A multifunctional magnetic bioactive glass, its preparation method and application

Abstract

This invention discloses a multifunctional magnetic bioactive glass, its preparation method, and its application, belonging to the field of bioactive material technology. The method includes the following steps: (1) mixing tetraethyl orthosilicate, sodium carbonate, ethanol, and water to form a mixed solution; (2) adding triethyl phosphate and calcium chloride to the mixed solution and mixing to obtain a white turbid solution; (3) adding ferric oxide and ferromanganese acid to the white mixed solution and mixing until a gel is formed; precipitating the gel with ethanol and collecting the solid insoluble matter; removing the ethanol residue from the solid insoluble matter and heat-treating it to obtain a solid powder; (4) calcining and purifying the solid powder to obtain the multifunctional magnetic bioactive glass. This method is simple, highly controllable, has a short synthesis cycle, and low cost, making it suitable for industrialization. The finished product exhibits good magnetocaloric effect and good biocompatibility, showing promising application prospects.

Description

Technical Field

[0001] This invention relates to the field of bioactive materials technology, and in particular to a multifunctional magnetic bioactive glass, its preparation method, and its applications. Background Technology

[0002] Bioactive glass has been widely used clinically due to its good biocompatibility and bioactivity. However, it is somewhat inadequate in treating bone tumors. This is mainly because, after lesion removal, the implanted material must have good osteogenic properties and be able to inhibit tumor recurrence, which traditional bioactive glass cannot do. Tumor cells are heat-sensitive cells; temperatures above 40°C can effectively kill them. Therefore, when bioactive glass is endowed with magnetothermal properties, magnetothermal therapy can achieve a long-term tumor cell killing effect. However, magnetothermal therapy alone also has its drawbacks, as heating can only be applied to the implantation area, and it cannot effectively inhibit tumor metastasis. By endowing the material with immunomodulatory capabilities, tumors can be treated through immunomodulation, which can effectively inhibit tumor metastasis. Thus, a combination of magnetothermal therapy and immunotherapy can be used to treat bone tumors.

[0003] Chinese patent CN113429127A discloses a magnetic bioactive glass, its preparation method, and its application. The magnetic bioactive glass is obtained by high-temperature calcination of a glass with a core-shell structure. The core-shell structure consists of a core layer of iron(III) oxide (Fe4O) and a shell layer of silicon dioxide and calcium oxide. After high-temperature calcination, the iron(III) oxide is oxidized to magnetic γ-iron oxide. The method includes: adding iron(III) oxide and magnesium oxide to a transparent sodium silicate colloid, then adding concentrated sulfuric acid until the pH reaches 7-8, reacting at 50-70°C, filtering, washing, filtering again, and drying to obtain a black solid powder; heat-treating in a saturated calcium nitrate tetrahydrate solution, followed by high-temperature calcination to obtain the magnetic bioactive glass. This invention features a simple process, low cost, and low calcination temperature, resulting in a microporous surface structure, a larger specific surface area, and improved mineralization and bioactivity.

[0004] The bioactive glass prepared by the above technology has a shell of silica and calcium oxide, with the calcium oxide obtained by calcining calcium nitrate at high temperature. This component still has high alkalinity, and its biocompatibility with human tissue components has greater room for optimization. Furthermore, while the temperature at which calcium nitrate is calcined to produce calcium oxide in this technology is lower than in traditional processes, the temperatures in the second and third stages are still as high as 500–750°C. At these temperatures, excessively high reaction temperatures can affect the formation of γ-iron oxide. Although this method can inhibit the conversion of magnetite to α-iron oxide, it cannot completely prevent the formation of α-iron oxide and the loss of magnetism in the product. The controllability of the product needs further improvement.

[0005] Therefore, developing a simple, low-cost, and uniform method for preparing multifunctional magnetic bioactive glass has become an urgent technical problem to be solved. Summary of the Invention

[0006] In view of the above-mentioned deficiencies of the prior art, in a first aspect of the present invention, a method for preparing a multifunctional magnetic bioactive glass with simple process and good controllability is provided, comprising the following steps:

[0007] (1) Mix tetraethyl orthosilicate, sodium carbonate, ethanol and water to form a mixed solution for later use;

[0008] (2) Add triethyl phosphate and calcium chloride to the mixed solution and mix to obtain a white turbid solution for later use;

[0009] (3) Add ferric oxide and ferromanganese acid to the white mixed solution and mix until a gel is formed; precipitate the gel with ethanol and collect the solid insoluble matter; remove the ethanol residue from the solid insoluble matter and heat-treat it to obtain a solid powder for later use;

[0010] (4) The solid powder is calcined and purified to obtain a multifunctional magnetic bioactive glass.

[0011] The technical solution of this invention employs a different synthetic route. Sodium carbonate, being alkaline, acts as a catalyst for the hydrolysis of tetraethyl orthosilicate, promoting rapid hydrolysis in the early stages. The rapid addition of triethyl phosphate and calcium chloride quickly forms calcium carbonate, lowering the pH of the system, slowing down hydrolysis, and ensuring thorough mixing and stability of the components. This avoids the need for additional acid or base catalysts. Simultaneously, sodium carbonate also serves as a raw material for reacting with calcium chloride to form calcium carbonate (Na₂CO₃ + CaCl₂ = CaCO₃ + NaCl). This allows the calcium carbonate formed to replace calcium nitrate, lowering the reaction temperature required for calcination and avoiding the adverse effects of excessively high reaction temperatures on the formation of γ-iron oxide, preventing its conversion to α-iron oxide and loss of magnetism. The calcium carbonate produced by this method, compared to the calcium oxide (obtained from the high-temperature calcination of calcium nitrate) in existing glass, has lower alkalinity, better biocompatibility, and is more similar to the composition of human tissue. Among other raw materials, iron(III) oxide is used to convert into γ-iron oxide (2Fe3O4+0.5O2=3γ-Fe2O3), providing the main magnetic properties. If all the magnetic materials are iron manganese acid, its excessive manganese ion content will lead to the toxicity of the material. At the same time, iron manganese acid has good stability, and its manganese can still maintain the divalent state at high temperatures, avoiding the formation of tetravalent manganese and losing its role in immunotherapy for tumors.

[0012] Preferably, in step (1), the feeding ratio of tetraethyl orthosilicate, ethanol, and water is 20.18g: 20-40mL: 20-40mL.

[0013] In this invention, the principle of raw material mixing is to form a well-dispersed mixture, and appropriate mixing conditions can be selected according to the specific type of raw material. For the process of tetraethyl orthosilicate, sodium carbonate, ethanol, and water, appropriately increasing the mixing temperature helps to mix and disperse the raw materials. Preferably, in step (1), the mixing temperature is 20-40°C, and the processing time is 10-60 min.

[0014] Preferably, the mass ratio of tetraethyl orthosilicate to sodium carbonate, triethyl phosphate, calcium chloride, iron(III) oxide, and ferromanganese is 20.18:3.40-6.80:1.46:3.55-7.10:0.5-2.0:0.05-0.2.

[0015] More complete gelation helps to further improve the stability of the gel and optimize the overall performance of the finished product. Preferably, in step (3), the gel is aged before precipitation, and the aging is carried out at room temperature for 1 to 3 days.

[0016] The residual ethanol in the precipitated solid can be completely evaporated by methods commonly used in the art (e.g., drying). Alternatively, ignition is a particularly suitable and unusual method, as igniting the solid insolubles can rapidly remove residual ethanol, preferentially dehydrating the material interface to form a protective layer. Furthermore, the combustion process results in less oxygen inside the material, making it less prone to oxidation, effectively reducing aggregation, and making the material particle size more stable. Preferably, in step (3), ignition is used to remove residual ethanol from the solid insolubles, and heat treatment is performed after the flame is extinguished.

[0017] Heat treatment can further dehydrate the material, avoiding excessively rapid dehydration during calcination that could affect the material's structural stability. Preferably, in step (3), the heat treatment temperature is 90–120°C, and the treatment time is 24–48 hours.

[0018] Using different synthetic routes to obtain calcium carbonate and replacing calcium oxide can simplify the calcination process and reduce the required temperature (i.e., it is not necessary to heat it to the temperature at which calcium nitrate forms calcium oxide). To optimize the product structure, calcination can be carried out in two stages; in the first stage, the mixture loses water at a lower temperature to form a silicon-based material coating of iron(III) oxide; in the second stage, the silicon-based material is heated to further lose water to stabilize the structure, while iron(III) oxide is converted into γ-iron oxide. Preferably, in step (4), the calcination is carried out in two stages, specifically as follows: in the first stage, the solid powder is heated from 25-35°C to 150-160°C at a rate of 5-10°C / min and held for 2-3 hours; in the second stage, the temperature is further increased to 400-450°C at a rate of 8-10°C / min and held for 1.5-2.5 hours.

[0019] In a second aspect of the present invention, a multifunctional magnetic bioactive glass with good biocompatibility and magnetocaloric effect is provided, which is prepared by the method provided in the first aspect of the present invention.

[0020] Preferably, the chemical composition of the multifunctional magnetic bioactive glass includes silicon dioxide, calcium carbonate, phosphorus pentoxide, γ-iron oxide, and ferric manganese acid.

[0021] More preferably, the mass ratio of silicon dioxide, calcium carbonate, phosphorus pentoxide, γ-iron oxide, and ferromanganese acid in the multifunctional magnetic bioactive glass is 5.82:3.21-6.42:0.57:0.5-2.0:0.05-0.2, respectively.

[0022] In a third aspect of the present invention, an application of the multifunctional magnetic bioactive glass of the second aspect of the present invention is provided, specifically its application in the preparation of human implant materials.

[0023] Based on the above technical solutions, the design concept of this invention lies in employing a special synthesis route to obtain a material free of calcium oxide and sodium oxide, thereby avoiding excessive alkalinity and reducing tissue irritation. The calcium carbonate composition is more similar to that of human bone tissue, exhibiting better biocompatibility compared to traditional glass. γ-iron oxide imparts excellent magnetocaloric properties to the material, effectively killing tumor cells. Ferromanganese acid forms a structure embedded in silica, reducing the rate at which divalent manganese ions are released, preventing excessive release and poisoning caused by excessive divalent manganese ions, while also playing a role in immunotherapy for tumors. The material is calcined at a low temperature, preventing ferromanganese acid and γ-iron oxide from transforming into other ineffective components. Simultaneously, the material surface possesses a microporous structure, facilitating mineralization. Through these improvements, this multifunctional magnetic bioactive glass exhibits excellent bioactivity, biocompatibility, and osteogenic capacity, while also possessing excellent magnetocaloric effects, making it suitable for treating bone tumors.

[0024] The process of this invention differs from the traditional sol-gel method. It introduces calcium carbonate via co-precipitation, where sodium carbonate acts as a reactant to form calcium carbonate and also as a catalyst. Its alkalinity promotes the hydrolysis of tetraethyl orthosilicate and triethyl phosphate, optimizing the reaction system. Simultaneously, the introduction of calcium carbonate lowers the calcination temperature, ensuring the stability of the components during the reaction. Rapid removal of residual ethanol through combustion allows for preferential dehydration of the material surface, ensuring more stable particle size and preventing aggregation during subsequent processing.

[0025] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0026] This invention provides a method for preparing multifunctional magnetic bioactive glass, which has a simple process, good controllability, short synthesis cycle, low cost, and is conducive to industrialization.

[0027] This invention provides a multifunctional magnetic bioactive glass with good magnetocaloric effect and good biocompatibility.

[0028] This invention also provides an application of a multifunctional magnetic bioactive glass for the preparation of human implant materials, which can assist in the combined treatment of bone tumors with magnetothermal therapy and immunotherapy, and has good application prospects. Attached Figure Description

[0029] Figure 1 In the image, (a) is a scanning electron microscope (SEM) image of the multifunctional magnetic bioactive glass of Example 1; (b) to (f) are its elemental distribution mapping diagrams.

[0030] Figure 2 The image shows the X-ray diffraction (XRD) pattern of the multifunctional magnetic bioactive glass of Example 1.

[0031] Figure 3 The results of the cytotoxicity test of the multifunctional magnetic bioactive glass in Example 1 are shown.

[0032] Figure 4 The hysteresis curve is shown for the multifunctional magnetic bioactive glass of Example 1. Detailed Implementation

[0033] The present invention is further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product instructions.

[0034] Example 1

[0035] The preparation method of multifunctional magnetic bioactive glass includes the following steps:

[0036] (1) Add 20.18g tetraethyl orthosilicate, 6.80g sodium carbonate, 25mL anhydrous ethanol and 20mL purified water to a beaker, and stir magnetically for 10min at 30℃ to form a mixed solution for later use.

[0037] (2) Dissolve 1.46g of triethyl phosphate and 7.10g of calcium chloride in 10mL of purified water, and then quickly add them to the mixture. After stirring and mixing, a white turbid solution is obtained and set aside.

[0038] (3) Add 1.0g of iron(II,III) oxide and 0.1g of iron(II,III) manganese acid to the resulting white turbid solution, continue stirring until a gel is formed, then stop stirring and age at room temperature for 1 day, add 100mL of anhydrous ethanol and sonicate for 10min, collect the solid insoluble matter by precipitation and filtration; ignite the solid insoluble matter, and after the flame is extinguished, keep it at 105℃ for 24h to obtain solid powder for later use;

[0039] (4) The obtained solid powder was calcined in two stages. First, it was heated from 30°C to 160°C at a rate of 10°C / min and held for 2 hours. Then, it was further heated to 400°C at a rate of 10°C / min and held for 2 hours. After cooling, the product was ultrasonically cleaned three times at 30°C for 10 minutes each time, and then dried at 105°C for 10 hours to obtain a multifunctional magnetic bioactive glass, denoted as Mn-BG.

[0040] The microstructure and elemental distribution of the multifunctional magnetic bioactive glass were observed and characterized by scanning electron microscopy (SEM) and elemental distribution mapping, respectively. The results are shown in [Figure number missing]. Figure 1 .like Figure 1As shown in (a), the multifunctional magnetic bioactive glass is a mixture of porous silica and short columnar calcium carbonate stacked together; in conjunction with Figure 1 The mapping diagrams (b) to (f) show that O, Si, Ca, and Fe elements are clearly visible on the material surface, but Mn elements are basically not observed. The external elements of the obtained multifunctional magnetic bioactive glass are mainly O, Si, Ca, and Fe, while the internal element is Mn, which is conducive to the slow release of manganese ions.

[0041] The multifunctional magnetic bioactive glass was characterized by X-ray diffraction (XRD), and the results are shown in [Figure number missing]. Figure 2 .like Figure 2 As shown, only characteristic peaks of γ-iron oxide and calcium carbonate were observed, while characteristic peaks of α-iron oxide were not observed. This spectrum indicates that no α-iron oxide was produced, and only magnetic γ-iron oxide was present, thus giving the material superior magnetic properties.

[0042] The cytotoxicity of the multifunctional magnetic bioactive glass was tested according to the methods and procedures provided in GB / T 16886.5-2017 "Biological Evaluation of Medical Devices - Part 5: In Vitro Cytotoxicity Tests". The results of the cytotoxicity test are shown in [link to results]. Figure 3 .like Figure 3 As can be seen, compared with the blank control group (C), the multifunctional magnetic bioactive glass (Mn-BG) of the present invention has no cytotoxicity and shows good biocompatibility.

[0043] The magnetic properties of the multifunctional magnetic bioactive glass were tested. The mass of the test sample was 45.63 mg, and its hysteresis curve is shown in the figure. Figure 4 .like Figure 4 As shown, the material exhibits paramagnetic properties, and combined with the XRD results, it indicates that the material possesses a good magnetocaloric effect.

[0044] In summary, compared to traditional bioactive glasses, the multifunctional magnetic bioactive glass of this invention exhibits superior biocompatibility due to the removal of relatively strong alkaline calcium oxide and sodium oxide, resulting in less tissue redness and exudation, due to its unique composition and structure. Its special surface structure (observed as a stack of porous silica and short columnar calcium carbonate) and composition facilitate the deposition of carbonate-containing hydroxyapatite on its surface after implantation, making it more similar to the composition of human bone tissue and enabling faster integration with surrounding tissues, thereby improving its biocompatibility and osteogenic capacity. Furthermore, this material possesses excellent magnetic properties, making it a potential treatment for bone tumors; the introduction of divalent manganese ions has the potential to inhibit tumors through immunomodulation. The functional magnetic bioactive glass exhibits good biocompatibility and can be used in combination with various materials, broadening its application range.

[0045] Example 2

[0046] The preparation method of multifunctional magnetic bioactive glass includes the following steps:

[0047] (1) Add 20.18g tetraethyl orthosilicate, 3.40g sodium carbonate, 30mL anhydrous ethanol and 20mL purified water to a beaker, and stir magnetically for 10min at 30℃ to form a mixed solution for later use.

[0048] (2) Dissolve 1.46g of triethyl phosphate and 3.55g of calcium chloride in 10mL of purified water, and then quickly add them to the mixed solution. After stirring and mixing, a white turbid solution is obtained and set aside.

[0049] (3) Add 0.5g of ferric oxide and 0.05g of ferric manganese acid to the resulting white turbid solution, continue stirring until a gel is formed, then stop stirring and age at room temperature for 1 day, add 100mL of anhydrous ethanol and sonicate for 10min, collect the solid insoluble matter by precipitation and filtration; ignite the solid insoluble matter, and after the flame is extinguished, keep it at 105℃ for 24h to obtain solid powder for later use;

[0050] (4) The obtained solid powder was calcined in two stages. First, it was heated from 30°C to 160°C at a rate of 10°C / min and held for 2 hours. Then, it was further heated to 400°C at a rate of 10°C / min and held for 2 hours. After cooling, the product was ultrasonically cleaned three times at 30°C for 10 minutes each time, and then dried at 105°C for 10 hours to obtain multifunctional magnetic bioactive glass.

[0051] Example 3

[0052] The preparation method of multifunctional magnetic bioactive glass includes the following steps:

[0053] (1) Add 20.18g tetraethyl orthosilicate, 3.40g sodium carbonate, 30mL anhydrous ethanol and 30mL purified water to a beaker, and stir magnetically for 30min at 20℃ to form a mixed solution for later use.

[0054] (2) Dissolve 1.46g of triethyl phosphate and 3.55g of calcium chloride in 10mL of purified water, and then quickly add them to the mixed solution. After stirring and mixing, a white turbid solution is obtained and set aside.

[0055] (3) Add 1.0g of ferric oxide and 0.05g of ferric manganese acid to the resulting white turbid solution, continue stirring until a gel is formed, then stop stirring and age at room temperature for 1 day, add 100mL of anhydrous ethanol and sonicate for 10min, collect the solid insoluble matter by precipitation and filtration; ignite the solid insoluble matter, and after the flame is extinguished, keep it at 105℃ for 24h to obtain solid powder for later use;

[0056] (4) The obtained solid powder was calcined in two stages. First, it was heated from 30°C to 160°C at a rate of 10°C / min and held for 2 hours. Then, it was further heated to 450°C at a rate of 10°C / min and held for 2 hours. After cooling, the product was ultrasonically cleaned three times at 30°C for 10 minutes each time, and then dried at 105°C for 10 hours to obtain multifunctional magnetic bioactive glass.

[0057] The preferred embodiments of the present invention have been described in detail above. It should be understood that those skilled in the art can make numerous modifications and variations based on the concept of the present invention without creative effort. Therefore, all technical solutions that can be obtained by those skilled in the art based on the concept of the present invention through logical analysis, reasoning, or limited experimentation on the basis of existing technology should be within the scope of protection defined by the claims.

Claims

1. A method for preparing a multifunctional magnetic bioactive glass, characterized in that, Includes the following steps: (1) Mix tetraethyl orthosilicate, sodium carbonate, ethanol and water to form a mixed solution for later use; (2) Add triethyl phosphate and calcium chloride to the mixed solution and mix to obtain a white turbid solution for later use; (3) Add ferric oxide and ferromanganese acid to the white turbid solution and mix until a gel is formed; precipitate the gel with ethanol and collect the solid insoluble matter; remove the ethanol residue from the solid insoluble matter and heat-treat it to obtain a solid powder for later use; (4) The solid powder is calcined and purified to obtain a multifunctional magnetic bioactive glass.

2. The method according to claim 1, characterized in that: In step (1), the feeding ratio of tetraethyl orthosilicate, ethanol, and water is 20.18g: 20-40mL: 20-40mL.

3. The method according to claim 1, characterized in that: The mass ratio of tetraethyl orthosilicate to sodium carbonate, triethyl phosphate, calcium chloride, iron tetroxide, and ferromanganese is 20.18: 3.40–6.80: 1.46: 3.55–7.10: 0.5–2.0: 0.05–0.

2.

4. The method according to claim 1, characterized in that: In step (3), the gel is aged before precipitation. The aging is carried out at room temperature for 1 to 3 days.

5. The method according to claim 1, characterized in that: In step (3), the ethanol residue in solid insoluble matter is removed by ignition, and heat treatment is performed after the flame is extinguished.

6. The method according to claim 1, characterized in that: In step (3), the heat treatment temperature is 90-120°C and the treatment time is 24-48h.

7. The method according to claim 1, characterized in that, In step (4), the calcination is carried out in two stages, as follows: in the first stage, the solid powder is heated from 25 to 35°C to 150 to 160°C at a rate of 5 to 10°C / min and held for 2 to 3 hours; in the second stage, the temperature is further increased to 400 to 450°C at a rate of 8 to 10°C / min and held for 1.5 to 2.5 hours.

8. A multifunctional magnetic bioactive glass, characterized in that: It is prepared by the method described in any one of claims 1 to 7.

9. The multifunctional magnetic bioactive glass according to claim 8, characterized in that: The chemical composition of the multifunctional magnetic bioactive glass includes silicon dioxide, calcium carbonate, phosphorus pentoxide, γ-iron oxide, and ferric manganese acid, with the mass ratio of each component being 5.82:3.21~6.42:0.57:0.5~2.0:0.05~0.

2.

10. An application of the multifunctional magnetic bioactive glass as described in claim 8 or 9, characterized in that: Application of multifunctional magnetic bioactive glass in the preparation of human implant materials.

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