Mesoporous silica functional filler and preparation method thereof, and composite resin material and preparation method and application thereof

Abstract

The invention belongs to the technical field of biomedical materials, and particularly relates to a mesoporous silica functional filler and a preparation method thereof, and a composite resin material and a preparation method and application thereof. The mesoporous silica functional filler provided by the invention has remineralization performance and pH response type. Functional modification is carried out on the surface of mesoporous silica, the modified mesoporous silica can load phosphorylated chitosan / amorphous calcium phosphate through electrostatic attraction, and the pH response performance is given to the modified mesoporous silica. The phosphorylated chitosan can simulate the effect of dentin matrix protein 1, can regulate the remineralization process of dentin, and can chelate calcium ions to stabilize amorphous calcium phosphate in the solution to form an amorphous nano precursor. The polyelectrolyte may be replaced with a biomimetic analog to initiate the remineralization process. The size of the mineral precursor and the deposition sequence and layer of the mineral precursor inside and outside the collagenous fiber can be regulated and controlled, and meanwhile nucleation and growth of apatite crystals inside and outside the collagenous fiber can be promoted.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedical materials, and particularly relates to a mesoporous silica functional filler, a preparation method thereof, a composite resin material, a preparation method thereof, and an application thereof. Background Art

[0002] At present, the main dental restoration materials are composite resins formed by photo-curing resins and inorganic fillers. However, during the use of such composite resins as teeth, they are extremely prone to falling off and cracking, and have a short service life. The main reason is that their mechanical properties are low, ultimately resulting in dental restoration failure.

[0003] Researchers have improved the mechanical properties of resin restorations by introducing SiO 2 fillers. The morphology of traditional SiO 2 fillers is usually irregular particles or spherical particles, and the interfacial bonding between the filler and the resin matrix is enhanced by surface chemical modification.

[0004] However, during the long-term use of composite resins in the oral cavity, the humid environment causes hydrolysis of silanols and ester bonds at the filler-resin interface, weakening the interfacial adhesion between the filler and the resin matrix, resulting in the peeling or fracture of the restoration. Summary of the Invention

[0005] The purpose of the present invention is to provide a mesoporous silica functional filler, a preparation method thereof, a composite resin material, a preparation method thereof, and an application thereof. The mesoporous silica functional filler provided by the present invention can improve the mechanical properties of the composite resin material, and at the same time regulate the dentin remineralization process, giving the composite resin material a longer service life.

[0006] To achieve the above purpose, the present invention provides the following technical solutions:

[0007] The present invention provides a mesoporous silica functional filler, which includes a Pchi / ACP complex and modified mesoporous silica electrostatically loaded with the complex; the Pchi / ACP complex includes phosphorylated chitosan and amorphous calcium phosphate.

[0008] Preferably, the preparation method of the phosphorylated chitosan is: stirring and mixing chitosan, methanesulfonic acid, and phosphorus pentoxide, and then precipitating.

[0009] Preferably, the mass ratio of the phosphorylated chitosan to the amorphous calcium phosphate is 20-25:35-40; the mass ratio of the modified mesoporous silica to the Pchi / ACP complex is 22.5:37.5.

[0010] Preferably, the particle size of the mesoporous silica functional filler is 320-380 nm.

[0011] The present invention also provides a method for preparing the mesoporous silica functional filler described in the above solution, comprising the following steps:

[0012] Heat the mesoporous silica solution to the boiling point, then add 3-aminopropyltriethoxysilane dropwise to the mesoporous silica solution and heat under reflux to obtain modified mesoporous silica;

[0013] Mix calcium chloride, phosphorylated chitosan, Na 2 HPO 4 and water, and then freeze-dry to obtain the Pchi / ACP composite;

[0014] Mix the modified mesoporous silica, the Pchi / ACP composite and a solvent, and then perform oscillation and freeze-drying in sequence to obtain the mesoporous silica functional filler.

[0015] The present invention also provides a composite resin material, comprising a mesoporous silica functional filler, a matrix monomer, a diluent monomer and an initiator; the mesoporous silica functional filler is the mesoporous silica functional filler described in the above solution or the mesoporous silica functional filler obtained by the preparation method described in the above solution.

[0016] Preferably, the matrix monomer is a polyester; the diluent monomer is an acrylate; the initiator comprises one or more of camphorquinone and dimethylaminoethyl methacrylate.

[0017] Preferably, the mass ratio of the matrix monomer to the diluent monomer is 70:29; the mass ratio of the matrix monomer to the initiator is 70:1; the mass content of the mesoporous silica functional filler in the composite resin material is 60 wt%.

[0018] The present invention also provides a method for preparing the composite resin material described in the above solution, comprising the following steps:

[0019] Mix the mesoporous silica functional filler, the matrix monomer, the diluent monomer and the initiator to obtain the composite resin material.

[0020] The present invention also provides the use of the composite resin material described in the above solution or the composite resin material obtained by the preparation method described in the above solution in the production of dental restorative materials.

[0021] The present invention provides a mesoporous silica functional filler. The mesoporous silica functional filler provided by the present invention (modified mesoporous silica loaded with phosphorylated chitosan / amorphous calcium phosphate, denoted as Pchi / ACP@A-MSNs) has remineralization performance and pH-responsive properties. The present invention functionalizes and modifies the surface of mesoporous silica (ammonification), and the modified mesoporous silica can load phosphorylated chitosan / amorphous calcium phosphate (Pchi / ACP) through electrostatic attraction, endowing it with pH-responsive properties.

[0022] Phosphorylated chitosan can mimic the function of dentin matrix protein 1 (DMP-1), can regulate the process of dentin remineralization, and can chelate calcium ions to stabilize amorphous calcium phosphate (ACP) in solution to form amorphous nano-precursors. Polyelectrolytes can be replaced with biomimetic analogs to initiate the remineralization process. The polyelectrolyte phosphorylated chitosan has a high negative charge density, thus having a high 2+ affinity for Ca, and can regulate the size of mineral precursors and the sequence and level of their deposition inside and outside collagen fibers. At the same time, it can also promote the nucleation and growth of apatite crystals inside and outside collagen fibers.

[0023] The present invention also provides a preparation method of the mesoporous silica functional filler described in the above solution. The preparation method provided by the present invention is simple to operate, has good stability, high safety, has no obvious impact on the environment, the raw materials are easy to obtain, and has broad application prospects.

[0024] The present invention also provides a composite resin material. The composite resin material provided by the present invention contains the mesoporous silica functional filler of the above solution. The resin monomer can penetrate into its special mesoporous channels with high specific surface area and large pore volume to construct an interpenetrating filler-resin network, forming a micro-mechanical interaction at the filler-resin interface and enhancing the mechanical strength of the composite resin material.

[0025] The mesoporous silica functional filler provided by the present invention is well-dispersed in the composite resin material, has uniform particle size, high biological safety, does not affect the biocompatibility of the material, and can improve the mechanical properties of the composite resin material, and has remineralization performance, enabling the remineralization of dentin at the dentin-composite resin bonding interface. In addition, the composite resin material provided by the present invention also has a pH-responsive function, and can rapidly and efficiently release calcium and phosphorus ions in an acidic environment, which is beneficial to improving the service life of dental composite resins and is expected to be used clinically.

[0026] The present invention also provides a preparation method of the composite resin material described in the above solution. The preparation method provided by the present invention has simple steps, low cost, no pollution, and is suitable for industrial production.

[0027] The present invention also provides the application of the composite resin material described in the above solution or the composite resin material obtained by the preparation method described in the above solution in the production of dental restoration materials. The composite resin material provided by the present invention has good mechanical properties, remineralization properties, a long service life when used to produce dental restoration materials, reduces the discomfort of patients caused by the short service life of existing dental restoration materials, and has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the embodiments. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0029] Figure 1 It is a scanning electron microscope image of the mesoporous silica functional filler provided by the present invention;

[0030] Figure 2 It is the N 2 adsorption / desorption isotherm of the mesoporous silica functional filler provided by the present invention;

[0031] Figure 3 It is the mesopore size distribution diagram of the mesoporous silica functional filler provided by the present invention;

[0032] Figure 4 It is the EDS energy spectrum analysis diagram of the mesoporous silica functional filler provided by the present invention;

[0033] Figure 5 It is a comparison diagram of the double bond conversion rates of the composite resin materials in Examples 1-2 and Comparative Examples 1-3;

[0034] Figure 6 It is a comparison diagram of the elastic modulus, flexural strength and Vickers hardness of the mechanical properties of the composite resin materials in Examples 1-2 and Comparative Examples 1-3;

[0035] Figure 7 It is a cross-sectional scanning electron microscope image of the composite resin materials in Examples 1-2 and Comparative Examples 1-3;

[0036] Figure 8 It is a SEM image of the dentin remineralization of the composite resin materials in Examples 1-2 and Comparative Examples 1-3;

[0037] Figure 9 It is a comparison diagram of the calcium ion release of the composite resin materials in Examples 1-2 and Comparative Examples 1-3;

[0038] Figure 10It is a comparison chart of cell survival when cells are cultured in the leaching solutions of the composite resin materials in Example 1 and Comparative Examples 1 to 3 for 1, 4, and 7 days respectively. Detailed implementation mode

[0039] The present invention provides a mesoporous silica functional filler, which includes a Pchi / ACP complex and modified mesoporous silica electrostatically loaded with the complex; the Pchi / ACP complex includes phosphorylated chitosan and amorphous calcium phosphate.

[0040] In the present invention, the preparation method of the phosphorylated chitosan is preferably: stirring and mixing chitosan, methanesulfonic acid and phosphorus pentoxide and then precipitating.

[0041] In the present invention, the mass-volume ratio of the chitosan to the methanesulfonic acid is preferably 2.0 g: 14 mL.

[0042] In the present invention, the mass ratio of the chitosan to the phosphorus pentoxide is preferably 1: 1.5.

[0043] In the present invention, the temperature of the stirring and mixing is preferably 10-15 °C, and the mixing time is preferably 1.5 h.

[0044] In the present invention, the precipitation is preferably precipitation with methanol.

[0045] In the present invention, after the precipitation, it preferably further includes washing, centrifuging and drying the obtained precipitate in sequence; the washing is preferably washing with acetone; the drying is preferably drying under vacuum at room temperature.

[0046] In the present invention, the mass ratio of the phosphorylated chitosan to the amorphous calcium phosphate is preferably 20-25: 35-40, and specifically can be 22.5: 37.5 or 24: 36.

[0047] In the present invention, the mass ratio of the modified mesoporous silica to the Pchi / ACP complex is preferably 22.5: 37.5.

[0048] In the present invention, the particle size of the mesoporous silica functional filler is preferably 320-380 nm, specifically can be 350 nm, and the average particle size is preferably 350 nm.

[0049] The present invention also provides a preparation method of the mesoporous silica functional filler described in the above scheme, including the following steps:

[0050] Heating the mesoporous silica solution to the boiling point, and then dropping 3-aminopropyltriethoxysilane into the mesoporous silica solution and heating under reflux to obtain modified mesoporous silica;

[0051] Mixing calcium chloride, phosphorylated chitosan, Na 2 HPO4 It is mixed with water and then freeze-dried to obtain the Pchi / ACP composite;

[0052] The modified mesoporous silica, the Pchi / ACP composite and a solvent are mixed and then subjected to oscillation and freeze-drying in sequence to obtain the mesoporous silica functional filler.

[0053] In the present invention, the mesoporous silica solution is heated (denoted as the first heating) to the boiling point. In the present invention, the solvent of the mesoporous silica solution is preferably a benzene homologue; the benzene homologue is preferably toluene.

[0054] In the present invention, the mass ratio of mesoporous silica to solvent in the mesoporous silica solution is preferably 6:1732.

[0055] In the present invention, the preparation method of the mesoporous silica solution is preferably: mesoporous silica and toluene are mixed (denoted as the first mixing); the first mixing is preferably ultrasonic mixing; the time of the ultrasonic mixing is preferably 30 min.

[0056] In the present invention, the preparation method of the mesoporous silica is preferably: urea, an organic template agent, tetraethyl orthosilicate, n-pentanol, cyclohexane and water are mixed (denoted as the second mixing) and then subjected to hydrothermal reaction and calcination.

[0057] In the present invention, the organic template agent is preferably cetyltrimethylammonium bromide; the mass ratio of urea to the organic template agent is preferably 1:2.

[0058] In the present invention, the mass ratio of urea to water is preferably 0.9:30.

[0059] In the present invention, the volume ratio of water to tetraethyl orthosilicate is preferably 30:6.

[0060] In the present invention, the volume ratio of tetraethyl orthosilicate to n-pentanol is preferably 1:1.

[0061] In the present invention, the volume ratio of tetraethyl orthosilicate to cyclohexane is preferably 6:30.

[0062] In the present invention, the second mixing is preferably: urea, the organic template agent and deionized water are mixed (denoted as mixing A) to obtain solution A, tetraethyl orthosilicate, n-pentanol and cyclohexane are mixed (denoted as mixing B) to obtain solution B, and the solution A and solution B are mixed (denoted as mixing C).

[0063] In the present invention, the temperature of the second mixing is preferably room temperature; the mixing A is preferably magnetic stirring until the solution becomes clear; the mixing B is preferably magnetic stirring, and the time of the magnetic stirring is preferably 10 min; the mixing C is preferably stirring and mixing, the rotation speed of the stirring and mixing is preferably 200-400 rpm, and the mixing time is preferably 40 min.

[0064] In the present invention, the temperature of the hydrothermal reaction is preferably 120 °C, and the heat preservation reaction time is preferably 8 h; the device for the hydrothermal reaction is preferably an autoclave containing a polytetrafluoroethylene inner lining.

[0065] In the present invention, preferably, a first temperature increase is included before the hydrothermal reaction; the rate of the first temperature increase is preferably 3-5 °C / min, and specifically can be 4 °C / min.

[0066] In the present invention, preferably, after the hydrothermal reaction, the resulting reaction system is cooled and then subjected to solid-liquid separation, washing by centrifugation, and drying in sequence.

[0067] In the present invention, the cooling is preferably natural cooling to room temperature; the solid-liquid separation is preferably centrifugation; the washing by centrifugation is preferably: the product is washed with deionized water and ethanol respectively in sequence and then centrifuged; the number of times of the washing by centrifugation is preferably 3 times; the centrifugation speed of the washing by centrifugation is preferably 8500 rpm; the temperature of the drying is preferably 60 °C, and the heat preservation drying time is preferably 12 h.

[0068] In the present invention, the temperature of the calcination is preferably 550 °C, and the heat preservation calcination time is preferably 6 h.

[0069] In the present invention, preferably, a second temperature increase is included before the calcination; the rate of the second temperature increase is preferably 3-5 °C / min, and specifically can be 4 °C / min.

[0070] In the present invention, preferably, after the calcination, the resulting product system is cooled and then the organic template agent is removed; the cooling is preferably natural cooling to room temperature.

[0071] In the present invention, the first heating is preferably carried out under stirring conditions; the rotation speed of the stirring is preferably 300 rpm, and the stirring time is preferably 15-60 min.

[0072] After the mesoporous silica solution is heated to the boiling point, in the present invention, 3-aminopropyltriethoxysilane is added dropwise to the mesoporous silica solution and then heated under reflux to obtain the modified mesoporous silica.

[0073] In the present invention, the dropwise addition is preferably dropwise addition one by one.

[0074] In the present invention, the mass ratio of mesoporous silica to 3-aminopropyltriethoxysilane in the mesoporous silica solution is preferably 600:3784. The functional group of the mesoporous silica is an amino group, and the raw material providing the amino group is 3-aminopropyltriethoxysilane.

[0075] In the present invention, the heating under reflux is preferably as follows: connecting the reaction device to a condenser reflux tube for heating and stirring. During the stirring process, the silane coupling agent undergoes alcoholysis, and the alcoholyzed silane coupling agent is more likely to be modified on the surface of the target.

[0076] In the present invention, the time for heating under reflux is preferably 18 - 30 h, and specifically can be 24 h.

[0077] In the present invention, after heating under reflux, it is preferably further included to cool the obtained reaction system; the cooling is preferably natural cooling.

[0078] In the present invention, after cooling, it is preferably further included to separate the obtained product into solid and liquid and then successively carry out washing and drying.

[0079] In the present invention, the solid-liquid separation is preferably centrifugation; the rotation speed of the centrifugation is preferably 4000 rpm.

[0080] In the present invention, the washing is preferably alcohol washing; the alcohol used for alcohol washing is preferably ethanol; the number of washing times is preferably more than 5 times. In the present invention, through washing, unreacted products and solvents are removed.

[0081] In the present invention, the drying is preferably drying in an oven; the drying temperature is preferably 80 °C, and the heat preservation drying time is preferably 4 h; the drying equipment is preferably an oven. In the present invention, through drying, residual washing liquid (ethanol) is removed.

[0082] The present invention mixes calcium chloride, phosphorylated chitosan, Na 2 HPO 4 and water (denoted as the third mixing) and then performs freeze-drying to obtain a Pchi / ACP composite. In the present invention, the calcium chloride is preferably CaCl 2 ·2H 2 O.

[0083] In the present invention, the mass ratio of calcium chloride to phosphorylated chitosan is preferably 100 mmol:50 g.

[0084] In the present invention, the molar ratio of calcium chloride to Na 2 HPO 4 is preferably 100:60.

[0085] In the present invention, the water is preferably deionized water.

[0086] In the present invention, the mass ratio of calcium chloride to water is preferably 5:100.

[0087] In the present invention, the third mixing is preferably continuous stirring and mixing.

[0088] In the present invention, the temperature of freeze-drying is preferably -80 °C, and the heat preservation and freezing time is preferably 24 h.

[0089] After obtaining the modified mesoporous silica and the Pchi / ACP composite, the present invention mixes the modified mesoporous silica, the Pchi / ACP composite and a solvent (denoted as the fourth mixing), then performs oscillation and freeze-drying in sequence to obtain the mesoporous silica functional filler. In the present invention, the solvent is preferably anhydrous ethanol.

[0090] In the present invention, the fourth mixing is preferably: mixing the Pchi / ACP composite and the solvent to obtain a Pchi / ACP composite solution, and then mixing the Pchi / ACP composite solution and the modified mesoporous silica.

[0091] In the present invention, the mass-to-volume ratio of the Pchi / ACP composite to the solvent is preferably (1.5 - 2.5) g : (45 - 75) mL, and specifically can be 2 g : 60 mL.

[0092] In the present invention, the mass-to-volume ratio of the modified mesoporous silica to the Pchi / ACP composite solution is preferably 300 mg : 60 mL.

[0093] In the present invention, the oscillation is preferably ultrasonic oscillation; the oscillation time is preferably 24 h. Through oscillation, the present invention promotes the electrostatic attraction of the Pchi / ACP composite by the modified mesoporous silica (A-MSNs).

[0094] In the present invention, after the oscillation, it is preferably further included to centrifuge the obtained product and then wash it with water; the rotation speed of the centrifugation is preferably 4000 rpm, and the centrifugation time is preferably 3 min; the water for washing is preferably deionized water; the number of times of washing is preferably 3 times. Through washing with water, the present invention removes the Pchi / ACP@A-MSNs with weak binding force.

[0095] In the present invention, the temperature of freeze-drying is preferably -80 °C, and the heat preservation and freezing time is preferably 1 h.

[0096] The present invention also provides a composite resin material, including a mesoporous silica functional filler, a matrix monomer, a diluent monomer and an initiator; the mesoporous silica functional filler is the mesoporous silica functional filler described in the above scheme or the mesoporous silica functional filler obtained by the preparation method described in the above scheme.

[0097] In the present invention, the matrix monomer is preferably a polyester; the polyester is preferably bisphenol A diglycidyl methacrylate (TMBPEA).

[0098] In the present invention, the preparation method of the bisphenol A diglycidyl methacrylate is preferably as follows: tetramethylbiphenol diglycidyl ether, a catalyst, an inhibitor and acrylic acid are mixed (denoted as the fifth mixing) for a polymerization reaction.

[0099] In the present invention, the preparation method of the tetramethylbiphenol diglycidyl ether is preferably as follows: tetramethylbiphenol, epichlorohydrin and tetrabutylammonium bromide are mixed (denoted as the sixth mixing) for an epoxy reaction to obtain tetramethylbiphenol diglycidyl ether, and then the tetramethylbiphenol diglycidyl ether, toluene and an aqueous sodium hydroxide solution are mixed (denoted as the seventh mixing) for a ring-closing reaction.

[0100] In the present invention, the molar volume ratio of the tetramethylbiphenol to the epichlorohydrin is preferably 0.1 mol: 160 mL.

[0101] In the present invention, the volume-mass ratio of the epichlorohydrin to the tetrabutylammonium bromide is preferably 160 mL: 0.2 g.

[0102] In the present invention, the temperature of the sixth mixing is preferably room temperature; the sixth mixing is preferably a stirring mixing.

[0103] In the present invention, the equipment for the epoxy reaction is preferably a reactor equipped with a mechanical stirring device, a thermometer and a reflux condenser; the temperature of the epoxy reaction is preferably 90 °C, and the reaction time is preferably 6 h.

[0104] In the present invention, after the epoxy reaction, it is preferably further included to subject the obtained product system to vacuum distillation. In the present invention, unreacted epichlorohydrin is removed by vacuum distillation.

[0105] In the present invention, the volume ratio of the epichlorohydrin to the toluene is preferably 160: 200.

[0106] In the present invention, the seventh mixing is preferably as follows: an aqueous sodium hydroxide solution is slowly added dropwise to the mixed solution of the tetramethylbiphenol diglycidyl ether and toluene using a constant pressure dropping funnel.

[0107] In the present invention, the concentration of the aqueous sodium hydroxide solution is preferably 30 wt%; the mass ratio of the aqueous sodium hydroxide solution to the tetrabutylammonium bromide is preferably 32: 0.2.

[0108] In the present invention, the temperature of the ring-closing reaction is preferably 90 °C, and the reaction time is preferably 3 h.

[0109] In the present invention, after the closed-loop reaction, it is preferably further included to wash the obtained product with water, distill under reduced pressure, and dry under vacuum in sequence.

[0110] In the present invention, the water used for washing is preferably distilled water, and the washing is carried out until the water layer is neutral; in the present invention, toluene and water are removed by distillation under reduced pressure; the temperature of the vacuum drying is preferably 60 °C, and the heat preservation drying time is preferably 24 h.

[0111] In the present invention, the catalyst is preferably triphenylphosphine; the mass ratio of the tetramethylbiphenol diglycidyl ether to the catalyst is preferably 99:0.5.

[0112] In the present invention, the inhibitor is preferably hydroquinone; the mass ratio of the tetramethylbiphenol diglycidyl ether to the inhibitor is preferably 99:0.5.

[0113] In the present invention, the molar ratio of the tetramethylbiphenol diglycidyl ether to acrylic acid is preferably 1:2.04.

[0114] In the present invention, the fifth mixing is preferably as follows: the tetramethylbiphenol diglycidyl ether, the catalyst and the inhibitor are mixed and heated to 90 °C, and then acrylic acid is quickly added to the obtained system.

[0115] In the present invention, the polymerization reaction is preferably carried out in a protective atmosphere; the protective atmosphere is preferably nitrogen; the polymerization reaction is preferably carried out under stirring conditions; the temperature of the polymerization reaction is preferably 105 °C, and the heat preservation reaction time is preferably 4 h.

[0116] In the present invention, the diluent monomer is preferably an acrylate; the acrylate is preferably 2-hydroxyethyl methacrylate.

[0117] In the present invention, the mass ratio of the matrix monomer to the diluent monomer is preferably 70:29.

[0118] In the present invention, the initiator preferably includes one or more of camphorquinone and dimethylaminoethyl methacrylate.

[0119] In the present invention, the mass ratio of the matrix monomer to the initiator is preferably 70:1.

[0120] In the present invention, the mass content of the mesoporous silica functional filler in the composite resin material is preferably 60 wt%.

[0121] The present invention also provides a preparation method of the composite resin material described in the above solution, including the following steps:

[0122] Mix the mesoporous silica functional filler, the matrix monomer, the diluent monomer and the initiator to obtain the composite resin material.

[0123] The present invention also provides the application of the composite resin material described in the above solution or the composite resin material obtained by the preparation method described in the above solution in the production of dental restoration materials.

[0124] The composite resin material provided by the present invention has good mechanical properties, has remineralization properties, has a long service life when used as a dental restoration material, reduces the discomfort of patients caused by the short service life of existing dental restoration materials, and has broad application prospects.

[0125] To further illustrate the present invention, the solutions of the present invention will be described in detail below in conjunction with the accompanying drawings and embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0126] In the embodiments, unless otherwise specified, the raw materials used can be obtained from public commercial channels, and the percentages are all mass percentages.

[0127] Example 1

[0128] A composite resin material, with the filler being Pchi / ACP@A-MSNs, and the preparation method includes the following steps:

[0129] (1) Add urea and cetyltrimethylammonium bromide to deionized water, and stir magnetically at room temperature until the solution is clear; among them, the dosage of urea is 0.9 g, the dosage of cetyltrimethylammonium bromide is 1.8 g, the dosage of deionized water is 30 mL, and the magnetic stirring time is 10 min.

[0130] (2) Add tetraethyl orthosilicate and n-pentanol to cyclohexane, and stir magnetically at room temperature for 10 min; among them, the dosage of tetraethyl orthosilicate is 6 mL, the dosage of n-pentanol is 6 mL, and the dosage of cyclohexane is 30 mL.

[0131] (3) Quickly add the mixed solution of step (2) to the mixed solution of step (1), stir at 300 rpm at room temperature for 40 min, then place it in a high-pressure autoclave with a polytetrafluoroethylene lining for hydrothermal reaction, with a heating rate of 4 °C / min, heat up to 120 °C and keep warm for 8 h, then naturally cool down to room temperature. After centrifuging the obtained reactants, wash the centrifuged product with deionized water and ethanol 3 times respectively, with a rotation speed of 8500 rpm. After centrifugation, dry the centrifuged product at 60 °C for 12 h, and finally control the heating rate to be 4 °C / min, heat up to 550 °C and calcine for 6 h, and naturally cool down to room temperature to remove the organic template agent CTAB to obtain mesoporous silica.

[0132] (4) Disperse 600 mg of mesoporous silica prepared in step (3) in 200 mL of toluene solution by ultrasonic for 30 min, stir at a speed of 300 rpm and heat to the boiling point, and slowly dropwise add 4 mL of 3-aminopropyltriethoxysilane. Connect a condenser reflux tube and continue heating and stirring for 24 h, then cool. Centrifuge at a speed of 4000 rpm, wash with alcohol 5 times, and dry in an oven at 80 °C for 4 h. The finally obtained white powder is the modified mesoporous silica.

[0133] (5) Dissolve 2.0 g of chitosan in 14 mL of methanesulfonic acid, and then add 2 g of P 2 O 5 . Stir at 12 °C for 1.5 h, then precipitate with methanol, wash the precipitate with acetone, centrifuge to collect the precipitate, and dry it under vacuum at room temperature to obtain white powdery Pchi solid particles.

[0134] (6) Add CaCl 2 ·2H 2 O, Pchi and Na 2 HPO 4 to deionized water in sequence, slowly add the Pchi prepared in step (5), and dissolve it with continuous stirring. The final solution concentration is: 50 g / L Pchi, 100 mmol / L CaCl 2 ·2H 2 O, 60 mmol / L Na 2 HPO 4 ; Place it in a -80 °C refrigerator and freeze for 24 h, then obtain the Pchi / ACP composite through freeze-drying.

[0135] (7) Put 300 mg of the ammoniated mesoporous silica powder prepared in step (4) into 60 mL of the solution of the Pchi / ACP composite prepared in step (6), and oscillate with an ultrasonic oscillator for 24 h. Pchi / ACP is electrostatically attracted by A-MSNs.

[0136] (8) Centrifuge at a speed of 4000 rpm for 3 min, then wash with deionized water 3 times. Finally, put the obtained white powder into a -80 °C refrigerator and freeze-dry for 1 h, and then freeze-dry the sample in a freeze-dryer to obtain a white powder, which is Pchi / ACP@A-MSNs. Its scanning electron microscope is as Figure 1 shown, the N 2 adsorption / desorption isotherm is as Figure 2 shown, the mesopore size distribution is as Figure 3 shown, and the EDS energy spectrum analysis is as Figure 4 shown.

[0137] It can be seen from Figure 1 that the particle size of the prepared mesoporous silica is about 350 nm.

[0138] According to Figure 2 it can be seen that the N 2 adsorption / desorption curve of MSNs is a closed loop at both ends, belonging to type Ⅳ isotherm, and there is an adsorption hysteresis loop. When P / P 0 = 1, the isotherm does not tend to be stable, indicating that there are mesopores and macropores of various sizes in the MSNs material. In addition, the pore size distribution calculated by the DFT method shows that all MSNs particles exhibit multiple peaks, further proving the multi-peak pore size distribution.

[0139] According to Figure 3 it can be seen that the pore size of MSNs is 6.18 nm.

[0140] According to Figure 4 it can be seen that the SEM of A-MSNs loaded with Pchi / ACP was performed, and its EDS element scanning was carried out. The b-d are the element distribution maps of Ca, P, and N respectively, where the Ca / P ratio is 1.7, close to the Ca / P ratio of dentin. Large pores can still be seen on the surface of A-MSNs loaded with Pchi / ACP, which leaves space for the subsequent resin matrix to enter the pores.

[0141] (9) At room temperature, 0.1 mol of tetramethylbiphenol, 160 mL of epichlorohydrin, and 0.2 g of TBAB were added to a three-necked flask equipped with a mechanical stirring device, a thermometer, and a reflux condenser, and stirred evenly. The system was heated to 90 °C and reacted for 6 h; under reduced pressure distillation, the unreacted epichlorohydrin was removed; then 200 mL of toluene was added, and 32 g of 30 wt% aqueous sodium hydroxide solution was slowly added dropwise using a constant pressure dropping funnel; the reaction was continued at 90 °C for 3 h; after the reaction was completed, it was washed with distilled water until the aqueous layer was neutral; then toluene and water were removed by reduced pressure distillation, and vacuum dried at 60 °C for 24 h to obtain tetramethylbiphenol diglycidyl ether.

[0142] (10) Tetramethylbiphenol diglycidyl ether, 0.50 wt% triphenylphosphine, and hydroquinone were added to a three-necked flask as a catalyst and an inhibitor respectively, under nitrogen protection, and heated and stirred to 90 °C. Then acrylic acid was quickly added, and the molar ratio of tetramethylbiphenol diglycidyl ether to acrylic acid was 1:2.04. The reaction temperature was controlled at 105 °C, and the reaction was terminated after 4 h to obtain a pale yellow viscous product, which is the TMBPEA monomer.

[0143] (11) Using TMBPEA as the matrix monomer, 2-hydroxyethyl methacrylate as the diluting monomer, camphorquinone and dimethylaminoethyl methacrylate as photoinitiators, the resin matrix and the initiators were uniformly mixed with a three-roll mill according to the percentages of 70 wt% of TMBPEA, 29 wt% of 2-hydroxyethyl methacrylate, and 0.5 wt% of camphorquinone and dimethylaminoethyl methacrylate respectively to obtain a TMBPEA resin matrix. The mesoporous silica functional filler and the resin matrix were mixed at a mass ratio of 6:4 (4.5 g of A-MSNs and 1.5 g of Pchi / ACP were put into 4 g of the resin matrix) to obtain a composite resin material, which was stored in the dark.

[0144] Example 2

[0145] The preparation method of this example is the same as that of Example 1, except that: in step (11), 2.25 g of A-MSNs and 3.75 g of Pchi / ACP@A-MSNs were put into 4 g of the resin matrix.

[0146] Comparative Example 1

[0147] The preparation method of this comparative example is the same as that of Example 1, except that: in step (11), 4.5 of non-porous silica and 1.5 g of Pchi / ACP were put into 4 g of the resin matrix curing system; the particle size of the non-porous silica was 350 nm.

[0148] Comparative Example 2

[0149] The preparation method of this comparative example is the same as that of Example 1, except that: in step (11), 1.5 g of Pchi / ACP was put into 4 g of the resin matrix curing system.

[0150] Comparative Example 3

[0151] The preparation method of this comparative example is the same as that of Example 1, except that: in step (11), no fillers such as silica and Pchi / ACP were added.

[0152] Test Example 1

[0153] Using the composite resin materials of Examples 1-2 and Comparative Examples 1-3, dental resin specimens were prepared respectively, including the following steps:

[0154] Preparation of dental resin splines: The composite resins of Examples 1-2 and Comparative Examples 1-3 were respectively placed in a rectangular mold of 25 mm×2 mm×2 mm. A polyethylene film and a glass slide were successively covered on the surface. The visible light curing lamp head was aligned with the center of the specimen and abutted against the glass slide, and irradiated for 60 s. The irradiated part of each time overlapped with the irradiated part of the previous time along the radius. The irradiation of one side of the specimen was completed in sequence. In the same way, the irradiation of the other side of the specimen was completed until the whole specimen was irradiated. All specimens were polished with 1500-grit silicon carbide sandpaper.

[0155] Preparation of dental resin calcium ion release specimens: The composite resins of Examples 1-2 and Comparative Examples 1-3 were respectively placed in a disc mold of 15 mm×2 mm. A polyethylene film and a glass slide were successively covered on the surface. The visible light curing lamp head was aligned with the center of the specimen and abutted against the glass slide, and irradiated for 60 s. The irradiated part of each time overlapped with the irradiated part of the previous time along the radius. The irradiation of one side of the specimen was completed in sequence. In the same way, the irradiation of the other side of the specimen was completed until the whole specimen was irradiated. All specimens were polished with 1500-grit silicon carbide sandpaper.

[0156] Preparation of dentin remineralization specimens: The composite resins of Examples 1-2 and Comparative Examples 1-3 were respectively placed in a disc mold of 10 mm×10 mm×3 mm. A polyethylene film and a glass slide were successively covered on the surface. The visible light curing lamp head was aligned with the center of the specimen and abutted against the glass slide, and irradiated for 60 s. The irradiated part of each time overlapped with the irradiated part of the previous time along the radius. The irradiation of one side of the specimen was completed in sequence. In the same way, the irradiation of the other side of the specimen was completed until the whole specimen was irradiated. All specimens were polished with 1500-grit silicon carbide sandpaper.

[0157] (1) Double bond conversion rate test

[0158] To illustrate the effect of Pchi / ACP@A-MSNs on the resin curing process, the double bond conversion rates of the dental resin splines of Examples 1-2 and Comparative Examples 1-3 were tested respectively. Using a Fourier transform infrared spectrometer, according to the change of the absorption intensity of a certain characteristic peak in a series of infrared spectra, the curing process of the sample was recorded. In this test, the changes in the peak areas of C=C double bonds and C=O were mainly recorded. On the infrared spectrum, the area (A -1 ) under the absorption peak of C=C in the composite resin at 1627.6 cm 1627.6 before and after curing of the resin system was compared. Taking the absorption area (A -1 ) under the absorption peak of C=O at 1720.1 cm 1720.1 as the internal standard, the double bond conversion rate was calculated using the formula, and the results are as Figure 5 shown.

[0159] According to Figure 5It can be seen that the double bond conversion rates of the dental resins in Examples 1-2 and Comparative Examples 1-3 all exceed 50%, and all can meet the clinical use of dental composite resins.

[0160] (2) Mechanical property test

[0161] To illustrate the effect of Pchi / ACP@A-MSNs on enhancing the mechanical properties of the resin, the mechanical properties of the dental resin splines in Examples 1-2 and Comparative Examples 1-3 were tested respectively. A universal testing machine was used to evaluate the elastic modulus (FM), flexural strength (FS) and Vickers hardness of the composite resin. The width w (mm) and height h (mm) of the specimens were measured, and a three-point bending test was carried out at a span of 20 mm and a crosshead speed of 0.75 mm / min, and the failure load F was recorded. The slope K of the straight line segment of the load-displacement curve was measured, and the elastic modulus and flexural strength were calculated according to the formula respectively. The Vickers hardness values of each group of composite resins were measured by a Vickers hardness tester, with a load of 100 g and a loading time of 10 s, and the arithmetic mean of each group of results was taken as the Vickers hardness value of the composite resin. The results are as Figure 6 and Figure 7 shown.

[0162] According to Figure 6 and Figure 7 It can be seen that the elastic modulus, flexural strength and Vickers hardness of Example 2 are 4.83 GPa, 94.5 MPa and 21.2 HV respectively, which are higher than those of Comparative Examples 1-3, and the effect on enhancing the mechanical properties of the resin is obvious.

[0163] (3) Dentin remineralization test

[0164] Intact and caries-free recently extracted third molars were selected and prepared into dentin specimens (5 mm * 5 mm * 3 mm). The dentin slices were placed in a 0.5 mol / L EDTA solution (pH value 8.0), continuously stirred at room temperature for 7 days, and then ultrasonically cleaned with deionized water for 10 min to obtain demineralized dentin slices, which were then stored in physiological saline at 4 °C for later use. Three disk specimens with a diameter of 15 mm * 2 mm were prepared for each group of composite resins, and the composite resin specimens were closely contacted with the demineralized dentin slices by a clamp. Then they were immersed in SBF together and incubated at 37 °C for 4 weeks. Finally, the remineralized dentin slices were taken out, rinsed with deionized water, dried and subjected to SEM detection. The results are as Figure 8 shown. Since Comparative Example 3 did not contain a remineralization filler, its remineralization performance was not detected.

[0165] According to Figure 8 It can be seen that different amounts of calcium phosphate deposition and occlusion of dentin tubules can be seen on the dentin surfaces of Examples 1-2 and Comparative Examples 1-2.

[0166] (4) Calcium ion release test

[0167] Prepare an NaCl solution (133 mmol / L) with deionized water and buffer it to two different pH values: 50 mmol / L lactic acid at pH 4 and a buffer solution containing 50 mmol / L HEPES at pH 7.4. According to previous studies, immerse three 2×2×12 mm samples in each group of A - D into 50 mL of solution at each pH value. The sample volume is close to 3.0 mm 3 / mL. Measure the concentration of Ca 2+ at 1, 3, 7, 14, 21, and 28 days. Since Comparative Example 3 is a simple resin matrix, the calcium ion release of this group was not designed. Detect the Ca 2+ concentration of the samples by spectrophotometry using known standards and calibration curves. The results are as Figure 9 shown.

[0168] According to Figure 9 it can be seen that when the pH value is 7.4, the Ca 2+ release concentration of the composite resin in Group D is the highest, followed by Groups C, B, and A. When the pH value is 4, the Ca 2+ release concentration and rate of the composite resin in Group B are the highest, followed by Groups A, D, and C. It can be confirmed that this filler is a pH-responsive filler and shows different Ca 2+ release amounts in different acid-base environments.

[0169] (5) Biocompatibility test

[0170] Take the dental resin specimens to be tested (8*5 mm*3 mm) for biocompatibility testing. Polish the surface of the resin spline with sandpaper, use ethanol for ultrasonic cleaning, and disinfect with ultraviolet light; add DMEM medium at a rate of 1 mL / cm 2 , soak for 24 h to obtain the resin extract; plate L929 cells, and after they adhere and grow, divide them into two groups for culture. Replace the culture medium of the experimental group with the resin extract, and use DMEM medium for the control group; after culturing for a certain period of time, use a CCK8 kit for cytotoxicity testing. The results are as Figure 10 shown.

[0171] According to Figure 10 it can be seen that when the cells are incubated with the resin extracts prepared in Examples 1 - 2 and Comparative Examples 1 - 3 on the 1st, 4th, and 7th days, no cytotoxicity is shown, and the cell growth and proliferation are good.

[0172] As can be seen from the above embodiments, the mesoporous silica functional filler provided by the present invention can improve the mechanical strength and hydrolysis stability of the composite resin, which is mainly due to its central radial wrinkle structure, enabling the resin matrix to better penetrate into the filler, thereby forming mechanical interlocking and improving the mechanical strength of the composite resin material. The Pchi / ACP@A-MSNs filler can promote the remineralization of dentin and improve the service life of the composite resin. In addition, Pchi / ACP@A-MSNs has pH-responsive properties and exhibits different Ca 2+ release amounts in different acid-base environments. Especially in an acidic environment, the Ca release of Pchi / ACP@A-MSNs shows an explosive growth in the first seven days, which is extremely beneficial for the remineralization of secondary caries with a locally acidic microenvironment.

[0173] Although the above embodiments have described the present invention in detail, they are only a part of the embodiments of the present invention, not all of them. Other embodiments can be obtained based on these embodiments without creative efforts, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A mesoporous silica functional filler, comprising a Pchi / ACP composite and modified mesoporous silica electrostatically loaded with the composite; the Pchi / ACP composite comprises phosphorylated chitosan and amorphous calcium phosphate.

2. The mesoporous silica functional filler according to claim 1, characterized in that: The method for preparing the phosphorylated chitosan comprises: mixing chitosan, methanesulfonic acid and phosphorus pentoxide and then precipitating the mixture.

3. The mesoporous silica functional filler according to claim 1 or 2, characterized in that: The mass ratio of the phosphorylated chitosan to the amorphous calcium phosphate is 20-25:35-40; the mass ratio of the modified mesoporous silica to the Pchi / ACP composite is 22.5:37.

5.

4. The mesoporous silica functional filler according to claim 1 or 2, characterized in that: The particle size of the mesoporous silica functional filler is 320-380 nm.

5. The method for preparing the mesoporous silica functional filler according to any one of claims 1 to 4, characterized in that: The following steps are involved: The mesoporous silica solution is heated to a boiling point, and then 3-aminopropyltriethoxysilane is added dropwise to the mesoporous silica solution, followed by heating under reflux to obtain modified mesoporous silica; Calcium chloride, phosphorylated chitosan, Na2HPO4 and water were mixed and freeze-dried to obtain Pchi / ACP complex; The modified mesoporous silica, the Pchi / ACP complex and a solvent are mixed, and then shaken and freeze-dried in sequence to obtain the mesoporous silica functional filler.

6. A composite resin material, characterized in that: The invention comprises a mesoporous silica functional filler, a matrix monomer, a diluent monomer and an initiator; the mesoporous silica functional filler is the mesoporous silica functional filler according to any one of claims 1 to 4 or the mesoporous silica functional filler obtained by the preparation method according to claim 5.

7. The composite resin material according to claim 6, characterized in that The matrix monomer is polyester; the diluent monomer is acrylate; and the initiator includes one or more of camphorquinone and dimethylaminoethyl methacrylate.

8. The composite resin material according to claim 6, characterized in that The mass ratio of the matrix monomer to the diluent monomer is 70:29; the mass ratio of the matrix monomer to the initiator is 70:1; and the mass content of the mesoporous silica functional filler in the composite resin material is 60wt%.

9. The method for preparing the composite resin material according to any one of claims 6 to 8, characterized in that: The following steps are involved: The mesoporous silica functional filler, the matrix monomer, the diluent monomer and the initiator are mixed to obtain the composite resin material.

10. Use of the composite resin material according to any one of claims 6 to 8 or the composite resin material obtained by the preparation method according to claim 9 in the preparation of tooth restoration materials.

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