based tricyclic oxidized monomer is prepared. And the special three-dimensional structure can effectively reduce the volume shrinkage of the material during curing. Good flexural strength (greater than or equal to 100 MPa) of the composite resin is maintained, and meanwhile, the polymerization shrinkage rate is as low as about 1%; more prominently, the antibacterial activity of the betulinol enables the material to have a remarkable inhibition effect on common cariogenic bacteria (such as streptococcus mutans). The invention provides an innovative solution with low shrinkage characteristic and active antibacterial function for dental caries repair, and has important clinical value.

Description

Technical Field

[0001] The present invention relates to the field of dental materials, and in particular to a betulin-based triepoxy monomer, a composite resin thereof and a preparation method thereof. Background Art

[0002] Dental caries is a common and frequently occurring oral disease, primarily caused by demineralization of tooth hard tissues induced by organic acids. The pathological process typically begins with an initial lesion in the enamel. As the lesion progresses, it may gradually extend to the dentin and even expose the dental pulp.

[0003] According to the 2018 China Oral Health Epidemiology Survey Report, the prevalence of dental caries has gradually increased, and with economic development and changes in eating habits, the occurrence of dental caries tends to be younger, which has become a major issue affecting health.

[0004] Dental composite resins are widely used in oral clinical treatment due to their good aesthetics, biocompatibility, wear resistance and other advantages. However, the high polymerization shrinkage of traditional dental composite resins can lead to microleakage at the interface, thereby forming marginal cracks, which become a microenvironment for bacterial colonization. This microleakage not only reduces the marginal sealing of the restoration, but also leads to the occurrence of secondary caries. In addition, traditional resin materials lack antibacterial function, and oral pathogens (such as Streptococcus mutans) are easy to reproduce at the restoration-tooth interface, accelerating the demineralization process. Therefore, the development of such dental composite resins with both low shrinkage and antibacterial functions is of great clinical significance.

[0005] Patent CN 119462813A discloses a betulin-based dendritic dental monomer and composite resin. The composite resin has a low shrinkage rate when used as a dental material. The preparation process of this material is complex, requiring multiple steps of deprotection anhydride esterification reactions, and there is no clear improvement in the shrinkage mechanism and antibacterial properties. Summary of the Invention

[0006] In response to the problems of the prior art, the present invention proposes a betulin-based triepoxy monomer, its composite resin, and a preparation method to address the problems of traditional resins with high polymerization shrinkage and lack of antibacterial properties, which can lead to secondary caries.

[0007] In order to achieve the above object, the technical solution of the present invention is achieved as follows:

[0008] A betulin-based triepoxy monomer, the structural formula of the epoxy monomer is as follows:

[0009]

[0010] Furthermore, the preparation method of the betulin-based triepoxy monomer comprises the following steps:

[0011] (1) mixing a solvent, betulin, a dehydrating agent, an olefinic acid, and a catalyst to react to obtain a crude product of diene acid-substituted betulin, which is then purified to obtain an intermediate diene acid-substituted betulin;

[0012] (2) mixing the diene acid-substituted betulin obtained in step (1), sodium bicarbonate and a solvent, adding an oxidant solution, reacting to obtain a crude product of a betulin-based triepoxy monomer, and purifying the crude product to obtain a betulin-based triepoxy monomer.

[0013] Furthermore, in step (1), the catalyst is triethylamine or 4-dimethylaminopyridine; the dehydrating agent is N,N-dicyclohexylcarbodiimide or 1-ethyl-(3-dimethylaminopropyl)carbodiimide; the olefinic acid is acrylic acid, 2-butenoic acid or 4-pentenoic acid; the solvent is toluene, dichloromethane or chloroform; and the reaction conditions are: reaction at room temperature for 20-24 hours.

[0014] Furthermore, in step (1), the molar ratio of betulin, dehydrating agent and olefinic acid is 1:2-3:2.2-3; and the amount of the catalyst is 1-2 wt% of the total mass of the reactants betulin, dehydrating agent and olefinic acid.

[0015] Furthermore, the purification method in step (1) is as follows: the crude product of the dienoic acid-substituted betulin is washed with a saturated sodium bicarbonate solution and deionized water, and then dried with anhydrous magnesium sulfate, filtered to obtain a yellow liquid, and then subjected to rotary evaporation at 30-50°C to obtain a column sample; the column sample is separated in a chromatography column, and the eluent is ethyl acetate and petroleum ether in a volume ratio of 1:5-7; then rotary evaporation is performed and vacuum drying is performed at room temperature to obtain the intermediate dienoic acid-substituted betulin.

[0016] Furthermore, in step (2), the oxidant is m-chloroperbenzoic acid; the molar ratio of the diene acid-substituted betulin, the oxidant and sodium bicarbonate is 1:2.5-3.5:2.5-3.5; the solvent of the oxidant solution and the reaction solvent are independently dichloromethane, toluene or chloroform; the reaction conditions are room temperature for 20-28 hours; the purification method is: centrifuging the crude product of the betulin-based triepoxy monomer, collecting the supernatant, and passing it through alkaline alumina column chromatography; and removing the solvent by rotary evaporation to obtain the betulin-based triepoxy monomer.

[0017] Furthermore, a composite resin is provided, wherein the composite resin is prepared from the betulin-based triepoxy monomer.

[0018] Furthermore, the preparation method of the composite resin comprises the following steps:

[0019] 1) mixing the betulin-based triepoxy monomer with a diluent monomer, adding a photoinitiator and mixing evenly in a dark environment to obtain a resin matrix;

[0020] 2) blending the resin matrix of step 1) with fillers to obtain a composite resin paste; and then curing the paste with visible light to obtain the composite resin.

[0021] Furthermore, in the step 1), the diluent monomer is pentaerythritol glycidyl ether, ethylene glycol glycidyl ether or triethylene glycol dimethacrylate; the mass ratio of the betulin-based triepoxy monomer to the diluent monomer is 1:1-1.2; the photoinitiator accounts for 2-4wt% of the resin matrix and is composed of a main initiator and a co-initiator, the mass ratio of the main initiator to the co-initiator is 3:1.1, wherein the main initiator is diphenyliodonium hexafluorophosphate, and the co-initiator is camphorquinone and ethyl 4-dimethylaminobenzoate, and the mass ratio of the two co-initiators is 1:0.1.

[0022] Furthermore, in step 2), the filler is silane-modified SiO2 or silane-modified barium glass powder; the silane is 3-(methacryloyloxy)propyltrimethoxysilane (γ-MPS); the particle size of the filler is 500nm-2μm, and the mass ratio of the filler to the resin matrix is ​​5-7:3; the wavelength of the photocuring is 430-490nm.

[0023] Furthermore, the composite resin is used in dental materials.

[0024] Beneficial effects of the present invention:

[0025] (1) The betulin-based triepoxy monomer and the low-shrinkage antibacterial dental composite resin based on betulin prepared by the present invention are characterized by introducing a double bond into betulin by esterifying betulin with an olefin, and then epoxidizing the double bond to obtain a betulin-based triepoxy monomer. The obtained epoxy monomer is then blended and photocured to prepare a composite resin. The preparation and purification methods are simple, the product is high in purity, and the efficiency is high. Compared with traditional organic resins, the mechanical properties of the composite resin prepared by ring-opening polymerization are not affected, and polymerization shrinkage is significantly reduced. This is because the betulin-based triepoxy monomer polymer has a triepoxy group, which increases the crosslinking density, thereby improving the molecular rigidity of the composite resin. Its special three-dimensional structure can effectively reduce the volume shrinkage of the material during curing.

[0026] (2) The low-shrinkage antibacterial dental composite resin based on betulin prepared by the present invention optimizes the interface between the filler and the resin, improves the mechanical properties, and while maintaining the good flexural strength of the composite resin (≥100MPa), the polymerization shrinkage rate is as low as about 1%. More importantly, the antibacterial activity of betulin itself enables the material to exhibit a significant inhibitory effect on common cariogenic bacteria (such as Streptococcus mutans), and has broad prospects for application in the field of dental composite restorative resins. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0028] Figure 1 The H NMR spectra of Betulin, the intermediate (bis-4-pentenoic acid-substituted betulin) (P2Bet), and the main monomer betulin-based triepoxy monomer (P2Bet-EO) in Example 1;

[0029] Figure 2 This is a flow chart for preparing the low-shrinkage antibacterial dental composite resin based on betulin in Example 4 of the present invention;

[0030] Figure 3 Figures showing mechanical testing of the composite resins of Example 4 (5P5RC), Comparative Example 1 (5B5TC), and Comparative Example 2 (5G5RC);

[0031] Figure 4 Graph showing the antibacterial test results of the composite resins of Example 4 (5P5RC), Comparative Example 1 (5B5TC), and Comparative Example 2 (5G5RC);

[0032] Figure 5 Graph showing polymerization shrinkage test results for the composite resins of Example 4 (5P5RC), Comparative Example 1 (5B5TC), and Comparative Example 2 (5G5RC). DETAILED DESCRIPTION

[0033] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without creative work are within the scope of protection of the present invention.

[0034] The raw materials used in the examples and comparative examples of the present invention are all commercially available products, among which the purity of bisphenol A glycerol dimethacrylate is >98.0%, and the purity of triethylene glycol dimethacrylate (triethylene glycol dimethacrylate) is 95.0%, and the seller is Sigma-Aldrich (Shanghai) Trading Co., Ltd.

[0035] Bisphenol A diglycidyl ether> 98.0%, sold by Shanghai Titan Technology Co., Ltd.

[0036] The purity of pentaerythritol glycidyl ether is 95.0%, and the seller is Shanghai Aladdin Biochemical Technology Co., Ltd.

[0037] Example 1

[0038] This embodiment provides a betulin-based triepoxy monomer and a preparation method thereof, and the steps are as follows:

[0039] (1) Dichloromethane (200 mL), betulin (3.01 g, 6.8 mmol), 4-dimethylaminopyridine (135 mg) and 4-pentenoic acid (1.66 mL) were added to a round-bottom flask and stirred at room temperature for 30 min on a magnetic stirrer. Subsequently, a dichloromethane solution (20 mL) containing N,N-dicyclohexylcarbodiimide (DCC 3.36 g, 16.3 mmol) was added dropwise to the round-bottom flask in an ice-water bath. The mixture was reacted at room temperature for 24 h to obtain a crude product of di-4-pentenoic acid-substituted betulin.

[0040] (2) The crude product of betulin substituted with di-4-pentenoic acid was washed with saturated sodium bicarbonate solution and deionized water, and then dried with anhydrous magnesium sulfate. After filtration, a yellow liquid was obtained, which was then rotary evaporated at 40°C to obtain a column sample. Finally, the column sample was added to a silica gel column and chromatographically separated using ethyl acetate: petroleum ether in a volume ratio of 1:6 to obtain the target product. The target product was rotary evaporated at 40°C and then placed in a vacuum oven and dried at room temperature under vacuum for 24 hours to obtain di-4-pentenoic acid substituted with betulin (yield 2.66 g, yield 65.9%).

[0041] (3) The di-4-pentenoic acid-substituted betulin (3 g, 4.95 mmol), sodium bicarbonate (1.24 g, 14.85 mmol) and dichloromethane (100 mL) obtained in step (2) were added to a round-bottom flask and stirred at room temperature for 30 min. Then, a dichloromethane solution (50 mL) containing m-chloroperbenzoic acid (2.56 g, 14.85 mmol) was added dropwise to the above round-bottom flask through a constant pressure addition funnel under ice-water bath conditions. The mixture was reacted at room temperature for 24 h to obtain a crude product of betulin triepoxy monomer;

[0042] (4) The crude product of the betulin-based triepoxy monomer was centrifuged for 10 min using an ultracentrifuge (8000 rpm), and the supernatant was collected and chromatographed on an alkaline alumina (300 mesh) column. The solvent was removed by rotary evaporation to obtain a yellow translucent viscous liquid, which was the betulin-based triepoxy monomer (yield: 1.53 g, yield: 47.2%).

[0043] The betulin, intermediate (bis-4-pentenoic acid substituted betulin) and main monomer (betulin-based triepoxy monomer) in Example 1 were analyzed by H NMR. Figure 1 As shown:

[0044] Betulin 1 The HNMR absorption peaks are as follows:

[0045] δ (ppm) = 4.70 (d, J = 2.4Hz, 1H), 4.60 (dt, J = 2.4, 1.4Hz, 1H), 3.82 (dd, J = 10.8, 1.9Hz, 1H), 3.35 (dd, J=11.0,1.2Hz,1H),3.21(dd,J=11.5,4.7Hz,1H),2.41(td,J=11.1,5.8Hz,1H),0.73-0.67(m,1H).

[0046] Di-4-pentenoic acid substituted betulin 1 The HNMR absorption peak distribution is as follows:

[0047] δ(ppm)=5.85(ddt,J=16.4,10.4,6.0Hz,2H),5.08(dp,J=17.3,1.7Hz,2H),5.04-4.98(m,2H),4.71(d,J=2.3Hz,1H),4.63-4.59( m,1H),4.50(dd,J=10.7,5.7Hz,1H),4.29(dd,J=11.2,2.0Hz,1H),3.87(d,J=11.0Hz,1H),2.56-2.32(m,9H),0.82-0.75(m,1H).

[0048] Comparison reveals that the signal at δ (ppm) = 4.50 in the di-4-pentenoate-substituted betulin corresponds to the hydrogen atom on the methine at the C-3 position of the betulin skeleton; multiple peaks at δ (ppm) = 5.85, 5.08, and 5.04 all originate from the hydrogen atoms on the newly formed terminal olefin (-CH=CH2) after 4-pentenoate esterification, with δ (ppm) = 5.08-5.04 corresponding to the proton at the inner end of the double bond; and the characteristic peak at δ (ppm) = 4.29 corresponds to the proton peak at the C-28 position. The integrated area ratio of these characteristic peaks is 1:2:4:2, consistent with the theoretical product.

[0049] Betulin-based triepoxy monomer 1 The HNMR absorption peak distribution is as follows:

[0050] δ(ppm)=4.52-4.46(m,1H),4.26(d,J=11.2Hz,1H),3.73-3.66(m,1H),2.98(dh,J=6.9,3.6Hz ,2H),2.76(q,J=3.0Hz,2H),2.65(d,J=4.7Hz,1H),2.59(d,J=4.7Hz,1H),2.55-2.41(m,6H).

[0051] The characteristic peaks were assigned as follows: the peak at δ (ppm) = 4.52 corresponds to the hydrogen atom at the C-3 position; the signals at δ (ppm) = 4.26 and 3.73 can be assigned to the hydrogen atom on the C-28 methylene group of the betulin backbone; the peak at δ (ppm) = 2.98 originates from the hydrogen atom attached to the tertiary carbon inside the epoxy group; the peaks at δ (ppm) = 2.76 and 2.65 correspond to the proton peaks of the epoxy methylene group; and the peak at δ (ppm) = 2.59 corresponds to the hydrogen atom on the methylene group adjacent to the ester group. The peak area ratio of these characteristic peaks is 1:2:2:6:4, which is consistent with the characteristic peak area ratio of the target product, the betulin-based triepoxy monomer.

[0052] Example 2

[0053] This embodiment provides a betulin-based triepoxy monomer and a preparation method thereof, and the steps are as follows:

[0054] (1) Toluene (200 mL), betulin (4.3 g, 9.7 mmol), 4-dimethylaminopyridine (97 mg) and acrylic acid (1.50 mL) were added to a round-bottom flask and stirred at room temperature for 30 min on a magnetic stirrer. Subsequently, a toluene solution (20 mL) containing 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC 3.8 g, 19.8 mmol) was added dropwise to the round-bottom flask in an ice-water bath. The mixture was reacted at room temperature for 20 h to obtain a crude product of betulin substituted with diacrylic acid.

[0055] (2) The crude product of betulin substituted with diacrylate was washed with saturated sodium bicarbonate solution and deionized water, and then dried with anhydrous magnesium sulfate. After filtration, a yellow liquid was obtained, which was then rotary evaporated at 30°C to obtain a column sample. Finally, the column sample was added to a silica gel column and chromatographically separated using ethyl acetate and petroleum ether in a volume ratio of 1:5 to obtain the target product. The target product was rotary evaporated at 35°C and then placed in a vacuum oven and dried under vacuum at room temperature for 24 hours to obtain diacrylate substituted with betulin (yield 3.77 g, yield 70.5%).

[0056] (3) The diacrylate-substituted betulin (3 g, 5.45 mmol), sodium bicarbonate (1.15 g, 13.69 mmol) and toluene (100 mL) obtained in step (2) were added to a round-bottom flask and stirred at room temperature for 30 min. Then, a toluene solution (50 mL) containing m-chloroperbenzoic acid (2.35 g, 13.61 mmol) was added dropwise to the round-bottom flask through a constant pressure addition funnel under ice-water bath conditions. The mixture was reacted at room temperature for 28 h to obtain a crude product of betulin triepoxy monomer;

[0057] (4) The crude product of the betulin-based triepoxy monomer was centrifuged for 10 min using an ultracentrifuge (8000 r / min), and the supernatant was collected and chromatographed on an alkaline alumina (300 mesh) column. The solvent was removed by rotary evaporation to obtain a yellow translucent viscous liquid, which was the betulin-based triepoxy monomer (yield: 2.03 g, yield: 62.2%).

[0058] Example 3

[0059] This embodiment provides a betulin-based triepoxy monomer and a preparation method thereof, and the steps are as follows:

[0060] (1) Add chloroform (200 mL), betulin (4.3 g, 9.7 mmol), 4-dimethylaminopyridine (174 mg) and 2-butenoic acid (2.28 mL) into a round-bottom flask and stir at room temperature for 30 min on a magnetic stirrer. Then, add chloroform solution (20 mL) containing N,N'-dicyclohexylcarbodiimide (5.6 g, 27.14 mmol) into a constant pressure addition funnel and add the solution dropwise into the round-bottom flask under ice-water bath conditions. React at room temperature for 28 h to obtain a crude product of betulin substituted with bis-2-butenoic acid.

[0061] (2) The crude product of the di-2-butenoic acid-substituted betulin was washed with a saturated sodium bicarbonate solution and deionized water, and then dried with anhydrous magnesium sulfate. After filtration, a yellow liquid was obtained, which was then rotary evaporated at 30°C to obtain a column sample. Finally, the column sample was added to a silica gel column and chromatographically separated using ethyl acetate and petroleum ether in a volume ratio of 1:7 to obtain the target product. The target product was rotary evaporated at 45°C and then placed in a vacuum oven and dried at room temperature under vacuum for 24 hours to obtain di-2-butenoic acid-substituted betulin (yield 3.57 g, yield 68.3%).

[0062] (3) The bis-2-butenoic acid-substituted betulin (3 g, 5.18 mmol), sodium bicarbonate (1.52 g, 18.09 mmol) and chloroform (100 mL) obtained in step (2) were added to a round-bottom flask and stirred at room temperature for 30 min. Then, a chloroform solution (50 mL) containing m-chloroperbenzoic acid (3.13 g, 18.14 mmol) was added dropwise to the above round-bottom flask through a constant pressure addition funnel under ice-water bath conditions. The mixture was reacted at room temperature for 28 h to obtain a crude product of betulin triepoxy monomer;

[0063] (4) The crude product of the betulin-based triepoxy monomer was centrifuged for 10 min using an ultracentrifuge (8000 r / min), and the supernatant was collected and subjected to column chromatography on an alkaline alumina (300 mesh). The solvent was removed by rotary evaporation to obtain a yellow translucent viscous liquid, which was the betulin-based triepoxy monomer (yield: 2.01 g, yield: 61.9%).

[0064] Example 4

[0065] This embodiment prepares a composite resin using the betulin-based triepoxy monomer of Example 1 as one of the raw materials, including the following steps:

[0066] 1) The betulin-based triepoxy monomer of Example 1 and pentaerythritol glycidyl ether were mixed in a mass ratio of 1:1, 3.1 wt% of a photoinitiator of the resin matrix was added, and the photoinitiator was diphenyliodonium hexafluorophosphate, camphorquinone, and ethyl 4-dimethylaminobenzoate in a mass ratio of 3:1:0.1. The mixture was mixed uniformly with a magnetic stirrer in the dark to obtain a resin matrix;

[0067] 2) SiO2 modified with 3-(methacryloyloxy)propyltrimethoxysilane to a particle size of 1 μm was blended with the resin matrix using a three-roll mill. The modification method was based on the prior art (MM Karabela, ID Sideridou, Effect of the structure of silane coupling agent on sorption characteristics of solvents by dental resin-nanocomposites, Dental Materials, 24 (2008) 1631-1639.): 5.0 g of SiO2 was ultrasonically dispersed in 100 mL of cyclohexane, and then 0.14 ml of propylamine and 0.53 mL of γ-MPS were added.

[0068] The mixture was stirred at room temperature for 30 minutes and then at 60°C for 1 hour. After the reaction, the precipitate was washed by centrifugation with cyclohexane and deionized water, respectively, and then dried in a vacuum oven (80°C) for 12 hours to obtain silanized SiO2. The ratio of the added amount to the resin matrix was 7:3, resulting in a composite resin paste. This was then photocured (at a wavelength of 468 nm) to obtain a composite resin designated 5P5RC.

[0069] The preparation process of the composite resin in this embodiment is as follows Figure 2 shown.

[0070] Example 5

[0071] This embodiment prepares a composite resin using the betulin-based triepoxy monomer of Example 1 as one of the raw materials, including the following steps:

[0072] 1) The betulin-based triepoxy monomer of Example 2 was mixed with triethylene glycol dimethacrylate in a mass ratio of 1:1.2, and 2 wt% of a photoinitiator of a resin matrix was added, wherein the photoinitiator was camphorquinone, diphenyliodonium hexafluorophosphate, and ethyl 4-dimethylaminobenzoate in a mass ratio of 1:3:0.1, and the mixture was uniformly mixed with a magnetic stirrer in a dark environment to obtain a resin matrix;

[0073] 2) Barium glass powder modified with 3-(methacryloyloxy)propyltrimethoxysilane and having a particle size of 2 μm was blended with a resin matrix using a three-roll mill. The barium glass powder modification method was the same as in Example 4. The ratio of the modified barium glass powder to the resin matrix was 5:3, and a composite resin paste was obtained. The composite resin was then photocured (wavelength of 490 nm) to obtain a composite resin.

[0074] Example 6

[0075] This embodiment prepares a composite resin using the betulin-based triepoxy monomer of Example 1 as one of the raw materials, including the following steps:

[0076] 1) The betulin-based triepoxy monomer of Example 2 was mixed with ethylene glycol glycidyl ether in a mass ratio of 1:1.1, and 4 wt% of a photoinitiator of the resin matrix was added, wherein the photoinitiator was camphorquinone, diphenyliodonium hexafluorophosphate, and ethyl 4-dimethylaminobenzoate in a mass ratio of 1:3:0.1, and the mixture was mixed uniformly with a magnetic stirrer in a dark environment to obtain a resin matrix;

[0077] 2) SiO2 with a particle size of 500 nm modified with 3-(methacryloyloxy)propyltrimethoxysilane was blended with a resin matrix using a three-roll mill. The silica modification method was the same as in Example 4; the ratio of modified silica addition to resin matrix was 2:1 to obtain a composite resin paste, which was then photocured (wavelength of 430 nm) to obtain a composite resin.

[0078] Comparative Example 1

[0079] A method for preparing a composite resin, comprising the following specific steps:

[0080] The resin matrix was prepared by using 50% each of bisphenol A glycerol dimethacrylate (Bis-GMA) and triethylene glycol dimethacrylate (TEGDMA) purchased from the market.

[0081] SiO2 with a particle size of 1 μm after silane modification was blended with a resin matrix using a three-roll mill. The silica modification method was the same as in Example 4. The ratio of the added amount to the resin matrix was 7:3 to obtain a composite resin paste. The composite resin was then photocured at a wavelength of 468 nm to obtain a composite resin, which was designated as 5B5TC.

[0082] Comparative Example 2

[0083] A method for preparing a composite resin, comprising the following specific steps:

[0084] The resin matrix was prepared by using 50% each of bisphenol A diglycidyl ether (BADGE) and pentaerythritol glycidyl ether (PRGE) purchased from the market.

[0085] SiO2 with a particle size of 1 μm after silane modification was blended with a resin matrix using a three-roll mill. The silica modification method was the same as in Example 4; the ratio of the added amount to the resin matrix was 7:3 to obtain a composite resin paste, which was then photocured at a wavelength of 468 nm to obtain a composite resin, designated 5G5RC.

[0086] Result analysis:

[0087] The composite resins prepared in Example 4 (5P5RC), Comparative Example 1 (5B5TC) and Comparative Example 2 (5G5RC) were tested for flexural strength mechanical properties, and the test method was based on the standard GB11749-89. Figure 3 As shown by Figure 3 It can be seen that the flexural strengths of the betulin-based composite resin of the present invention and the epoxy composite resins of Comparative Examples 1 and 2 are all in the range of 110-130 MPa, both meeting the requirement that the flexural strength of dental composite resins should be no less than 80 MPa.

[0088] The antibacterial properties of the composite resins prepared in Example 4 (5P5RC), Comparative Example 1 (5B5TC), and Comparative Example 2 (5G5RC) were tested, and the bacteria used were Streptococcus mutans (ATCC 25175). The antibacterial test process is as follows: the dental composite resin material to be tested is cured according to the conditions in the examples or comparative examples, and a disc sample with a diameter of (2 mm) x thickness of (1 mm) is prepared. The surface is polished and disinfected (e.g., ultraviolet irradiation for 30 minutes or treatment with 75% ethanol). Streptococcus mutans (ATCC 25175) is revived in brain heart infusion medium (BHI) and anaerobically cultured (85% N2, 10% H2, 5% CO2) at 37°C until the logarithmic growth phase (OD 600 ≈0.5, about 10 8 CFU / mL). Dilute the bacterial suspension with PBS buffer to 1×10 6 CFU / mL: 100 μL was evenly spread on the surface of the sample, covered with sterile polyethylene film (to prevent evaporation), and incubated anaerobically at 37°C for 24 hours. After incubation, the sample was immersed in 5 mL of PBS and ultrasonicated (40 kHz, 1 minute) to elute the adherent colonies. After serial dilution, the sample was inoculated onto a BHI agar plate and incubated at 37°C for 48 hours. The number of viable colonies (CFU / mL) was counted.

[0089] The three groups of antibacterial tests of Example 4 and Comparative Examples 1 and 2 were tested in parallel. Figure 4 As shown, the betulin-based composite resin of the present invention has the best antibacterial performance against Streptococcus mutans.

[0090] The composite resins prepared in Example 4 (5P5RC), Comparative Example 1 (5B5TC) and Comparative Example 2 (5G5RC) were subjected to polymerization shrinkage test. The polymerization shrinkage test method was based on the standard ISO 17304:2013. The test results are shown in FIG. Figure 5 shown. Figure 5 The composite resin based on betulin-based triepoxy monomers exhibits a polymerization shrinkage as low as approximately 1%, significantly lower than the shrinkage of the epoxy composite resins in Comparative Examples 1 and 2 (9% and 3%, respectively). The composite resin prepared by the present invention exhibits significantly reduced polymerization shrinkage. The betulin-based triepoxy monomer polymer is a rigid molecule with a three-dimensional structure, and the triepoxy polymer increases crosslinking density.

[0091] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A betulin-based triepoxy monomer, characterized in that: The structural formula of the epoxy monomer is shown below:

2. The method for preparing the betulin-based triepoxy monomer according to claim 1, characterized in that: The following steps are involved: (1) mixing a solvent, betulin, a dehydrating agent, an olefinic acid, and a catalyst to react to obtain a crude product of diene acid-substituted betulin, which is then purified to obtain an intermediate diene acid-substituted betulin; (2) mixing the diene acid-substituted betulin obtained in step (1), sodium bicarbonate and a solvent, adding an oxidant solution, reacting to obtain a crude product of a betulin-based triepoxy monomer, and purifying the crude product to obtain a betulin-based triepoxy monomer.

3. The method for preparing the betulin-based triepoxy monomer according to claim 2, wherein: In step (1), the catalyst is triethylamine or 4-dimethylaminopyridine; the dehydrating agent is N,N-dicyclohexylcarbodiimide or 1-ethyl-(3-dimethylaminopropyl)carbodiimide; the olefinic acid is acrylic acid, 2-butenoic acid or 4-pentenoic acid; the solvent is toluene, dichloromethane or chloroform; and the reaction conditions are: reaction at room temperature for 20-24 hours.

4. The method for preparing the betulin-based triepoxy monomer according to claim 2, wherein: In the step (1), the molar ratio of betulin, dehydrating agent and olefinic acid is 1:2-3:2.2-3; the amount of the catalyst is 1-2 wt% of the total mass of the reactants betulin, dehydrating agent and olefinic acid.

5. The method for preparing the betulin-based triepoxy monomer according to claim 2, wherein: The purification method in step (1) is as follows: washing the above-mentioned crude product of dienoic acid-substituted betulin with a saturated sodium bicarbonate solution and deionized water, drying it with anhydrous magnesium sulfate, filtering it to obtain a yellow liquid, and then rotary evaporating it at 30-50° C. to obtain a column sample; separating the column sample on a chromatography column, and using ethyl acetate and petroleum ether in a volume ratio of 1:5-7 as the eluent; then rotary evaporating it, and vacuum drying it at room temperature to obtain the intermediate dienoic acid-substituted betulin.

6. The method for preparing the betulin-based triepoxy monomer according to claim 2, wherein: In step (2), the oxidant is m-chloroperbenzoic acid; the molar ratio of diene acid-substituted betulin, the oxidant and sodium bicarbonate is 1:2.5-3.5:2.5-3.5; the solvent of the oxidant solution and the reaction solvent are independently dichloromethane, toluene or chloroform; the reaction conditions are room temperature for 20-28 hours; the purification method is: centrifuging the crude product of the betulin-based triepoxy monomer, collecting the supernatant, and passing it through alkaline alumina column chromatography; and removing the solvent by rotary evaporation to obtain the betulin-based triepoxy monomer.

7. A composite resin, characterized in that: The composite resin is prepared from the betulin-based triepoxy monomer according to claim 1.

8. The method for preparing the composite resin according to claim 7, characterized in that: The following steps are involved: 1) mixing the betulin-based triepoxy monomer with a diluent monomer, adding a photoinitiator and mixing evenly in a dark environment to obtain a resin matrix; 2) blending the resin matrix of step 1) with fillers to obtain a composite resin paste; and then curing the paste with visible light to obtain the composite resin.

9. The method for preparing the composite resin according to claim 8, characterized in that: In the step 1), the diluent monomer is pentaerythritol glycidyl ether, ethylene glycol glycidyl ether or triethylene glycol dimethacrylate; the mass ratio of the betulin-based triepoxy monomer to the diluent monomer is 1:1-1.2; the photoinitiator is composed of a main initiator and a co-initiator, accounting for 2-4wt% of the resin matrix, and the mass ratio of the main initiator to the co-initiator is 3:1.1, wherein the main initiator is diphenyliodonium hexafluorophosphate, and the co-initiator is camphorquinone and ethyl 4-dimethylaminobenzoate, and the mass ratio of the two co-initiators is 1:0.

1.

10. The method for preparing the composite resin according to claim 8, characterized in that: The filler in step 2) is silane-modified SiO2 or barium glass powder; the silane is 3-(methacryloyloxy)propyltrimethoxysilane; the particle size of the filler is 500nm-2μm, and the mass ratio of the filler to the resin matrix is ​​5-7:3; the wavelength of the light curing is 430-490nm.

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