A dendritic organic monomer of betulin, a composite resin and a preparation method thereof

Abstract

The application belongs to the field of dental restoration material preparation, and particularly relates to a dendritic organic monomer based on betulin, a composite resin and a preparation method. The application provides a dendritic organic monomer based on betulin, which has mild reaction conditions, a light product color and good mixing effect with a resin matrix. The application also provides a composite resin prepared by using the above organic monomer, which exhibits significant biocompatibility and low polymerization shrinkage. The application also provides a preparation method of the above composite resin.

Description

Technical Field

[0001] This invention belongs to the field of dental restorative material preparation, and specifically relates to a dendritic organic monomer, composite resin, and preparation method based on betulin. Background Technology

[0002] Dental caries, commonly known as tooth decay, is a chronic disease caused by bacteria and microorganisms in the oral cavity breaking down food debris, producing acidic substances that erode healthy teeth. Essentially, it's a process mediated by biofilms and driven by sugars. The formation of dental caries mainly involves the demineralization of inorganic matter and the decomposition of organic matter, pathologically manifesting as a gradual change in tooth color and progressive lesions in the hard tissues of the teeth. Traditionally, people used willow branches (mainly containing Panax notoginseng) to make toothbrushes and dried and crushed pine resin and Poria cocos into powder to make toothpaste to prevent caries. In the 1970s, Professors Kyes and Newbrun proposed that food (fermentable carbohydrates), the host (susceptible tooth surface), cariogenic bacteria (mainly Streptococcus mutans), and time constitute the four major factors in the modern etiology of dental caries.

[0003] The 2018 Fourth National Oral Health Epidemiological Survey Report showed that the caries rate in deciduous teeth among 5-year-old children in my country was as high as 70.1%, and the caries rate in permanent teeth among 12-year-old children reached 34.5%. The detection rates of dental calculus and gingival bleeding among residents aged 35-44 were as high as 96.7% and 87.4%, respectively, indicating that with the continuous improvement of living standards, oral health problems in my country are showing a trend of affecting younger people. The WHO has listed dental caries as one of the three major non-communicable diseases that should be prioritized for prevention and control in the 21st century. Therefore, dental materials used for caries restoration and treatment have become a research hotspot.

[0004] The earliest dental restorative material used was amalgam, which hardens quickly and can withstand the chewing forces between teeth, and has been used for over 160 years. However, traditional amalgam not only has poor aesthetics and flowability, but also poses a potential risk of heavy metals being released into the dental pulp and gums after being filled into caries. These substances are subsequently absorbed by saliva and blood, and can be conducted throughout the body, damaging the renal and nervous systems. Compared to traditional amalgam, dental restorative resins offer superior aesthetics and workability, along with good bonding ability and lower toxicity. Therefore, composite resins have gradually replaced amalgam as the primary material for dental restorations. However, resins are prone to polymerization shrinkage during light curing, creating gaps between the dentin and resin, leading to microleakage. Simultaneously, oral bacteria adhere to the surface of the restorative resin, forming a biofilm, ultimately causing restoration failure. Furthermore, Bis-GMA in the resin matrix is ​​reproductively toxic to humans. Therefore, dental restorative resins not only need sufficient mechanical strength but also low polymerization shrinkage and biocompatibility to reduce and avoid secondary caries and material damage to the human body. Summary of the Invention

[0005] To address the problems and shortcomings of existing technologies, this invention provides a dendritic organic monomer based on betulin, a composite resin, and a preparation method thereof. The structural formula of the aforementioned organic monomer is as follows:

[0006]

[0007] , where R1 is R2 is

[0008] Furthermore, the present invention also provides a composite resin, which is prepared from the organic monomer described in claim 1.

[0009] Furthermore, the present invention provides a method for preparing a composite resin, wherein the preparation method comprises the following steps:

[0010] The betulin and tancilimide side chains undergo esterification under the action of solvent, dehydrating agent and catalyst to obtain the first compound;

[0011] The first compound was deprotected under the action of solvent and acid to obtain a betulinol-based intermediate.

[0012] The betulinol-based intermediate and the acid anhydride are reacted in the presence of a solvent and a catalyst to obtain the betulinol-based dendritic organic monomer.

[0013] The dendritic organic monomers and the traditional resin matrix are premixed to obtain a composite resin paste;

[0014] The composite resin paste is cured under visible light to obtain the composite resin.

[0015] Optionally, the preparation method includes:

[0016] (1) Add the solvent, betulin, dehydrating agent and catalyst to a round bottom flask, stir at 500-700 r / min for 30-60 min on a magnetic stirrer, then add the tancilimide side chain to the flask and react for 20-24 h to obtain the first compound;

[0017] (2) The first compound was filtered to obtain a yellowish-brown liquid, which was then mixed with silica gel for sample preparation. The sample was obtained by rotary evaporation at 40-42°C.

[0018] (3) The sample is packed into a silica gel column for chromatography to obtain the target product. The target product is then rotary evaporated at 40-45°C and placed in a vacuum oven. It is then dried at room temperature for 20-24 hours to obtain the first intermediate. The first intermediate is the betulin intermediate.

[0019] (4) The first intermediate, solvent and concentrated sulfuric acid are added to a round-bottom flask, placed on a magnetic stirring heating table, and reacted at 20-30°C for 2-3 hours. After washing with sodium carbonate solution and sodium chloride solution, anhydrous magnesium sulfate is added for drying. After filtration, a colorless liquid is obtained. After rotary evaporation at 40-45°C, it is placed in a vacuum oven and dried at room temperature for 20-24 hours. After deprotection, the second intermediate is obtained. The second intermediate is the deprotected betulin intermediate.

[0020] (5) Add the second intermediate, solvent and catalyst to a round-bottom flask and stir at 500-700 r / min for 5-10 min on a magnetic stirrer. Then add a solution of acid anhydride in a constant pressure feeding funnel and add it dropwise to the flask at 20-25°C. React for 20-24 h to obtain the second compound.

[0021] (6) After filtration of the second compound, a yellowish-brown liquid was obtained, which was then mixed with silica gel for sample preparation. The sample was obtained by rotary evaporation at 40-42°C.

[0022] (7) The sample was packed into a silica gel column for chromatography separation, and after rotary evaporation at 40-45°C, it was placed in a vacuum oven and then dried at room temperature for 20-24 hours to obtain the dendritic organic monomer.

[0023] (8) The dendritic organic monomer and the traditional resin matrix are premixed three times by a dual-center disperser to obtain an uncured dental composite resin paste, which is then cured by visible light to obtain a dental composite resin.

[0024] Optionally, before step (7), the following steps are included: adding a portion of the second intermediate, solvent, dehydrating agent and catalyst into a round-bottom flask, stirring at 500-700 r / min on a magnetic stirrer for 30-60 min, then adding tancilimus side chain into the flask, reacting for 20-24 h to obtain the first compound;

[0025] Repeat steps (2) to (8) to obtain dental composite resin.

[0026] Optionally, the dehydrating agent is one of N,N'-dicyclohexylcarbodiimide and 1-ethyl-(3-dimethylaminopropyl)carbodiimide.

[0027] Optionally, the catalyst is one of triethylamine and 4-dimethylaminopyridine.

[0028] Optionally, the solvent is one of dichloromethane, chloroform, tetrahydrofuran, methanol, and dimethyl sulfoxide.

[0029] Optionally, the anhydride is one of methacrylic anhydride, maleic anhydride, and acrylic anhydride.

[0030] Optionally, the resin matrix comprises a resin monomer and a photoinitiator system. The resin monomer is one of bisphenol A-diglyceride dimethacrylate (Bis-GMA), triethylene dimethacrylate (TEGDMA), bisphenol A polyoxyethylene ether dimethacrylate (EBPDMA), and urethane dimethacrylate (UDMA).

[0031] Optionally, the photoinitiator system consists of a main initiator and a co-initiator, with a mass ratio of 1:4, accounting for 1% of the total mass of the resin matrix. The main initiator is camphorquinone, and the co-initiator is ethyl 4-dimethylaminobenzoate.

[0032] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0033] (1) The betulinol-based dendritic organic monomer prepared by this invention has mild reaction conditions, light product color, and good mixing effect with resin matrix, and can be applied to the field of dental composite restorative resin.

[0034] (2) The dendritic organic monomers based on betulin prepared in this invention, compared with traditional organic resins, can be prepared by controlling the degree of dendration so that the mechanical properties of the composite resin are not affected, while exhibiting significant biocompatibility and low polymerization shrinkage.

[0035] The above and other objects, advantages and features of the present invention will become more apparent to those skilled in the art from the following detailed description of specific embodiments of the invention in conjunction with the accompanying drawings. Attached Figure Description

[0036] The following sections will describe some specific embodiments of the invention in a detailed manner by way of example and not limitation, with reference to the accompanying drawings. The same reference numerals in the drawings denote the same or similar parts or portions. Those skilled in the art should understand that these drawings are not necessarily drawn to scale. In the drawings:

[0037] Figure 1 A flowchart illustrating the synthesis of betulinol-based dendritic organic monomers in one embodiment;

[0038] Figure 2 Infrared spectra of betulinol-based dendritic organic monomers;

[0039] Figure 3 The mechanical test diagram of the composite resin is shown.

[0040] Figure 4 The results are from the resin cell compatibility test.

[0041] Figure 5 The results are from the polymer shrinkage test of the composite resin. Detailed Implementation

[0042] The following reference Figures 1 to 5 This invention describes a dendritic organic monomer, composite resin, and preparation method based on betulinol according to embodiments of the present invention. In this description, it should be understood that the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of indicated technical features. Thus, a feature defined with "first" or "second" may explicitly or implicitly include at least one of that feature, that is, include one or more of that feature. In the description of the present invention, "a plurality of" means at least two, such as two, three, etc., unless otherwise explicitly specified. When a feature "includes or contains" one or more of the features it encompasses, unless otherwise specifically described, this indicates that other features are not excluded and may be further included.

[0043] In the description of this embodiment, the terms "one embodiment," "some embodiments," "illustrative embodiment," "example," "specific example," or "some examples," etc., refer to specific features, structures, materials, or characteristics described in connection with that embodiment or example, which are included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0044] Figure 1This is a flowchart illustrating the synthesis of betulinol-based dendritic organic monomers according to an embodiment of the present invention. Figure 1 The synthetic route shown yields a betulinol-based dendritic organic monomer with the following structural formula:

[0045]

[0046] In some other embodiments of the present invention, the structural formula of the betulinol-based dendritic organic monomer is as follows:

[0047]

[0048] The betulin-based dendritic organic monomers prepared in the above embodiments exhibit mild reaction conditions, light-colored products, and good mixing properties with the resin matrix. They can be used to prepare composite resins for dental restorations.

[0049] Furthermore, the present invention also provides a composite resin, which is prepared from the above-mentioned betulinol-based dendritic organic monomer.

[0050] In this embodiment, compared with traditional organic resins, the composite resin prepared by controlling the degree of dendration does not affect the mechanical properties, while exhibiting significant biocompatibility and low polymerization shrinkage. It can be applied to dental restoration.

[0051] Furthermore, the present invention provides a method for preparing a composite resin, the method comprising the following steps:

[0052] In step S10, betulin and tansimolix side chains undergo esterification reaction in the presence of solvent, dehydrating agent and catalyst to obtain the first compound;

[0053] In step S20, the first compound is deprotected under the action of solvent and acid to obtain betulinol intermediate;

[0054] In step S30, the betulinol intermediate and the acid anhydride react in the presence of a solvent and a catalyst to obtain the betulinol dendritic organic monomer.

[0055] Step S40: Dendritic organic monomers and traditional resin matrix are premixed to obtain composite resin paste;

[0056] Step S50: The composite resin paste is cured under visible light to obtain the composite resin.

[0057] In this embodiment, adding a dehydrating agent during the synthesis of the first compound is beneficial to promoting the esterification reaction.

[0058] In other embodiments of the present invention, the method for preparing the composite resin includes:

[0059] (1) First, add the solvent, dendritic organic monomer, dehydrating agent and catalyst into a round bottom flask and stir at 500-700 r / min for 30-60 min on a magnetic stirrer. Then add the tancimus side chain into the flask and react for 20-24 h to obtain the first compound.

[0060] (2) The first compound was filtered to obtain a yellowish-brown liquid, which was then mixed with silica gel for sample preparation. The sample was obtained by rotary evaporation at 40-42℃.

[0061] (3) The sample was packed into a silica gel column for chromatography to obtain the target product. The target product was then rotary evaporated at 40-45℃ and placed in a vacuum oven. It was then dried at room temperature for 20-24 hours to obtain the first intermediate and the second intermediate.

[0062] (4) Add the first or second intermediate, solvent and concentrated sulfuric acid to a round-bottom flask, place it on a magnetic stirring heating table, react at 20-30°C for 2-3 hours, wash with sodium carbonate solution and sodium chloride solution, add anhydrous magnesium sulfate for drying, filter to obtain a colorless liquid, evaporate at 40-45°C and place in a vacuum oven, dry at room temperature for 20-24 hours, and after deprotection, obtain the third and fourth intermediates;

[0063] (5) Finally, the intermediate, solvent and catalyst are added to a round-bottom flask and stirred at 500-700 r / min for 5-10 min on a magnetic stirrer. Then, a solution containing acid anhydride is added to a constant pressure feeding funnel and added dropwise to the flask at 20-25 °C. The reaction is carried out for 20-24 h to obtain the second compound.

[0064] (6) After filtration of the second compound, a yellowish-brown liquid was obtained, which was then mixed with silica gel for sample preparation. The sample was obtained by rotary evaporation at 40-42℃.

[0065] (7) The sample was packed into a silica gel column for chromatography separation to obtain the target product. The target product was rotary evaporated at 40-45℃ and then placed in a vacuum oven and dried at room temperature for 20-24 hours to obtain target product 1 and target product 2.

[0066] (8) Repeat steps (1) to (7) on the deprotected third intermediate obtained in step (4) to obtain target product 3;

[0067] (9) The organic monomers and traditional resin matrix obtained in steps (7) and (8) are premixed three times by a dual-center disperser to obtain uncured dental composite resin paste, which is then cured by visible light to obtain dental composite resin.

[0068] In some embodiments of the present invention, the dehydrating agent is one of N,N'-dicyclohexylcarbodiimide and 1-ethyl-(3-dimethylaminopropyl)carbodiimide.

[0069] In some embodiments of the present invention, the catalyst is one of triethylamine and 4-dimethylaminopyridine.

[0070] In some embodiments of the present invention, the solvent is one of dichloromethane, chloroform, tetrahydrofuran, methanol, and dimethyl sulfoxide.

[0071] In some embodiments of the present invention, the acid anhydride is one of methacrylic anhydride, maleic anhydride, and acrylic anhydride.

[0072] In some embodiments of the present invention, the resin matrix comprises a resin monomer and a photoinitiator system. The resin monomer is one of bisphenol A-dimethylglycidyl acrylate (Bis-GMA), triethylene glycol dimethacrylate (TEGDMA), bisphenol A polyoxyethylene ether dimethacrylate (EBPDMA), and urethane dimethacrylate (UDMA).

[0073] In some embodiments of the present invention, the photoinitiator system consists of a main initiator and a co-initiator, with a mass ratio of the main initiator to the co-initiator of 1:4, accounting for 1% of the total mass of the resin matrix. The main initiator is camphorquinone, and the co-initiator is ethyl 4-dimethylaminobenzoate.

[0074] The present invention will be explained in detail below with several embodiments. The technical solutions in the embodiments of the present invention will be clearly and completely described. The described embodiments are only some embodiments of the present invention, and not all embodiments.

[0075] Example 1

[0076] A method for preparing a composite resin, comprising the following specific steps:

[0077] Example 1: A betulinol-based dendritic monomer D1, the structure of which is as follows:

[0078] (1) Add 80 mL of dichloromethane, 4.4 g (10.0 mmol) betulin, 5.2 g (30.0 mmol) TDCA and 1.6 g DMAP to a 250 mL round-bottom flask, and stir magnetically for 20 min to dissolve completely (600 r / min). Then add 6.2 g (30.0 mmol) DCC and react at a constant speed at 25 °C for 48 h to obtain the crude product.

[0079] (2) After the reaction is completed, the product in step (1) is filtered to remove solid impurities and obtained by rotary evaporation. The product is purified by preparing an eluent (petroleum ether: ethyl acetate = 6:1). The obtained product is collected and rotary evaporated at 40°C. After drying in a vacuum drying oven at 38°C for 24 hours, the betulinol monosubstituted product can be obtained.

[0080] (3) Weigh 1.2 g of the product from (2) and add it to a 500 mL round-bottom flask. Add 5 mL of dichloromethane and 50 mL of methanol to the flask and stir magnetically (600 r / min) for 10 min to dissolve it completely. Then add 400 μL of concentrated sulfuric acid dropwise and react at room temperature for 2 h. Monitor the reaction with a petroleum ether:ethyl acetate ratio of 2:1.

[0081] (4) After the reaction was completed, 50 mL of ethyl acetate was added to the flask and stirred for 10 min. The sample was washed twice with 1 mol / L Na2CO3 solution and NaCl solution, respectively. Then, MgSO4 was added to dry the sample. After removing MgSO4 by filtration, the sample was dried in a rotary evaporator (45℃) and a vacuum drying oven at 45℃ for 24 h to obtain the deprotected product.

[0082] (5) Weigh 5.59 g (10 mmol) of the product from (4) and 1.2 g of DMAP and add them to a 500 mL round-bottom flask. After adding 80 mL of dichloromethane, stir magnetically (600 r / min) for 20 min to dissolve it. Then, measure 4.5 mL (30 mmol) of methacrylic anhydride and dissolve it in 30 mL of dichloromethane. Add the solution dropwise into the flask through a constant pressure separatory funnel. After the addition is complete, continue the reaction at room temperature (25 °C) for 24 h.

[0083] (6) After the reaction, a crude product was obtained. It was washed three times with 5 wt% NaOH solution and deionized water, respectively. After drying with anhydrous MgSO4, a pale yellow liquid was obtained by filtration. The sample was obtained by rotary evaporation. The sample was purified by column chromatography using an eluent (petroleum ether: ethyl acetate = 4:1). The product was collected and rotary evaporated to obtain a white powdery solid. The powder was dried in a vacuum drying oven for 24 hours to obtain 2.83 g of the target product, with a yield of 40.7%.

[0084] (7) The modified monomer obtained in step (6) is mixed with bisphenol A-dimethacrylate (Bis-GMA) and triethylene glycol dimethacrylate (TEGDMA) in a mass ratio of 1:4:5. Camphor quinone and ethyl 4-dimethylaminobenzoate in a mass ratio of 1:4 are added, and the mixture is light-cured (wavelength 430-490nm) to obtain a dental composite resin without inorganic fillers.

[0085] Example 2

[0086] A method for preparing a composite resin, comprising the following specific steps:

[0087] (1) Add 80 mL of dichloromethane, 4.4 g (10.0 mmol) betulin, 5.2 g (30.0 mmol) TDCA and 1.6 g DMAP to a 250 mL round-bottom flask, and stir magnetically for 20 min to dissolve completely (600 r / min). Then add 6.2 g (30.0 mmol) DCC and react at a constant speed at 25 °C for 48 h to obtain the crude product.

[0088] (2) After the reaction is completed, the product in step (1) is filtered to remove solid impurities and obtained by rotary evaporation. The product is purified by preparing an eluent (petroleum ether: ethyl acetate = 6:1). The obtained product is collected and rotary evaporated at 40°C. After drying in a vacuum drying oven at 38°C for 24 hours, the betulinol disubstituted product can be obtained.

[0089] (3) Weigh 1.2 g of the product from (2) and add it to a 500 mL round-bottom flask. Add 5 mL of dichloromethane and 50 mL of methanol to the flask and stir magnetically (600 r / min) for 10 min to dissolve it completely. Then add 400 μL of concentrated sulfuric acid dropwise and react at room temperature for 2 h. Monitor the reaction with a petroleum ether:ethyl acetate ratio of 2:1.

[0090] (4) After the reaction was completed, 50 mL of ethyl acetate was added to the flask and stirred for 10 min. The sample was washed twice with 1 mol / L Na2CO3 solution and NaCl solution, respectively. Then, MgSO4 was added to dry the sample. After removing MgSO4 by filtration, the sample was dried in a rotary evaporator (45℃) and a vacuum drying oven at 45℃ for 24 h to obtain the deprotected product.

[0091] (5) Weigh 5.59 g (10 mmol) of the product from (4) and 1.2 g of DMAP and add them to a 500 mL round-bottom flask. After adding 80 mL of dichloromethane, stir magnetically (600 r / min) for 20 min to dissolve it. Then, measure 9.0 mL (60 mmol) of methacrylic anhydride and dissolve it in 30 mL of dichloromethane. Add the solution dropwise into the flask through a constant pressure separatory funnel. After the addition is complete, continue the reaction at room temperature (25 °C) for 24 h.

[0092] (6) After the reaction, a crude product was obtained. It was washed three times with 5 wt% NaOH solution and deionized water, respectively. After drying with anhydrous MgSO4, a pale yellow liquid was obtained by filtration. The sample was obtained by rotary evaporation. The sample was purified by column chromatography using an eluent (petroleum ether: ethyl acetate = 4:1). The product was collected and rotary evaporated to obtain a white powdery solid. The powder was dried in a vacuum drying oven for 24 hours to obtain 3.78 g of the target product, with a yield of 37.7%.

[0093] (7) The modified monomer obtained in step (6) is mixed with bisphenol A-dimethacrylate (Bis-GMA) and triethylene glycol dimethacrylate (TEGDMA) in a mass ratio of 1:4:5. Camphor quinone and ethyl 4-dimethylaminobenzoate in a mass ratio of 1:4 are added, and the mixture is light-cured (wavelength 430-490nm) to obtain a dental composite resin without inorganic fillers.

[0094] Example 3

[0095] A method for preparing a composite resin, comprising the following specific steps:

[0096] (1) Add 80 mL of dichloromethane, 4.4 g (10.0 mmol) betulin, 5.2 g (30.0 mmol) TDCA and 1.6 g DMAP to a 250 mL round-bottom flask, and stir magnetically for 20 min to dissolve completely (600 r / min). Then add 6.2 g (30.0 mmol) DCC and react at a constant speed at 25 °C for 48 h to obtain the crude product.

[0097] (2) After the reaction is completed, the product in step (1) is filtered to remove solid impurities and obtained by rotary evaporation. The product is purified by preparing an eluent (petroleum ether: ethyl acetate = 6:1). The obtained product is collected and rotary evaporated at 40°C. After drying in a vacuum drying oven at 38°C for 24 hours, the betulinol monosubstituted product can be obtained.

[0098] (3) Weigh 1.2 g of the product from (2) and add it to a 500 mL round-bottom flask. Add 5 mL of dichloromethane and 50 mL of methanol to the flask and stir magnetically (600 r / min) for 10 min to dissolve it completely. Then add 400 μL of concentrated sulfuric acid dropwise and react at room temperature for 2 h. Monitor the reaction with a petroleum ether:ethyl acetate ratio of 2:1.

[0099] (4) After the reaction was completed, 50 mL of ethyl acetate was added to the flask and stirred for 10 min. The sample was washed twice with 1 mol / L Na2CO3 solution and NaCl solution, respectively. Then, MgSO4 was added to dry the sample. After removing MgSO4 by filtration, the sample was dried in a rotary evaporator (45℃) and a vacuum drying oven at 45℃ for 24 h to obtain the deprotected product.

[0100] (5) Weigh 5.59 g (10 mmol) of the product from (4), 5.2 g (30.0 mmol) of TDCA, 1.6 g of DMAP and 80 mL of dichloromethane into a 250 mL round-bottom flask, and stir magnetically for 20 min to dissolve completely (600 r / min). Then add 6.2 g (30.0 mmol) of DCC and react at a constant speed at 25 °C for 48 h to obtain the crude product.

[0101] (6) After the reaction is completed, the product in step (5) is filtered to remove solid impurities and obtained by rotary evaporation. The product is purified by preparing an eluent of (petroleum ether: ethyl acetate = 6:1). The obtained product is collected and rotary evaporated at 40°C. After drying in a vacuum drying oven at 38°C for 24 hours, the betulinol monosubstituted product can be obtained.

[0102] (7) Weigh 1.2 g of the product from (6) and add it to a 500 mL round-bottom flask. Add 5 mL of dichloromethane and 50 mL of methanol to the flask and stir magnetically (600 r / min) for 10 min to dissolve it completely. Then add 400 μL of concentrated sulfuric acid dropwise and react at room temperature for 2 h. Monitor the reaction with a petroleum ether:ethyl acetate ratio of 2:1.

[0103] (8) After the reaction was completed, 50 mL of ethyl acetate was added to the flask and stirred for 10 min. The sample was washed twice with 1 mol / L Na2CO3 solution and NaCl solution, respectively. Then, MgSO4 was added to dry the sample. After removing MgSO4 by filtration, the sample was dried in a rotary evaporator (45℃) and a vacuum drying oven at 45℃ for 24 h to obtain the deprotected product.

[0104] (9) Weigh 7.91 g (10 mmol) of the product from (8) and 1.2 g of DMAP and add them to a 500 mL round-bottom flask. After adding 80 mL of dichloromethane, stir magnetically (600 r / min) for 20 min to dissolve it. Then, measure 9.0 mL (60 mmol) of methacrylic anhydride and dissolve it in 30 mL of dichloromethane. Add the solution dropwise into the flask through a constant pressure separatory funnel. After the addition is complete, continue the reaction at room temperature (25 °C) for 24 h.

[0105] (10) After the reaction was completed, the crude product was obtained. It was washed three times with 5wt% NaOH solution and deionized water, respectively. After drying with anhydrous MgSO4, it was filtered to obtain a pale yellow liquid. After rotary evaporation, the sample was obtained. The sample was purified by column chromatography using an eluent (petroleum ether: ethyl acetate = 4:1). The product was collected and rotary evaporated to obtain a white powdery solid. It was dried in a vacuum drying oven for 24 hours to obtain 4.40 g of the target product, with a yield of 41.1%.

[0106] (11) The modified monomer obtained in step (6) is mixed with bisphenol A-dimethyl methacrylate (Bis-GMA) and triethylene glycol dimethacrylate (TEGDMA) in a mass ratio of 1:4:5. Camphor quinone and ethyl 4-dimethylaminobenzoate in a mass ratio of 1:4 are added, and the mixture is light-cured (wavelength 430-490nm) to obtain a dental composite resin without inorganic fillers.

[0107] Comparative Example

[0108] A method for preparing a composite resin, comprising the following specific steps:

[0109] A composite resin was prepared using 50% each of commercially available bisphenol A-glycerol dimethacrylate (Bis-GMA) and triethylene dimethacrylate (TEGDMA).

[0110] The purity of bisphenol A glycerol dimethacrylate is >98.0%, and the purity of diethylene glycol dimethacrylate is 95.0%. The seller is Sigma-Aldrich (Shanghai) Trading Co., Ltd.

[0111] The betulinol-based dendritic organic monomers obtained in Examples 1 to 3 were subjected to NMR analysis, and the results are as follows:

[0112] Example 1: δ (ppm) = 173.08, 166.71, 149.95, 135.77, 135.74, 126.17, 126.13, 109.98, 78.94, 65.97, 65.92, 63.62, 55.28, 50.33, 48.78, 47.70, 46.80, 46.47, 42 .70, 40.82, 38.86, 38.70, 37.63, 37.14, 34.47, 34.15, 29.66, 29.46, 27.99, 27.38, 26.95, 25.15, 20.75, 19.11, 18.26, 18.02, 16.09, 15.99, 15.37, 14.78.

[0113] Example 2: δ (ppm) = 173.08, 172.37, 166.78, 166.76, 166.73, 166.70, 149.92, 135.80, 135.78, 135.74, 126.16, 126.12, 126.10, 110.02, 81.79, 65.96, 65.91, 65.87, 65.84, 63.59, 55.34, 50.20, 48.75, 47 .71, 46.79, 46.76, 46.47, 42.69, 40.82, 38.25, 37.90, 37.59, 37.03, 34.46, 34.02, 29.63, 29.44, 27.90, 26.93, 25.07, 23.47, 20.76, 19.09, 18.26, 18.09, 18.05, 18.02, 16.63, 16.09, 15.97, 14.75.

[0114] Example 3: δ (ppm) = 173.04, 172.33, 166.72, 166.71, 166.67, 166.64, 149.87, 135.79, 135.76, 135.72, 126.13, 126.08, 126.06, 110.01, 81.75, 65.94, 65.89, 65.85, 65.81, 63.56, 55.32, 50.18, 48.73, 47 .69, 46.78, 46.75, 46.45, 42.67, 40.81, 38.23, 37.88, 37.58, 37.01, 34.44, 34.01, 29.62, 29.42, 27.88, 26.91, 25.05, 23.45, 20.75, 19.08, 18.24, 18.08, 18.03, 17.99, 16.61, 16.07, 15.95, 14.73.

[0115] Infrared detection was performed on the betulinol-based dendritic organic monomers obtained in Examples 1 to 3, and the resulting infrared spectra are shown below. Figure 2 As shown.

[0116] Both NMR and infrared spectroscopy results show that the substance we synthesized is a betulinol-based dendritic organic monomer.

[0117] The mechanical properties of the composite resins obtained in Examples 1 to 3 and the comparative examples were tested, and the test results are as follows: Figure 3 As shown. (Through) Figure 3 It can be seen that the substitution of betulin-based dendritic organic monomers does not affect the mechanical properties of the composite resin. This shows that:

[0118] Cell compatibility experiments were conducted on the composite resins obtained in Examples 1 to 3 and the comparative examples. The experimental conditions were 37°C and 5% CO2. The CCK-8 assay was used for testing. Dental pulp stem cells were co-cultured with betulinol-based dental composite resin extract diluted at 25%, 50%, 75%, and 100% for 24 hours. After 7 days, the OD values ​​were measured using CCK-8. The results are as follows: Figure 4 As shown in the graph, the composite resins obtained in Examples 1 to 3 exhibit better cell compatibility than the comparative examples, demonstrating that the composite resins prepared using the betulinol-based dendritic organic monomers of this invention have higher compatibility.

[0119] Shrinkage tests were conducted on the composite resins obtained in Examples 1 to 3 and the comparative examples. The test results are as follows: Figure 5 As shown, the composite resin prepared using the betulinol-based dendritic organic monomer of the present invention has a smaller shrinkage rate.

[0120] Therefore, those skilled in the art should recognize that although numerous exemplary embodiments of the present invention have been shown and described in detail herein, many other variations or modifications conforming to the principles of the present invention can be directly determined or derived from the disclosure of the present invention without departing from the spirit and scope of the invention. Thus, the scope of the present invention should be understood and construed as covering all such other variations or modifications.

Claims

1. A betulin-based dendritic organic monomer, characterized in that, The structural formula of the organic monomer is: 、 or 。 2. A composite resin, characterized in that, The composite resin is prepared from the organic monomer described in claim 1; the preparation method of the composite resin includes the following steps: (1) The betulin and tancilimide side chains were esterified at 25°C in a molar ratio of 1:3 under the action of dichloromethane solvent, dehydrating agent and catalyst to obtain the first compound; (2) The first compound was deprotected under the action of solvent and acid to obtain betulinol intermediate; (3) The betulinol intermediate and the acid anhydride are reacted in the presence of a solvent and a catalyst to obtain the betulinol dendritic organic monomer of claim 1; (4) The dendritic organic monomer and the traditional resin matrix are premixed to obtain a composite resin paste; (5) The composite resin paste is cured under visible light to obtain the composite resin; The conventional resin matrix includes a resin monomer and a photoinitiator system; the resin monomer is one or more of bisphenol A-dimethyl methacrylate, triethylene glycol dimethacrylate, bisphenol A polyoxyethylene ether dimethacrylate, and urethane dimethacrylate. The solvent is one of dichloromethane, chloroform, tetrahydrofuran, methanol, and dimethyl sulfoxide; the dehydrating agent is one of N,N'-dicyclohexylcarbodiimide and 1-ethyl-(3-dimethylaminopropyl)carbodiimide; and the catalyst is one of triethylamine and 4-dimethylaminopyridine.

3. The method for preparing the composite resin according to claim 2, characterized in that, The method includes the following steps: (1) Add the solvent, betulin, dehydrating agent and catalyst to a round bottom flask and stir at 500-700 r / min for 30-60 min on a magnetic stirrer. Then add the tancilimus side chain to the flask and react for 20-24 h to obtain the first compound. (2) The first compound was filtered to obtain a yellowish-brown liquid, which was then mixed with silica gel for sample preparation. The sample was obtained by rotary evaporation at 40-42 °C. (3) The sample is packed into a silica gel column for chromatography to obtain the target product. The target product is then rotary evaporated at 40-45°C and placed in a vacuum oven, and then dried at room temperature for 20-24 h to obtain the first intermediate. The first intermediate is betulin intermediate. (4) The first intermediate, solvent and concentrated sulfuric acid were added to a round-bottom flask and placed on a magnetic stirring heating table. After reacting at 20-30 °C for 2-3 h, the mixture was washed with sodium carbonate solution and sodium chloride solution, and dried with anhydrous magnesium sulfate. After filtration, a colorless liquid was obtained. After rotary evaporation at 40-45 °C, the liquid was placed in a vacuum oven and dried at room temperature for 20-24 h. After deprotection, the second intermediate was obtained. The second intermediate is the deprotected betulin intermediate. (5) Add the second intermediate, solvent and catalyst to a round-bottom flask and stir at 500-700 r / min for 5-10 min on a magnetic stirrer. Then add a solution of acid anhydride in a constant pressure feeding funnel and add it dropwise to the flask at 20-25 °C. React for 20-24 h to obtain the second compound. (6) After filtration of the second compound, a yellowish-brown liquid was obtained, which was then mixed with silica gel for sample preparation. The sample was obtained by rotary evaporation at 40-42 °C. (7) The sample was packed into a silica gel column for chromatography separation, and after rotary evaporation at 40-45°C, it was placed in a vacuum oven and dried at room temperature for 20-24 h to obtain the dendritic organic monomer. (8) The dendritic organic monomer and the traditional resin matrix are premixed three times by a dual-center disperser to obtain an uncured dental composite resin paste, which is then cured by visible light to obtain a dental composite resin.

4. The method for preparing the composite resin according to claim 3, characterized in that, Before step (7), the following steps are also included: adding a portion of the second intermediate, solvent, dehydrating agent and catalyst into a round-bottom flask, stirring at 500-700 r / min for 30-60 min on a magnetic stirrer, then adding tancimus side chain to the flask and reacting for 20-24 h to obtain the first compound; Repeat steps (2) to (8) to obtain dental composite resin.

5. The method for preparing the composite resin according to claim 3, characterized in that, The photoinitiator system consists of a main initiator and a co-initiator, with a mass ratio of 1:4, accounting for 1% of the total mass of the resin matrix. The main initiator is camphorquinone, and the co-initiator is ethyl 4-dimethylaminobenzoate.

Images