Preparation method and application of fluorine-based diopside bioactive ceramic material

Abstract

The invention discloses a preparation method and application of a fluorine-based diopside bioactive ceramic material, and the fluorine-based diopside bioactive ceramic material is obtained by doping diopside with fluorine-containing compounds with different concentrations. When the fluorine-doped diopside bioactive ceramic material is prepared, under the condition that the molar ratio of Ca to Mg to Si is not changed, the content of fluorine can be regulated and controlled by increasing fluorine-containing compounds, meanwhile, the pH value does not need to be regulated in the reaction process, the raw materials are wide in source and cheap, the preparation process is simple and convenient, and the preparation process is free of pollution and environmentally friendly. According to the prepared fluorine-based diopside bioactive ceramic material, in an environment of simulating oral saliva, the rate of forming apatite through induction is higher than that of common calcium-silicon-based ceramic, and meanwhile, the fluorine-based diopside bioactive ceramic material shows good biocompatibility. The prepared fluorine-doped diopside bioactive ceramic can be used as a biomimetic mineralization reagent, and can effectively promote remineralization of demineralized teeth and prevention of early decayed teeth.

Description

Technical Field

[0001] The present invention relates to a preparation method and application of a fluorine-based diopside bioactive ceramic material, and in particular to a preparation method and application of a fluorine-based diopside bioactive ceramic material capable of adjusting fluoride ion concentration, and belongs to the technical field of biomaterials. Background Art

[0002] Teeth are an extremely complex organ and the hardest biomineralized tissue in nature. The structure of teeth from the inside to the outside is mainly pulp, dentin and enamel. Among them, enamel is the most vulnerable to damage in daily life, and it is difficult for enamel to completely repair itself. According to the fourth national oral health epidemiological survey, the rate of permanent caries in 12-year-old children is 34.5%, the rate of caries in deciduous teeth in 5-year-old children is 70.9%, and 89% of adults suffer from caries. The main causes of caries today are unhealthy eating habits, lack of attention to oral hygiene and bacterial infection. Frequent intake of high-sugar foods and carbonated drinks, sugar provides a rich source of energy for bacteria in the mouth and promotes bacterial reproduction. Acidic foods will directly destroy tooth enamel and cause mineral loss, thereby increasing the risk of caries. Carbonated drinks are not only high-sugar foods, but also their pH value is usually between 2.2 and 4.9, which can easily damage tooth enamel. The content of inorganic matter in tooth enamel is very high, accounting for about 95% to 97% of the total mass of tooth enamel. These inorganic substances are mainly hydroxyapatite, and a small amount of fluoroapatite. Long-term acid erosion will damage the surface enamel, causing mineral loss, exposing the dentin, and eventually leading to tooth decay. Due to the protective effect of enamel on teeth and its impact on oral health, repairing damaged enamel is of great significance.

[0003] Calcium magnesium silicate bioceramic materials can reach a supersaturated state through the dissolution of ions, thereby promoting the deposition of hydroxyapatite at the tissue interface, and it has good biocompatibility. Silicon ions and calcium ions are also released during the degradation process in the body. These two ions have the effect of promoting cell proliferation and differentiation and stimulating osteogenic gene expression within a certain concentration range. While inducing new bone formation, they can be gradually replaced by new bone. Magnesium is a very important trace element in the human body. This element exists in large quantities in bones, dentin and enamel, and plays an important role in the formation of human bones and teeth. After adding fluoride ions, through the process of ion exchange, the hydroxyl groups of hydroxyapatite are replaced in tissues and teeth, and converted into fluoroapatite. Fluorapatite has better stability and density, and can form a harder apatite layer on the surface of teeth, thereby enhancing the acid erosion resistance of teeth.

[0004] At present, the fluoride in fluoride toothpaste that people mainly use generally includes sodium fluoride, sodium monofluorophosphate, stannous fluoride, etc. These ingredients can effectively prevent tooth decay by reducing tooth demineralization and promoting tooth remineralization, as well as inhibiting caries-causing bacteria in the mouth. The main function of sodium fluoride toothpaste is to prevent tooth decay by enhancing the acid resistance of teeth and promoting the remineralization of early caries lesions, thereby reducing the occurrence of tooth decay. However, the release of fluoride ions alone does not have good biological activity, so we need to synthesize a calcium magnesium silicate bioactive ceramic containing fluoride ions, which can not only quickly induce the formation of hydroxyapatite in a saliva environment, but also prevent tooth decay and remineralize damaged enamel. Summary of the invention

[0005] In view of the above problems, the present invention provides a method for preparing and applying a fluorine-based diopside bioactive ceramic material which can quickly induce the formation of an apatite layer in oral saliva and has good biological activity and adjustable fluoride ion concentration.

[0006] The present invention provides a method for preparing a fluorine-based diopside bioactive ceramic material, wherein diopside is doped with fluorine-containing compounds of different concentrations to obtain a fluorine-based diopside bioactive ceramic material, wherein:

[0007] The diopside is a calcium magnesium silicate with the chemical formula of CaMgSi2O6; the fluorine-containing compound is magnesium fluoride or calcium fluoride.

[0008] Furthermore, the preparation method of the fluorine-based diopside bioactive ceramic material comprises the following steps:

[0009] (1) According to the molar ratio of calcium, magnesium and silicon elements in the chemical formula CaMgSi2O6 (Ca:Mg:Si=1:1:2), weigh a compound containing calcium ions, a compound containing magnesium ions and a compound containing silicon ions, and introduce magnesium fluoride or calcium fluoride as a fluorine source for doping without changing the molar ratio of calcium, magnesium and silicon. The calcium ions and magnesium ions added due to the introduction of fluorine ions need to be subtracted from the compounds containing calcium ions and the compounds containing magnesium ions;

[0010] (2) using ethanol as a solvent and 2 mol / L hydrochloric acid as a catalyst, weighing the silicon ion-containing compound, anhydrous ethanol, deionized water, and hydrochloric acid in a molar ratio of 1:1:8:0.16, first dissolving the silicon ion-containing compound in an appropriate amount of ethanol at room temperature, adding hydrochloric acid while stirring for hydrolysis, and finally adding deionized water for dilution, stirring sufficiently to allow the compound to be fully hydrolyzed to obtain a clear sol containing silicon ions;

[0011] (3) dissolving the calcium ion-containing compound, the magnesium ion-containing compound, and the fluorine ion-containing compound in dilute hydrochloric acid, respectively, diluting with deionized water, stirring and mixing to obtain a mixed solution containing each ion, and adding the solution to the clear sol containing silicon ions obtained in step (2) to obtain a mixed solution;

[0012] (4) the mixed solution in step (3) is fully stirred at room temperature to obtain a completely dissolved sol, and after aging, it is placed in an oven to dry to obtain a xerogel;

[0013] (5) The dry gel powder obtained by ball milling and sieving the dry gel is calcined, and the fluorine-based diopside bioactive ceramic material is obtained after natural cooling.

[0014] Furthermore, the compound containing calcium ions is selected from: one of calcium chloride, calcium nitrate, calcium oxide, and calcium hydroxide; the compound containing magnesium ions is selected from: one of magnesium chloride, magnesium nitrate, magnesium oxide, and magnesium hydroxide; the compound containing silicon ions is tetraethyl orthosilicate; and the compound containing fluoride ions is selected from calcium fluoride or magnesium fluoride.

[0015] Furthermore, in step (1), the molar mass of calcium and magnesium elements increased due to the addition of the fluorine-containing compound, which needs to be subtracted from the compound containing calcium ions and the compound containing magnesium ions according to the molar mass of the introduced element, so as to always maintain the molar ratio of calcium, magnesium and silicon at 1:1:2.

[0016] Furthermore, the stirring time in step (2) is 1-2 hours.

[0017] Furthermore, in step (4), the stirring time is 3-8 hours, the aging temperature is 30-60° C., and the aging time is 24-72 hours; the drying temperature in the oven is 80-120° C., and the drying time is 48-96 hours.

[0018] Furthermore, in step (5), the ball-to-material ratio of the ball milling is 2:1, the time is 4-6 hours, and the sieve is 200 mesh.

[0019] Furthermore, the calcination in step (5) is carried out in an air atmosphere, the calcination temperature is 800-1000° C., and the calcination time is 8-12 hours.

[0020] The invention also discloses a fluorine-based diopside bioactive ceramic material prepared according to any one of the above preparation methods.

[0021] The present invention also discloses a method for adding and applying related products as a biomimetic mineralization reagent based on the research on the above-mentioned fluorine-based diopside bioactive ceramic material in hard tissue (bone, tooth) repair.

[0022] Furthermore, the application includes: after mineralizing the fluorine-based diopside bioactive ceramic material in simulated oral saliva, a hydroxyapatite layer is deposited on its surface to obtain a bioactive fluorine-doped diopside bioceramic material, which can be used in the production and preparation of enamel repair materials, tooth desensitizers and bone repair materials.

[0023] Although the commonly used calcium-magnesium-silicon-based bioactive ceramics have good biocompatibility, they are slow in the apatite induction rate and do not have the function of in-situ mineralization. In the fluorine-doped diopside bioactive ceramic material of the present invention, silicon ions have the effect of promoting cell proliferation and stimulating the gene expression of bone formation; calcium ions have the effect of promoting osteoblast differentiation; magnesium ions exist in large quantities in bones, dentin and enamel, and play an important role in the formation of human bones and teeth. 60% of the total magnesium in the human body is deposited in bones. Magnesium ions are widely present in biological fluids and are considered to be an important factor that can inhibit the spontaneous formation of hydroxyapatite precipitation. Fluorine is one of the trace elements in the human body. A certain concentration of fluoride ions can promote the deposition of hydroxyapatite and improve cell activity. Therefore, the fluorine-doped diopside bioactive ceramic provided by the present invention is a biomaterial with good biological activity and rapid induction of hydroxyapatite formation.

[0024] The beneficial effects of the present invention are:

[0025] During the preparation of the fluorine-doped diopside bioactive ceramic material of the present invention, the fluorine content can be controlled by adding fluorine-containing compounds while ensuring that the molar ratio of Ca, Mg and Si remains unchanged. At the same time, the pH value does not need to be adjusted during the reaction process. The raw material source is wide and cheap, the preparation process is simple and convenient, and there is no pollution during the preparation process, which is environmentally friendly. The prepared fluorine-based diopside bioactive ceramic material, in an environment simulating oral saliva, induces the formation of apatite at a rate greater than that of ordinary calcium-silicon-based ceramics, and at the same time shows good biocompatibility. The prepared fluorine-doped diopside bioactive ceramic can be used as an added component of a biomimetic mineralization reagent, which can effectively promote the remineralization of demineralized teeth and prevent the occurrence of dental caries. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 It is an X-ray diffraction (XRD) spectrum of the fluorine-based diopside bioactive ceramic material prepared by the present invention.

[0027] Figure 2 The figures are Fourier transform infrared spectra (FIRT) of the fluorine-based diopside bioactive ceramic material prepared by the present invention before (b) and after (a) mineralization when immersed in simulated oral saliva.

[0028] Figure 3 It is an energy dispersive X-ray spectrum (EDS) diagram of the fluorine-based diopside bioactive ceramic material prepared by the present invention.

[0029] Figure 4 The present invention is a scanning electron microscope (SEM) comparison diagram of the fluorine-based diopside bioactive ceramic material prepared by the present invention before and after being immersed in simulated oral saliva, wherein (a) is before being immersed in simulated oral saliva, and (b) is after being immersed in simulated oral saliva. DETAILED DESCRIPTION

[0030] The present invention will be further described below in conjunction with the accompanying drawings and embodiments.

[0031] Embodiment 1:

[0032] (1) 2% mol fluoride ion was used for doping, and the molar ratio of calcium, magnesium and silicon elements (Ca:Mg:Si=1:1:2) was always maintained. 11.098 g of anhydrous calcium chloride CaCl2 (analytical grade), 8.568 g of anhydrous magnesium chloride MgCl2 (analytical grade), 0.623 g of magnesium fluoride MgF2 (analytical grade), and ethyl orthosilicate C8H 20 O4Si (analytical grade) 44.66 ml.

[0033] (2) using ethanol as a solvent and 2 mol / L hydrochloric acid as a catalyst, mixing ethyl orthosilicate, anhydrous ethanol, deionized water, and hydrochloric acid in a molar ratio of 1:1:8:0.16, first dissolving ethyl orthosilicate in ethanol at room temperature, adding hydrochloric acid while stirring for hydrolysis, and finally adding deionized water for dilution, stirring for 2 hours to fully hydrolyze to obtain a clear sol containing silicon ions;

[0034] (3) Dissolve the weighed calcium chloride, magnesium chloride and magnesium fluoride in hydrochloric acid respectively, dilute with deionized water, stir thoroughly and mix to obtain a mixed solution containing each ion. Add the mixed solution of each ion into the ethyl orthosilicate solution, stir at room temperature for 6 hours to obtain a completely dissolved sol. Aging at room temperature for 48 hours, drying in an oven at 80°C for 48 hours to obtain a dry gel.

[0035] (4) The dry gel was placed in a ball mill for ball milling at a ball-to-material ratio of 2:1 for 4 hours, and then passed through a 200-mesh sieve.

[0036] (5) The sieved powder is sintered at 800° C. for 10 hours in an air atmosphere, and then naturally cooled to obtain a fluorine-based diopside bioactive ceramic material.

[0037] The fluorine-based diopside bioactive ceramic material powder sample prepared above was taken for X-ray diffraction (XRD) component analysis and energy dispersive X-ray spectroscopy (EDS) analysis, and then the sample was immersed in simulated oral saliva for 72 hours, and its mineralization effect was observed by X-ray diffraction (XRD) component analysis, Fourier transform infrared spectroscopy (FIRT) analysis, and scanning electron microscopy (SEM).

[0038] The above results are analyzed as follows:

[0039] 1. XRD result analysis Figure 1 As shown. The main diffraction peaks of the prepared fluorine-based diopside bioactive ceramic material all appear and have high crystallinity. At the same time, due to the doping of fluoride, the intensity and sharpness of the main diffraction peak at 2θ=33.5° are increased, and the crystallinity is good.

[0040] 2. Fourier transform infrared spectroscopy (FIRT) results are as follows: Figure 2 shown. Figure 2 (a) is the infrared spectrum without mineralization treatment. Figure 2 (b) is the infrared spectrum after mineralization after immersion in simulated oral saliva for 72 hours. - and 815cm - It is considered to be a Si-O bond. For the functional groups of fluorine-doped silicates, fluorine replaces part of the oxygen, at 874 cm - The stretching of Si-F bonds is shown in (b). Considering the doping amount, the number of Si-O bonds is still higher than that of Si-F bonds. Fourier transform infrared spectroscopy (FIRT) confirms that fluoride is doped by replacing oxygen. - and 1465cm - Carbonate (C03 2- ) absorption peak, the absorption peak is sharp. At 1076cm - 、964cm - and 528cm - Phosphate (PO4 3- ) peak, indicating that apatite precipitation was formed in the simulated oral saliva. - Hydroxyl groups (OH - ) peak, indicating that the formed apatite contains hydroxyapatite, and fluoride partially replaces the hydroxyl group to form fluoroapatite. The incorporation of fluoride enhances the chemical stability of apatite and inhibits its redissolution.

[0041] 3. EDS spectrum analysis Figure 3 The content of calcium, magnesium, silicon and fluorine in the spectrum proves that the fluorine-doped diopside bioactive ceramics were successfully prepared.

[0042] 4. SEM photo comparison results are as follows Figure 3 As shown. Figure (a) is a scanning electron microscope image of the fluorine-based diopside bioactive ceramic material before immersion in simulated oral saliva, and Figure (b) is a scanning electron microscope image after 72 hours of immersion in simulated oral saliva. In Figure (a), the columns are smooth and the axons are not very obvious. After immersion in simulated oral saliva (b), an apatite layer with uniform particle size, denseness and small axons is formed, indicating that the fluorine-based diopside bioactive ceramic material has a good ability to induce hydroxyapatite deposition on the surface.

[0043] Embodiment 2:

[0044] (1) 3% mol fluoride ion was used for doping, and the molar ratio of calcium, magnesium and silicon elements (Ca:Mg:Si=1:1:2) was always maintained. 5.832 g of magnesium hydroxide Mg(OH)2 (analytical grade), 6.297 g of calcium hydroxide Ca(OH)2 (analytical grade), 1.171 g of calcium fluoride CaF2 (analytical grade), and ethyl orthosilicate C8H 20 O4Si (analytical grade) 44.66 ml.

[0045] (2) using ethanol as a solvent and 2 mol / L hydrochloric acid as a catalyst, mixing tetraethyl orthosilicate, anhydrous ethanol, deionized water, and hydrochloric acid in a molar ratio of 1:1:8:0.16, first dissolving tetraethyl orthosilicate in ethanol at room temperature, adding hydrochloric acid while stirring for hydrolysis, and finally adding deionized water for dilution, stirring for 1 hour to fully hydrolyze to obtain a clear sol containing silicon ions;

[0046] (3) Dissolve the weighed calcium chloride, magnesium chloride and magnesium fluoride in hydrochloric acid respectively, dilute with deionized water, stir thoroughly and mix to obtain a mixed solution containing each ion. Add the mixed solution of each ion into the ethyl orthosilicate solution, stir at room temperature for 8 hours to obtain a completely dissolved sol. Aging at 60°C for 72 hours, drying in an oven at 120°C for 72 hours to obtain a xerogel.

[0047] (4) The dry gel was placed in a ball mill for ball milling at a ball-to-material ratio of 2:1 for 5 hours, and then passed through a 200-mesh sieve.

[0048] (5) The sieved powder is sintered at 900° C. for 12 hours in an air atmosphere, and then naturally cooled to obtain a fluorine-based diopside bioactive ceramic material.

[0049] The fluorine-based diopside bioactive ceramic material powder sample prepared above was taken for X-ray diffraction (XRD) component analysis and energy dispersive X-ray spectroscopy (EDS) analysis, and then the sample was immersed in simulated oral saliva for 7 days, and its mineralization effect was observed by X-ray diffraction (XRD) component analysis, Fourier transform infrared spectroscopy (FIRT) analysis, and scanning electron microscopy (SEM).

[0050] The main structural properties and biomineralization ability of the obtained fluorine-based diopside bioactive ceramic material are similar to those of Example 1.

Claims

1. A method for preparing a fluorine-based diopside bioactive ceramic material, comprising doping diopside with fluorine-containing compounds of different concentrations to obtain a fluorine-based diopside bioactive ceramic material, wherein: This diopside is a calcium magnesium silicate with the chemical formula of CaMgSi2O6; The fluorine-containing compound is magnesium fluoride or calcium fluoride.

2. The preparation method according to claim 1, comprising: (1) according to the molar ratio of calcium, magnesium and silicon elements corresponding to the chemical formula of diopside CaMgSi2O6, a compound containing calcium ions, a compound containing magnesium ions and a compound containing silicon ions are weighed, and at the same time, a fluorine-containing compound is introduced for doping without changing the molar ratio of calcium, magnesium and silicon; (2) using anhydrous ethanol as a solvent and 2 mol / L hydrochloric acid as a catalyst, weighing the silicon-containing ion compound, anhydrous ethanol, deionized water, and hydrochloric acid in a molar ratio of 1:1:8:0.16, first dissolving the silicon-containing ion compound in anhydrous ethanol at room temperature, adding hydrochloric acid while stirring for hydrolysis, and finally adding deionized water for dilution, stirring sufficiently to allow the compound to be fully hydrolyzed to obtain a clear sol containing silicon ions; (3) dissolving compounds containing calcium ions, magnesium ions, and fluoride ions in dilute hydrochloric acid, diluting with deionized water, stirring and mixing to obtain a mixed solution containing each ion, and adding the solution to a clear sol containing silicon ions to obtain a mixed solution; (4) After the mixed solution is fully stirred at room temperature, a completely dissolved sol is obtained, and after aging treatment, it is placed in an oven for drying to obtain a xerogel; (5) The dry gel powder obtained by ball milling and sieving the dry gel is calcined, and a fluorine-based diopside bioactive ceramic material is obtained after natural cooling.

3. The preparation method according to claim 2, wherein: The compound containing calcium ions in step (1) is selected from the group consisting of calcium chloride, calcium nitrate, calcium oxide and calcium hydroxide; The compound containing magnesium ions in step (1) is selected from the group consisting of magnesium chloride, magnesium nitrate, magnesium oxide and magnesium hydroxide; The compound containing silicon ions in step (1) is tetraethyl orthosilicate; In step (3), the compound containing fluoride ions is selected from calcium fluoride or magnesium fluoride.

4. The preparation method according to claim 2, wherein: In step (1), the molar ratio of calcium, magnesium and silicon in the diopside chemical formula CaMgSi2O6 is 1:1:

2.

5. The preparation method according to claim 2, wherein: The stirring time in step (2) is 1-2 hours.

6. The preparation method according to claim 2, wherein: The stirring time in step (4) is 3-8 hours, the aging temperature is 30-60° C., and the aging time is 24-72 hours; The oven drying temperature is 80-120° C., and the drying time is 48-96 hours.

7. The preparation method according to claim 2, wherein: In step (5), the ball-to-material ratio of the ball milling is 2:1, the ball milling time is 4 hours, and the sieve mesh number is 200 mesh; The calcination is carried out in an air atmosphere at a temperature of 800-1000° C. and a calcination time of 8-10 hours.

8. A fluorine-based diopside bioactive ceramic material prepared according to any one of the preparation methods of claims 1 to 7.

9. Use of the fluorine-based diopside bioactive ceramic material according to claim 8 in bone repair materials and tooth enamel repair materials.

10. The use according to claim 9, comprising: After the fluorine-based diopside bioactive ceramic material was mineralized in simulated oral saliva, a hydroxyapatite layer was deposited on its surface to obtain a bioactive fluorine-doped diopside bioceramic material, which can be used in oral repairs such as enamel restoration materials and tooth allergies caused by exposed dental tubules.

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