A green preparation method and application of bioactive glass

Abstract

This invention provides a green preparation method and application for bioactive glass. The preparation method of this invention does not generate nitrogen oxide gases, uses readily available calcium sources, has a simple preparation process with high raw material utilization, and produces no toxic or harmful gases during the preparation process, meeting the requirements of green chemistry. The bioactive glass prepared by this invention exhibits good bioactivity and is preferably used for bone repair, bone wound healing, and periodontal tissue repair.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to a green preparation method and application of bioactive glass. Background Technology

[0002] Bioactive glass is a type of biomaterial with excellent osteogenic, osteoconductive, and osseointegrative properties, and it is now widely used in clinical practice for bone repair, wound healing, and periodontal tissue repair. The main components of bioactive glass include SiO2, CaO, Na2O, and P2O5, and small amounts of other components such as MgO, ZnO, SrO, Fe2O3, CuO, Ag2O, and K2O can be added to modify the bioactive glass, enhancing its original functions or imparting new functions. Currently, there are two main methods for preparing bioactive glass: the melt-quench method and the sol-gel method. The melt-quench method involves adding the required raw materials to a crucible in the appropriate stoichiometric ratio and heating it above its melting point to prepare bioactive glass. Although the melt-quench method is simple to operate, it usually requires heating the materials to above 1200℃. This not only consumes a lot of energy, but also results in samples with poor bioactivity. Bioactive glasses prepared by the sol-gel method have advantages such as large specific surface area and high bioactivity, and the processing temperature is relatively low, making it a relatively ideal method for preparing bioactive glasses. Calcium compounds used in the traditional sol-gel method for preparing bioactive glasses can be divided into calcium salts and calcium alcohols. Calcium salts, represented by calcium nitrate, are currently the most widely used calcium compounds. However, to ensure good bioactivity of the sample and to allow calcium to enter the glass network, calcination is required to remove nitrate ions. This process generates a large amount of nitrogen oxide gases, which can cause significant harm to the environment and operators. Another type of calcium compound is calcium alcohol, mainly calcium methoxyethanol. Calcium methoxyethanol is obtained by reacting metallic calcium with methoxyethanol under an inert gas atmosphere. However, the prepared calcium methoxyethanol is very sensitive to water vapor in the environment and will deteriorate due to moisture absorption after prolonged exposure to air. Meanwhile, the preparation of metallic calcium is also very difficult; industrially, it is mainly obtained by electrolyzing molten calcium chloride, a process with high energy consumption. Summary of the Invention

[0003] To address the aforementioned problems, the technical solution of this invention is as follows:

[0004] A bioactive glass, wherein the composition of the bioactive glass comprises, by mole fraction:

[0005] SiO2, the molar content of which is x, where x is 30 mol.% to 80 mol.%, for example, 30 mol.%, 40 mol.%, 50 mol.%, 60 mol.%, 70 mol.%, and 80 mol.%.

[0006] CaO, whose molar content is y, where y is 15 mol.% to 40 mol.%, for example, 15 mol.%, 20 mol.%, 25 mol.%, 30 mol.%, 35 mol.%, and 40 mol.%.

[0007] P2O5, whose molar content is m, where m is 0 mol.% to 11 mol.%, for example, 0 mol.% , 1 mol.% , 2 mol.% , 3 mol.% , 4 mol.% , 5 mol.% , 6 mol.% , 7 mol.% , 8 mol.% , 9 mol.% , 10 mol.% , 11 mol.%;

[0008] Na₂O, whose molar content is n, where n ranges from 0 mol.% to 25 mol.%, for example, 0 mol.%, 5 mol.%, 10 mol.%, 15 mol.%, 20 mol.%, and 25 mol.%.

[0009] According to an embodiment of the present invention, the bioactive glass has an amorphous structure.

[0010] According to an embodiment of the present invention, in the composition of the bioactive glass, P2O5 is derived from a phosphorus-containing compound. Preferably, the phosphorus-containing compound may be selected from alkyl phosphates and / or phosphorus-containing inorganic substances. Further, the alkyl phosphate is, for example, at least one selected from trimethyl phosphate, triethyl phosphate, etc. Further, the phosphorus-containing inorganic substance is, for example, phosphoric acid, etc.

[0011] According to an embodiment of the present invention, in the composition of the bioactive glass, SiO2 is derived from a silicon-containing compound. Preferably, the silicon-containing compound may be selected from alkyl silicates and / or silicon-containing inorganic substances. Further, the alkyl silicate is, for example, at least one selected from tetramethyl silicate, tetraethyl silicate, etc. Further, the silicon-containing inorganic substance is, for example, silicic acid, etc.

[0012] According to an embodiment of the present invention, in the composition of the bioactive glass, Na₂O is derived from a sodium-containing compound, which may be selected from inorganic sodium salts, sodium hydroxide, or sodium alkoxides. Preferably, the inorganic sodium salt is at least one of sodium nitrate, sodium chloride, sodium carbonate, etc. Preferably, the sodium alkoxide is at least one of sodium methoxide, sodium ethoxide, etc.

[0013] According to an embodiment of the present invention, in the composition of the bioactive glass, the CaO is derived from a calcium source, which comprises a mixture of a polyol and a calcium compound. Preferably, the calcium compound is selected from at least one of calcium oxide and calcium hydroxide. Preferably, the polyol is selected from at least one of diols and / or triols containing 2-10 carbon atoms. Exemplarily, the diol is, for example, at least one of ethylene glycol, propylene glycol, butanediol, hexanediol, etc. Exemplarily, the triol is, for example, glycerol.

[0014] Preferably, the ratio of the calcium compound to the polyol is (1-10)g:(1-100)mL, more preferably (1-10)g:(10-100)mL, for example 3g:50mL.

[0015] Preferably, the mixture is obtained by reacting under heating conditions. Further, the reaction conditions include: a reaction temperature of 20–200°C and a reaction time of 1–96 hours.

[0016] According to an exemplary embodiment of the present invention, the bioactive glass is composed of 70 mol.% SiO2 and 30 mol.% CaO.

[0017] According to an exemplary embodiment of the present invention, the bioactive glass is composed of 54.2 mol.% SiO2, 35 mol.% CaO, and 10.8 mol.% P2O5.

[0018] According to an exemplary embodiment of the present invention, the bioactive glass is composed of 46.1 mol.% SiO2, 26.9 mol.% CaO, 2.6 mol.% P2O5, and 24.4 mol.% Na2O.

[0019] According to an embodiment of the present invention, the composition of the bioactive glass may further include a modified component, wherein the molar content of the modified component, in molar fraction, does not exceed 10 mol.%, preferably 0 mol.% to 10 mol.%, for example, 0 mol.%, 1 mol.%, 2 mol.%, 3 mol.%, 4 mol.%, 5 mol.%, 6 mol.%, 7 mol.%, 8 mol.%, 9 mol.%, and 10 mol.%.

[0020] According to an embodiment of the present invention, the modified component is selected from at least one of MgO, ZnO, SrO, Fe2O3, CuO, Ag2O, K2O, etc.

[0021] According to an exemplary embodiment of the present invention, the bioactive glass is composed of 60 mol.% SiO2, 33 mol.% CaO, 4 mol.% P2O5, and 3 mol.% MgO.

[0022] According to an exemplary embodiment of the present invention, the bioactive glass is composed of 60 mol.% SiO2, 33 mol.% CaO, 4 mol.% P2O5, and 3 mol.% MgO.

[0023] According to an embodiment of the present invention, in the bioactive glass, the modifying component is derived from a modifier. Preferably, the modifier is selected from inorganic salts, hydroxides, or alkoxides of Mg, Zn, Sr, Fe, Cu, Ag, and K. Exemplarily, the modifier is selected from at least one of magnesium chloride, potassium chloride, zinc chloride, magnesium hydroxide, potassium hydroxide, zinc hydroxide, potassium ethoxide, magnesium ethoxide, etc.

[0024] The present invention also provides a method for preparing the above-mentioned bioactive glass, the method comprising the following steps:

[0025] (S1) A calcium compound is mixed with a polyol to obtain a mixture;

[0026] (S2) Add the silicon-containing compound and at least one of the optional sodium-containing compound, phosphorus-containing compound, and modifier to the mixture obtained in step (S1) according to the above molar ratio of molar fractions, and add a certain amount of co-solvent and water under stirring to form a sol.

[0027] (S3) The sol obtained in step (S2) is allowed to stand to gel, and then the gel is aged and dried to obtain a dry gel;

[0028] (S4) The dry gel obtained in step (S3) is calcined to obtain the bioactive glass.

[0029] According to embodiments of the present invention, the calcium compound, polyol, silicon-containing compound, sodium-containing compound, phosphorus-containing compound, and modifier have the meanings described above.

[0030] According to an embodiment of the present invention, in step (S1), the ratio of the calcium compound to the polyol is (1-10)g:(1-100)mL, preferably (1-10)g:(10-100)mL, for example 3g:50mL.

[0031] According to an embodiment of the present invention, in step (S1), the mixture is obtained after reacting under heating conditions.

[0032] Preferably, the reaction can be carried out under inert gas conditions and / or closed conditions. Further, the inert gas is selected from, but is not limited to, at least one of nitrogen, helium, argon, and other inert gases.

[0033] Preferably, the reaction conditions include: a reaction temperature of 20–200°C and a reaction time of 1–96 hours.

[0034] According to an embodiment of the present invention, in step (S1), the mixture may further remove insoluble substances by filtration methods known in the art, such as centrifugation. Exemplarily, the centrifugation speed may be 100–12000 rpm, and the centrifugation time may be 1–30 minutes.

[0035] According to an embodiment of the present invention, in step (S1), the content of Ca in the mixture is 0.01-10 g / mL, preferably 0.01-0.1 g, for example 0.01 g, 0.03 g, 0.05 g, 0.08 g, or 0.1 g.

[0036] According to an embodiment of the present invention, in step (S2), the molar ratio of water, co-solvent and silicon-containing compound is 1-20:1-20:0.5-2, preferably 1-10:1-10:0.5-2, for example 4:1:1 or 4:2:1.

[0037] According to an embodiment of the present invention, the co-solvent is selected from an organic solvent miscible with water, and the organic solvent has a certain solubility for all substances in the reaction system.

[0038] Preferably, the organic solvent is selected from, but not limited to, at least one of alcohols, ethers, acetone, pyridine, acetic acid, acetonitrile, ethyl acetate, etc. Further, the alcohols are, for example, at least one of methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol, 1-octanol, 1-decanol, 2-propanol, 2-methyl-1-propanol, 2-butanol, 2-methyl-2-propanol, cyclopentanol, cyclohexanol, benzyl alcohol, etc. Further, the ethers are, for example, at least one of methyl ether, methyl ethyl ether, diethyl ether, n-propyl ether, n-butyl ether, methyl butyl ether, diethyl butyl ether, ethylene glycol monomethyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, 1,4-dioxane, ethylene oxide, 1,2-epoxypropane, 1,2-epoxybutane, cis-2,3-epoxybutane, trans-2,3-epoxybutane, etc.

[0039] According to an embodiment of the present invention, in step (S3), the aging conditions include: an aging temperature of 20 to 120°C, for example, 20°C, 30°C, 40°C, 50°C, 60°C, 70°C, 80°C, 90°C, 100°C, 110°C, or 120°C; and an aging time of 1 to 30 days, for example, 1 day, 5 days, 10 days, 15 days, 20 days, 25 days, or 30 days.

[0040] According to an embodiment of the present invention, in step (S3), the drying conditions include: a drying temperature of 60 to 250°C, for example, 60°C, 100°C, 150°C, 200°C, or 250°C; and a drying time of 1 to 30 days, for example, 1 day, 5 days, 10 days, 15 days, 20 days, 25 days, or 30 days.

[0041] According to an embodiment of the present invention, in step (S4), the calcination conditions include: a calcination temperature of 400-800°C, for example, 400°C, 500°C, 600°C, 700°C, or 800°C; and a calcination time of 1-3 hours, for example, 1 hour, 2 hours, or 3 hours.

[0042] The present invention also provides a bioactive glass prepared by the above preparation method, wherein the bioactive glass has the meaning as described above.

[0043] The present invention also provides applications of the above-mentioned bioactive glass, preferably for use in biomaterials.

[0044] The present invention also provides a class of biomaterials, the biomaterials including the above-mentioned bioactive glass.

[0045] According to an embodiment of the present invention, the biomaterial has at least one of good osteogenic properties, osteoconductive properties, and osteointegrative properties.

[0046] The present invention also provides applications of the above-mentioned bioactive glass and / or biomaterials, preferably for bone repair, bone wound healing and periodontal tissue repair.

[0047] The beneficial effects of this invention are:

[0048] 1. The raw materials used in this invention for preparing the calcium source are readily available and can be obtained by reacting common polyols (such as ethylene glycol, glycerol, etc.) with calcium compounds (such as calcium oxide, calcium hydroxide, etc.). Compared with traditional calcium nitrate (a potentially explosive hazardous chemical) and methoxyethanol calcium or ethoxycalcium (which require metallic calcium as a raw material), the raw materials are inexpensive and readily available.

[0049] 2. The calcium source used in this invention is simple to prepare; it can be obtained by mixing a polyol and a calcium compound under heating conditions, and the reaction process does not require inert gas protection. The resulting calcium compound mixture also requires no special treatment during storage. Therefore, the preparation method of this invention overcomes the problems of stringent preparation conditions and unstable raw materials associated with traditional calcium compounds (such as calcium methoxyethoxylate and calcium ethoxide), and also achieves high raw material utilization.

[0050] 3. Existing technologies often produce large amounts of nitrogen oxides (NOx) during the calcination process of preparing bioactive glass using calcium nitrate. NOx is a common air pollutant with varying degrees of toxicity. However, the calcium compound used in the preparation method of this invention does not produce NOx during calcination, resulting in less pollution to the atmosphere and surrounding environment, and less impact on the health of operators. The preparation method of this invention does not produce NOx, uses a simple and readily available calcium source at low cost, and has high raw material utilization, meeting the requirements of green chemistry.

[0051] 4. The bioactive glass prepared by this invention has good bioactivity and is preferably used for bone repair, bone wound healing and periodontal tissue repair. Attached Figure Description

[0052] Figure 1 The image shows the X-ray diffraction pattern of the bioactive glass prepared in Example 1.

[0053] Figure 2 The image shows the infrared absorption spectrum of the bioactive glass prepared in Example 1.

[0054] Figure 3 The images show a comparison of the calcium mixture prepared in Example 1 and the calcium mixture prepared in Comparative Example 1 before and after storage in an atmospheric environment for 3 days; where A and C are photos of the sample of Comparative Example 1 before and after storage, respectively; and B and D are photos of the sample of Example 1 before and after storage, respectively.

[0055] Figure 4 The X-ray diffraction patterns of the bioactive glass prepared in Example 1 after immersion in simulated body fluid for different times are shown.

[0056] Figure 5 The infrared absorption spectra of the bioactive glass prepared in Example 1 after immersion in simulated body fluid for different times are shown.

[0057] Figure 6 This is a scanning electron microscope image of the bioactive glass prepared in Example 1 after immersion in simulated body fluid for 7 days. Detailed Implementation

[0058] The technical solution of the present invention will be further described in detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanatory of the present invention, and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are covered within the scope of protection intended by the present invention.

[0059] Unless otherwise stated, the raw materials and reagents used in the following examples are commercially available products or can be prepared by known methods.

[0060] Comparative Example 1

[0061] Weigh 2g of metallic calcium and add it to 48mL of methoxyethanol. Stir at 80°C for 24h under argon protection. Centrifuge the resulting mixture at 8000rpm for 10 minutes and collect the supernatant. Place the supernatant obtained in Example 1 and the supernatant obtained in Comparative Example 1 under atmospheric conditions for 3 days.

[0062] like Figure 3 As shown, after 3 days, the supernatant obtained in Comparative Example 1 became turbid. Figure 3 Photographs A and C in Comparative Example 1, taken before and after sample placement respectively, are no longer usable; while the supernatant obtained in Example 1 remains clear and transparent. Figure 3 (Photos B and D in Example 1 are taken before and after sample placement, respectively).

[0063] Example 1

[0064] Bioactive glass was prepared from the following components: 54.2 mol.% SiO2, 35 mol.% CaO, and 10.8 mol.% P2O5. The preparation method is as follows:

[0065] (1) Weigh 3g of calcium oxide and add it to 50mL of ethylene glycol. Stir at 80℃ for 24h in a sealed environment. Centrifuge the resulting mixture at 8000rpm for 10 minutes and collect the supernatant. Quantitative analysis of the calcium content in the supernatant using a thermogravimetric analyzer showed that the Ca content in the supernatant was 2.11wt%.

[0066] (2) Weigh 9.107 mL of tetraethyl orthosilicate and 2.773 mL of triethyl phosphate, then add 50 g of the supernatant from step (1) according to the molar ratio of the components of the above bioactive glass, and add 2.938 mL of water and 4.759 mL of ethanol under vigorous stirring in a molar ratio of tetraethyl orthosilicate:water:ethanol = 1:4:2 until a gel is obtained.

[0067] (3) Place the gel obtained in step (2) in a 60°C oven and age it for 3 days. After aging, place the gel in an open container in a 60°C oven and dry it for 7 days. Then, dry it in a 120°C oven for 7 days to remove most of the solvent from the gel, and obtain a dry gel.

[0068] (4) Finally, the above-mentioned dry gel is placed in a muffle furnace and heated to 600℃ at a heating rate of 10℃ / min and held for 2 hours to obtain a bioactive glass sample. The raw material utilization rate (the mass of the obtained sample divided by the sum of the masses of all raw materials) is 6.48%. Among them, the sum of the masses of all raw materials in the raw material utilization rate includes the total mass of calcium compounds, polyols, silicon-containing compounds, sodium-containing compounds, phosphorus-containing compounds, modifiers, water, and co-solvents.

[0069] like Figure 1-2 The image shows the X-ray diffraction pattern and infrared absorption spectrum of the calcined bioactive glass sample, which shows that the bioactive glass sample remains in an amorphous state.

[0070] Comparative Example 2

[0071] This comparative example is basically the same as Example 1, except that in step (1), 3g of calcium hydroxide is added to 50mL of ethylene glycol and sonicated for 30min to disperse it fully. Then, after centrifugation at 8000rpm for 10min, the supernatant is taken. The content of calcium in the supernatant is quantitatively analyzed by thermogravimetric analyzer. It can be seen that the content of Ca in the supernatant is 0.28wt%.

[0072] Calculations show that the raw material utilization rate (the mass of the obtained sample divided by the sum of the masses of all raw materials) of the bioactive glass sample in this comparative example is 1.33%.

[0073] Comparative Example 3

[0074] The preparation method for bioactive glass is as follows:

[0075] 0.1755 g of calcium hydroxide was added to 30 mL of ethylene glycol solvent and sonicated for 30 min to ensure thorough dispersion. Then, 0.819 mL of tetraethyl orthosilicate was added to the system and stirred at room temperature for 1 h. Next, 0.249 mL of triethyl phosphate was added to the system and stirred at room temperature for 2 h. The reaction system was then transferred to a reaction vessel and reacted at 200 °C for 5 h. A white precipitate was obtained by centrifugation, washed three times each with ethanol and water, and then freeze-dried. Finally, the dried bioactive glass was sintered in a muffle furnace at 700 °C for 2 h to obtain the bioactive glass. The raw material utilization rate (the mass of the obtained sample divided by the sum of the masses of all raw materials) was 1.33%.

[0076] Application Example 1

[0077] According to YY / T 1447-2016, 60 mg of the bioactive glass sample prepared in Example 1 was immersed in 40 mL of simulated body fluid (a solution with an inorganic ion concentration similar to that in human plasma) to test the bioactivity of the bioactive glass sample in Example 1. The simulated body fluid was prepared according to the method given in the standard. After immersion for 12 hours, 1, 3, and 7 days, the bioactive glass sample was taken out, washed three times with distilled water, and then dried at 60°C for 24 hours.

[0078] like Figure 4-6 The images show the X-ray diffraction patterns, infrared absorption spectra, and scanning electron microscope images of bioactive glass samples after immersion for different times. Figure 4As can be seen, after immersion in simulated body fluid, characteristic peaks corresponding to hydroxyapatite appeared at positions 26° and 32° in the X-ray diffraction pattern of the sample, indicating that the sample has good biological activity. Figure 5 It can be seen from 607cm -1 and 567cm -1 A double-shoulder absorption peak of crystalline orthophosphate appeared at the location; from Figure 6 The presence of typical needle-like aggregates of hydroxyapatite on the sample surface is evident. This indicates that hydroxyapatite was generated after the sample was immersed in simulated body fluid, thus demonstrating the sample's good biological activity.

[0079] Example 2

[0080] Bioactive glass was prepared from the following components: 54.2 mol.% SiO2, 35 mol.% CaO, and 10.8 mol.% P2O5. The preparation method is as follows:

[0081] (1) Add 3g of calcium hydroxide to a round-bottom flask containing 50mL of ethylene glycol and stir at 80℃ for 24h. Centrifuge the resulting mixture at 8000rpm for 10 minutes and collect the supernatant. Quantitative analysis of the calcium content in the solution using a thermogravimetric analyzer showed that the Ca content in the supernatant was 1.81wt%.

[0082] (2) Weigh 7.809 mL of tetraethyl orthosilicate and 2.377 mL of triethyl phosphate, then add 50 g of the supernatant from step (1) according to the molar ratio of the components of the above bioactive glass, and add 2.519 mL of water and 4.080 mL of ethanol under vigorous stirring in a molar ratio of tetraethyl orthosilicate:water:ethanol = 1:4:2 until a gel is obtained.

[0083] (3) Place the gel obtained in step (2) in a 60°C oven and age it for 3 days. After aging, place the gel in an open container in a 60°C oven and dry it for 7 days. Then, dry it in a 120°C oven for 7 days to remove most of the solvent from the gel, and obtain a dry gel.

[0084] (4) Finally, the above-mentioned dry gel was placed in a muffle furnace and heated to 600℃ at a heating rate of 10℃ / min and held at that temperature for 2 hours to obtain the bioactive glass sample. The raw material utilization rate (the mass of the obtained sample divided by the sum of the masses of all raw materials) was 5.91%.

[0085] Example 3

[0086] Bioactive glass was prepared from the following components: 54.2 mol.% SiO2, 35 mol.% CaO, and 10.8 mol.% P2O5. The preparation method is as follows:

[0087] (1) Add 3g of calcium oxide to a round-bottom flask containing 50mL of glycerol and stir at 80℃ for 24h. Centrifuge the resulting mixture at 8000rpm for 10 minutes and collect the supernatant. Quantitative analysis of the calcium content in the solution using a thermogravimetric analyzer showed that the Ca content in the supernatant was 2.11wt%.

[0088] (2) Measure 9.107 mL of tetraethyl orthosilicate and 2.773 mL of triethyl phosphate, and then add 50 g of the supernatant from step (1) according to the molar ratio of the components of the above bioactive glass. Under vigorous stirring, add 2.938 mL of water and 4.759 mL of ethanol in a molar ratio of tetraethyl orthosilicate:water:ethanol = 1:4:2 until a gel is obtained.

[0089] (3) Place the gel obtained in step (2) in a 60°C oven and age it for 3 days. After aging, place the gel in an open container in a 60°C oven and dry it for 7 days. Then, dry it in a 120°C oven for 7 days to remove most of the solvent from the gel, and obtain a dry gel.

[0090] (4) Finally, the above-mentioned dry gel was placed in a muffle furnace and heated to 600℃ at a heating rate of 10℃ / min and held at that temperature for 2 hours to obtain the bioactive glass sample. The raw material utilization rate (the mass of the obtained sample divided by the sum of the masses of all raw materials) was 6.48%.

[0091] The bioactive glass samples obtained in Examples 2-3 are basically the same as those in Example 1.

[0092] Example 4

[0093] Bioactive glass was prepared from 70 mol% SiO2 and 30 mol% CaO. The preparation method is as follows:

[0094] (1) Add 3g of calcium oxide to a round-bottom flask containing 50mL of ethylene glycol and stir at 80℃ for 24h. Centrifuge the resulting mixture at 8000rpm for 10 minutes and collect the supernatant. Quantitative analysis of the calcium content in the solution using a thermogravimetric analyzer showed that the Ca content in the supernatant was 2.11wt%.

[0095] (2) Measure 13.723 mL of tetraethyl orthosilicate, and then add 50 g of the supernatant from step (1) according to the molar ratio of the components of the above bioactive glass. Under vigorous stirring, add 4.426 mL of water and 7.170 mL of ethanol in a molar ratio of tetraethyl orthosilicate:water:ethanol = 1:4:2 until a gel is obtained.

[0096] (3) Place the gel obtained in step (2) in a 60°C oven and age it for 3 days. After aging, place the gel in an open container in a 60°C oven and dry it for 7 days. Then, dry it in a 120°C oven for 7 days to remove most of the solvent from the gel, and obtain a dry gel.

[0097] (4) Finally, the above-mentioned dry gel was placed in a muffle furnace and heated to 600℃ at a heating rate of 10℃ / min and held at that temperature for 2 hours to obtain the bioactive glass sample. The raw material utilization rate (the mass of the obtained sample divided by the sum of the masses of all raw materials) was 6.38%.

[0098] Application Example 2

[0099] The bioactive glass sample prepared in Example 4 was used to test the bioactivity of the bioactive glass sample in Example 4, referring to Application Example 1.

[0100] After immersion in simulated body fluid for 7 days, the sample prepared in Example 4 was basically the same as the sample in Example 1, with hydroxyapatite forming on its surface, indicating that the sample had good biological activity.

[0101] Example 5

[0102] Bioactive glass was prepared from the following components: 60 mol.% SiO2, 36 mol.% CaO, and 4 mol.% P2O5. The preparation method is as follows:

[0103] (1) Weigh 3g of calcium oxide and add it to a round-bottom flask containing 50mL of ethylene glycol. Stir at 80℃ for 24h. Centrifuge the resulting mixture at 8000rpm for 10 minutes and collect the supernatant. Quantitative analysis of the calcium content in the solution using a thermogravimetric analyzer showed that the Ca content in the supernatant was 2.11wt%.

[0104] (2) Measure 9.802 mL of tetraethyl orthosilicate and 0.998 mL of triethyl phosphate, and then add 50 g of the supernatant from step (1) according to the molar ratio of the components of the above bioactive glass. Under vigorous stirring, add 3.162 mL of water and 5.122 mL of ethanol in a molar ratio of tetraethyl orthosilicate:water:ethanol = 1:4:2 until a gel is obtained.

[0105] (3) Place the gel obtained in step (2) in a 60°C oven and age it for 3 days. After aging, place the gel in an open container in a 60°C oven and dry it for 7 days. Then, dry it in a 120°C oven for 7 days to remove most of the solvent from the gel, and obtain a dry gel.

[0106] (4) Finally, the above-mentioned dry gel was placed in a muffle furnace and heated to 600℃ at a heating rate of 10℃ / min and held at that temperature for 2 hours to obtain the bioactive glass sample. The raw material utilization rate (the mass of the obtained sample divided by the sum of the masses of all raw materials) was 5.99%.

[0107] Example 6

[0108] Bioactive glass was prepared from the following components: 46.1 mol.% SiO2, 26.9 mol.% CaO, 2.6 mol.% P2O5, and 24.4 mol.% Na2O. The preparation method is as follows:

[0109] (1) Weigh 3g of calcium oxide and add it to a round-bottom flask containing 50mL of ethylene glycol. Stir at 80℃ for 24h. Centrifuge the resulting mixture at 8000rpm for 10 minutes and collect the supernatant. Quantitative analysis of the calcium content in the solution using a thermogravimetric analyzer showed that the Ca content in the supernatant was 2.11wt%.

[0110] (2) Measure 10.079 mL of tetraethyl orthosilicate, 0.868 mL of triethyl phosphate, and 1.907 g of sodium hydroxide. Then add 50 g of the supernatant from step (1) according to the molar ratio of the components of the bioactive glass. Under vigorous stirring, add 3.251 mL of water and 5.266 mL of ethanol in a molar ratio of tetraethyl orthosilicate:water:ethanol = 1:4:2 until a gel is obtained.

[0111] (3) Place the gel obtained in step (2) in a 60°C oven and age it for 3 days. After aging, place the gel in an open container in a 60°C oven and dry it for 7 days. Then, dry it in a 120°C oven for 7 days to remove most of the solvent from the gel, and obtain a dry gel.

[0112] (4) Finally, the above-mentioned dry gel was placed in a muffle furnace and heated to 600℃ at a heating rate of 10℃ / min and held for 2 hours to obtain the bioactive glass sample. The raw material utilization rate (the mass of the obtained sample divided by the sum of the masses of all raw materials) was 7.75%.

[0113] Application Example 3

[0114] The bioactive glass sample prepared in Example 6 was used to test the bioactivity of the bioactive glass sample in Example 6, referring to Application Example 1.

[0115] After immersion in simulated body fluid for 7 days, the sample prepared in Example 6 was basically the same as the sample in Example 1. Hydroxyapatite was generated on the surface of the sample, indicating that the sample had good biological activity.

[0116] Example 7

[0117] Bioactive glass was prepared from the following components: 60 mol.% SiO2, 33 mol.% CaO, 4 mol.% P2O5, and 3 mol.% MgO. The preparation method is as follows:

[0118] (1) Weigh 3g of calcium oxide and add it to a round-bottom flask containing 50mL of ethylene glycol. Stir at 80℃ for 24h. Centrifuge the resulting mixture at 8000rpm for 10 minutes and collect the supernatant. Quantitative analysis of the calcium content in the solution using a thermogravimetric analyzer showed that the Ca content in the supernatant was 2.11wt%.

[0119] (2) Measure 10.693 mL of tetraethyl orthosilicate, 1.089 mL of triethyl phosphate, and 0.139 g of magnesium hydroxide. Then add 50 g of the supernatant from step (1) according to the molar ratio of the components of the above bioactive glass. Under vigorous stirring, add 3.449 mL of water and 5.587 mL of ethanol in a molar ratio of tetraethyl orthosilicate:water:ethanol = 1:4:2 until a gel is obtained.

[0120] (3) Place the gel obtained in step (2) in a 60°C oven and age it for 3 days. After aging, place the gel in an open container in a 60°C oven and dry it for 7 days. Then, dry it in a 120°C oven for 7 days to remove most of the solvent from the gel, and obtain a dry gel.

[0121] (4) Finally, the above-mentioned dry gel was placed in a muffle furnace and heated to 600℃ at a heating rate of 10℃ / min and held at that temperature for 2 hours to obtain the bioactive glass sample. The raw material utilization rate (the mass of the obtained sample divided by the sum of the masses of all raw materials) was 6.35%.

[0122] Application Example 4

[0123] The bioactive glass sample prepared in Example 7 was used to test the bioactivity of the bioactive glass sample in Example 7, referring to Application Example 1.

[0124] After immersion in simulated body fluid for 7 days, the sample prepared in Example 7 was basically the same as the sample in Example 1. Hydroxyapatite was generated on the surface of the sample, indicating that the sample had good biological activity.

[0125] Example 8

[0126] Bioactive glass was prepared from the following components: 60 mol.% SiO2, 33 mol.% CaO, 4 mol.% P2O5, and 3 mol.% ZnO. The preparation method is as follows:

[0127] (1) Weigh 3g of calcium oxide and add it to a round-bottom flask containing 50mL of ethylene glycol. Stir at 80℃ for 24h. Centrifuge the resulting mixture at 8000rpm for 10 minutes and collect the supernatant. Quantitative analysis of the calcium content in the solution using a thermogravimetric analyzer showed that the Ca content in the supernatant was 2.11wt%.

[0128] (2) Measure 10.693 mL of tetraethyl orthosilicate, 1.089 mL of triethyl phosphate, and 0.238 g of zinc hydroxide. Then add 50 g of the supernatant from step (1) according to the molar ratio of the components of the above bioactive glass. Under vigorous stirring, add 7.31 mL of water and 16.93 mL of ethanol in a molar ratio of tetraethyl orthosilicate:water:ethanol = 1:4:2 until a gel is obtained.

[0129] (3) Place the obtained gel in a 60℃ oven for 3 days to keep it warm. Place the aged gel in an open 60℃ oven for 7 days to dry, and then in a 120℃ oven for 7 days to remove most of the solvent in the gel, to obtain a dry gel.

[0130] (4) Finally, the above-mentioned dry gel was placed in a muffle furnace and heated to 600℃ at a heating rate of 10℃ / min and held for 2 hours to obtain the bioactive glass sample. The raw material utilization rate (the mass of the obtained sample divided by the sum of the masses of all raw materials) was 6.50%.

[0131] Application Example 5

[0132] The bioactive glass sample prepared in Example 8 was used to test the bioactivity of the bioactive glass sample in Example 8, referring to Application Example 1.

[0133] After immersion in simulated body fluid for 7 days, the sample prepared in Example 8 was basically the same as the sample in Example 1. Hydroxyapatite was generated on the surface of the sample, indicating that the sample had good biological activity.

[0134] The exemplary embodiments of the present invention have been described above. However, the scope of protection of this application is not limited to the above embodiments. Any modifications, equivalent substitutions, improvements, etc., made by those skilled in the art within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method of making a bioactive glass, characterized by, The preparation method includes the following steps: (S1) A mixture is obtained by reacting a calcium compound with a polyol under heating conditions. The calcium compound is selected from at least one of calcium oxide and calcium hydroxide. The ratio of the calcium compound to the polyol is 1-10 g: 1-100 mL. When the polyol is hexanediol or glycerol, the reaction temperature is 80-200°C and the reaction time is 24-96 hours. Alternatively, when the polyol is at least one of ethylene glycol, propylene glycol, and butanediol, the reaction temperature is 80°C and the reaction time is 24-96 hours. (S2) At least one of the following: a silicon-containing compound, a sodium-containing compound, a phosphorus-containing compound, and a modifier, is added to the mixture obtained in step (S1) according to the molar ratio of the components of the bioactive glass. Under stirring, a certain amount of co-solvent and water are added to form a sol. The molar ratio of water, co-solvent, and silicon-containing compound is 1~20:1~20:0.5~2. The co-solvent is selected from organic solvents miscible with water. The organic solvent is selected from at least one of alcohols, ethers, acetone, pyridine, acetic acid, acetonitrile, and ethyl acetate. (S3) The sol obtained in step (S2) is allowed to stand to gel, and then the gel is aged and dried to obtain a dry gel; The aging conditions include: an aging temperature of 20~120℃; and an aging time of 1~10 days. (S4) The dry gel obtained in step (S3) is calcined to obtain the bioactive glass; the calcination conditions include: calcination temperature of 400~800 ℃; calcination time of 1~3 hours.

2. The production method according to claim 1, characterized by, In step (S1), the reaction is carried out under inert gas conditions and / or closed conditions; the inert gas is selected from at least one of nitrogen, helium, and argon. In step (S1), the Ca content in the mixture is 0.01-10 g / mL.

3. The preparation method according to claim 1, characterized in that, In step (S1), the Ca content in the mixture is 0.01-0.1 g / mL.

4. The preparation method according to claim 1, characterized in that, The phosphorus-containing compound is selected from alkyl phosphates and / or phosphorus-containing inorganic substances; the alkyl phosphate is at least one of trimethyl phosphate and triethyl phosphate; The silicon-containing compound is selected from alkyl silicate esters and / or silicon-containing inorganic substances; the alkyl silicate ester is at least one of tetramethyl silicate and tetraethyl silicate; The sodium-containing compound is selected from inorganic sodium salts, sodium hydroxide, or sodium alkoxides; the inorganic sodium salt is at least one of sodium nitrate, sodium chloride, and sodium carbonate; the sodium alkoxide is at least one of sodium methoxide and sodium ethoxide. The modifier is selected from inorganic salts, hydroxides, or alkoxides of Mg, Zn, Sr, Fe, Cu, Ag, and K.

5. The preparation method according to claim 1, characterized in that, The modifier is selected from at least one of magnesium chloride, potassium chloride, zinc chloride, magnesium hydroxide, potassium hydroxide, zinc hydroxide, potassium ethoxide, and magnesium ethoxide.

6. The preparation method according to claim 1, characterized in that, In step (S3), the drying conditions include: a drying temperature of 60~250 ℃; and a drying time of 1~30 days.

7. A bioactive glass, characterized in that, The bioactive glass is prepared by the preparation method according to any one of claims 1-5.

8. The bioactive glass according to claim 7, characterized in that, The bioactive glass comprises, by mole fraction: SiO2, with a molar content of x, where x ranges from 30 mol.% to 80 mol.%. CaO, with a molar content of y, where y is 15 mol.%~40 mol.%; P2O5, with a molar content of m, where m ranges from 0 mol.% to 11 mol.%. Na₂O, with a molar content of n, where n ranges from 0 mol.% to 25 mol.%.

9. The bioactive glass according to claim 7, characterized in that, The bioactive glass has an amorphous, non-crystalline structure. In the composition of the bioactive glass, P2O5 is derived from phosphorus-containing compounds; SiO2 is derived from the silicon-containing compound; Na2O is derived from the sodium-containing compound; CaO is derived from a calcium source, which includes a mixture of the polyol and a calcium compound; the mixture is obtained by reacting under heating conditions; when the polyol is hexanediol or glycerol, the reaction temperature is 80~200℃ and the reaction time is 24~96 hours; or, when the polyol is at least one of ethylene glycol, propylene glycol, and butanediol, the reaction temperature is 80℃ and the reaction time is 24~96 hours.

10. The bioactive glass according to claim 7, characterized in that, The bioactive glass also includes a modifying component, the molar content of which does not exceed 10 mol.%. The modifying component is selected from at least one of MgO, ZnO, SrO, Fe2O3, CuO, Ag2O, and K2O; In the bioactive glass, the modifying component is derived from the modifier.

11. A biomaterial comprising the bioactive glass according to any one of claims 7-10.

12. The biomaterial according to claim 11, characterized in that, The biomaterial possesses at least one of the following properties: good osteogenic properties, osteoconductive properties, and osteointegrative properties.

13. The application of the bioactive glass according to any one of claims 7-10 and / or the biomaterial according to claim 11 or 12.

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