Synthesis formula and large-scale production method of pH-value-adjustable bioactive glass nanoparticles

Abstract

The invention discloses a pH-value-adjustable bioactive glass nanoparticle and a large-scale production method thereof.The pH-value-adjustable bioactive glass nanoparticle is prepared from a silicon source, a calcium source, alkali, a pH value regulator and a solvent, the dosage of the silicon source is 20%-60% of the total reactant mass, the dosage of the calcium source is 2%-10% of the total reactant mass, the dosage of the alkali is 1%-6% of the total reactant mass, the dosage of the pH value regulator is 1%-6% of the total reactant mass, and the dosage of the solvent is 1%-5% of the total reactant mass. The dosage of the pH regulator is 1%-5% of the total reactant mass, and the dosage of the solvent is 35%-65% of the total reactant mass. The specific production method comprises the following steps: (1) respectively preparing a solution A containing a calcium source, a silicon source and a pH regulator and a solution B containing alkali; (2) realizing rapid mixing of double solutions through a hedging mixer, and reacting at 20-60 DEG C to generate particles with the particle size of 80-300nm; and (3) washing and separating to obtain a final product. The material is suitable for the fields of dentistry and bone repair, and has the characteristic of accurate pH regulation and control.

Description

TECHNICAL FIELD

[0001] The present application relates to the preparation technology of bioactive glass materials, in particular to a synthesis formula of bioactive glass nanoparticles with adjustable pH value and a large-scale production method thereof. BACKGROUND

[0002] Bioactive glass particles have a wide application prospect in the medical field of dental repair and bone tissue regeneration due to their good biocompatibility, biodegradability, and excellent bone conduction and bone induction performance. The material is often used to be compounded with other biomedical materials to prepare bone cement, tissue engineering scaffold, dental repair material, and tooth desensitizer, etc. In recent years, bioactive glass nanoparticles have attracted more and more attention due to their higher specific surface area, more excellent bioactivity and faster degradation rate. Controlling the particle size at the nanoscale not only helps to improve the dispersibility and bioactivity of the material, but also reduces the stimulation to the tissue, which is one of the key technologies to optimize the performance of the material. However, there are still two technical bottlenecks in the preparation process of bioactive glass nanoparticles at present: first, most of the existing preparation methods are difficult to realize the large-scale production of nanoparticles. Although the traditional mechanical grinding method can reduce the particle size to a certain extent, it often relies on expensive equipment, has a complex process and has the risk of particle contamination, and the commonly used solution synthesis method is difficult to meet the industrialization demand due to low reactant concentration, low yield and high cost; second, bioactive glass is prone to calcium ion burst in the body fluid environment, which leads to rapid increase of local pH value. This alkaline environment not only inhibits cell proliferation, but also may cause aseptic inflammation, affecting the clinical application effect of the material. Therefore, how to effectively control the ion release behavior of bioactive glass in the body fluid and thus control its influence on the environmental pH value is another key problem of the current research. In order to solve the above problems, the present application provides a method for realizing large-scale preparation of bioactive glass nanoparticles by adjusting the proportion of reactants to control the pH value. The reaction liquid opposed mixer with a specific structure is used in the method to quickly synthesize bioactive glass particles with nanoscale particle size under high concentration reaction conditions, which has high efficiency, low cost and good environmental adaptability. The particles prepared by the method of the present application not only have controllable particle size and a yield of kilograms, but also have a stable pH value of 6-9 in the aqueous solution under normal concentration, which effectively avoids the adverse effects of pH mutation on the tissue environment. SUMMARY

[0003] In order to solve the problems in the prior art, the first object of the present application is to provide a formula of bioactive nanoglass particles with adjustable pH value, and the second object of the present application is to provide a method for rapidly and large-scale producing the bioactive nanoglass particles, wherein the bioactive nanoglass particles prepared have a particle size of 80-500 nm, and the pH value of the aqueous solution of the bioactive nanoglass particles is 6-9.

[0004] In order to achieve the above-mentioned application, the technical method adopted by the present application is as follows:

[0005] The bioactive nanoglass particles with adjustable pH value comprise a synthetic formula containing a silicon source, a calcium source, an alkali, a pH value regulator and a solvent.

[0006] Preferably, the silicon source is any one or several of tetraethyl orthosilicate, silicon tetraacetate, sodium silicate and potassium silicate, and the amount is 20%-60% of the total mass of the reaction substances in the synthetic formula.

[0007] Preferably, the calcium source is any one of calcium nitrate and calcium chloride, and the amount is 2%-10% of the total mass of the reaction substances in the synthetic formula.

[0008] Preferably, the alkali is any one or several of sodium hydroxide, potassium hydroxide, calcium hydroxide and ammonia water, and the amount is 1%-6% of the total mass of the reaction substances in the synthetic formula.

[0009] Preferably, the pH value regulator is one or several of sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium hydrogen phosphate, potassium dihydrogen phosphate, ammonium phosphate, potassium phosphate and sodium phosphate, and the amount is 1%-5% of the total mass of the reaction substances in the synthetic formula.

[0010] Preferably, the solvent is one or several of deionized water, distilled water, ethanol, methanol, n-propanol and isopropanol, and the amount is 35%-65% of the total mass of the reaction substances in the synthetic formula.

[0011] The present application also provides a method for rapidly and large-scale producing the bioactive nanoglass particles by using a reaction liquid opposed mixer for rapid mixing, which specifically comprises the following steps:

[0012] (1) uniformly mixing the silicon source, the calcium source, the pH value regulator and the solvent according to the specific mass ratio, specifically, first, pouring the calcium source and the solvent into a container or beaker for uniform stirring and mixing, then adding the silicon source for stirring and mixing, after uniform mixing, finally adding the pH value regulator, stirring for a period of time, and observing to determine that the above reagents are completely and uniformly mixed to form a reaction liquid A;

[0013] (2) the base and the solvent are uniformly mixed according to a specific mass ratio, and the specific operation is as follows: first, the solvent is poured into a beaker and stirring is started, then the base is quickly added to the container or beaker and stirring is performed, the stirring process is sealed, and it is observed that the above reagents are completely mixed and uniformly formed into a reaction liquid B;

[0014] (3) the reaction liquid A and B are filled into a large syringe, then injected into a reaction liquid collision mixer to ensure that the reaction liquid is quickly mixed, then a container or beaker is used to collect the reaction mixture of the reaction liquid A and B, and the reaction is continued under the condition of quick stirring at a temperature of 20-60°C;

[0015] (4) the reaction mixture of the reaction liquid A and B is stirred and mixed, stirring is stopped and the lower sediment in the reaction mixture is obtained, the sediment is washed several times with deionized water, and the bioactive glass nanoparticles are obtained by free sedimentation or centrifugation or filtration separation.

[0016] Further, the reaction liquid collision mixer controls the outlet flow rate of the reaction mixture to be 1.0-10.0 L / min.

[0017] Further, the reaction mixture of the reaction liquid A and B is continuously stirred for about 1 hour after falling into the container or beaker.

[0018] Further, the particle size of the bioactive glass nanoparticles produced by the scale production of the collision quick mixing method is 80-500 nm.

[0019] The beneficial effects of the present application are as follows:

[0020] (1) The bioactive glass nanoparticles of the present application have low cost and are easy to purchase because each component in the synthesis formula is relatively common in the actual market.

[0021] (2) The bioactive glass nanoparticles of the present application can be dissolved in an aqueous solution, and the pH value of the dissolved aqueous solution can be stably controlled between 6 and 9, effectively avoiding the adverse effects of pH mutation on the tissue environment, promoting cell proliferation in dental and bone repair problems, and avoiding the occurrence of aseptic inflammation and affecting the clinical application effect of the material.

[0022] (3) The reaction liquid collision mixer used in the scale production process of the bioactive glass nanoparticles of the present application can effectively reduce the instrument and time cost in the production process, and can stably produce 80-500 nm particle size bioactive glass nanoparticles with a kilogram-level output. The bioactive glass with a particle size controlled at the nanometer level has a high specific surface area, which not only helps to improve the dispersibility and bioactivity of the material, but also reduces the stimulation to the tissue. BRIEF DESCRIPTION OF DRAWINGS

[0023] Figure 1 It is a structure diagram of the reaction liquid mixer of the application, which is a sectional view of the structure of the reaction liquid mixer, and only describes the basic structure and principle of the real device.

[0024] Figure 2 It is a morphology and particle size diagram of the bioactive glass nanoparticles of the application, wherein: Figure 2 (1) is a scanning electron microscope diagram of bioactive glass nanoparticles with a particle size of 100 nanometers; Figure 2 (2) is a scanning electron microscope diagram of bioactive glass nanoparticles with a particle size of 100 nanometers; Figure 2 (3) is a scanning electron microscope diagram of bioactive glass nanoparticles with a particle size of 80 nanometers; Figure 2

[0025] (4) is a scanning electron microscope diagram of bioactive glass nanoparticles with a particle size of 200 nanometers; Figure 2 (5) is a scanning electron microscope diagram of bioactive glass nanoparticles with a particle size of 90 nanometers; Figure 2 (6) is a scanning electron microscope diagram of bioactive glass nanoparticles with a particle size of 80 nanometers; Figure 2 (7) is a scanning electron microscope diagram of bioactive glass nanoparticles with a particle size of 200 nanometers. DETAILED DESCRIPTION

[0026] In order to illustrate the content of the application in detail, the technical solutions of the application are described in the following embodiments combined with the drawings of the specification, which will help the person skilled in the art to further understand the application, but do not limit the application in any form. It should be pointed out that the embodiments are preferred solutions of the application, which are intended to illustrate the implementation conditions that can be used to realize the application, rather than to limit the experimental conditions.

[0027] I. A production formula of bioactive glass nanoparticles with adjustable pH value:

[0028] The application provides a bioactive glass nanoparticle with adjustable pH value, and a synthesis formula of the bioactive glass nanoparticle comprises a silicon source, a calcium source, an alkali, a pH value regulator and a solvent, wherein the amount of the silicon source is 20% to 60% of the total reactant mass, the amount of the calcium source is 2% to 10% of the total reactant mass, the amount of the alkali is 1% to 6% of the total reactant mass, the amount of the pH value regulator is 1% to 5% of the total reactant mass, and the amount of the solvent is 35% to 65% of the total reactant mass.

[0029] II. A large-scale production method of bioactive glass nanoparticles:

[0030] The application adopts a reaction liquid opposite-mixing device for large-scale production of bioactive glass nanoparticles, and the main operation process is as follows: reaction liquid A and reaction liquid B are pressed into independent channels by high pressure; a plurality of parallel microchannels are distributed in the channels, and high-pressure reaction liquid forms a small-diameter high-speed jet after flowing through the microchannels; the high-speed jets of the reaction liquid A and the reaction liquid B are mixed oppositely, the reaction mixture flows out of the mixing device, and a container or a beaker is used to collect the mixed liquid, which is continuously stirred for about 1 hour at a temperature of 20-60 ℃.

[0031] Example 1

[0032] 1. General reaction for large-scale production of bioactive glass nanoparticles with adjustable pH value:

[0033] Silicon source: silicon tetracarboxylate, amounting to 40% of the total reaction mass;

[0034] Calcium source: calcium chloride, amounting to 10% of the total reaction mass;

[0035] Base: sodium hydroxide, amounting to 1% of the total reaction mass;

[0036] pH regulator: sodium dihydrogen phosphate, amounting to 5% of the total reaction mass;

[0037] Solvent: deionized water, amounting to 14%, and anhydrous ethanol, amounting to 30% of the total reaction mass.

[0038] 2. Specific method for large-scale production of bioactive glass nanoparticles with adjustable pH value: (1) first pour 10% of the total reaction mass of calcium chloride into a beaker, add 4% of the total reaction mass of deionized water and 4% of the total reaction mass of anhydrous ethanol as solvents for stirring, wait for the calcium chloride to completely dissolve, then add 40% of the total reaction mass of silicon tetracarboxylate, continue stirring, and observe the complete mixing of the reagents, then add 5% of the total reaction mass of sodium dihydrogen phosphate, wait for the reagents to completely dissolve and mix, and mark as liquid A; (2) pour 10% of the total reaction mass of deionized water and 26% of the total reaction mass of anhydrous ethanol into another beaker, then pour 1% of the total reaction mass of sodium hydroxide, seal and stir, wait for the reagents to completely mix, and mark as liquid B; (3) quickly mix the reaction liquid A and the reaction liquid B through a reaction liquid opposite-mixing device, collect the mixed liquid using a container or a beaker after the reaction mixture flows out of the mixing device, continuously stir the mixed liquid, the stirring temperature is 40 ℃, and the stirring time is about 1 hour; finally, bioactive glass nanoparticles with a particle size of 100 nanometers are obtained, the pH value is measured to be 8.6 by using a pH value measurement method, and the bioactive glass nanoparticles are as shown in Figure 2 (1).

[0039] Example 2

[0040] 1. General reaction for large-scale production of bioactive glass nanoparticles with adjustable pH value:

[0041] Silicon source: tetraethyl orthosilicate, amounting to 60% of the total reaction mass;

[0042] Calcium source: calcium nitrate, amounting to 6% of the total reaction mass;

[0043] Base: potassium hydroxide, amounting to 3% of the total reaction mass;

[0044] pH regulator: ammonium phosphate, amounting to 2% of the total reaction mass;

[0045] Solvent: deionized water, amounting to 10% of the total reaction mass, and anhydrous ethanol, amounting to 19% of the total reaction mass.

[0046] 2. Specific method for large-scale production of bioactive glass nanoparticles with adjustable pH value: (1) First, pour 6% of the total reaction mass of calcium nitrate into a beaker, add 2% of the total reaction mass of deionized water and 2% of the total reaction mass of anhydrous ethanol as solvent for stirring, wait until the calcium nitrate is completely dissolved, then add 60% of the total reaction mass of tetraethyl orthosilicate, continue stirring, and after observing that the reagents are completely mixed, add 2% of the total reaction mass of ammonium phosphate, wait until the reagents are completely dissolved and mixed, and mark it as liquid A; (2) Pour 8% of the total reaction mass of deionized water and 17% of the total reaction mass of anhydrous ethanol into another beaker, then pour 3% of the total reaction mass of potassium hydroxide, seal and stir, and after waiting until the reagents are completely mixed, mark it as liquid B; (3) Mix the two liquids of reaction liquid A and reaction liquid B quickly through a reaction liquid counterflow mixer, collect the mixed liquid with a beaker after it flows out of the mixer, continue to stir the mixed liquid, and the stirring temperature is 50°C and the stirring time is about 1 hour; finally, obtain bioactive glass nanoparticles with a particle size of 100 nanometers, and the pH value is 7.2, which is measured by a pH value measurement method, and the bioactive glass nanoparticles are as shown in Figure 2 (2).

[0047] Example 3

[0048] 1. General reaction for large-scale production of bioactive glass nanoparticles with adjustable pH value:

[0049] Silicon source: mixture of tetraethyl orthosilicate and potassium silicate, amounting to 20% and 20% of the total reaction mass, respectively;

[0050] Calcium source: calcium chloride, amounting to 2% of the total reaction mass;

[0051] Base: sodium hydroxide, amounting to 2% of the total reaction mass;

[0052] pH regulator: ammonium phosphate, amounting to 4% of the total reactant mass;

[0053] Solvent: deionized water, amounting to 20% of the total reactant mass, and anhydrous ethanol, amounting to 32% of the total reactant mass.

[0054] 2. A specific method for large-scale production of pH-adjustable bioactive glass nanoparticles: (1) First, pour calcium chloride accounting for 2% of the total reactant mass into a beaker, add deionized water accounting for 6% of the total reactant mass and anhydrous ethanol accounting for 10% of the total reactant mass as a solvent for stirring. After waiting for the calcium chloride to completely dissolve, add tetraethyl orthosilicate accounting for 20% of the total reactant mass and potassium silicate accounting for 20% of the total reactant mass, continue stirring, and after observing that the reagents are completely mixed, add ammonium phosphate accounting for 4% of the total reactant mass. After waiting for the reagents to completely dissolve and mix, mark it as A liquid; (2) Pour deionized water accounting for 14% of the total reactant mass and anhydrous ethanol accounting for 22% of the total reactant mass into another beaker, then pour sodium hydroxide accounting for 2% of the total reactant mass, seal and stir, and after waiting for the reagents to completely mix, mark it as B liquid; (3) Mix the reaction liquid A and the reaction liquid B through a reaction liquid opposite mixing device, use a beaker to collect the mixed liquid after the mixed liquid flows out of the mixer, continue to stir the mixed liquid, and the stirring temperature is 30°C and the stirring time is about 1 hour; finally, the bioactive glass nanoparticles with a particle size of 80 nanometers are obtained, and the pH value is measured to be 6.2. The bioactive glass nanoparticles are as shown in Figure 2 (3).

[0055] Example 4

[0056] 1. The total reactant for large-scale production of pH-adjustable bioactive glass nanoparticles:

[0057] Silicon source: sodium silicate, amounting to 50% of the total reactant mass;

[0058] Calcium source: calcium chloride, amounting to 2.5% of the total reactant mass;

[0059] Alkali: sodium hydroxide, amounting to 1.5% of the total reactant mass;

[0060] pH regulator: potassium dihydrogen phosphate, amounting to 1% of the total reactant mass.

[0061] Solvent: deionized water, amounting to 10% of the total reactant mass, and anhydrous ethanol, amounting to 35% of the total reactant mass.

[0062] 2、The specific method for large-scale production of pH-adjustable bioactive glass nanoparticles is as follows: (1) First, pour 2.5% of calcium chloride into a beaker, add 1% of deionized water and 4% of anhydrous ethanol as a solvent, and stir until the calcium chloride is completely dissolved. Then, add 50% of sodium silicate to the mixture, continue stirring, and observe the complete mixing of the reagents. After that, add 1% of potassium dihydrogen phosphate, wait for the reagents to completely dissolve and mix, and mark it as liquid A; (2) Pour 9% of deionized water and 31% of anhydrous ethanol into another beaker, then pour in 1.5% of sodium hydroxide, seal and stir, and wait for the reagents to completely mix, marking it as liquid B; (3) Mix the two liquids by using a reaction liquid counter-current mixing device, and collect the mixed liquid in a beaker after it flows out of the mixer. Continue stirring the mixed liquid at a temperature of 40°C for about 1 hour. Finally, obtain bioactive glass nanoparticles with a particle size of 200 nanometers, and measure the pH value to be 7.6 using a pH measurement method. The bioactive glass nanoparticles are shown in FIG. 4. Figure 2 (4) as shown.

[0063] Example 5

[0064] 1、The total reactants for large-scale production of pH-adjustable bioactive glass nanoparticles are as follows:

[0065] Silicon source: potassium silicate, amounting to 20% of the total reactant mass;

[0066] Calcium source: calcium chloride, amounting to 1.5% of the total reactant mass;

[0067] Alkali: ammonia, amounting to 6% of the total reactant mass;

[0068] pH adjuster: ammonium phosphate, amounting to 1.5% of the total reactant mass;

[0069] Solvent: deionized water, amounting to 5% of the total reactant mass, and anhydrous ethanol, amounting to 66% of the total reactant mass.

[0070] 2、The specific method for large-scale production of pH-adjustable bioactive glass nanoparticles is as follows: (1) first, pour 1.5% of calcium chloride into a beaker, add 1% of deionized water and 15% of anhydrous ethanol as a solvent, and stir until the calcium chloride is completely dissolved. Then, add 20% of potassium silicate to the mixture, continue stirring, and observe the complete mixing of the reagents. After that, add 1.5% of ammonium phosphate to the mixture, wait for the reagents to completely dissolve and mix, and mark it as liquid A; (2) pour 4% of deionized water and 51% of anhydrous ethanol into another beaker, then pour in 6% of ammonia water, seal and stir, and wait for the reagents to completely mix, marking it as liquid B; (3) quickly mix the reaction liquid A and the reaction liquid B through a reaction liquid counter-current mixing device. After the mixed liquid flows out of the mixer, use a beaker to collect the mixed liquid, continue to stir the mixed liquid, and the stirring temperature is 30°C, and the stirring time is about 1 hour. Finally, the bioactive glass nanoparticles with a particle size of 90 nanometers are obtained, and the pH value is measured to be 8.3. The bioactive glass nanoparticles are shown in FIG. 5. Figure 2 (5).

[0071] Example 6

[0072] 1、The total reactants for large-scale production of pH-adjustable bioactive glass nanoparticles are as follows:

[0073] Silicon source: tetraethyl orthosilicate, amounting to 55% of the total reactant mass;

[0074] Calcium source: calcium nitrate, amounting to 4.4% of the total reactant mass;

[0075] Alkali: potassium hydroxide, amounting to 1.6% of the total reactant mass;

[0076] pH adjuster: potassium dihydrogen phosphate, amounting to 4% of the total reactant mass;

[0077] Solvent: deionized water, amounting to 20% of the total reactant mass, and anhydrous ethanol, amounting to 25% of the total reactant mass.

[0078] 2、The specific method for large-scale production of pH-adjustable bioactive glass nanoparticles is as follows: (1) first, pour 4.4% of calcium nitrate into a beaker, add 2% of deionized water and 4% of anhydrous ethanol as solvents, and stir until the calcium nitrate is completely dissolved. Then, add 55% of tetraethyl orthosilicate to the mixture, continue stirring, and observe the complete mixing of the reagents. Then, add 4% of potassium dihydrogen phosphate, wait for the reagents to completely dissolve and mix, and mark it as solution A; (2) pour 18% of deionized water and 21% of anhydrous ethanol into another beaker, then pour in 1.6% of potassium hydroxide, seal and stir, and wait for the reagents to completely mix and mark it as solution B; (3) quickly mix solutions A and B through a reaction liquid counterflow mixing device. After the reaction mixture flows out of the mixer, use a beaker to collect the mixture, continue stirring the mixture, and stir at a temperature of 40°C for about 1 hour. Finally, obtain bioactive glass nanoparticles with a particle size of 80 nm, and use a pH measurement method to determine that the pH value is 9. The bioactive glass nanoparticles are shown in FIG. 6. Figure 2 (6).

[0079] Example 7

[0080] 1、The total reactants for large-scale production of pH-adjustable bioactive glass nanoparticles are as follows:

[0081] Silicon source: potassium silicate, amounting to 15% of the total reactant mass; tetraacetate silicon, amounting to 30% of the total reactant mass;

[0082] Calcium source: calcium nitrate, amounting to 3.4% of the total reactant mass;

[0083] Alkali: potassium hydroxide, amounting to 2.1% of the total reactant mass;

[0084] pH adjuster: ammonium dihydrogen phosphate, amounting to 2.5% of the total reactant mass;

[0085] Solvent: deionized water, amounting to 15% of the total reactant mass; anhydrous ethanol, amounting to 32% of the total reactant mass.

[0086] 2. The specific method for large-scale production of pH-adjustable bioactive glass nanoparticles is as follows: (1) first, pour 3.4% of calcium nitrate in the total reactant mass into a beaker, add 2% of deionized water in the total reactant mass and 7% of anhydrous ethanol in the total reactant mass as a solvent for stirring, wait for the complete dissolution of calcium nitrate, then add 15% of potassium silicate in the total reactant mass and 30% of silicon tetracetic acid in the total reactant mass, continue to stir, and observe the complete mixing of the reagents, then add 2.5% of ammonium dihydrogen phosphate in the total reactant mass, wait for the complete dissolution and mixing of the reagents, and mark as liquid A; (2) pour 13% of deionized water in the total reactant mass and 25% of anhydrous ethanol in the total reactant mass into another beaker, then pour 2.1% of potassium hydroxide in the total reactant mass, seal and stir, and wait for the complete mixing of the reagents to mark as liquid B; (3) quickly mix the two liquids of reaction liquid A and reaction liquid B through a reaction liquid opposite-mixing device, collect the mixed liquid after the reaction mixed liquid flows out of the mixer, continue to stir the mixed liquid, and the stirring temperature is 60°C and the stirring time is about 1 hour; finally, the bioactive glass nanoparticles with a particle size of 200 nanometers are obtained, and the pH value is 7 measured by the pH value measurement method, and the bioactive glass nanoparticles are as shown in FIG. 7. Figure 2 (7).

[0087] III. The pH measurement method

[0088] The specific operation of the pH measurement method used in the present application is as follows: weigh 2g of bioactive glass nanoparticles, pour the bioactive glass nanoparticles into a 20mL beaker, pour pre-boiled and cooled distilled water into the beaker, then fully stir and mix, observe the complete dissolution of the bioactive glass nanoparticles, use a pH meter to measure at room temperature, wait for the pH meter value to be stable within 10 minutes to read the indicated value, repeat the measurement three times, and take the arithmetic mean value as the measurement result of the pH value.

[0089] The above is only an optional embodiment of the present application, and does not limit the patent scope of the present application, and any equivalent structural transformation made by the present application specification and drawings, or direct / indirect application in other related technical fields is included in the patent protection scope of the present application.

Claims

1. A pH-adjustable bioactive glass nanoparticle, characterized in that, The formulation for synthesizing bioactive glass nanoparticles includes a silicon source, a calcium source, an alkali, a pH adjuster, and a solvent.

2. The pH-adjustable bioactive glass nanoparticles according to claim 1, characterized in that, The silicon source is any one or more of tetraethyl orthosilicate, silicon tetraacetate, sodium silicate, and potassium silicate, and the amount used is 20% to 60% of the total reactant mass of the synthetic formulation.

3. The pH-adjustable bioactive glass nanoparticles according to claim 1, characterized in that, The calcium source is either calcium nitrate or calcium chloride, and the amount used is 2% to 10% of the total reactant mass of the synthetic formula.

4. The pH-adjustable bioactive glass nanoparticles according to claim 1, characterized in that, The alkali is any one or more of sodium hydroxide, potassium hydroxide, calcium hydroxide, and ammonia water, and the amount used is 1% to 6% of the total reactant mass of the synthetic formula.

5. The pH-adjustable bioactive glass nanoparticles according to claim 1, characterized in that, The pH adjuster is one or more of sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium hydrogen phosphate, potassium dihydrogen phosphate, ammonium phosphate, potassium phosphate, and sodium phosphate, and the amount used is 1% to 5% of the total reactant mass of the synthetic formulation.

6. The pH-adjustable bioactive glass nanoparticles according to claim 1, characterized in that, The solvent is one or more of deionized water, distilled water, ethanol, methanol, n-propanol, and isopropanol, and its amount is 35% to 65% of the total reactant mass of the synthetic formulation.

7. The method for producing pH-adjustable bioactive glass nanoparticles according to any one of claims 1 to 6, characterized in that, The large-scale production of bioactive glass nanoparticles using a counter-mixing rapid mixing method includes the following steps: (1) Mix silicon source, calcium source, pH adjuster and solvent in a specific mass ratio. The specific operation is as follows: First, pour calcium source and solvent into container or beaker and stir and mix evenly. Then add silicon source and stir and mix. After waiting for the mixture to be even, add pH adjuster and stir for a period of time. Observe and confirm that the above reagents are completely mixed evenly to form reaction solution A. (2) Mix the alkali and solvent evenly according to a specific mass ratio. The specific operation is as follows: First, pour the solvent into a beaker and start stirring. Then, quickly add the alkali into the container or beaker and stir to mix. During the stirring process, the container must be sealed. Observe and confirm that the above reagents are completely mixed evenly to form reaction solution B. (3) Fill reaction solutions A and B into a large syringe, then inject them into the reaction solution flushing mixer to ensure rapid mixing of the reaction solutions. Then use a container or beaker to collect the reaction mixture of reaction solutions A and B and continue to react under rapid stirring conditions at a temperature of 20℃~60℃. (4) Stir and mix the reaction mixture of reaction solution A and B, stop stirring and let stand, obtain the lower sediment in the reaction mixture, wash the sediment repeatedly with deionized water, and then separate the bioactive glass nanoparticles by free sedimentation, centrifugation or filtration.

8. The method according to claim 7, characterized in that, The reaction mixture counter-mixer controls the outlet flow rate of the reaction mixture to be 1.0–10.0 L / min; the reaction mixture of A and B is continuously stirred for about 1 hour after falling into the container or beaker.

9. The method according to claim 7, characterized in that, The bioactive glass nanoparticles produced on a large scale by the hedging rapid mixing method have a particle size of 80–500 nanometers.

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