Preparation method and application of an antibacterial borate bioactive glass material

Abstract

The application provides a preparation method of an antibacterial boric acid salt bioactive glass material, mainly comprising the following steps: (1) dissolving boric acid in deionized water, and then adding a mixture of calcium salt and iron salt to carry out stirring reaction; (2) adding an ammonia water complex containing copper salt and silver salt and a surfactant to continue stirring reaction; (3) placing the mixture after reaction into a closed reaction kettle, aging, drying, finally carrying out heat treatment and crushing. The antibacterial boric acid salt bioactive glass material has the effects of antibacterial, hemostasis and promoting angiogenesis, and can be used for preparing antibacterial bioactive dressings, toothpaste, skin cream and mouthwash.

Description

Technical Field

[0001] This invention relates to the field of antibacterial bioactive materials, and more specifically, to a method for preparing and applying an antibacterial borate bioactive glass material. Background Technology

[0002] Bioactive glass (BG) is a class of inorganic biomaterials based on the Si-Ca-P system, used for the repair of tissues such as bone, teeth, and skin. It exhibits good biocompatibility, readily forming chemical bonds with bone and soft tissues, and has been widely used clinically in orthopedic and dental care. Furthermore, the amorphous nature of BG allows for easy modification of its chemical composition, enabling the addition of bioactive ions. The release of these ions can provide additional functions, such as immunomodulation and antibacterial activity, extending its applications to soft tissue repair / regeneration, such as wound healing and muscle growth. However, reports on borate bioactive glass materials are scarce; related research is still based on the classic Si-Ca-P system, primarily focusing on applications in bone regeneration.

[0003] Meanwhile, the current method of preparing bioactive glass materials by high-temperature melting and quenching has the drawback of irregular morphology, large particle size, and small specific surface area. Bioactive glass materials prepared by the sol-gel method have small particle size (nanoscale), and although they have a large specific surface area, they are easy to agglomerate during application, and the application effect is not as good as that of micron-scale bioactive glass materials.

[0004] Finally, the orthopedic and soft tissue repair process is prone to bacterial infection. The best way to deal with this is to take antibiotics. However, the use of antibiotics can lead to drug resistance and has significant side effects on the human body. Adding antibacterial components to bioactive materials can reduce the need for antibiotics.

[0005] In view of this, the present invention is hereby proposed. Summary of the Invention

[0006] This invention provides a method for preparing and applying an antibacterial borate bioactive glass material, wherein the bioactive glass material has a specific surface area exceeding 600 m². 2 / g, with regular morphology and an average particle size of about 1 micrometer, has antibacterial, hemostatic and angiogenesis-promoting effects, and can be used to prepare antibacterial bioactive dressings, toothpaste, skin cream and mouthwash.

[0007] The objective of this invention can be achieved through the following technical solutions: A method for preparing an antibacterial borate bioactive glass material, characterized by comprising the following steps: (1) Dissolve 5 g of boric acid in 100 mL of deionized water, then add 0.01-3 g of a mixture of calcium and iron salts, and continue stirring the reaction at 20-100°C to obtain a clear solution. (2) Dissolve 0.001-0.03 g of a mixture of copper salt and silver salt in 50 mL of ammonia water containing surfactant at room temperature, and then add the above copper salt and silver salt complex solution dropwise to the clear solution in step (1) and continue to stir the reaction. (3) The mixture after the reaction in step (2) is placed in a sealed reaction vessel, aged at 60-100°C for 96-240 hours, dried at 100-120°C, and then heat-treated at 390-460°C for 2-4 hours. After further pulverization, antibacterial borate bioactive glass material is obtained.

[0008] Boron exhibits enhanced angiogenesis both in vitro and in vivo. In this invention, boron replaces Si and P in the classic BG composition, which can play a positive role in promoting angiogenesis.

[0009] Furthermore, in step (1), the calcium salt and iron salt are chlorides, nitrates, or sulfates of the corresponding metals. Compared with the classic BG composition, this invention adds an iron component, which can prevent infection, improve the body's immunity, prevent anemia, maintain the body's acid-base balance, and promote growth and development. More preferably, the iron salt in this invention is a divalent iron salt, wherein the mass ratio of calcium salt to iron salt, calculated as oxides, is 100:1-10:1.

[0010] This invention further incorporates copper and silver components. Copper plays a role in maintaining normal hematopoietic function, preserving the integrity of the central nervous system, and promoting the health of bones, blood vessels, and skin in the human body. Silver ions do not damage normal cells but have a strong bactericidal effect. In step (2), the copper salt and silver salt are chlorides, nitrates, or sulfates of the corresponding metals, wherein the mass ratio of silver salt to copper salt, calculated as oxides, is 1:1 to 1:10.

[0011] To further obtain a monodisperse antibacterial bioactive glass material with a regular morphology, this invention further introduces a surfactant as a template agent and dispersant. In step (2), the surfactant is any one of hexadecyltrimethylammonium bromide, hexadecyltrimethylammonium chloride, tetradecyltrimethylammonium bromide, tetradecyltrimethylammonium chloride, and tetradecyldimethylbenzylammonium chloride, and its mass percentage in ammonia water is 0.1-1 wt%; the concentration of ammonia water is 0.01-10 wt%.

[0012] Furthermore, this invention also limits the process conditions during the reaction, such as the reaction temperature and the mass ratio of each raw material. If these limits are exceeded, the structure and size of the antibacterial bioactive glass material particles will become uncontrollable.

[0013] This invention discloses an antibacterial borate bioactive glass material that has antibacterial, hemostatic, and angiogenesis-promoting effects, and can be used to prepare antibacterial bioactive dressings, toothpaste, skin creams, and mouthwash.

[0014] The beneficial effects of this invention are as follows: This invention provides a method for preparing and applying an antibacterial borate bioactive glass material, wherein the bioactive glass material has a specific surface area exceeding 600 m². 2 The particles, with a regular morphology and an average particle size of approximately 1 micrometer, exhibit a large number of pores within their surface area and particle size. Testing revealed a total pore volume exceeding 0.349 cm³. 3 / g. This bioactive glass material has antibacterial, hemostatic, and angiogenesis-promoting effects, and has passed in vitro cytotoxicity experiments. It can be used as a bioactive material for preparing bioactive dressings, toothpaste, skin creams, and mouthwashes. Attached Figure Description

[0015] Figure 1 Scanning electron microscope image of bioactive glass material in Example 1; Figure 2 Transmission electron microscopy image of bioactive glass material in Example 1; Figure 3 Example 1: BET specific surface area test report of bioactive glass material; Figure 4 Example 1: Minimum Inhibitory Concentration (MIC) Test Report for Bioactive Glass Materials; Figure 5 Example 1: Clotting time of bioactive glass materials; Figure 6 Example 1: In vitro cytotoxicity test report of bioactive glass materials; Figure 7 Scanning electron microscope image of the bioactive glass material in Comparative Example 1; Figure 8 Scanning electron microscope images of the bioactive glass material in Comparative Example 2; Figure 9 Comparative scanning electron microscope images of the bioactive glass material in Example 3; Figure 10 Comparative scanning electron microscope images of the bioactive glass material in Example 4; Figure 11 Comparative scanning electron microscope image of the bioactive glass material in Example 5; Figure 12 Comparative scanning electron microscope images of the bioactive glass material in Example 6; Figure 13 Example 2: Scanning electron microscope image of bioactive glass material; Figure 14 Example 3: Scanning electron microscope image of bioactive glass material; Figure 15 Example 4: Scanning electron microscope image of bioactive glass material; Figure 16 Example 5: Transmission electron micrograph of bioactive glass material; Figure 17 Comparative Example 1: BET specific surface area test report of bioactive glass material; Figure 18 Comparative Example 2: BET specific surface area test report of bioactive glass material. Detailed Implementation

[0016] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0017] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0018] Example The embodiments of the present invention will be described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are for illustrative purposes only and should not be considered as limiting the scope of the invention. Unless otherwise specified in the examples, conventional conditions or conditions recommended by the manufacturer are followed. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0019] In this invention, the morphology of the powder was analyzed using scanning electron microscopy and transmission electron microscopy, the BET specific surface area of ​​the powder was analyzed using ASAP 2460Version 3.00, and the minimum inhibitory concentration (MIC) of the powder was evaluated.

[0020] Coagulation test: 5 mg of antimicrobial bioactive glass material (BG) was placed in 1 ml of cell culture medium and shaken at 37°C for 24 hours. 100 μL of the supernatant was then collected, and 100 ml of preheated deionized water (37°C) was added. Finally, 100 ml of anemic platelet-rich plasma (PPP) was added, and the coagulation level was measured. Anemic platelet-rich plasma (PPP) was used as a negative control (blank), and the coagulation time of CaCl2 (2.5 mg / ml) was used as a positive control for evaluation.

[0021] The following experiments were conducted to verify the effectiveness of the present invention.

[0022] Example 1: Dissolve 5 g of boric acid in 100 mL of deionized water, then add a mixture of 0.15 g of calcium chloride and 0.03 g of ferrous chloride. Continue stirring the reaction at 45°C to obtain a clear solution. Dissolve 0.006 g of silver nitrate and 0.01 g of copper sulfate in 50 mL of ammonia water (5 wt%) containing 0.2 g of hexadecyltrimethylammonium chloride at room temperature. Then add the complexed solution dropwise to the above clear solution and continue stirring the reaction. The mixture after the above reaction was placed in a sealed reaction vessel, aged at 75°C for 100 hours, dried at 120°C, and then heat-treated at 410°C for 2 hours. After further pulverization, antibacterial borate bioactive glass material was obtained.

[0023] Scanning electron microscope image of the antibacterial borate bioactive glass material prepared in Example 1 ( Figure 1 They exhibit a regular shape and a particle size of approximately 1 micrometer; transmission electron microscopy (TEM) images ( Figure 2 This further confirms that its particle size is approximately 1 micrometer; BET specific surface area test report ( Figure 3 The results showed that it could reach 684.3752m. 2 / g, the specific surface area within the micropores is 645.9513m². 2 / g, total pore volume is 0.34949cm³ 3 / g; Minimum Inhibitory Concentration (MIC) Test Report ( Figure 4 The results showed that the MIC for both Escherichia coli 8099 and Staphylococcus aureus ATCC6538 was 800 mg / L; the clotting time of bioactive glass materials ( Figure 5 The results showed that the bioactive glass material exhibited significantly faster coagulation compared to the PPP control group, with a coagulation time comparable to that of CaCl2; the in vitro cytotoxicity test report ( Figure 6 The results showed that the Ames test was negative.

[0024] Comparative Example 1: The system is largely the same as Example 1, except that the mass of calcium chloride in the system is adjusted to 3.5 g. (As shown in the scanning electron microscope...) Figure 7 The resulting particles had uneven morphology, with an average particle size of about 2 micrometers and no obvious mesoporous structure on the surface. Therefore, the antibacterial borate bioactive glass material described in this invention could not be obtained. (BET specific surface area test report) Figure 17 The data shows that its specific surface area is 2.5656 m². 2 / g.

[0025] Comparative Example 2: The system is largely the same as Example 1, except that the mass of calcium chloride was adjusted to 0.0006 g and the mass of ferric chloride to 0.00008 g. (As shown in the scanning electron microscope...) Figure 8 The resulting particles had uneven morphology, with an average particle size of about 0.2 micrometers and no obvious mesoporous structure on the surface. Therefore, the antibacterial borate bioactive glass material described in this invention could not be obtained. (BET specific surface area test report) Figure 18 The data shows that its specific surface area is 88.3007 m². 2 / g.

[0026] Comparative Example 3: The system is largely the same as Example 1, except that the heat treatment temperature was adjusted to 550°C. (As shown in the scanning electron microscope...) Figure 9 The resulting particles have uneven morphology, their regular morphology is destroyed, and their surface lacks obvious mesoporous structure, thus failing to obtain the antibacterial borate bioactive glass material described in this invention.

[0027] Comparative Example 4: The system is largely the same as Example 1, except that the aging temperature in the system was adjusted to 25°C. (As shown in the scanning electron microscope...) Figure 10 The resulting particles have uneven morphology, their regular morphology is destroyed, and their surface lacks obvious mesoporous structure, thus failing to obtain the antibacterial borate bioactive glass material described in this invention.

[0028] Comparative Example 5: The system is largely the same as Example 1, except that the mass of hexadecyltrimethylammonium chloride in the system is adjusted to 1 gram. As shown in the scanning electron microscope (SEM)... Figure 11 The resulting particles have uneven morphology, their regular morphology is destroyed, and their surface lacks obvious mesoporous structure, thus failing to obtain the antibacterial borate bioactive glass material described in this invention.

[0029] Comparative Example 6: The system is largely the same as Example 1, except that the heat treatment temperature was adjusted to 350°C and the heat treatment time was adjusted to 8 hours. (As shown in the scanning electron microscope...) Figure 12 The resulting particles have uneven morphology, their regular morphology is destroyed, and their surface lacks obvious mesoporous structure, thus failing to obtain the antibacterial borate bioactive glass material described in this invention.

[0030] Example 2: Unlike Example 1, in this example, the mass of calcium chloride was adjusted to 2 grams, the temperature for obtaining the clear solution was adjusted to 80°C, the aging temperature was adjusted to 90°C, and the aging time was adjusted to 200 hours. (Scanning electron microscope image) Figure 13 The results show that the antibacterial borate bioactive glass material of the present invention has been obtained.

[0031] Example 3: Unlike Example 1, in this example, the mass of calcium chloride was adjusted to 0.05 grams, and the scanning electron microscope image (...) Figure 14 The results show that the antibacterial borate bioactive glass material of the present invention has been obtained.

[0032] Example 4: Unlike Example 1, in this example, the mass of silver nitrate was adjusted to 0.02 grams, the heat treatment temperature was adjusted to 390°C, and the scanning electron microscope image (…) Figure 15 The results show that the antibacterial borate bioactive glass material of the present invention has been obtained.

[0033] Example 5: Unlike Example 1, in this example, ferric chloride is used instead of ferrous chloride, and the heat treatment time is adjusted to 4 hours. Transmission electron microscopy images (…) Figure 16 The results show that the antibacterial borate bioactive glass material of the present invention has been obtained.

[0034] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A method for preparing an antibacterial borate bioactive glass material, characterized in that, Includes the following steps: (1) Dissolve 5 g of boric acid in 100 mL of deionized water, then add 0.01-3 g of a mixture of calcium salt and iron salt, and stir the mixture at 20-100 °C to obtain a clear solution; wherein the calcium salt and iron salt are chlorides, nitrates or sulfates of the corresponding metals, and the mass ratio of calcium salt and iron salt based on their oxides is 100:1-10:1; (2) Dissolve 0.001-0.03 g of a mixture of copper and silver salts in 50 mL of ammonia water containing a surfactant at room temperature, and then add the resulting copper and silver salt complex solution dropwise to the clear solution in step (1) and stir to react; wherein the copper and silver salts are chlorides, nitrates or sulfates of the corresponding metals, and the mass ratio of silver and copper salts based on their oxides is 1:1-1:10; the surfactant is any one of hexadecyltrimethylammonium bromide, hexadecyltrimethylammonium chloride, tetradecyltrimethylammonium bromide, tetradecyltrimethylammonium chloride, and tetradecyldimethylbenzylammonium chloride, and the mass percentage of the surfactant in the ammonia water is 0.1-1 wt%; the concentration of the ammonia water is 0.01-10 wt%; (3) The mixture after the reaction in step (2) is placed in a sealed reaction vessel, aged at 60-100℃ for 96-240 hours, dried at 100-120℃, and then heat-treated at 390-460℃ for 2-4 hours. After pulverization, antibacterial borate bioactive glass material is obtained. The obtained antibacterial borate bioactive glass material has a regular morphology, with an average particle size of 1 micrometer, a BET specific surface area of ​​over 600 m² / g, and a total pore volume of over 0.349 cm³ / g.

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