Dendritic organic monomer of betulinol, composite resin and preparation method

Abstract

The invention belongs to the field of preparation of dental restoration materials, and particularly relates to a betulinol-based dendritic organic monomer, composite resin and a preparation method. The invention provides the betulin-based dendritic organic monomer which is mild in reaction condition, light in product color and good in mixing effect with a resin matrix. The invention further provides composite resin which is prepared from the organic monomer and shows remarkable biocompatibility and low polymerization shrinkage. The invention also provides a preparation method of the composite resin.

Description

Technical Field

[0001] The invention belongs to the field of preparation of dental restoration materials, and particularly relates to a dendritic organic monomer based on betulin, a composite resin and a preparation method. Background Art

[0002] Dental caries, commonly known as tooth decay, is a chronic disease caused by the decomposition of food residues by bacteria and microorganisms in the oral cavity, which produces acidic substances that corrode healthy teeth. It is essentially a process mediated by biofilm and driven by sugar. The formation process of dental caries mainly includes the demineralization of inorganic matter and the decomposition of organic matter. Pathologically, it manifests as a gradual change in tooth color visible to the naked eye to progressive lesions in the hard tissue of the teeth. In traditional methods, people use willow branches (mainly containing Panax notoginseng ingredients) to make toothbrushes, and use rosin and Poria cocos as raw materials, which are dried and crushed into powder to make toothpaste to prevent dental caries. In the 1970s, Professors Kyes and Newbrun successively proposed that food (fermentable carbohydrates), host (susceptible tooth surface), cariogenic bacteria (mainly Streptococcus mutans) and time together constitute the four major factors in the etiology of modern dental caries.

[0003] The 2018 "Fourth National Oral Health Epidemiological Survey Report" shows that the caries rate of deciduous teeth in 5-year-old children in my country is as high as 70.1%, and the caries rate of permanent teeth in 12-year-old children is as high as 34.5%; the detection rate of dental calculus and gingival bleeding in residents aged 35-44 is as high as 96.7% and 87.4% respectively, indicating that with the continuous improvement of the material living standards of society, oral problems in my country are showing a trend of becoming younger. WHO has listed caries as one of the three major non-communicable diseases that humans should focus on preventing and treating in the 21st century. Therefore, dental materials used for caries repair and treatment have become a research hotspot.

[0004] The earliest dental restoration material used was amalgam, which can harden quickly and withstand the chewing force between teeth. It has a history of more than 160 years. However, traditional amalgam not only has poor aesthetics and fluidity, but also has the potential risk of heavy metals being released into the pulp and gums after filling the carious area with amalgam, which will then be absorbed by saliva and blood and transmitted to the whole body, damaging the kidney system and nervous system. Compared with traditional amalgam, dental restoration resin has better aesthetics and operability, as well as good bonding ability and low toxic side effects. Therefore, composite resin gradually replaced amalgam as the main material for dental restoration. However, since the resin is prone to polymerization shrinkage during light curing, gaps are generated between the dentin and the resin, resulting in microleakage. At the same time, oral bacteria attach to the surface of the restoration resin to form a biofilm, which eventually leads to restoration failure. In addition, Bis-GMA in the resin matrix is ​​also reproductively toxic to the human body. Therefore, dental restoration resins not only require sufficient mechanical strength, but also require low polymerization shrinkage and biocompatibility to reduce and avoid secondary caries and material damage to the human body. Summary of the invention

[0005] In order to solve the problems and deficiencies in the prior art, the present invention provides a dendritic organic monomer, a composite resin and a preparation method based on betulin. The structural formula of the organic monomer is:

[0006]

[0007] , where R 1 for 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, which is used to prepare the composite resin, and the preparation method comprises the following steps:

[0010] The betulin and the side chain of temsirolimus are subjected to an esterification reaction under the action of a solvent, a dehydrating agent and a catalyst to obtain a first compound;

[0011] The first compound is deprotected under the action of a solvent and an acid to obtain a betulin-based intermediate;

[0012] Allowing the betulin-based intermediate and anhydride to react under the action of a solvent and a catalyst to obtain the betulin-based dendritic organic monomer;

[0013] Premixing the dendritic organic monomer and a conventional resin matrix to obtain a composite resin paste;

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

[0015] Optionally, the preparation method comprises:

[0016] (1) adding a solvent, the betulin, a dehydrating agent and a catalyst into a round-bottom flask, stirring at a speed of 500-700 r / min for 30-60 min on a magnetic stirrer, then adding the temsirolimus side chain into the flask, reacting for 20-24 h, to obtain the first compound;

[0017] (2) filtering the first compound to obtain a yellow-brown liquid, then mixing it with silica gel for sample preparation, and rotary evaporating it at 40-42° C. to obtain a column sample;

[0018] (3) Filling the upper column sample into a silica gel column for chromatographic separation to obtain a target product, rotary evaporating the target product at 40-45° C. and placing it in a vacuum oven, and then drying it at room temperature for 20-24 hours to obtain a 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, reacted at 20-30° C. for 2-3 hours, washed with sodium carbonate solution and sodium chloride solution, and dried with anhydrous magnesium sulfate. After filtration, a colorless liquid is obtained, which is rotary evaporated at 40-45° C. and placed in a vacuum oven. It is dried at room temperature for 20-24 hours and deprotected to obtain a second intermediate; the second intermediate is the deprotected betulin intermediate.

[0020] (5) adding the second intermediate, solvent and catalyst into a round-bottom flask, stirring at 500-700 r / min for 5-10 min on a magnetic stirrer, then adding a solution of anhydride into a constant pressure addition funnel, adding dropwise into the flask at 20-25° C., reacting for 20-24 h, to obtain a second compound;

[0021] (6) filtering the second compound to obtain a yellow-brown liquid, then mixing it with silica gel for sample preparation, and performing rotary evaporation at 40-42° C. to obtain a column sample;

[0022] (7) filling the upper column sample into a silica gel column for chromatographic separation, and placing it in a vacuum oven after rotary evaporation at 40 to 45° C., and then drying it at room temperature for 20 to 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 method further comprises: adding part of the second intermediate, a solvent, a dehydrating agent and a catalyst into a round-bottom flask, stirring the mixture on a magnetic stirrer at a speed of 500-700 r / min for 30-60 min, then adding the temsirolimus side chain into the flask, and reacting the mixture for 20-24 h to obtain the first compound;

[0025] Repeat steps (2) to (8) to obtain a 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 acid anhydride is one of methacrylic anhydride, maleic anhydride and acrylic anhydride.

[0030] Optionally, the resin matrix includes a resin monomer and a photoinitiator system. The resin monomer is one of bisphenol A-dimethacrylate glycidyl ester (Bis-GMA), triethylene glycol 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, the mass ratio of the main initiator to the co-initiator is 1:4, accounting for 1% of the total mass of the resin matrix, wherein the main initiator is camphorquinone and the co-initiator is ethyl 4-dimethylaminobenzoate.

[0032] Compared with the prior art, the present invention has the following beneficial effects:

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

[0034] (2) Compared with traditional organic resins, the dendritic organic monomers based on betulin prepared in the present invention have a composite resin whose mechanical properties are not affected by regulating the degree of dendrite formation, and exhibit significant biocompatibility and low polymerization shrinkage.

[0035] Based on the following detailed description of specific embodiments of the present invention in conjunction with the accompanying drawings, those skilled in the art will become more aware of the above and other objects, advantages and features of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Hereinafter, some specific embodiments of the present invention will be described in detail in an exemplary and non-limiting manner with reference to the accompanying drawings. The same reference numerals in the accompanying drawings indicate the same or similar components or parts. It should be understood by those skilled in the art that these drawings are not necessarily drawn to scale. In the accompanying drawings:

[0037] Figure 1 The synthetic flow chart of betulin-based dendritic organic monomer according to one embodiment;

[0038] Figure 2 This is the infrared test spectrum of betulin-based dendritic organic monomer;

[0039] Figure 3 This is a mechanical test diagram of the composite resin;

[0040] Figure 4 The results of the resin cell compatibility test;

[0041] Figure 5 This is the test result of composite resin polymerization shrinkage. DETAILED DESCRIPTION

[0042] Refer to the following Figures 1 to 5 To describe a dendritic organic monomer, composite resin and preparation method based on betulin in an embodiment of the present invention. In the description of this embodiment, it should be understood that the terms "first" and "second" are only used for descriptive purposes, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Therefore, the features defined as "first" and "second" may explicitly or implicitly include at least one of the features, that is, include one or more of the features. In the description of the present invention, the meaning of "multiple" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined. When a feature "includes or contains" one or some of the features it covers, unless otherwise specifically described, this indicates that other features are not excluded and may further include other features.

[0043] In the description of the present embodiment, the description with reference to the terms "one embodiment", "some embodiments", "illustrative embodiments", "examples", "specific examples", or "some examples" means that the specific features, structures, materials, or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described may be combined in any one or more embodiments or examples in a suitable manner.

[0044] Figure 1 is a synthesis flow chart of betulin-based dendritic organic monomers according to one embodiment of the present invention. Figure 1 The synthetic route shown in , the structure of the synthesized betulin-based dendritic organic monomer is

[0045]

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

[0047]

[0048] The betulin-based dendritic organic monomer prepared in the above embodiment has mild reaction conditions, light product color, good mixing effect with the resin matrix, and can be used to prepare composite resin for dental restoration.

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

[0050] In this embodiment, compared with traditional organic resins, the mechanical properties of the composite resin prepared by adjusting the degree of dendrite formation are not affected, and at the same time, significant biocompatibility and low polymerization shrinkage are exhibited, which can be applied to tooth restoration.

[0051] Furthermore, the present invention provides a method for preparing a composite resin, which is used to prepare the composite resin. The preparation method comprises the following steps:

[0052] Step S10, betulin and the side chain of temsirolimus are subjected to an esterification reaction under the action of a solvent, a dehydrating agent and a catalyst to obtain a first compound;

[0053] Step S20, deprotecting the first compound under the action of a solvent and an acid to obtain a betulin-based intermediate;

[0054] Step S30, the betulin-based intermediate and the acid anhydride react under the action of a solvent and a catalyst to obtain a betulin-based dendritic organic monomer;

[0055] Step S40, premixing the dendritic organic monomer and the traditional resin matrix to obtain a composite resin paste;

[0056] Step S50, curing the composite resin paste with visible light to obtain a composite resin.

[0057] In this embodiment, a dehydrating agent is added during the synthesis of the first compound, which 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) firstly add a solvent, a dendritic organic monomer, a dehydrating agent and a catalyst into a round-bottom flask, stir the mixture on a magnetic stirrer at a speed of 500-700 r / min for 30-60 min, then add the temsirolimus side chain into the flask, and react for 20-24 h to obtain a first compound;

[0060] (2) filtering the first compound to obtain a yellow-brown liquid, then mixing it with silica gel for sample preparation, and performing rotary evaporation at 40-42° C. to obtain a column sample;

[0061] (3) Filling the upper column sample into a silica gel column for chromatographic separation to obtain the target product, rotary evaporating the target product at 40-45° C. and placing it in a vacuum oven, and then drying it at room temperature for 20-24 hours to obtain the first intermediate and the second intermediate;

[0062] (4) Add the first intermediate or the second intermediate, a solvent and concentrated sulfuric acid into 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., place in a vacuum oven, dry at room temperature for 20-24 hours, and deprotect to obtain a third intermediate and a fourth intermediate;

[0063] (5) Finally, the intermediate, solvent and catalyst are added to a round-bottom flask, stirred on a magnetic stirrer at a speed of 500-700 r / min for 5-10 min, and then a solution containing anhydride is added to the constant pressure addition funnel, and added dropwise to the above flask at 20-25° C., and reacted for 20-24 h to obtain a second compound;

[0064] (6) After the second compound is filtered, a yellow-brown liquid is obtained, which is then mixed with silica gel for sample preparation, and then rotary evaporated at 40-42° C. to obtain a column sample;

[0065] (7) The upper column sample is filled into a silica gel column for chromatographic separation to obtain the target product, the target product is rotary evaporated at 40-45° C. and placed in a vacuum oven, and then dried at room temperature for 20-24 h to obtain target product 1 and target product 2;

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

[0067] (9) The organic monomers obtained in steps (7) and (8) and the traditional resin matrix are premixed three times by a dual-center disperser to obtain an uncured dental composite resin paste, and finally cured by visible light to obtain a 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 includes a resin monomer and a photoinitiator system. The resin monomer is one of bisphenol A-dimethacrylate glycidyl ester (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, the mass ratio of the main initiator to the co-initiator is 1:4, accounting for 1% of the total mass of the resin matrix, wherein the main initiator is camphorquinone and the co-initiator is ethyl 4-dimethylaminobenzoate.

[0074] The present invention is specifically explained below using several embodiments, and the technical solutions in the embodiments of the present invention are clearly and completely described. The described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments.

[0075] Example 1

[0076] A method for preparing a composite resin, the specific steps are as follows:

[0077] Example 1: A betulin-based dendrimer D 1 , which has the following structure:

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

[0079] (2) After the reaction is completed, post-treatment is performed, the product in step (1) is filtered to remove solid impurities and a sample is obtained by rotary evaporation, and an eluent (petroleum ether: ethyl acetate = 6:1) is prepared to purify the product, the obtained product is collected and rotary evaporated at 40° C., and dried in a vacuum drying oven at 38° C. for 24 h to obtain a betulin-based monosubstituted product.

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

[0081] (4) After the reaction was completed, 50 mL of ethyl acetate was added to the flask and stirred for 10 min. 2 CO 3 solution and washed twice with NaCl solution, and then MgSO 4 The sample was dried and filtered to remove MgSO 4 After rotary evaporation (45°C) and drying in a 45°C vacuum drying oven for 24 hours, the deprotected product was obtained.

[0082] (5) 5.59 g (10 mmol) of the product in (4) and 1.2 g of DMAP were weighed and added to a 500 mL round-bottom flask. After adding 80 mL of dichloromethane, the mixture was magnetically stirred (speed 600 r / min) for 20 min to dissolve the mixture. Subsequently, 4.5 mL (30 mmol) of methacrylic anhydride was weighed and dissolved in 30 mL of dichloromethane. The mixture was added to a constant pressure separatory funnel and slowly dripped into the flask. After the addition was completed, the reaction was continued at room temperature of 25°C for 24 h.

[0083] (6) After the reaction, the crude product was washed three times with 5 wt% NaOH solution and deionized water, respectively, and then washed with anhydrous MgSO 4After drying, suction filtration can obtain a light yellow liquid, and the sample can be obtained after rotary evaporation. Prepare an eluent (petroleum ether: ethyl acetate = 4:1) to purify the sample by column chromatography, collect the product and rotary evaporate to obtain a white powder solid, place it in a vacuum drying oven and dry it for 24 hours to obtain 2.83g 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 glycidyl ester Bis-GMA and triethylene glycol dimethacrylate TEGDMA in a mass ratio of 1:4:5, camphorquinone and ethyl 4-dimethylaminobenzoate in a mass ratio of 1:4 are added, and light curing (wavelength of 430-490 nm) is performed to obtain a dental composite resin without adding inorganic fillers.

[0085] Example 2

[0086] A method for preparing a composite resin, the specific steps are as follows:

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

[0088] (2) After the reaction is completed, post-treatment is performed, the product in step (1) is filtered to remove solid impurities and a sample is obtained by rotary evaporation, and an eluent (petroleum ether: ethyl acetate = 6:1) is prepared to purify the product, the obtained product is collected and rotary evaporated at 40° C., and dried in a vacuum drying oven at 38° C. for 24 h to obtain a betulin-based disubstituted product.

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

[0090] (4) After the reaction was completed, 50 mL of ethyl acetate was added to the flask and stirred for 10 min. 2 CO 3 solution and washed twice with NaCl solution, and then MgSO 4 The sample was dried and filtered to remove MgSO 4After rotary evaporation (45°C) and drying in a 45°C vacuum drying oven for 24 hours, the deprotected product was obtained.

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

[0092] (6) After the reaction, the crude product was washed three times with 5 wt% NaOH solution and deionized water, respectively, and then washed with anhydrous MgSO 4 After drying, suction filtration can obtain a light yellow liquid, and the sample can be obtained after rotary evaporation. Prepare an eluent (petroleum ether: ethyl acetate = 4:1) to purify the sample by column chromatography, collect the product and rotary evaporate to obtain a white powder solid, place it in a vacuum drying oven and dry it for 24 hours to obtain 3.78g 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 glycidyl ester Bis-GMA and triethylene glycol dimethacrylate TEGDMA in a mass ratio of 1:4:5, camphorquinone and ethyl 4-dimethylaminobenzoate in a mass ratio of 1:4 are added, and light curing (wavelength of 430-490 nm) is performed to obtain a dental composite resin without adding inorganic fillers.

[0094] Example 3

[0095] A method for preparing a composite resin, the specific steps are as follows:

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

[0097] (2) After the reaction is completed, post-treatment is performed, the product in step (1) is filtered to remove solid impurities and a sample is obtained by rotary evaporation, and an eluent (petroleum ether: ethyl acetate = 6:1) is prepared to purify the product, the obtained product is collected and rotary evaporated at 40° C., and dried in a vacuum drying oven at 38° C. for 24 h to obtain a betulin-based monosubstituted product.

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

[0099] (4) After the reaction was completed, 50 mL of ethyl acetate was added to the flask and stirred for 10 min. 2 CO 3 solution and washed twice with NaCl solution, and then MgSO 4 The sample was dried and filtered to remove MgSO 4 After rotary evaporation (45°C) and drying in a 45°C vacuum drying oven for 24 hours, the deprotected product was obtained.

[0100] (5) Weigh 5.59 g (10 mmol) of the product in (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 fully dissolve the mixture (speed 600 r / min). Then, add 6.2 g (30.0 mmol) of DCC and keep the speed constant at 25°C for 48 h to obtain a crude product.

[0101] (6) After the reaction is completed, post-treatment is performed, the product in step (5) is filtered to remove solid impurities and a sample is obtained by rotary evaporation, and an eluent (petroleum ether: ethyl acetate = 6:1) is prepared to purify the product, the obtained product is collected and rotary evaporated at 40° C., and dried in a vacuum drying oven at 38° C. for 24 h to obtain a betulin-based monosubstituted product.

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

[0103] (8) After the reaction was completed, 50 mL of ethyl acetate was added to the flask and stirred for 10 min. 2 CO 3 solution and washed twice with NaCl solution, and then MgSO 4 The sample was dried and filtered to remove MgSO 4 After rotary evaporation (45°C) and drying in a 45°C vacuum drying oven for 24 hours, the deprotected product was obtained.

[0104] (9) 7.91 g (10 mmol) of the product in (8) and 1.2 g of DMAP were weighed and added to a 500 mL round-bottom flask. After adding 80 mL of dichloromethane, the mixture was magnetically stirred (speed 600 r / min) for 20 min to dissolve the mixture. Subsequently, 9.0 mL (60 mmol) of methacrylic anhydride was weighed and dissolved in 30 mL of dichloromethane. The mixture was added to a constant pressure separatory funnel and slowly dripped into the flask. After the addition was completed, the reaction was continued at room temperature of 25°C for 24 h.

[0105] (10) After the reaction, the crude product was washed three times with 5 wt% NaOH solution and deionized water, respectively, and then washed with anhydrous MgSO 4 After drying, a light yellow liquid was obtained by suction filtration, and a sample was obtained by rotary evaporation. The eluent (petroleum ether: ethyl acetate = 4:1) was prepared to purify the sample by column chromatography, and the product was collected and rotary evaporated to obtain a white powdery solid, which was placed in a vacuum drying oven and dried 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-dimethacrylate glycidyl ester Bis-GMA and triethylene glycol dimethacrylate TEGDMA in a mass ratio of 1:4:5, camphorquinone and ethyl 4-dimethylaminobenzoate in a mass ratio of 1:4 are added, and light curing (wavelength of 430-490 nm) is performed to obtain a dental composite resin without adding inorganic fillers.

[0107] Comparative Example

[0108] A method for preparing a composite resin, the specific steps are as follows:

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

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

[0111] The betulin-based dendritic organic monomers obtained in Examples 1 to 3 were subjected to nuclear magnetic resonance detection, and the results obtained were 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] The betulin-based dendritic organic monomers obtained in Examples 1 to 3 were subjected to infrared detection, and the infrared test spectra obtained were as follows: Figure 2 shown.

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

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

[0118] The cell compatibility test was performed on the composite resins obtained in Examples 1 to 3 and the comparative example. The experimental conditions were 37°C, 5% CO 2 Under the same conditions, the CCK-8 method was used for testing. Dental pulp stem cells were used. The extract of betulin-based dental composite resin was diluted by 25%, 50%, 75% and 100%. After co-culture with dental pulp stem cells for 24 hours, the OD value was measured by CCK-8 after 7 days. The results are as follows Figure 4 It can be seen from the graph that the cell compatibility of the composite resins obtained in Examples 1 to 3 is better than that of the comparative example, indicating that the composite resin prepared by using the betulin-based dendritic organic monomer in the present invention has higher compatibility.

[0119] The composite resins obtained in Examples 1 to 3 and the comparative example were tested for shrinkage. The test results are as follows: Figure 5 As shown, it is shown that the composite resin prepared by using the betulin-based dendritic organic monomer of the present invention has a smaller shrinkage rate.

[0120] At this point, those skilled in the art should recognize that, although multiple exemplary embodiments of the present invention have been shown and described in detail herein, many other variations or modifications that conform to the principles of the present invention can still be directly determined or derived based on the content disclosed in the present invention without departing from the spirit and scope of the present invention. Therefore, the scope of the present invention should be understood and recognized as covering all these other variations or modifications.

Claims

1. A betulin-based dendritic organic monomer, characterized in that: The structural formula of the organic monomer is: ， Where R1 is R2 is 2. A composite resin, characterized in that: The composite resin is prepared from the organic monomers described in claim 1.

3. A method for preparing a composite resin, for preparing the composite resin as claimed in claim 2, characterized in that: The preparation method comprises the following steps: (1) the betulin and the side chain of temsirolimus are subjected to an esterification reaction under the action of a solvent, a dehydrating agent and a catalyst to obtain a first compound; (2) deprotecting the first compound under the action of a solvent and an acid to obtain a betulin-based intermediate; (3) reacting the betulin-based intermediate and anhydride in the presence of a solvent and a catalyst to obtain the betulin-based dendritic organic monomer; (4) premixing the dendritic organic monomer and a conventional resin matrix to obtain a composite resin paste; (5) Curing the composite resin paste by visible light to obtain the composite resin.

4. The method for preparing the composite resin according to claim 3, characterized in that: The steps include: (1) adding a solvent, the betulin, a dehydrating agent and a catalyst into a round-bottom flask, stirring at a speed of 500-700 r / min for 30-60 min on a magnetic stirrer, then adding the temsirolimus side chain into the flask, reacting for 20-24 h, to obtain the first compound; (2) filtering the first compound to obtain a yellow-brown liquid, then mixing it with silica gel for sample preparation, and rotary evaporating it at 40-42° C. to obtain a column sample; (3) Filling the upper column sample into a silica gel column for chromatographic separation to obtain a target product, rotary evaporating the target product at 40-45° C. and placing it in a vacuum oven, and then drying it at room temperature for 20-24 hours to obtain a first intermediate; the first intermediate is the betulin intermediate; (4) The first intermediate, solvent and concentrated sulfuric acid are added to a round-bottom flask, placed on a magnetic stirring heating table, reacted at 20-30° C. for 2-3 hours, washed with sodium carbonate solution and sodium chloride solution, and dried with anhydrous magnesium sulfate. After filtration, a colorless liquid is obtained, which is rotary evaporated at 40-45° C. and placed in a vacuum oven. It is dried at room temperature for 20-24 hours and deprotected to obtain a second intermediate; the second intermediate is the deprotected betulin intermediate. (5) adding the second intermediate, solvent and catalyst into a round-bottom flask, stirring at 500-700 r / min for 5-10 min on a magnetic stirrer, then adding a solution of anhydride into a constant pressure addition funnel, adding dropwise into the flask at 20-25° C., reacting for 20-24 h, to obtain a second compound; (6) filtering the second compound to obtain a yellow-brown liquid, then mixing it with silica gel for sample preparation, and performing rotary evaporation at 40-42° C. to obtain a column sample; (7) filling the upper column sample into a silica gel column for chromatographic separation, and placing it in a vacuum oven after rotary evaporation at 40 to 45° C., and then drying it at room temperature for 20 to 24 hours 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.

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

6. The method for preparing a composite resin according to claim 4 or 5, characterized in that: The dehydrating agent is one of N,N'-dicyclohexylcarbodiimide and 1-ethyl-(3-dimethylaminopropyl)carbodiimide.

7. The method for preparing a composite resin according to claim 4 or 5, characterized in that: The catalyst is one of triethylamine and 4-dimethylaminopyridine.

8. The method for preparing a composite resin according to claim 4 or 5, characterized in that: The solvent is one of dichloromethane, chloroform, tetrahydrofuran, methanol and dimethyl sulfoxide.

9. The method for preparing a composite resin according to claim 4 or 5, characterized in that: The resin matrix comprises a resin monomer and a photoinitiator system. The resin monomer is one of bisphenol A-dimethacrylate glycidyl ester (Bis-GMA), triethylene glycol dimethacrylate (TEGDMA), bisphenol A polyoxyethylene ether dimethacrylate (EBPDMA), and urethane dimethacrylate (UDMA).

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

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