阅读说明：本技术 一种具有生物活性的齿科修复复合树脂及其制备方法 (Dental repair composite resin with bioactivity and preparation method thereof ) 是由 魏吉瑞 任志伟 屈长宏 李思纯 王丹 陈振华 刘启省 张东刚 于 2021-08-19 设计创作，主要内容包括：本发明公开了一种具有生物活性的齿科修复复合树脂及其制备方法。本发明首先提供一种硅烷化改性的白硅钙石粉体,按照如下方法制备：将硅烷偶联剂与正丙胺的混合物滴加至白硅钙石的悬浮液中,加热条件下进行搅拌,去除熔剂后经干燥即得；将有机单体、光引发剂和助引发剂混合得到树脂基体,将硅烷化改性的白硅钙石粉体,或硅烷化改性的白硅钙石粉体与无机填料的混合物加入至树脂基体中,进行混合得到未固化的光固化复合树脂膏体,即为齿科修复复合树脂。本发明对白硅钙石进行了硅烷化改性,使无机结构带有有机基团,可与有机单体更好的结合,将其与有机单体、引发体系及其他无机填料混合在一起,得到有机无机界面相容性更好的齿科修复树脂,提高了树脂的力学性能。(The invention discloses a dental restoration composite resin with bioactivity and a preparation method thereof. The invention firstly provides silanization modified whitish wollastonite powder which is prepared according to the following method: dripping the mixture of the silane coupling agent and the n-propylamine into the suspension of the whitish calcium stone, stirring under a heating condition, removing the flux, and drying to obtain the calcium silicate white calcium stone; mixing an organic monomer, a photoinitiator and an auxiliary initiator to obtain a resin matrix, adding silanized modified whinesite powder or a mixture of silanized modified whinesite powder and an inorganic filler into the resin matrix, and mixing to obtain uncured photocuring composite resin paste, namely the dental repair composite resin. The present invention performs silanization modification on the whitlockite, so that an inorganic structure has organic groups which can be well combined with organic monomers, and the inorganic groups are mixed with the organic monomers, an initiation system and other inorganic fillers to obtain dental repair resin with good organic-inorganic interface compatibility, and the mechanical properties of the resin are improved.)

1. A preparation method of silanization modified whitish wollastonite powder comprises the following steps:

and (3) dropwise adding the mixture of the silane coupling agent and the n-propylamine into the suspension of the whitish limestone, stirring under a heating condition, removing the flux, and drying to obtain the calcium silicate.

2. The method of claim 1, wherein: the suspension was formulated with the following solvents:

cyclohexane, methanol, isopropanol or n-propanol;

the proportion of the whitlockite to the solvent is 1 g: 20-120 mL;

and mixing the whitlockite and the solvent, and stirring for 10-30 min at the temperature of 8-35 ℃ and at the speed of 700-750 r/min to obtain the suspension.

The silane coupling agent is gamma-methacryloxypropyltrimethoxysilane (gamma-MPS), methyltrimethoxysilane, methyltriethoxysilane, vinyltris (beta-methoxyethoxy) silane or vinyltriethoxysilane.

3. The production method according to claim 1 or 2, characterized in that: the mass ratio of the silane coupling agent to the n-propylamine to the whinesite is 0.1-0.3: 0.4-0.5: 1;

the heating temperature is 60-65 ℃;

the stirring conditions are as follows:

the rotating speed is 700-750 r/min, and the time is 30-90 min;

the drying is vacuum drying, and the conditions are as follows:

the temperature is 85-95 ℃, and the time is 12-18 h.

4. A silanized modified whitish limestone powder prepared by the process of any one of claims 1 to 3.

5. Use of the silanized and modified whitish wollastonite powder of claim 4 in the preparation of dental restorative composite resins.

6. A preparation method of dental restoration composite resin comprises the following steps:

mixing an organic monomer, a photoinitiator and an auxiliary initiator to obtain a resin matrix, adding the silanized and modified whinesite powder of claim 4 or a mixture of the silanized and modified whinesite powder of claim 4 and an inorganic filler into the resin matrix, and mixing to obtain an uncured photocuring composite resin paste, namely the dental repair composite resin.

7. The method of claim 6, wherein: the organic monomer components are 1) and 2) as follows:

1) any one of bisphenol a glycidyl methacrylate, ethoxylated bisphenol a epoxy methacrylate, and urethane dimethacrylate;

2) any one of triethylene glycol dimethacrylate and 1, 12-dodecanediol dimethacrylate;

the initiator is camphorquinone;

the auxiliary initiator is 4-ethyl dimethylaminobenzoate.

8. The production method according to claim 6 or 7, characterized in that: the inorganic filler is micron barium glass powder, nano barium glass powder and/or nano silicon dioxide;

the mass ratio of the silanization modified whinesite powder to the inorganic filler is 1: 0-15, but not zero;

in the resin matrix, the mass percentage of the photoinitiator is 0.05-0.20%.

9. The production method according to any one of claims 6 to 8, characterized in that: the mass percentage of the silanization modified whinesite powder in the mixed material is 0.1-80%;

the mixed material refers to the mixture of the resin matrix and the silanization modified whinesite powder or the mixture of the resin matrix, the silanization modified whinesite powder and the inorganic filler.

10. A dental restorative composite resin prepared by the method of any of claims 6-9.

Technical Field

The invention relates to a dental restoration composite resin with bioactivity and a preparation method thereof, belonging to the field of dental restoration materials.

Background

The fourth national oral health epidemiological survey in 2015: the prevalence rate of oral diseases of children in China is in an increasing trend, wherein the prevalence rate of caries of children aged 5 years and children aged 12 years is 71.9 percent and 38.5 percent respectively, and is increased by 5.9 percent and 9.6 percent respectively compared with that before 10 years; periodontal health of middle-aged people is not optimistic, and caries and dentition defects are main reasons affecting oral health of adults in China. The prevalence rate of the permanent tooth caries of the middle-aged and the elderly is higher, the repair proportion of the people with tooth deficiency of the elderly is improved from 48.8% to 63.2%, but the average number of the tooth deficiency is still as high as 7.5. Caries is a disease characterized by demineralization of teeth and decomposition of organic matter, forming caries cavities on teeth. The key of caries repair is a repair material, and the composite resin is favored by doctors and patients by virtue of excellent mechanical property, aesthetic property and operation convenience, and replaces the traditional silver-mercury alloy.

The composite resin mainly comprises organic monomers, inorganic filler, photoinitiator, coupling agent, colorant and the like. The inorganic filler plays an important role as a disperse phase and influences the mechanical property, the aesthetic property, the wear resistance and the like of the composite resin. The inorganic filler can reduce polymerization shrinkage due to a decrease in the intermolecular distance of the organic monomer after polymerization, which is expressed as macroscopic volume reduction, i.e., polymerization shrinkage. However, the compatibility between the organic monomer and the inorganic filler is poor due to the different polarities. It is therefore desirable to modify the inorganic filler to provide better integration with the organic monomer.

Whitlockite (Ca) is compared with conventional inorganic fillers such as glass powder, silica, etc₇MgSi₄O₁₆) Has excellent bioactivity, can induce the formation of hydroxyapatite in oral cavity, and fill up the tiny gaps of teeth. However, the surface of the existing whitlockite shows water absorption, the surface of an organic monomer commonly used in dental repair resin has hydrophobicity, the compatibility between the organic monomer and the inorganic filler is poor, the continuity of the organic monomer is easily influenced by the inorganic filler, the interface is difficult to form effective combination, and the performance of the dental repair resin is seriously influenced, so the existing whitlockite needs to be modified for being used in the dental repair resin.

Disclosure of Invention

The invention aims to provide a dental restoration composite resin with bioactivity, which can be used for preparing a dental restoration resin by performing silanization modification on whitlockite to enable inorganic fillers to be better combined with organic monomers and obtaining the dental restoration resin with good organic-inorganic phase compatibility and bioactivity.

The invention firstly provides a preparation method of silanization modified whitish wollastonite powder, which comprises the following steps:

and (3) dropwise adding the mixture of the silane coupling agent and the n-propylamine into the suspension of the whitish calcium, stirring under a heating condition, removing the solvent, and drying to obtain the calcium silicate.

In the above preparation method, the suspension is prepared by using the following solvents:

cyclohexane, methanol, isopropanol or n-propanol;

the proportion of the whitlockite to the solvent is 1 g: 20-120 mL;

mixing the whitlockite and the solvent, and stirring for 10-30 min at the temperature of 28-35 ℃ and at the speed of 700-750 r/min to obtain the suspension;

the silane coupling agent is gamma-methacryloxypropyltrimethoxysilane (gamma-MPS), methyltrimethoxysilane, methyltriethoxysilane, vinyltris (beta-methoxyethoxy) silane or vinyltriethoxysilane.

In the above preparation method, the mass ratio of the silane coupling agent, the n-propylamine, and the whitish calcium silicate is 0.1-0.3: 0.01-0.05: 1;

the heating temperature is 60-65 ℃;

the stirring conditions are as follows:

the rotating speed is 700-750 r/min, and the time is 30-90 min;

the drying is vacuum drying, and the conditions are as follows:

the temperature is 85-95 ℃, and the time is 12-18 h.

On the basis of silanization modified whitish wollastonite powder, the invention further provides dental repair composite resin, which is prepared according to the following method:

mixing an organic monomer, a photoinitiator and an auxiliary initiator to obtain a resin matrix, adding the silanized and modified whinesite powder or a mixture of the silanized and modified whinesite powder and an inorganic filler into the resin matrix, and mixing to obtain an uncured photocuring composite resin paste, namely the dental repair composite resin;

preferably, the non-medium homogenizer is used for mixing, and then a three-roll grinder is used for grinding and mixing to obtain the light-cured composite resin paste.

Specifically, the organic monomer components are the following 1) and 2):

1) any one of bisphenol a glycidyl methacrylate, ethoxylated bisphenol a epoxy methacrylate, and urethane dimethacrylate;

2) any one of triethylene glycol dimethacrylate and 1, 12-dodecanediol dimethacrylate;

the initiator may be camphorquinone;

the coinitiator may be ethyl 4-dimethylaminobenzoate.

Specifically, the inorganic filler may be micro-barium glass powder, nano-barium glass powder and/or nano-silica;

the mass ratio of the silanization modified whinesite powder to the inorganic filler is 1: 0-1000, but not zero, such as 1: 1-15, 1: 1.67, 1: 7 or 1: 15.

in the resin matrix, the mass percentage of the photoinitiator is 0.05-0.20%;

the mass ratio of the photoinitiator to the co-initiator is preferably 1: 4.

specifically, the mass percentage content of the silanization modified whinesite powder in the mixed material is 0.1-80%, preferably 5-30%, 5-10% or 10-30%, 5%, 10% or 30%;

the mixed material refers to the mixture of the resin matrix and the silanization modified whinesite powder or the mixture of the resin matrix, the silanization modified whinesite powder and the inorganic filler.

According to the invention, after the whitlockite is modified by using the silane coupling agent, the hydrophilic group and the hydrophobic group exist on the surface of the whitlockite simultaneously, so that a good interface effect can be formed between the whitlockite and an organic monomer interface, and the performance of the dental repair resin is improved.

According to the invention, the bredigite and the organic monomer are compounded to obtain the repair resin, the resin filled with the bredigite is placed in the simulated body fluid, after a period of time, the mineralization result is observed through a scanning electron microscope, and the existence of calcium and magnesium is also verified through an energy spectrum; after the composite resin is placed in purified water, calcium and magnesium are detected to be contained in the water, and the fact that the xonotlite can release the calcium and the magnesium is proved. The whitlockite can improve the oral environment, improve the concentration of calcium ions and magnesium ions in saliva, promote the formation of hydroxyapatite crystals, promote the progress of tooth remineralization, induce the restoration resin to self-restore surface microcracks and defects in clinical service, and prevent secondary dental caries.

In the repair resin prepared by the invention, the mass content of the silanized and modified whitlockite is 0.1-80%, preferably 5-30%, 5-10% or 10-30%, 5%, 10% or 30%.

The invention has the following beneficial technical effects:

(1) according to the invention, the whitlockite containing Ca, Mg and Si is selected as an inorganic filler, and the whitlockite has good capability of inducing hydroxyapatite formation and biological activity; the dental restoration composite resin applying the whitlockite can improve the oral environment, improve the concentration of calcium ions and magnesium ions in saliva, promote the formation of hydroxyapatite, promote the remineralization of teeth, release Ca ions and Mg ions in water, induce the restoration resin to restore surface microcracks and defects in clinical service, and prevent secondary dental caries.

(2) The present invention has silanized and modified whitlockite to make inorganic structure with organic radical capable of combining with organic monomer, and the inorganic radical is mixed with organic monomer, initiating system and other inorganic stuffing to obtain dental repair resin with high organic-inorganic interface compatibility and raised mechanical performance.

Drawings

FIG. 1 is a scanning electron micrograph of silanized and modified whitish wollastonite according to example 1 of the present invention.

FIG. 2 is an infrared spectrum of whitish calciumite before and after the silylation modification in example 1 of the present invention.

FIG. 3 is a graph showing the thermal weight loss of whitish calcia before and after silanization modification in example 1 of the present invention.

FIG. 4 is a graph showing the appearance of mineralized layers induced in physiological saline by the modified whitlockite-filled resin of example 1 of the present invention.

FIG. 5 is a graph showing the energy spectrum of the mineralized layer induced in physiological saline by the modified whitlockite-filled resin in example 1 of the present invention.

FIG. 6 is a graph showing the flexural strength of the modified and unmodified xonotlite-filled resins of example 1 of the present invention.

FIG. 7 is a graph showing the modulus of elasticity of the modified and unmodified xonotlite-filled resins of example 1 of the present invention.

FIG. 8 is a graph showing the compressive strength of the modified and unmodified xonotlite-filled resins of example 1 of the present invention.

Detailed Description

The experimental procedures used in the following examples are all conventional procedures unless otherwise specified.

Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.

Examples 1,

(1) Preparation of whitlockite

224ml of ethyl orthosilicate is mixed with 144ml of water and added with a nitric acid solution, the pH value is adjusted to 3, the mixture is stirred well for 30min at room temperature, then 0.25mol of magnesium nitrate hexahydrate and 1.75mol of calcium nitrate tetrahydrate are added, the mixture is stirred for 4h, sealed, aged at 60 ℃ for 2 days and dried at 120 ℃ for 2 days. And calcining the dried xerogel at 1350 ℃ for 3 hours to obtain pure whitlockite powder.

(2) Silanization modified whitlockite

Weighing 30.0g of whitlockite powder, pouring into a 1000mL flask, weighing 600mL (the proportion of the two is 1 g: 20mL) of cyclohexane, pouring into the flask, adding a rotor, putting into a heat collection type magnetic stirrer, and stirring for 15min at the temperature of 30 ℃ at 700 r/min. While stirring, 3.00g of gamma-methacryloxypropyltrimethoxysilane (gamma-MPS) was weighed into a centrifuge tube, 0.60g of n-propylamine was added dropwise thereto, and the mixture was shaken and mixed uniformly. Then slowly added dropwise to the flask containing the whitlockite, and stirring was continued for 30 min. After the time, the oil bath temperature was adjusted to 65 ℃ and stirred at 700r/min for 60 min. Removing excessive solvent by rotary evaporation, and performing vacuum drying for 16h at 95 ℃ to obtain the silanized and modified white calcium silicate powder.

Scanning electron micrographs, infrared spectrograms and thermogravimetry of the bredigite before and after modification are respectively shown in fig. 1-3. By analyzing the infrared spectrum test chart of FIG. 2, the patterns of the modified whitlockite are 1720, 1634 and 2945cm^-1The characteristic peaks of (A) show obvious characteristic peaks which respectively correspond to a C ═ O stretching vibration peak, a C ═ C bond and a C-H bond in gamma-MPS, and prove that the whitish wollastonite is successfully subjected to surface silanization modification. And the analysis is carried out by combining the thermogravimetric plot of figure 3, and the decomposition of the modified whitlockite is obvious after 500 ℃, which is the decomposition of the gamma-MPS after the grafting is successful, and further proves that the whitlockite is decomposedThe limestone is successfully silanized and modified.

(3) 2.4g of bisphenol A-glycidyl methacrylate, 1.6g of triethylene glycol dimethacrylate, 0.006g of camphorquinone and 0.024g of ethyl 4-dimethylaminobenzoate are mixed for 5min by using a non-medium homogenizer to obtain a uniformly mixed organic matrix. Weighing 16g of modified whitlockite, adding the modified whitlockite into an organic matrix, and dispersing and mixing to obtain preliminarily and uniformly mixed paste resin. And then further mixing the mixture by using a three-roll grinder again to obtain the photocuring composite resin containing 80 wt% of silanized modified whitish calcium.

Resins of different silanized modified canasite contents were obtained according to the method of this example:

(a) weighing 2.4g of bisphenol A-glycidyl methacrylate, 1.6g of triethylene glycol dimethacrylate, 0.006g of camphorquinone and 0.024g of ethyl 4-dimethylaminobenzoate to obtain an organic matrix, sequentially weighing 6g of modified whitish wollastonite, 8g of silanized modified micron barium glass and 2g of silanized modified nano barium glass, and adding the materials into the organic matrix to obtain the photocuring composite resin containing 30 wt% of silanized modified whitish wollastonite.

(b) Weighing 2.4g of bisphenol A-glycidyl methacrylate, 1.6g of triethylene glycol dimethacrylate, 0.006g of camphorquinone and 0.024g of ethyl 4-dimethylaminobenzoate to obtain an organic matrix, sequentially weighing 2g of modified whitish wollastonite, 12g of silanized modified micron barium glass and 2g of silanized modified nano barium glass, and adding the materials into the organic matrix to obtain the photocuring composite resin containing 10 wt% of silanized modified whitish wollastonite.

(c) Weighing 2.4g of bisphenol A-glycidyl methacrylate, 1.6g of triethylene glycol dimethacrylate, 0.006g of camphorquinone and 0.024g of ethyl 4-dimethylaminobenzoate to obtain an organic matrix, sequentially weighing 1g of modified whitisite, 12g of silanized modified micron barium glass and 3g of silanized modified nano-silica, and adding the materials into the organic matrix to obtain the photocuring composite resin containing 5 wt% of silanized modified whitisite.

(d) 3.6g of bisphenol A-glycidyl methacrylate, 2.4g of triethylene glycol dimethacrylate, 0.009g of camphorquinone and 0.036g of ethyl 4-dimethylaminobenzoate are weighed to obtain an organic matrix, and 14g of modified whitish calcium is weighed and added into the organic matrix to obtain the photocuring composite resin containing 70 wt% of silanized and modified whitish calcium.

(e) 3g of bisphenol A-glycidyl methacrylate, 2g of triethylene glycol dimethacrylate, 0.0075g of camphorquinone and 0.03g of ethyl 4-dimethylaminobenzoate are weighed to obtain an organic matrix, and 15g of modified whitisite is weighed and added into the organic matrix to obtain the photocuring composite resin containing 75 wt% of silanized and modified whitisite.

The repair resin (5 wt% and 30 wt%) filled with the xonotlite of example 1 was placed in a simulated body fluid, placed in an oven at 37 ℃ to simulate the environment of a human body, and after being placed for 7 days, the surface of the resin was sprayed with gold and tested using a field emission scanning electron microscope, and it was observed that the sample surface had a lamellar structure and a needle-like structure (fig. 4A to 4D, in which fig. 4A to 4B show the surface morphology of the resin containing 5 wt% of the silanized modified xonotlite, fig. 4C to 4D show the surface morphology of the resin containing 30 wt% of the silanized modified xonotlite), while the morphology of the resin not filled with the xonotlite was observed using a scanning electron microscope, that is the morphology of the inorganic filler and matrix of the resin itself (fig. 4E to 4F), i.e. the whitish limestone promotes mineralization. Further, the structure produced on the surface of the resin filled with the whitish calcium silicate was subjected to a spectrum test (fig. 5) in conjunction with an EDS mapping chart, and the two resins having different filling amounts of the whitish calcium silicate (fig. 5A to 5C show a resin containing 5 wt% of the silanized modified whitish calcium silicate, and fig. 5D to 5F show a resin containing 30 wt% of the silanized modified whitish calcium silicate) were tested, and it was found that the structures produced by the two resins each contain three elements, P, Ca, and Mg. The mineralized layer is hydroxyapatite according to the calculation of the ratio of Ca and P and the results of X-ray diffraction tests. The resin for repairing the wollastonite can induce the deposition of P, Ca, Mg and other ions in saliva to generate hydroxyapatite of a mineralized layer, and the generated hydroxyapatite of the mineralized layer can reduce the generation of micro cracks in the service process of an oral cavity, fill up gaps of teeth and has biological activity.

The resin filled with the whinesite with different contents is subjected to mechanical test to obtain three data (fig. 6-8) of flexural strength, elastic modulus and compressive strength, and it can be seen that the flexural strength, elastic modulus and compressive strength of the resin filled with the silane-modified whinesite are improved to different degrees, which proves that the whinesite has an enhanced effect on the resin mechanics.

Specifically, as shown in fig. 6 to 8, the mechanical properties of the resin to which the modified whinesite was added were analyzed, wherein when the content of the silanized modified whinesite was 5% to 30%, both the elastic modulus and the compressive strength of the composite resin were significantly improved as compared with the resin to which no whinesite was added, and only the flexural strength was reduced to some extent when the filling amount reached 30%, but the numerical value was still high, so that it was determined that the optimum filling range of the silanized modified whinesite was 5% to 30%.

The resin mechanical strength (flexural strength, compressive strength and elastic modulus) of the unmodified whinesite with the addition content of 5 percent and 10 percent is far lower than that of the modified whinesite added with silanization, which shows that the modified whinesite and the organic monomer can have better binding force and the compatibility between the organic monomer and the inorganic filler is increased.