Zirconia ceramic, in vivo implant, firing powder, and method for producing zirconia ceramic

Abstract

The zirconia ceramic according to an embodiment has a crystal structure comprising zirconium, silver, and oxygen ions. The method for producing a zirconia ceramic according to an embodiment includes a sediment formation step (S1) and a firing step (S3). In the sediment formation step (S1), a zirconium compound and a silver compound are mixed in a solution or suspension state and a precipitant is then added to the solution or suspension, thereby obtaining a sediment comprising zirconia derived from the zirconium compound and silver derived from the silver compound. In the firing step (S3), a firing powder obtained by drying the sediment is fired to obtain a zirconia ceramic with which silver ions have combined.

Description

Zirconia ceramic, in vivo implant, powder for firing, and method for producing zirconia ceramic

[0001] The present invention relates to a zirconia ceramic, an in vivo implant, a powder for firing, and a method for producing a zirconia ceramic.

[0002] As disclosed in Patent Document 1, zirconia ceramics are used as a material for in vivo implants. In addition, zirconia ceramics are also used in various products such as blades.

[0003] Japanese Unexamined Patent Publication No. 63-277061

[0004] An object of the present invention is to provide a novel zirconia ceramic, a bioimplant, a powder for firing, and a method for producing the zirconia ceramic.

[0005] The zirconia ceramic according to the present invention has a crystal structure consisting of zirconium ions, silver ions and oxygen ions.

[0006] The silver ions may form a solid solution together with the zirconium ions and the oxygen ions.

[0007] At room temperature, the crystal structure may be a mixture of monoclinic and tetragonal crystals, or may be tetragonal crystals.

[0008] The content of the silver ions may be 0.01 mol % or more relative to the zirconium ions.

[0009] The zirconia ceramic according to the present invention may contain 20% or more of tetragonal crystals.

[0010] The zirconia ceramic may be in the form of a block, powder, or coating.

[0011] The in vivo implant according to the present invention comprises the above-described zirconia ceramic according to the present invention.

[0012] The sintering powder according to the present invention is used for producing zirconia ceramics, and contains silver in zirconia powder.

[0013] The method for producing zirconia ceramic according to the present invention includes a precipitate formation step of mixing a zirconium compound and a silver compound in the form of a solution or suspension, and then adding a precipitant to the solution or suspension to obtain a precipitate containing zirconium derived from the zirconium compound and silver derived from the silver compound; and a firing step of drying the precipitate to obtain a powder for firing, and thereby obtaining zirconia ceramic in which silver ions are composited.

[0014] According to the present invention, a novel zirconia ceramic, an in vivo implant, a powder for firing, and a method for producing the zirconia ceramic are provided.

[0015] 1. A flowchart illustrating a method for manufacturing a zirconia ceramic according to an embodiment. 2. A conceptual diagram illustrating the structure of a zirconia ceramic according to an embodiment. 3. A graph showing the relative values ​​of the silver content in the zirconia ceramic according to Examples A1 to A7. 4. A graph showing the X-ray diffraction waveform of the zirconia ceramic according to Example C. 5. A graph showing the amount of silver eluted into PBS from the zirconia ceramic according to Examples A-C and the Comparative Example. 6. A graph showing the amount of silver eluted into αMEM from the zirconia ceramic according to Examples A-C and the Comparative Example. 7. A graph showing the results of a first antibacterial test of the zirconia ceramic according to Examples A-C and the Comparative Example. 8. A graph showing the results of a second antibacterial test of the zirconia ceramic according to Examples D-F and the Comparative Example. 9. A graph showing the results of a third antibacterial test of the zirconia ceramic according to Examples D-F and the Comparative Example.

[0016] [Embodiment] A method for producing zirconia ceramic according to an embodiment will be described with reference to Figure 1. First, a zirconium compound (hereinafter referred to as a zirconium compound) and a silver compound (hereinafter referred to as a silver compound) are mixed in the form of a solution or suspension. Next, a precipitant is added to the solution or suspension to obtain a precipitate (precipitate generation step S1).

[0017] The zirconium compound may be a salt, such as zirconium chloride, zirconium oxyoxide, zirconium oxynitrate, zirconium oxysulfide, zirconium oxyacetate, or zirconium butoxide.

[0018] The silver compound may be a salt, such as silver nitrate, silver chloride, silver sulfide, or silver acetate.

[0019] The solvent may be either a non-polar or polar solvent as long as it dissolves or suspends the zirconium compound and silver compound used. Examples of solvents that can be used include water, alcohols, acetone, phenol, toluene, dimethyl sulfoxide, carboxylic acids, alkanes, carboxylic acid esters, and mixtures thereof. The solvent used can be selected depending on the properties of the zirconium compound and silver compound.

[0020] The term "alcohols" as used herein refers to organic molecules having one or more hydroxy groups in the molecule. Examples of alcohols include monohydric alcohols such as methanol, ethanol, 1-butanol, 1-pentanol, 1-hexanol, 1-octanol, isopropyl alcohol, 2-butanol, 2-pentanol, 2-hexanol, and tert-butanol, dihydric alcohols such as ethylene glycol, diethylene glycol, and propylene glycol, and trihydric alcohols such as glycerin.

[0021] The term "carboxylic acids" as used herein refers to organic molecules having one or more carboxy groups in the molecule, including saturated fatty acids such as caproic acid, enanthic acid, lauric acid, capric acid, palmitic acid, and stearic acid, and unsaturated fatty acids such as oleic acid, linoleic acid, arachidonic acid, and sorbic acid.

[0022] The alkanes referred to here are those of the general formula C ｎ H ２ｎ＋２Alkanes refer to chain saturated hydrocarbons represented by the formula: Examples of alkanes include pentane, hexane, heptane, octane, nonane, decane, undecane, dodecane, and octadecane.

[0023] The term "carboxylic acid ester" used herein refers to a molecule formed by polymerizing an organic molecule containing a carboxyl group and an organic molecule containing a hydroxyl group via an ester bond. Examples of carboxylic acid esters include ethyl acetate, methyl salicylate, ethyl formate, methyl butyrate, ethyl propionate, and pentyl valerate.

[0024] The precipitant increases the pH of the solution or suspension containing the zirconium compound and the silver compound, thereby promoting the formation of the precipitate. Examples of precipitants that can be used include those that produce alkaline aqueous solutions, such as ammonia, sodium hydroxide, ammonium carbonate, arginine, lysine, trisaminomethane, sodium bicarbonate, and sodium carbonate.

[0025] The precipitate is an aggregate of substances containing zirconia derived from the zirconium compound and silver derived from the silver compound. Next, the precipitate is dried to obtain a powder for firing in which silver is contained in zirconia powder (powder for firing formation step S2). The powder for firing may contain zirconia powder and silver or silver compound powder.

[0026] The powder for firing is preferably a substance composed of zirconia and silver. The content of silver in the powder for firing is preferably 0.01 mol% or more, more preferably 0.01 mol% or more and 10 mol% or less, still more preferably 0.5 mol% or more and 10 mol% or less, and even more preferably 1.0 mol% or more and 5 mol% or less, relative to the zirconium ions constituting the zirconia.

[0027] In the above-mentioned powder for firing and the above-mentioned precipitate, the silver may be silver ions. In this specification, "powder for firing containing silver ions" means that in the powder for firing, silver atoms are present in a form ionically bonded to other atoms such as zirconium atoms. In other words, silver is not present in a free ionic form. The same applies to the above-mentioned precipitate. However, in the above-mentioned powder for firing and the above-mentioned precipitate, the silver does not necessarily have to be ionically bonded to other atoms, and ionic bonds between silver atoms and other atoms may be formed by firing, which will be described later.

[0028] Next, the above-mentioned powder for firing is fired. Alternatively, the powder for firing may be molded and then the resulting molded body may be fired. By firing, a zirconia ceramic is obtained (firing step S3). The firing temperature of the powder for firing or the molded body (hereinafter referred to as the object to be fired) is preferably, for example, 500°C or higher and 700°C or lower. In this specification, the "firing temperature" means the maximum temperature reached. In the firing step S3, it is preferable to hold the object to be fired at the maximum temperature reached for a period of 1 hour or higher and 3 hours or lower.

[0029] According to the above-described embodiment, a novel zirconia ceramic is provided. The zirconia ceramic may be in the form of a block, a powder, or a coating. The thickness of the coating is not particularly limited. The thickness of the coating may be, for example, 10 nm or more and 10 μm or less. Furthermore, the object constituting the base on which the coating is formed is not particularly limited. The coating may be formed on the surface of a plate-shaped object such as a substrate. The substrate may be made of, for example, ceramic, metal, polymer, or the like. The zirconia ceramic powder may be obtained by firing a powder for firing without molding, or by pulverizing a block or block of zirconia ceramic.

[0030] Furthermore, according to this embodiment, there is also provided a powder to be fired obtained in the above-described powder to be fired forming step S2. As described above, the powder to be fired is used to manufacture zirconia ceramic. That is, the powder to be fired is molded as necessary and then subjected to firing.

[0031] The zirconia ceramic according to this embodiment has a crystalline structure (hereinafter referred to as crystalline zirconia). At room temperature, the crystalline zirconia is preferably a mixture of monoclinic and tetragonal crystals, or is composed of tetragonal crystals. However, the crystalline zirconia may also contain cubic crystals. In this specification, "room temperature" refers to a temperature of 5°C or higher and 35°C or lower.

[0032] The zirconia ceramic according to this embodiment contains a composite of silver. Specifically, silver is contained in the zirconia crystal in the form of silver ions. That is, the zirconia crystal is composed of zirconium ions, silver ions, and oxygen ions. Here, "composed of zirconium ions, silver ions, and oxygen ions" means that in the zirconia crystal, each of the zirconium atoms, silver atoms, and oxygen atoms is present in the form of an ionic bond with the other atom. This does not mean that each atom is present in a free ionic form. Note that the silver ions may form a solid solution together with the zirconium ions and oxygen ions that constitute the zirconia ceramic.

[0033] Furthermore, in the zirconia ceramic according to this embodiment, silver can function as a stabilizing element. Silver as a stabilizing element exists in the tetragonal structure in the form of a solid solution in the tetragonal crystal. Here, the term "stabilizing element" refers to an element that acts as a stabilizer, expanding the temperature range in which the tetragonal or cubic crystal, which is originally a high-temperature phase, can exist stably to a temperature range including room temperature. In particular, "stabilization" refers to expanding the temperature range in which the tetragonal crystal can exist to a temperature range including room temperature. By stabilizing the tetragonal crystal with a stabilizing element, the phase transition from the tetragonal crystal to the monoclinic crystal is suppressed. This suppresses the occurrence of cracks due to the volume expansion accompanying the phase transition.

[0034] The zirconia ceramic according to this embodiment preferably contains 20% or more of tetragonal crystals when measured by X-ray diffraction at room temperature, which allows the zirconia ceramic to exhibit excellent toughness.

[0035] One of the reasons why silver can function as a stabilizing element is that the ionic radius of silver (1.0 to 1.15 Å) is similar to the ionic radius of yttrium (0.90 Å), a typical stabilizing element. This is because the ionic radius of the stabilizing element that has entered the crystal is an important factor in preventing transformation of the crystal structure.

[0036] Yttrium can function as a stabilizing element even when the amount added to zirconium ions is 0.01 mol% or less (excluding 0 mol%). Therefore, like silver, it is thought that yttrium can function as a stabilizing element even when the amount added to zirconium ions is 0.01 mol% or less (excluding 0 mol%).

[0037] The content of silver ions in the zirconia ceramic according to this embodiment is preferably 0.01 mol% or more relative to zirconium ions, more preferably 0.01 mol% or more and 10 mol% or less, even more preferably 0.5 mol% or more and 10 mol% or less, and even more preferably 1.0 mol% or more and 5 mol% or less. Note that, when a firing temperature at which the amount of silver evaporation is negligible is adopted in the firing step S3, the content of silver ions relative to zirconium ions in the zirconia ceramic is equal to the content of silver relative to zirconium ions in the firing powder described above.

[0038] However, the zirconia ceramic according to this embodiment may further contain, as a stabilizer, an oxide other than the silver compound, such as calcium oxide, magnesium oxide, yttrium oxide, sodium oxide, lanthanum oxide, praseodymium oxide, neodymium oxide, ytterbium oxide, or gadolinium oxide.

[0039] The zirconia ceramic according to this embodiment can be used as a component of an in vivo implant. In this specification, the concept of an in vivo implant includes not only intraoral implants such as dental restorations (e.g., crowns and bridges) and implant fixtures (artificial tooth roots) embedded in the jawbone, but also implants used in parts of the body other than the oral cavity, such as artificial joints and artificial bones.

[0040] 2 is a conceptual diagram showing the structure of the zirconia ceramic according to this embodiment. Silver atoms are coordinated to at least a portion of the surface of the zirconia ceramic according to this embodiment. Because silver exhibits antibacterial properties, bacteria are less likely to grow on the surface of the zirconia ceramic according to this embodiment.

[0041] In other words, silver not only serves as a stabilizing element that stabilizes the tetragonal crystal structure, but also provides an antibacterial effect to the surface of the zirconia ceramic. Therefore, when the zirconia ceramic according to this embodiment is used as, for example, an oral implant, the growth of bacteria in the oral cavity is suppressed. Therefore, it is expected to be effective in preventing oral inflammation, aspiration pneumonia, etc.

[0042] Furthermore, even if cracks occur in the zirconia ceramic during use, silver atoms are exposed on the cracked surface. In this way, the surface where silver atoms are coordinated is always exposed, so even if a crack occurs, the area is unlikely to become a site of infection.

[0043] Furthermore, silver atoms exist in the structure of zirconia ceramic in a form chemically bonded to other atoms. Specifically, silver atoms are chemically bonded to oxygen atoms in the form of substitution for zirconium atoms. Therefore, silver atoms are less likely to be eluted from the surface of zirconia ceramic. In other words, the above-mentioned antibacterial effect is exerted not by silver ions eluted from the structure but by silver atoms present on the surface of the structure.

[0044] As described above, the zirconia ceramic according to this embodiment is resistant to discoloration and exhibits stable aesthetics over a long period of time because silver ions are less likely to be eluted from the surface. Furthermore, because the zirconia ceramic according to this embodiment is resistant to discoloration of living tissues when used as an in vivo implant, even when silver functions as a stabilizing element, the zirconia ceramic is less likely to discolor living tissues.

[0045] [Example] Hereinafter, an example of a method for producing zirconia ceramic having a crystal structure consisting of zirconium ions, silver ions, and oxygen ions will be described.

[0046] First, a first experiment conducted to investigate the preferred range of the firing temperature will be described.

[0047] Zirconium oxychloride octahydrate (ZrCl ２ O・8H ２ Zirconium oxychloride solution with a concentration of 2 mol / L was obtained by dissolving silver nitrate (AgNO ３ ) was dissolved in distilled water to obtain a silver nitrate solution with a concentration of 200 mmol / L. The zirconium oxychloride solution and silver nitrate solution were then thoroughly mixed with pure water to obtain a mixed solution.

[0048] In this manner, zirconium oxychloride octahydrate and silver nitrate were mixed in the form of a solution. Here, zirconium oxychloride octahydrate is an example of the zirconium compound shown in Figure 1. Silver nitrate is an example of the silver compound shown in Figure 1.

[0049] Next, a 28% aqueous ammonia solution was added to the mixed solution to form a precipitate. The amount of ammonium ions added was 50 mol % or more relative to the zirconium ions dissolved in the mixed solution. Here, the ammonia in the aqueous ammonia solution is an example of the precipitant shown in FIG. 1.

[0050] The mixed solution containing the aqueous ammonia solution was further stirred for at least one hour to uniformly disperse the precipitate. The precipitate was then thoroughly dried and pulverized to obtain a powder for firing.

[0051] The obtained powder for firing contained 1 mol % of silver relative to 100 mol % of zirconium. That is, the mixing ratio of the zirconium oxychloride solution and the silver nitrate solution was adjusted in the step of preparing the mixed solution so that the silver content in the powder for firing was 1 mol % relative to zirconium.

[0052] Next, the obtained powder for firing was fired in an electric furnace under an air atmosphere to obtain zirconia ceramics. In the above manner, the zirconia ceramics according to Examples A1 to A7, which were different from each other only in the firing temperature condition of the powder for firing, were obtained.

[0053] The firing temperatures for each example are shown in parentheses in Figure 3. That is, for the zirconia ceramics of Examples A1, A2, A3, A4, A5, A6, and A7, the firing powder was fired at 400°C, 500°C, 600°C, 700°C, 800°C, 900°C, and 1000°C, respectively.

[0054] In this experiment, "calcining the powder to be calcined at T°C" specifically refers to the procedure of raising the temperature of the powder to be calcined from room temperature to T°C at a temperature increase rate of 8°C / min, then holding it at T°C for 2 hours, and then cooling it from T°C to room temperature at a temperature decrease rate of 5°C / min.

[0055] In Figure 3, the silver content of the zirconia ceramic according to each example is shown in a bar graph. The height of each bar represents the relative value of the silver content. The silver content was measured by X-ray fluorescence (XRF) analysis. In each example, the silver content was measured three times (n number). The 95% confidence interval is also shown at the top of each bar.

[0056] As shown in Figure 3, the higher the firing temperature of the firing powder, the more significantly the silver content in the resulting zirconia ceramic decreased. This is thought to be due to the evaporation of silver by heating. In other words, the lower the firing temperature, the more likely silver is to remain.

[0057] According to the results of this experiment, the firing temperature of the powder to be fired is preferably less than 1000° C., more preferably 800° C. or less, more preferably 700° C. or less, and even more preferably 600° C. or less. The firing temperature of the powder to be fired is preferably 400° C. or more, and more preferably 500° C. or more.

[0058] The first experiment was described above, in which the silver content in the powder for firing was a common value among the examples, and the firing temperature was different among the examples. Next, the second experiment was described, in which the silver content in the powder for firing was different among the examples, and the firing temperature was a common value among the examples.

[0059] Zirconium oxychloride octahydrate (ZrCl ２ O・8H ２ Zirconium oxychloride solution with a concentration of 2 mol / L was obtained by dissolving silver nitrate (AgNO ３ ) was dissolved in distilled water to obtain a silver nitrate solution with a concentration of 200 mmol / L. The zirconium oxychloride solution, silver nitrate solution, and pure water were then added dropwise in predetermined amounts to a beaker using a pipette, and the mixture was thoroughly mixed using a stirrer.

[0060] As described above, zirconium oxychloride octahydrate and silver nitrate were mixed in the form of a solution to prepare a mixed solution. Note that zirconium oxychloride octahydrate is an example of the zirconium compound shown in Figure 1. Silver nitrate is an example of the silver compound shown in Figure 1.

[0061] Finally, in order to obtain the zirconia ceramics of Examples A to F, which have different silver ion contents, mixed solutions of Examples A to F, each containing a different amount of zirconium oxychloride solution, silver nitrate solution, and pure water, were prepared. Furthermore, in order to obtain the zirconia ceramics of Comparative Example, which does not contain silver ions, a mixed solution of a zirconium oxychloride solution and pure water was prepared as the mixed solution of Comparative Example.

[0062] Next, a 28% aqueous ammonia solution was added to each of the mixed solutions of Examples A-F and the Comparative Example, thereby depositing precipitates in each of the solutions. The amount of ammonium ions added was 50 mol % or more relative to the zirconium ions dissolved in each mixed solution. Here, the ammonia in the aqueous ammonia solution is an example of the precipitant shown in Figure 1. The specific composition of each solution of Examples A-F and the Comparative Example is shown in Table 1 below.

[0063]

[0064] The solutions of Examples A to F and the Comparative Example were then stirred for at least one hour to uniformly distribute the precipitate in the solution. The resulting precipitate was then thoroughly dried in a thermostatic oven at 80°C for at least 12 hours, and the dried precipitate was then pulverized to obtain powders for firing of Examples A to F and the Comparative Example.

[0065] Next, each of the firing powders according to Examples A to F and the comparative example was molded into a block shape, and the resulting molded body was fired in an electric furnace under an air atmosphere to obtain zirconia ceramics according to Examples A to F and the comparative example.

[0066] In all of Examples A to F and the Comparative Example, the firing temperature of the firing powder was 600°C. Specifically, firing was performed by raising the temperature of the compact from room temperature to 600°C at a heating rate of 8°C / min, then holding it at 600°C for 2 hours, and then cooling it to room temperature at a heating rate of 5°C / min. In other words, the experimental conditions for Example A shown in Table 1 were the same as the experimental conditions for Example A3 shown in Figure 3.

[0067] In Table 1, "Ag / Zr" means the content of silver ions relative to zirconium ions in each of the zirconia ceramics according to Examples A to F and the Comparative Example. When the firing temperature is 600°C, the amount of silver evaporated during firing is negligibly small, and therefore the content of silver ions relative to zirconium ions in the zirconia ceramic can be considered to be equal to the content of silver relative to zirconium ions in the firing powder.

[0068] By adjusting the mixing ratio of the zirconium oxychloride solution, silver nitrate solution, and pure water, the silver ion contents relative to zirconium ions in the zirconia ceramics of Examples A, B, C, D, E, and F were adjusted to 1 mol%, 3 mol%, 5 mol%, 0.01 mol%, 0.1 mol%, and 0.5 mol%, respectively, as shown in Table 1. The zirconia ceramic of the comparative example did not contain silver ions.

[0069] Figure 4 shows the X-ray diffraction pattern of the zirconia ceramic of Example C at room temperature. A peak indicating the presence of the (111) plane of tetragonal zirconia appears at 2θ = 30.2°. This confirms that tetragonal zirconia, which is originally a high-temperature phase, exists stably even at room temperature. In other words, it was confirmed that silver certainly played the role of a stabilizing element.

[0070] For the zirconia ceramic of Example C, the amount of tetragonal crystals in the zirconia ceramic was determined in the following manner.

[0071] First, the amount of monoclinic crystals in the zirconia ceramic was calculated using the following formula, which is adapted from the formula described in 4.4.3 of ISO-13356.

[0072] Monoclinic amount [%] = 100 × {M(-111) + M(111)} / {M(-111) + T(111) + M(111)}

[0073] In the above formula, M represents monoclinic crystals, and T represents tetragonal crystals. The numbers in parentheses represent plane indices. That is, M(-111) represents the diffraction intensity (2θ=28.2°) of the (-111) plane of monoclinic zirconia. M(111) represents the diffraction intensity (2θ=31.3°) of the (111) plane of monoclinic zirconia. T(111) represents the diffraction intensity (2θ=30.2°) of the (111) plane of tetragonal zirconia.

[0074] The above-mentioned diffraction intensities were determined using the X-ray diffraction waveform, and the results were M(-111) = 6293, M(111) = 4859, and T(111) = 16988. Therefore, from the above formula, the amount of monoclinic crystals in the zirconia ceramic is 39.6%.

[0075] Furthermore, since the firing temperature indicates that no cubic crystals are formed, the zirconia ceramic is considered to be a polycrystalline body consisting of monoclinic and tetragonal crystals. Therefore, the amount of tetragonal crystals in the zirconia ceramic is 100 - 39.6 = 60.4%.

[0076] Next, a description will be given of an elution test that was conducted to confirm that silver is not easily eluted from zirconia ceramic.

[0077] The zirconia ceramics of Examples A-C and Comparative Example were crushed to obtain powders. Then, 0.1 g of each of the zirconia ceramic powders of Examples A-C and Comparative Example was added to 10 mL of phosphate-buffered saline (PBS) and alpha Modified Eagle Minimum Essential Medium (αMEM), respectively, and the mixture was shaken at a repetition rate of 60 rpm at 37°C in a sealed container. After 1 and 3 days, the medium solution in the sealed container was sampled, filtered through a syringe filter with a 220 nm mesh size, and diluted 20 times with a 2% nitric acid solution. The silver concentration in the diluted solution was measured. An ICP atomic emission spectrometer was used for the measurements.

[0078] 5A shows the measurement results of the concentration of silver eluted into PBS. Graph D1p shows the concentration of silver eluted into PBS from the zirconia ceramic powder according to the comparative example after one day has passed. Graph A1p shows the concentration of silver eluted into PBS from the zirconia ceramic powder according to Example A after one day has passed. Graph B1p shows the concentration of silver eluted into PBS from the zirconia ceramic powder according to Example B after one day has passed. Graph C1p shows the concentration of silver eluted into PBS from the zirconia ceramic powder according to Example C after one day has passed.

[0079] Graph D3p shows the concentration of silver eluted into PBS from the zirconia ceramic powder of the Comparative Example after 3 days. Graph A3p shows the concentration of silver eluted into PBS from the zirconia ceramic powder of Example A after 3 days. Graph B3p shows the concentration of silver eluted into PBS from the zirconia ceramic powder of Example B after 3 days. Graph C3p shows the concentration of silver eluted into PBS from the zirconia ceramic powder of Example C after 3 days.

[0080] 5B shows the measurement results of the concentration of silver eluted into αMEM. Graph D1a shows the concentration of silver eluted into αMEM from the zirconia ceramic powder according to the comparative example after one day has elapsed. Graph A1a shows the concentration of silver eluted into αMEM from the zirconia ceramic powder according to Example A after one day has elapsed. Graph B1a shows the concentration of silver eluted into αMEM from the zirconia ceramic powder according to Example B after one day has elapsed. Graph C1a shows the concentration of silver eluted into αMEM from the zirconia ceramic powder according to Example C after one day has elapsed.

[0081] Graph D3a shows the concentration of silver eluted into αMEM from the zirconia ceramic powder of the Comparative Example after 3 days. Graph A3a shows the concentration of silver eluted into αMEM from the zirconia ceramic powder of Example A after 3 days. Graph B3a shows the concentration of silver eluted into αMEM from the zirconia ceramic powder of Example B after 3 days. Graph C3a shows the concentration of silver eluted into αMEM from the zirconia ceramic powder of Example C after 3 days.

[0082] As shown in Figure 5B, the maximum concentration of silver eluted into α-MEM was 1.2 ppm, as shown by graph C1a. Also, as shown in Figure 5A, the concentration of silver eluted into PBS was 0.4 ppm or less in all of Examples A to C. From the above, it was confirmed that the zirconia ceramics of Examples A to C are less likely to elute silver during use, even when used as an in vivo implant, for example.

[0083] Next, an antibacterial test conducted to confirm the antibacterial effect of zirconia ceramic will be described.

[0084] First, the first antibacterial test, which examined the antibacterial activity against Streptococcus mutans (type culture strain: NBRC No. 13955T), a typical cariogenic bacterium, will be described.

[0085] The Streptococcus mutans was purchased from the NITE Biotechnology Center and inoculated into a bouillon medium (Pearl Core Infusion, manufactured by Eiken Chemical Industry Co., Ltd.) and cultured overnight in a constant temperature shaking incubator at 37°C under atmospheric conditions to prepare a bacterial solution.

[0086] Separately, a bouillon medium was prepared by adding powder obtained by crushing the zirconia ceramic of each of Examples A-C (hereinafter referred to as zirconia ceramic powder). The zirconia ceramic powder was added at a ratio of 100 mg per 1 mL of bouillon medium. Immediately after addition, the above-mentioned bacterial solution was inoculated into the bouillon medium in an L-shaped tube so that the viable cell count was 106 / mL. The inoculated mixture was then cultured for 24 hours in an incubator set at 37°C while shaking at 60 rpm. After the culture, the bouillon medium was diluted with PBS, and 200 μL of the diluted solution was applied to an agar medium using a large cone stick.

[0087] Hereinafter, the agar medium to which the bouillon medium containing the zirconia ceramic powder of Example A has been applied will be referred to as the "medium of Example A." The agar medium to which the bouillon medium containing the zirconia ceramic powder of Example B has been applied will be referred to as the "medium of Example B." The agar medium to which the bouillon medium containing the zirconia ceramic powder of Example C has been applied will be referred to as the "medium of Example C."

[0088] An agar medium was prepared by applying the bouillon medium containing the zirconia ceramic powder according to the comparative example (hereinafter referred to as the medium according to the comparative example in this first antibacterial test).For comparison, an agar medium was prepared by applying the bouillon medium without the zirconia ceramic powder (hereinafter referred to as the additive-free medium in this first antibacterial test).

[0089] Then, after one day and two days had passed, the number density of colonies was measured in each of the medium according to Example A, the medium according to Example B, the medium according to Example C, the medium according to the comparative example, and the additive-free medium.

[0090] The results of measuring the colony number density are shown in Figure 6. The culture medium according to Example A, the culture medium according to Example B, and the culture medium according to Example C all exhibited sufficiently superior antibacterial activity compared to the culture medium according to the comparative example.

[0091] As previously described with reference to the results of the elution test shown in Figures 5A and 5B, silver is difficult to elute from zirconia ceramic. Despite this, the culture medium according to Example A, the culture medium according to Example B, and the culture medium according to Example C exhibited sufficient antibacterial activity. This supports the idea that, as shown in Figure 2, silver is coordinated on the surface of the zirconia ceramic, and that the antibacterial activity is exerted by the silver on that surface.

[0092] Separately, the antibacterial activity value of the zirconia ceramic of Example A was measured in accordance with the JIS Z2801 standard and was found to be 2.0. This indicates that sufficient antibacterial activity can be obtained even when the amount of silver added to zirconia is 1 mol%. However, as shown in Figure 6, there is a tendency for the higher the silver content in the zirconia ceramic, the better the antibacterial activity. From this perspective, it is believed that a higher silver content is preferable from the standpoint of antibacterial activity.

[0093] Next, a second antibacterial test will be described, which examines the antibacterial activity against Staphylococcus aureus (NBRC100910T), a typical Gram-positive bacterium, as specified in ISO 22196:2011.

[0094] The Staphylococcus aureus was purchased from NBRC (NITE Biological Resource Center). The purchased Staphylococcus aureus was cultured in the same manner as in the first antibacterial test to prepare a bacterial solution.

[0095] Meanwhile, the zirconia ceramic powders according to Examples D-F were sterilized with 70% ethanol, washed with PBS, and then added to bouillon medium. The zirconia ceramic powder was added at a ratio of 100 mg per 1 mL of bouillon medium. Immediately after addition, 0.1 mL of the bacterial solution was inoculated into 4.9 mL of the bouillon medium, and the inoculated mixture was cultured with shaking for 24 hours in an incubator (BioShaker BR-13LP, TAITEC) set at 37°C to obtain a suspension. The resulting suspension was then diluted and pipetted onto an agar medium, followed by overnight culture at 37°C.

[0096] Hereinafter, in this second antibacterial test, the agar media onto which the suspensions containing the zirconia ceramic powder of Examples D, E, and F were pipetted will be referred to as "the medium of Example D," "the medium of Example E," and "the medium of Example F," respectively. For comparison, an agar medium onto which the suspension containing no zirconia ceramic powder was applied (hereinafter, in this second antibacterial test, this will be referred to as an additive-free medium) was also prepared.

[0097] 7 shows the results of measuring the colony density in the culture media of Examples D-F and in the additive-free medium. It was confirmed that the colony density in the culture media of Examples D-F was significantly lower than that in the additive-free medium. In other words, the antibacterial properties of the zirconia ceramic powders of Examples D-F against Staphylococcus aureus were confirmed.

[0098] Next, we will explain the third antibacterial test, which examines the antibacterial activity against Escherichia coli (NBRC102203T), a typical gram-negative bacterium, as specified in ISO22196:2011.

[0099] The E. coli was purchased from NBRC (NITE Biological Resource Center). The purchased E. coli was cultured in the same manner as in the first antibacterial test to prepare a bacterial solution.

[0100] On the other hand, suspensions containing the zirconia ceramic powders of Examples D to F were obtained in the same manner as in the second antibacterial test, except for the bacterial solution used. The obtained suspensions were diluted and pipetted onto agar media, and cultured overnight at 37°C.

[0101] Hereinafter, in this third antibacterial test, the agar media into which the suspensions containing the zirconia ceramic powders of Examples D, E, and F were pipetted will be referred to as "the medium of Example D," "the medium of Example E," and "the medium of Example F," respectively. Also, an agar medium into which the bacterial solution containing the zirconia ceramic of a comparative example was added instead of the zirconia ceramic powders of Examples D, E, and F was pipetted (hereinafter, in this third antibacterial test, this will be referred to as the medium of the comparative example).

[0102] 8 shows the results of measuring the colony number density in the culture media of Examples D-F and the comparative example. It was confirmed that the colony number density in the culture media of Examples D-F was significantly lower than that in the comparative example. In other words, the antibacterial properties of the zirconia ceramic powders of Examples D-F against E. coli were confirmed.

[0103] Although the embodiment and examples have been described above, the present invention is not limited to these and the following modifications are possible.

[0104] In the above examples, zirconia ceramics containing tetragonal zirconia crystals were used as examples, but the zirconia ceramic does not necessarily have to contain tetragonal crystals. For example, the zirconia ceramic may be made of monoclinic zirconia crystals. In this case, silver ions do not function as a stabilizer, but the inclusion of silver ions in the zirconia crystals provides antibacterial activity.

[0105] In the above examples, the firing powder used in the production of zirconia ceramics contains zirconia powder and silver powder, but a silver compound powder may be used instead of or in combination with the silver powder.

[0106] The present invention can be modified in various ways without departing from its broad spirit and scope. The above-described embodiments and examples are intended to illustrate the present invention and do not limit the scope of the present invention. The scope of the present invention is defined by the claims, not by the embodiments and examples. Various modifications made within the scope of the claims and within the meaning of the invention equivalent thereto are considered to be within the scope of the present invention.

[0107] This application is based on Japanese Patent Application No. 2022-165432 filed in Japan on October 14, 2022. The entire specification, claims, and drawings of Japanese Patent Application No. 2022-165432 are incorporated herein by reference.

[0108] The zirconia ceramic according to the present invention is particularly suitable for applications requiring antibacterial properties, specifically for use in in vivo implants. However, the applications of the zirconia ceramic according to the present invention are not limited to in vivo implants. The zirconia ceramic according to the present invention can also be used as a material for various products such as cutlery and jewelry (e.g., rings and earrings), and as a radiosensitizer.

Claims

1. A substitutional crystal structure containing zirconium ions, silver ions and oxygen ions, wherein some of the zirconium ions in the crystal structure of zirconia are substituted by silver ions. A zirconia ceramic having the above structure.

2. The silver ions form a solid solution together with the zirconium ions and the oxygen ions. The zirconia ceramic according to Claim 1.

3. At room temperature, the substitutional crystal structure is a mixture of monoclinic and tetragonal crystals, or consists of tetragonal crystals. The zirconia ceramic according to Claim 1.

4. The content of the silver ions is 0.01 mol% or more relative to the zirconium ions. The zirconia ceramic according to Claim 1.

5. Containing 20% or more of tetragonal crystals. The zirconia ceramic according to Claim 3.

6. The form of the zirconia ceramic is a block, powder or coating. The zirconia ceramic according to Claim 1.

7. Having the zirconia ceramic according to any one of Claims 1 to 6. An in-vivo implant.

8. A firing powder used for manufacturing the zirconia ceramic according to any one of Claims 1 to 6, The firing powder contains silver in the zirconia powder.

9. A precipitate generation step of mixing a zirconium compound and a silver compound in the form of a solution or a suspension, and then adding a precipitating agent to the solution or the suspension to obtain a precipitate containing zirconia derived from the zirconium compound and silver derived from the silver compound; A firing step of firing the firing powder obtained by drying the precipitate to obtain a zirconia ceramic in which silver ions are complexed. A method for manufacturing a zirconia ceramic having the above steps.