An antibacterial magnesium- and strontium-reinforced bioactive glass-ceramic and its applications

Abstract

This invention belongs to the field of biomaterials technology, specifically an antibacterial magnesium and strontium-reinforced bioactive glass ceramic and its applications. Its composition, by weight percentage, is as follows: SiO2: 30-50; P2O5: 5-20; CaO: 10-35; Na2O: 10-20; SrO: 5-20; MgO: 2-10; ZnO: 5-15; B2O3: 0-10; K2O: 3-10; CuO: 0.05-5; F: 1.5-5; Ag: 0.05-0.9. It possesses good biocompatibility, is non-toxic and harmless to the human body, and effectively inhibits and kills bacteria. It can be used as a special additive in oral care products such as toothpaste, mouthwash, tooth powder, tooth gel, and chewing gum, promoting tooth surface mineralization and reducing dentin hypersensitivity during the teeth cleaning process.

Description

Technical Field

[0001] This invention relates to the field of biomaterials technology, specifically to an antibacterial magnesium and strontium-reinforced bioactive glass ceramic and its applications. Background Technology

[0002] Biologically active materials, when implanted into living tissue, form a strong bond between the material and the surrounding tissue. The bioactivity of these materials results from a series of complex physiological and chemical reactions on their surface under physiological conditions. When bioactive materials come into contact with body fluids, ion exchange occurs, where Na, K, Ca, Mg, Zn, and Cu from the interstitial spaces of the bioactive material are replaced by protons from the body fluids, forming non-stoichiometric hydrogen-bonded complexes. The alkaline pH at the interface between the bioactive material and body fluids favors the precipitation and crystallization of the hydroxyapatite phase. The resulting hydroxyapatite layer is structurally and chemically identical to the minerals of bone, and interfacial bonding occurs between the surface of the bioactive material and the living tissue. Hydroxyapatite is bioactive and can interact with living tissue to support the bone mineralization phase.

[0003] Bioactive materials are used as additives in oral care products. Their bioactivity manifests as an affinity that can induce the formation of new enamel on the tooth surface, seal dentinal tubules, and repair eroded areas of the tooth, thereby achieving the effects of desensitization and prevention of molar erosion.

[0004] Existing bioactive materials exhibit poor bioactivity, low strength and toughness, and limited functionality. To address these issues, we present an antibacterial magnesium- and strontium-reinforced bioactive glass-ceramic and its applications. Summary of the Invention

[0005] The purpose of this section is to outline some aspects of the embodiments of the present invention and to briefly describe some preferred embodiments. Simplifications or omissions may be made in this section, as well as in the abstract and title of this application, to avoid obscuring the purpose of these documents; however, such simplifications or omissions should not be construed as limiting the scope of the invention.

[0006] To solve the above-mentioned technical problems, according to one aspect of the present invention, the present invention provides the following technical solution: an antibacterial magnesium and strontium-reinforced bioactive glass ceramic, the composition of which, by weight percentage, is as follows: SiO2: 30-50; P2O5: 5-20; CaO: 10-35; Na2O: 10-20; SrO: 5-20; MgO: 2-10; ZnO: 5-15; B2O3: 0-10; K2O: 3-10; CuO: 0.05-5; F: 1.5-5; Ag: 0.05-0.9.

[0007] As a preferred embodiment of the antibacterial magnesium and strontium-reinforced bioactive glass ceramic of the present invention, its microcrystalline components are calcium strontium hydroxyphosphate Ca8Sr2(PO4)6(OH)2 and calcium magnesium phosphate (Ca,Mg)3(PO4)2.

[0008] Application of an antibacterial magnesium and strontium-reinforced bioactive glass ceramic in oral care products, skin care products, and antibacterial, bacteriostatic, and anti-inflammatory products.

[0009] Compared with existing technologies, the beneficial effects of this invention are as follows: The antibacterial magnesium and strontium-reinforced bioactive glass-ceramic material of this invention exhibits strong bioactivity during the process of binding with biological tissues. During the melting process, calcium strontium phosphate and calcium magnesium phosphate are generated; therefore, compared with existing bioactive glasses and bioactive glass-ceramics, the magnesium and strontium-reinforced bioactive glass-ceramic material of this invention possesses inherent bioactivity. Due to the presence of a large number of microcrystalline particles in the magnesium and strontium-reinforced bioactive glass-ceramic, the material's density increases, and its strength is significantly improved. This is not only higher than that of calcium magnesium phosphate ceramics but also higher than that of bioactive glasses. Magnesium and strontium ions partially replace calcium in calcium hydroxyphosphate and enter the glass-ceramic structure, further improving the strength and toughness of the glass-ceramic of this invention. The stable strength and toughness of the glass-ceramic ensure its durability as a dental material. The addition of zinc, copper, and silver ions gives the glass-ceramic material of this invention bactericidal, bacteriostatic, and anti-inflammatory effects. Attached Figure Description

[0010] To more clearly illustrate the technical solutions of the embodiments of the present invention, the present invention will be described in detail below with reference to the accompanying drawings and detailed embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort. Wherein:

[0011] Figure 1 This is the XRD pattern of a sample of an antibacterial magnesium and strontium-reinforced bioactive glass-ceramic and its application according to the present invention. Standard hydroxyapatite Ca... 10 Correspondence diagram between (PO4)6(OH)2 and crystallized sample;

[0012] Figure 2 The XRD patterns of the sample of the antibacterial magnesium and strontium-reinforced bioactive glass ceramic and its application are shown in the figure below. The XRD pattern of strontium-reinforced hydroxyapatite Ca8Sr2(PO4)6(OH)2 is also shown.

[0013] Figure 3 The XRD pattern of the sample of the antibacterial magnesium and strontium-reinforced bioactive glass ceramic and its application of the present invention is shown in the sample XRD pattern of magnesium-reinforced calcium magnesium phosphate (Ca,Mg)3(PO4)2.

[0014] Figure 4 The images show the inhibition zones of different dosages of an antibacterial magnesium and strontium-reinforced bioactive glass ceramic and its application in different bacterial species. A is a complete image of a culture dish of Trichomonas testis (CT), and B is a complete image of a culture dish of Escherichia coli (BL21). The dosages of the drug in the two plates are 0.1g and 0.05g, respectively, and the amount of powder sprinkled is 0.1g.

[0015] Figure 5 Images show the overall inhibition zone of an Escherichia coli (BL21) culture dish made of an antibacterial magnesium and strontium-reinforced bioactive glass ceramic and its application, which is based on a silver-free, zinc- and copper-free glass ceramic (left) and an antibacterial magnesium and strontium-reinforced bioactive glass ceramic (right). Detailed Implementation

[0016] To make the objectives, technical solutions, and advantages of the present invention clearer, the embodiments of the present invention will be described in further detail below with reference to the accompanying drawings.

[0017] This invention introduces strontium into bioactive glass-ceramics. Strontium is an essential trace element for the human body, accounting for approximately 0.01% of bone mass. Strontium enhances bone strength and can effectively desensitize and increase tooth density in oral health applications. This invention alters the bioactivity of antibacterial magnesium- and strontium-reinforced bioactive glass-ceramics. Because strontium ions are larger than calcium ions, the substitution of calcium ions by strontium ions in these glass-ceramics causes the glass-ceramic network to expand, improving its degradability and deposition rate.

[0018] This invention introduces magnesium into bioactive glass-ceramics. The introduction of magnesium ions reduces the crystallite size of hydroxyapatite in the bioactive glass-ceramics, thereby lowering the coefficient of thermal expansion. This holds promise for the application of bioactive glass-ceramics in alloy coatings such as Ti6Al14V. Magnesium ions are the fourth most abundant cation in the human body after sodium, potassium, and calcium, and also the second most abundant cation in cells. They participate in many key biochemical reactions, exerting a profound impact on the body. Magnesium ions can regulate blood pressure by combating arrhythmia and modulating vascular tone.

[0019] This invention introduces potassium into bioactive glass ceramics. Potassium is a major intracellular cation and is widely recognized for its role in the prevention and treatment of hypertension. In addition, potassium can reduce urinary calcium excretion, increase calcium intake, and reduce the occurrence of osteoporosis and kidney stones.

[0020] This invention introduces zinc into bioactive glass ceramics. It has been found that the introduction of zinc into bioactive glass ceramics can promote wound healing and aid in the repair and reconstruction of damaged bone tissue. Zinc ions also possess bactericidal and bacteriostatic functions. The anti-inflammatory effect of zinc ions also contributes to the body's natural immune system. Zinc ions are crucial for the normal development of various cells and for both innate and acquired immune functions. After killing bacteria, zinc ions can be released from the cells and repeat the above bactericidal process, which explains the long-lasting antibacterial effect of zinc ion antibacterial agents. Under sunlight, especially under strong ultraviolet light, nano-zinc ion antibacterial agents can self-decompose in water and air, releasing freely moving negatively charged electrons while leaving behind positively charged electron holes. These holes can convert oxygen in the air into reactive oxygen species, which have very strong chemical activity and can react with various organic substances to kill most bacteria.

[0021] This invention introduces copper into bioactive glass ceramics, which has been found to possess bactericidal and bacteriostatic functions. Copper has a strong anti-cancer function, which has been confirmed. Copper ions are beneficial to the human body, primarily acting as a bactericide and deodorizer; most bacteria cannot survive in the vicinity of copper. The main mechanism of copper ion bactericidal action is through the release of copper ions, interfering with the normal cellular physiological metabolic processes of microorganisms, thereby achieving a bactericidal effect. Within the cell membrane of microorganisms, copper ions can bind to proteins, forming a flocculant that reduces cell membrane strength, causing the cell membrane to lose its selective permeability. They can also bind to DNA in the cytoplasm, causing DNA strand breaks, thereby killing microorganisms. Copper ions have strong antibacterial properties, and their primary function is to disrupt the cell wall and cell membrane structure of microorganisms. Copper ions can bind to fatty acids in the cell membrane, causing them to lose electrons and lose their function, thus destroying the cell membrane and causing death. Furthermore, copper ions can also bind to carboxyl groups in the cell wall, leading to cell wall destruction and thus killing microorganisms.

[0022] This invention introduces silver into bioactive glass ceramics, and it has been found that the introduction of silver into bioactive glass ceramics has bactericidal and bacteriostatic functions.

[0023] The metal ions silver, zinc and copper exhibit a synergistic bactericidal effect, with the bactericidal rate decreasing as follows: bactericidal rate of three metal ions ≥ bactericidal rate of two metal ions ≥ bactericidal rate of a single metal ion.

[0024] Specifically, an antibacterial magnesium and strontium-reinforced bioactive glass-ceramic has the following composition by weight percentage: SiO2: 30-50; P2O5: 5-20; CaO: 10-35; Na2O: 10-20; SrO: 5-20; MgO: 2-10; ZnO: 5-15; B2O3: 0-10; K2O: 3-10; CuO: 0.05-5; F: 1.5-5; Ag: 0.05-0.9. Its microcrystalline components are calcium strontium hydroxyphosphate Ca8Sr2(PO4)6(OH)2 and calcium magnesium phosphate (Ca,Mg)3(PO4)2.

[0025] Antibacterial magnesium and strontium-reinforced bioactive glass ceramics contain SiO2 as the main glass network generator.

[0026] Antibacterial magnesium and strontium-reinforced bioactive glass ceramics contain phosphorus sources, which combine with calcium to form calcium strontium phosphate and calcium magnesium phosphate. Furthermore, P2O5 has a beneficial effect on the viscosity-temperature dependence of glass, increasing the operating temperature range and promoting glass ceramic formation.

[0027] Antibacterial magnesium and strontium-reinforced bioactive glass ceramics contain B2O3, which is introduced in the form of boric acid (H3BO3) to increase the operating temperature range and is beneficial to the formation of glass ceramics.

[0028] Antibacterial magnesium and strontium-strengthened bioactive glass ceramics contain calcium sources, which are introduced in the form of calcium carbonate (CaCO3), calcium sulfate (CaSO4), or calcium fluoride (CaF2). Calcium combines with phosphorus to form hydroxyapatite.

[0029] Antibacterial magnesium and strontium-strengthened bioactive glass ceramics contain sodium sources, introduced in the form of sodium carbonate (Na2CO3), sodium nitrate (NaNO3), sodium sulfate (Na2SO4), or sodium fluoride (NaF). Sodium acts as a co-solvent and a network modifier.

[0030] Antibacterial magnesium and strontium-reinforced bioactive glass ceramics contain strontium sources, introduced in the form of strontium carbonate (SrCO3), strontium nitrate (Sr(NO3)2), strontium sulfate (SrSO4), or strontium fluoride (SrF2). Strontium acts as a glass network modifier. Strontium also has various beneficial effects on bone metabolism, directly stimulating osteoblasts and increasing the strength and deposition rate of hydroxyapatite. It can prevent and treat dental tissue damage.

[0031] Antibacterial and antimicrobial magnesium- and strontium-reinforced bioactive glass ceramics contain zinc sources, introduced in the form of zinc oxide (ZnO), zinc carbonate (ZnCO3), zinc sulfate (ZnSO4), or zinc nitrate (Zn(NO3)2). Zinc ions have bactericidal and anti-inflammatory effects, can promote wound healing, and can repair and reconstruct damaged bone tissue. Zinc is also a glass network modifier, which can reduce the size of the formed calcium hydroxyphosphate crystals and lower the coefficient of thermal expansion of magnesium- and strontium-reinforced bioactive glass ceramics.

[0032] Antibacterial magnesium and strontium-reinforced bioactive glass ceramics contain potassium sources, introduced in the form of potassium carbonate (K₂CO₃), potassium nitrate (KNO₃), or potassium sulfate (K₂SO₄). Potassium acts as a solubilizer and network modifier. Potassium is a major intracellular cation, and besides its widespread recognition in the prevention and treatment of hypertension, it can also reduce urinary calcium excretion, increase calcium intake, and reduce the incidence of osteoporosis and kidney stones.

[0033] The antibacterial magnesium and strontium-reinforced bioactive glass-ceramics contain a fluorine source. At least one of the aforementioned calcium fluoride (CaF2), strontium fluoride (SrF2), and sodium fluoride (NaF) is selected. The introduced fluoride ions act as nucleating agents in the glass-ceramics, directly affecting the formation and quality of calcium hydroxyphosphate microcrystals. Adding fluorides can also lower the melting temperature of the antibacterial magnesium and strontium-reinforced bioactive glass-ceramics of this invention.

[0034] Antibacterial magnesium and strontium-reinforced bioactive glass ceramics contain copper sources, introduced in the form of copper oxide (CuO) or copper chloride (CuCl2). Copper ions help provide magnesium and strontium-reinforced bioactive glass ceramics with antibacterial and bactericidal properties.

[0035] An antibacterial magnesium and strontium-reinforced bioactive glass ceramic is used in oral care products, where it can significantly inhibit bacteria, kill bacteria, and alleviate symptoms such as dentin hypersensitivity, plaque, gingival bleeding, and loose teeth; it can also be used in skin care creams with anti-ultraviolet radiation, antimicrobial, and skin damage repair effects; and it can also be used in other products that require sterilization, bacteriostasis, and anti-inflammation.

[0036] Antibacterial magnesium and strontium-reinforced bioactive glass ceramics are prepared using a high-temperature powder melting method. Specifically, the raw materials are thoroughly mixed and placed in a silicon carbide (silicon molybdenum) rod electric furnace, then melted at 1350℃–1420℃ using a platinum or clay crucible. The melting time depends on the volume. After melting, the mixture is cooled to a certain temperature to form glass ceramics. The ceramics are then removed, poured into water to cool, and dried. The dried raw materials are then pulverized into micron or submicron particles using a ball mill to obtain magnesium and strontium-reinforced bioactive glass ceramic materials.

[0037] Example 1

[0038] Using SiO2, P2O5, CaCO3, Na2CO3, SrCO3, ZnO, KNO3, H3BO3, CaF2, CuO, and AgNO3 as raw materials, the following are the weight percentages (Wt%):

[0039] SiO2: 35; P2O5: 8; CaO: 20; Na2O: 15; SrO: 5; MgO: 3; K2O: 3.8; ZnO: 6; B2O3: 2; CuO: 0.3; F: 2; Ag: 0.05.

[0040] After being mixed evenly, the mixture is placed in a silicon carbide rod (silicon molybdenum rod) electric furnace and melted at 1390℃ in a platinum crucible or clay crucible for 2 hours. After melting, the mixture is cooled to a certain temperature to form a glass ceramic. The mixture is then removed and poured into water to cool. The dried raw material is then pulverized into micron or submicron particles using a ball mill to obtain antibacterial magnesium and strontium-reinforced bioactive glass ceramic material.

[0041] Example 2

[0042] Using SiO2, P2O5, CaCO3, NaNO3, SrCO3, ZnO, KNO3, H3BO3, CaF2, CuO, and AgNO3 as raw materials, the following are the weight percentages (Wt%):

[0043] SiO2: 35; P2O5: 8; CaO: 18; Na2O: 14; SrO: 5; MgO: 3; K2O: 3.5; ZnO: 10; B2O3: 2; CuO: 0.5; F: 2; Ag: 0.1.

[0044] After being mixed evenly, the mixture is placed in a silicon carbide rod (silicon molybdenum rod) electric furnace and melted at 1390℃ in a platinum crucible or clay crucible for 2 hours. After melting, the mixture is cooled to a certain temperature to form a glass ceramic. The mixture is then removed and poured into water to cool. The dried raw material is then pulverized into micron or submicron particles using a ball mill to obtain antibacterial magnesium and strontium-reinforced bioactive glass ceramic material.

[0045] Example 3

[0046] Using SiO2, P2O5, CaCO3, Na2CO3, SrCO3, ZnO, KNO3, CaF2, CuO, and AgNO3 as raw materials, the following are the weight percentages (Wt%):

[0047] SiO2: 35; P2O5: 8; CaO: 20; Na2O: 15; SrO: 5; MgO: 3; K2O: 3.6; ZnO: 8; CuO: 1; F: 2; Ag: 0.3.

[0048] After being mixed evenly, the mixture is placed in a silicon carbide rod (silicon molybdenum rod) electric furnace and melted at 1390℃ in a platinum crucible or clay crucible for 2 hours. After melting, the mixture is cooled to a certain temperature to form a glass ceramic. The mixture is then removed and poured into water to cool. The dried raw material is then pulverized into micron or submicron particles using a ball mill to obtain antibacterial magnesium and strontium-reinforced bioactive glass ceramic material.

[0049] Please see Figure 1-3 The crystallized glass-ceramic sample was obtained by melting according to the aforementioned high-temperature melting method. The composition of the crystallized glass-ceramic sample was analyzed using X-ray diffraction (XRD) at 40 kV / 20 mA with a step size of 0.4 kΩ. o The range of angles for the 2Θ pattern is 10-80°. o The reference card was Ca8Sr2(PO4)6(OH)2. After comparison with the standard card, from... Figure 2 It can be seen that the sample exhibits both a glassy phase and a crystalline phase, with the crystalline phase being predominantly Sr. 2+ Replacing part of Ca 2+ Calcium hydroxyphosphate, mainly composed of the Ca8Sr2(PO4)6(OH)2 crystalline phase, from Figure 3 It can be seen that there is also a magnesium calcium phosphate (Ca,Mg)3(PO4)2 crystalline phase. This is the desired crystalline phase of the magnesium and strontium-reinforced bioactive glass-ceramic of the present invention.

[0050] The main mineral component of human bone tissue is calcium hydroxyphosphate, so the main component of our bioactive glass-ceramics is also calcium hydroxyphosphate. It can bind to biological tissues, thus giving the material its corresponding bioactivity. Compared to other additives, this material has a strong affinity, can protect teeth, and has no toxic side effects.

[0051] Please see Figure 4 As can be seen from the image, the size of the inhibition zone did not change with the sample dosage; the size of the inhibition zone was similar for different dosages of the drug, proving that the antibacterial effect of this sample was stable and good.

[0052] Please see Figure 5 This material introduces strontium (Sr) 2+ ), Strontium (Sr 2+ Sr replaces calcium in the calcium hydroxyphosphate structure. XRD analysis revealed the formation of calcium hydroxyphosphate grains in the glass phase, with some calcium in the resulting calcium hydroxyphosphate structure being replaced by strontium. 2+ The presence of [a substance] enhances bone (teeth) strength, improves the mechanical properties of bioactive glass ceramics, and increases their hardness. It significantly and relatively stably improves the strength and toughness of the material.

[0053] By adding silver ions, zinc ions, and copper ions, it acquires bactericidal and anti-inflammatory effects. + and Cu 2+ Zn 2+ The introduction of this material enhances its bactericidal effect on the oral environment. Furthermore, its effect on bacteria is to kill rather than inhibit their growth, thereby promoting the growth of bone and soft tissues and accelerating wound healing. Therefore, it can be concluded that this bioactive glass-ceramic has a positive effect on the treatment of gingivitis, bleeding gums, and relieving tooth loosening symptoms.

[0054] The antibacterial ions in this bioactive glass-ceramic are evenly distributed, ensuring that its bactericidal effect is not significantly altered by particle size; even very small particles exhibit a noticeable bactericidal effect. When used as an additive, it effectively achieves its bactericidal purpose.

[0055] Although the present invention has been described above with reference to embodiments, various modifications can be made and components can be replaced with equivalents without departing from the scope of the invention. In particular, as long as there is no structural conflict, the features in the disclosed embodiments can be combined with each other in any manner. The lack of an exhaustive description of these combinations in this specification is merely for the sake of brevity and resource conservation. Therefore, the present invention is not limited to the specific embodiments disclosed herein, but includes all technical solutions falling within the scope of the claims.

Claims

1. An antimicrobial magnesium, strontium fortified bioactive glass-ceramic, characterized in that, by weight percent: SiO2: 30-50; P2O5: 5-20; CaO: 10-35; Na2O: 10-20; SrO: 5-20; MgO: 2-10; ZnO: 5-15; B2O3: 0-10; K2O: 3-10; CuO: 0.05-5; F：1.5-5； Ag: 0.05-0.

9.

2. The antimicrobial magnesium, strontium fortified bioactive glass-ceramic according to claim 1, characterized in that, The microcrystalline components are strontium calcium hydroxyapatite Ca8Sr2(PO4)6(OH)2 and magnesium calcium phosphate (Ca, Mg)3(PO4)2.

3. Use of the antibacterial magnesium, strontium reinforced bioactive glass-ceramics according to any one of claims 1-2 in oral care products, skin care products and antiseptic, bacteriostatic, anti-inflammatory products.

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