Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
  • A61C8/00—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K6/00—Preparations for dentistry
  • A61K6/80—Preparations for artificial teeth, for filling teeth or for capping teeth
  • A61K6/802—Preparations for artificial teeth, for filling teeth or for capping teeth comprising ceramics
  • A61K6/818—Preparations for artificial teeth, for filling teeth or for capping teeth comprising ceramics comprising zirconium oxide
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/02—Inorganic materials
  • A61L27/10—Ceramics or glasses
• • C—CHEMISTRY; METALLURGY
  • C01—INORGANIC CHEMISTRY
  • C01G—COMPOUNDS CONTAINING METALS NOT COVERED BY SUBCLASSES C01D OR C01F
  • C01G25/00—Compounds of zirconium
  • C01G25/02—Oxides
• • C—CHEMISTRY; METALLURGY
  • C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
  • C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
  • C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
  • C04B35/01—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products based on oxide ceramics
  • C04B35/48—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products based on oxide ceramics based on zirconium or hafnium oxides, zirconates, zircon or hafnates
  • C04B35/486—Fine ceramics

Definitions

• the present invention relates to zirconia ceramics, in vivo implants, powders for firing, and methods for producing zirconia ceramics.
• zirconia ceramics are used as a material for in vivo implants.
• zirconia ceramics are also used in various products such as blades.
• the object of the present invention is to provide a novel zirconia ceramic, an in vivo implant, a powder for sintering, and a method for producing zirconia ceramic.
• the zirconia ceramic according to the present invention is It has a crystal structure consisting of zirconium ions, silver ions and oxygen ions.
• the silver ions may form a solid solution together with the zirconium ions and the oxygen ions.
• the crystal structure may be a mixture of monoclinic and tetragonal crystals, or may be tetragonal crystals.
• the content of the silver ions may be 0.01 mol% or more relative to the zirconium ions.
• the zirconia ceramic according to the present invention may contain 20% or more of tetragonal crystals.
• the zirconia ceramic may be in the form of a block, powder, or coating.
• the in vivo implant according to the present invention comprises:
• the present invention has the zirconia ceramic described above.
• the powder for firing according to the present invention is A sintering powder used in the production of zirconia ceramics, comprising:
• the zirconia powder contains silver.
• the method for producing zirconia ceramic according to the present invention comprises the steps of: a precipitate generating 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; a firing step of firing the powder obtained by drying the precipitate to obtain a zirconia ceramic composite with silver ions; has.
• the present invention provides a novel zirconia ceramic, an in vivo implant, a powder for sintering, and a method for producing zirconia ceramic.
• FIG. 1 is a flow chart illustrating a method for making a zirconia ceramic according to an embodiment.
• FIG. 2 is a conceptual diagram showing the structure of a zirconia ceramic according to an embodiment. Graph showing the relative values of the silver content in the zirconia ceramics according to Examples A1 to A7. Graph showing the X-ray diffraction waveform of the zirconia ceramic according to Example C. 1 is a graph showing the amount of silver eluted into PBS from zirconia ceramics according to Examples A to C and a comparative example. Graph showing the amount of silver dissolved from zirconia ceramics into ⁇ MEM according to Examples A to C and a comparative example.
• 1 is a graph showing the results of a first antibacterial test of zirconia ceramics according to Examples A to C and a comparative example.
• 13 is a graph showing the results of a second antibacterial test of the zirconia ceramics according to Examples D to F and a comparative example.
• 13 is a graph showing the results of a third antibacterial test of the zirconia ceramics according to Examples D to F and a comparative example.
• a method for producing a zirconia ceramic Referring to FIG. 1, a method for producing a zirconia ceramic according to an embodiment will be described. 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, and then a precipitant is added to the solution or suspension to obtain a precipitate (precipitate generation step S1).
• a zirconium compound hereinafter referred to as a zirconium compound
• a silver compound hereinafter referred to as a silver compound
• the zirconium compound a salt can be used.
• the zirconium compound can be zirconium chloride, zirconium oxide, zirconium nitrate, zirconium sulfide, zirconium acetate, zirconium butoxide, etc.
• a salt can be used as the silver compound. Specifically, silver nitrate, silver chloride, silver sulfide, silver acetate, etc. can be used as the silver compound.
• the solvent may be either a non-polar or polar solvent, so long as it dissolves or suspends the zirconium compound and silver compound used.
• a non-polar or polar solvent for example, water, alcohols, acetone, phenol, toluene, dimethyl sulfoxide, carboxylic acids, alkanes, carboxylate esters, and mixtures thereof can be used as the solvent.
• the solvent used can be selected according to the properties of the zirconium compound and silver compound.
• alcohols refers to organic molecules that have one or more hydroxyl 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.
• Carboxylic acids here refer to organic molecules that have one or more carboxy groups in the molecule.
• Examples of carboxylic acids include 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.
• alkanes refers to chain saturated hydrocarbons represented by the general formula CnH2n +2 .
• alkanes include pentane, hexane, heptane, octane, nonane, decane, undecane, dodecane, and octadecane.
• carboxylate ester refers to a molecule formed by polymerizing an organic molecule containing a carboxyl group and an organic molecule containing a hydroxyl group through an ester bond.
• carboxylate esters include ethyl acetate, methyl salicylate, ethyl formate, methyl butyrate, ethyl propionate, and pentyl valerate.
• the precipitant increases the pH of the solution or suspension containing the zirconium compound and the silver compound, promoting the formation of the above-mentioned precipitate.
• Precipitants that can be used include those that produce alkaline aqueous solutions, specifically, ammonia, sodium hydroxide, ammonium carbonate, arginine, lysine, trisaminomethane, sodium bicarbonate, sodium carbonate, etc.
• the precipitate is an aggregate of substances containing zirconia derived from the zirconium compound and silver derived from the silver compound.
• 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.
• the powder for sintering is preferably a material composed of zirconia and silver.
• the content of silver in the powder for sintering is preferably 0.01 mol% or more relative to the zirconium ions constituting the zirconia, 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.
• the silver may be silver ions.
• "sintering powder containing silver ions” means that in the sintering powder, silver atoms are present in a form ionic bonded to other atoms such as zirconium atoms. In other words, silver is not present in a free ionic form.
• the silver does not necessarily have to be ionic bonded to other atoms, and ionic bonds between the silver atoms and other atoms may be formed by the sintering described below.
• the powder for firing may be molded and the resulting molded body may be fired.
• Zirconia ceramic is obtained by firing (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.
• the "firing temperature” means the maximum temperature reached.
• the above-described embodiment provides a novel zirconia ceramic.
• 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 ⁇ m or less.
• 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-like object such as a substrate.
• the substrate may be made of, for example, ceramic, metal, polymer, etc.
• the zirconia ceramic powder may be obtained by firing the firing powder without molding, or by crushing a block or chunk of zirconia ceramic.
• a powder for firing obtained in the above-mentioned powder for firing formation step S2.
• the powder for firing is used to manufacture zirconia ceramics. That is, the powder for firing is molded as necessary and then subjected to firing.
• the zirconia ceramic according to this embodiment has a crystalline structure (hereinafter referred to as zirconia crystal).
• the zirconia crystal is preferably a mixture of monoclinic and tetragonal crystals, or is made of tetragonal crystals.
• the zirconia crystal may also contain cubic crystals.
• room temperature refers to a temperature of 5°C or higher and 35°C or lower.
• the zirconia ceramic according to this embodiment contains silver in a composite. Specifically, silver is contained in the zirconia crystal in the form of silver ions.
• the zirconia crystal is composed of zirconium ions, silver ions, and oxygen ions.
• "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 exists in the form of an ionic bond with the other atom. It does not mean that each atom exists in a free ionic form.
• the silver ions may form a solid solution with the zirconium ions and oxygen ions that constitute the zirconia ceramic.
• 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.
• the term "stabilizing element” refers to an element that acts as a stabilizer to expand 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.
• stabilization refers to expanding the temperature range in which the tetragonal crystal can exist to a temperature range including room temperature.
• the stabilization of the tetragonal crystal by the stabilizing element suppresses the phase transition from the tetragonal crystal to the monoclinic crystal. This suppresses the occurrence of cracks due to the volume expansion accompanying the phase transition.
• the zirconia ceramic according to this embodiment preferably has 20% or more tetragonal crystals when the crystal phase is measured at room temperature by X-ray diffraction. This allows the zirconia ceramic to exhibit excellent toughness.
• silver can act as a stabilizing element.
• the ionic radius of silver (1.0-1.15 ⁇ ) is similar to the ionic radius of yttrium (0.90 ⁇ ), a typical stabilizing element. This is because the ionic radius of the stabilizing element that has entered the crystal can be said to be an important factor in preventing transformation of the crystal structure.
• Yttrium can function as a stabilizing element even when added in an amount of 0.01 mol% or less (excluding 0 mol%) to zirconium ions. Therefore, like silver, it is believed to function as a stabilizing element even when added in an amount of 0.01 mol% or less (excluding 0 mol%) to zirconium ions.
• the content of silver ions in the zirconia ceramic according to this embodiment is preferably 0.01 mol% or more relative to the zirconium ions, more preferably 0.01 mol% or more and 10 mol% or less, 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.
• the content of silver ions relative to the zirconium ions in the zirconia ceramic is equal to the content of silver relative to the zirconium ions in the firing powder described above.
• the zirconia ceramic according to this embodiment may further contain oxides other than silver compounds as stabilizers, such as calcium oxide, magnesium oxide, yttrium oxide, sodium oxide, lanthanum oxide, praseodymium oxide, neodymium oxide, ytterbium oxide, and gadolinium oxide.
• oxides other than silver compounds such as calcium oxide, magnesium oxide, yttrium oxide, sodium oxide, lanthanum oxide, praseodymium oxide, neodymium oxide, ytterbium oxide, and gadolinium oxide.
• the zirconia ceramic according to this embodiment can be used as a component of an in vivo implant.
• an in vivo implant includes intraoral implants such as dental restorations (e.g. crowns and bridges) and implant fixtures (artificial tooth roots) embedded in the jawbone, as well as artificial joints and bones that are used in parts of the body other than the oral cavity.
• FIG. 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. Since silver exhibits antibacterial properties, bacteria are less likely to grow on the surface of the zirconia ceramic according to this embodiment.
• silver not only acts as a stabilizing element that stabilizes the tetragonal crystal, but also provides an antibacterial effect on the surface of the zirconia ceramic. Therefore, when the zirconia ceramic according to this embodiment is used as an intraoral implant, for example, the proliferation of bacteria in the oral cavity is suppressed. Therefore, a preventive effect against intraoral inflammation, aspiration pneumonia, etc. is expected.
• 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 a form substituted for zirconium atoms. For this reason, silver atoms are not easily eluted from the surface of zirconia ceramic. In other words, the antibacterial effect described above is exerted not by silver ions eluted from the structure, but by silver atoms that appear on the surface of the structure.
• the zirconia ceramic according to this embodiment is less susceptible to discoloration because silver ions are less likely to be eluted from the surface, and therefore exhibits stable aesthetics over the long term. Furthermore, because the zirconia ceramic according to this embodiment is less susceptible to discoloration of biological tissues when used as an in vivo implant, even when silver functions as a stabilizing element, it is less likely to discolor biological tissues.
• Zirconium oxychloride octahydrate ZrCl2O.8H2O was dissolved in distilled water to obtain a zirconium oxychloride solution with a concentration of 2 mol/L.
• Silver nitrate AgNO3 was also dissolved in distilled water to obtain a silver nitrate solution with a concentration of 200 mmol/L.
• the zirconium oxychloride solution and the silver nitrate solution were then thoroughly mixed with pure water to obtain a mixed solution.
• zirconium oxychloride octahydrate and silver nitrate were mixed in the form of a solution.
• 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.
• ammonia in the aqueous ammonia solution is an example of the precipitant described in Figure 1.
• the mixed solution to which the aqueous ammonia solution was added was stirred for at least one hour to disperse the precipitate evenly. After that, the precipitate was thoroughly dried, and the dried precipitate was pulverized to obtain a powder for firing.
• the resulting powder for firing contains 1 mol% silver relative to 100 mol% zirconium.
• the mixing ratio of the zirconium oxychloride solution and the silver nitrate solution was adjusted in the stage of preparing the above mixed solution so that the silver content in the powder for firing is 1 mol% relative to zirconium.
• the obtained powder for firing was fired in an electric furnace under air atmosphere to obtain zirconia ceramic.
• the zirconia ceramics according to Examples A1-A7 which differ only in the firing temperature condition of the powder for firing, were obtained.
• the firing temperature for each example is shown in parentheses. That is, the zirconia ceramics for Examples A1, A2, A3, A4, A5, A6, and A7 were obtained by firing the powder at 400°C, 500°C, 600°C, 700°C, 800°C, 900°C, and 1000°C, respectively.
• "calcining the powder to be calcined at T°C” specifically refers to raising the temperature of the powder to be calcined from room temperature to T°C at a heating 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 cooling rate of 5°C/min.
• the silver content in the zirconia ceramic of 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.
• XRF X-ray fluorescence
• the silver content was measured three times (n number).
• the 95% confidence interval is also shown at the top of each bar.
• the higher the firing temperature of the firing powder the more significantly the silver content in the resulting zirconia ceramic tends to decrease. This is thought to be due to silver evaporating when heated. In other words, the lower the firing temperature, the more likely silver is to remain.
• 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.
• Zirconium oxychloride octahydrate ZrCl2O.8H2O was dissolved in distilled water to obtain a zirconium oxychloride solution with a concentration of 2 mol/L.
• Silver nitrate AgNO3 was also dissolved in distilled water to obtain a silver nitrate solution with a concentration of 200 mmol/L.
• the zirconium oxychloride solution, the silver nitrate solution, and pure water were then dropped into a beaker in predetermined amounts using a pipette, and thoroughly mixed using a stirrer.
• zirconium oxychloride octahydrate and silver nitrate were mixed in the form of a solution to prepare a mixed solution.
• 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.
• Examples A-F which have different silver ion contents
• mixed solutions of Examples A-F were prepared in which the mixing ratios of zirconium oxychloride solution, silver nitrate solution, and pure water were different.
• a mixed solution of zirconium oxychloride solution and pure water was prepared as the mixed solution of the Comparative Example.
• a 28% aqueous ammonia solution was added to each of the mixed solutions of Examples A-F and the Comparative Example to cause a precipitate to precipitate in each solution of Examples A-F and the Comparative Example.
• the amount of ammonium ions added was 50 mol % or more relative to the zirconium ions dissolved in each mixed solution.
• the ammonia in the aqueous ammonia solution is an example of the precipitant shown in Figure 1.
• the composition of each solution of Examples A-F and the Comparative Example is specifically shown in Table 1 below.
• each solution of Examples A-F and Comparative Example was stirred for at least one hour to distribute the precipitate evenly throughout the solution.
• the precipitate obtained was then thoroughly dried in a thermostatic chamber at 80°C for at least 12 hours, and the dried precipitate was pulverized to obtain the powders for firing of Examples A-F and Comparative Example.
• each of the sintering powders according to Examples A-F and the Comparative Example was molded into a block shape, and the resulting molded bodies were fired in an electric furnace under air atmosphere to obtain the zirconia ceramics according to Examples A-F and the Comparative Example.
• the sintering temperature of the sintering powder was 600°C. Specifically, the sintering was performed by heating the molded body 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.
• the experimental conditions for Example A shown in Table 1 are the same as those for Example A3 shown in Figure 3 and described above.
• Al/Zr refers to the content of silver ions relative to zirconium ions in each of the zirconia ceramics according to Examples A-F and the Comparative Example.
• the firing temperature is 600°C
• the amount of silver evaporated during firing is negligibly small, so 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.
• the silver ion content of the zirconia ceramics of Examples A, B, C, D, E, and F is adjusted to 1 mol%, 3 mol%, 5 mol%, 0.01 mol%, 0.1 mol%, and 0.5 mol% relative to the zirconium ions, respectively, as shown in Table 1.
• the zirconia ceramic of the comparative example does not contain silver ions.
• Figure 4 shows the X-ray diffraction waveform of the zirconia ceramic of Example C at room temperature.
• a peak indicating the presence of the (111) plane of tetragonal zirconia appears at 2 ⁇ 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.
• the amount of tetragonal crystals in the zirconia ceramic was determined as follows.
• the amount of monoclinic crystals in the zirconia ceramic was calculated using the formula below. Note that this formula is adapted from the formula described in 4.4.3 of ISO-13356.
• Monoclinic crystal amount [%] 100 x ⁇ M(-111) + M(111) ⁇ / ⁇ M(-111) + T(111) + M(111) ⁇
• M indicates monoclinic crystals
• T indicates tetragonal crystals.
• the zirconia ceramics of Examples A-C and Comparative Example were crushed to obtain powders.
• 0.1 g of the zirconia ceramic powders of Examples A-C and Comparative Example were then placed in 10 mL of PBS (Phosphate-buffered saline) and ⁇ MEM (alpha Modified Eagle Minimum Essential Medium), respectively, and shaken at a repetitive speed of 60 rpm in a sealed container at a temperature of 37°C. After 1 and 3 days had passed, the medium liquid in the sealed container was sampled, filtered through a syringe filter with a mesh size of 220 nm, and diluted 20 times with a 2% nitric acid solution, and the silver concentration contained therein was measured. An ICP emission spectrometer was used for the measurements.
• FIG. 5A shows the measurement results of the elution concentration of silver into PBS.
• Graph D1p shows the concentration of silver dissolved into PBS from the zirconia ceramic powder according to the comparative example after one day had elapsed.
• Graph A1p shows the concentration of silver dissolved into PBS from the zirconia ceramic powder of Example A after one day.
• Graph B1p shows the concentration of silver dissolved into PBS from the zirconia ceramic powder of Example B after one day.
• Graph C1p shows the concentration of silver dissolved from the zirconia ceramic powder of Example C into PBS after one day.
• Graph D3p shows the concentration of silver dissolved into PBS from the zirconia ceramic powder according to the comparative example after three days.
• Graph A3p shows the concentration of silver dissolved into PBS from the zirconia ceramic powder of Example A after three days.
• Graph B3p shows the concentration of silver dissolved into PBS from the zirconia ceramic powder of Example B after three days.
• Graph C3p shows the concentration of silver dissolved into PBS from the zirconia ceramic powder of Example C after three days.
• FIG. 5B shows the results of measuring the concentration of silver dissolved in ⁇ MEM.
• Graph D1a shows the concentration of silver dissolved into ⁇ -MEM from the zirconia ceramic powder according to the comparative example after one day had elapsed.
• Graph A1a shows the concentration of silver dissolved from the zirconia ceramic powder of Example A into ⁇ -MEM after one day.
• Graph B1a shows the concentration of silver dissolved from the zirconia ceramic powder of Example B into ⁇ -MEM after one day.
• Graph C1a shows the concentration of silver dissolved from the zirconia ceramic powder of Example C into ⁇ -MEM after one day.
• Graph D3a shows the concentration of silver dissolved into ⁇ -MEM from the zirconia ceramic powder according to the comparative example after three days.
• Graph A3a shows the concentration of silver dissolved from the zirconia ceramic powder of Example A into ⁇ -MEM after three days.
• Graph B3a shows the concentration of silver dissolved from the zirconia ceramic powder of Example B into ⁇ -MEM after three days.
• Graph C3a shows the concentration of silver dissolved from the zirconia ceramic powder of Example C into ⁇ -MEM after three days.
• the maximum concentration of silver dissolved into ⁇ MEM was 1.2 ppm, as shown by graph C1a.
• the concentration of silver dissolved into PBS was 0.4 ppm or less in all of Examples A-C. From the above, it was confirmed that the zirconia ceramics of Examples A-C are unlikely to cause silver to dissolve during use, even when used as an in vivo implant, for example.
• the above Streptococcus mutans was purchased from the NITE Biotechnology Center. It was inoculated into bouillon medium (Pearl Core Infusion: manufactured by Eiken Chemical Industry Co., Ltd.) and cultured overnight in a constant temperature shaking incubator in an air atmosphere at 37°C to prepare a bacterial solution.
• bouillon medium Pearl Core Infusion: manufactured by Eiken Chemical Industry Co., Ltd.
• a bouillon medium was prepared by adding powder (hereinafter referred to as zirconia ceramic powder) obtained by crushing the zirconia ceramic of each of Examples A-C.
• the zirconia ceramic powder was added at a ratio of 100 mg per 1 mL of bouillon medium.
• the above-mentioned bacterial liquid was inoculated into this bouillon medium in an L-shaped tube so that the viable cell count was 106/mL, and the inoculated medium was cultured for 24 hours in an incubator set at 37°C while shaking at 60 rpm.
• the bouillon medium was diluted with PBS, and 200 ⁇ L of the diluted solution was applied to the agar medium using a corn large stick.
• the agar medium to which the bouillon medium to which the zirconia ceramic powder of Example A has been added is referred to as the "medium of Example A.”
• the agar medium to which the bouillon medium to which the zirconia ceramic powder of Example B has been added is referred to as the "medium of Example B.”
• the agar medium to which the bouillon medium to which the zirconia ceramic powder of Example C has been added is referred to as the "medium of Example C.”
• An agar medium was also prepared to which the above bouillon medium to which the zirconia ceramic powder according to the comparative example had been added (hereinafter, in this first antibacterial test, this will be referred to as the medium according to the comparative example).
• An agar medium was also prepared to which the above bouillon medium to which the zirconia ceramic powder had not been added (hereinafter, in this first antibacterial test, this will be referred to as the additive-free medium).
• the colony density 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.
• Figure 6 shows the results of measuring the colony density.
• 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.
• the antibacterial activity value of the zirconia ceramic of Example A was measured in accordance with the provisions of JIS Z2801, and was found to be 2.0. This shows that sufficient antibacterial action 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 a better antibacterial action to be obtained as the silver content in the zirconia ceramic increases. From this perspective, it is believed that from the standpoint of antibacterial action, the higher the silver content, the better.
• the above 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.
• the zirconia ceramic powders according to each of 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.
• 0.1 mL of the bacterial solution was inoculated into 4.9 mL of this bouillon medium, and the inoculated mixture was cultured for 24 hours with shaking in an incubator (BioShaker BR-13LP, TAITEC) set at 37°C to obtain a suspension.
• the resulting suspension was then diluted and pipetted into an agar medium, and cultured overnight at 37°C.
• the agar medium into which the suspension containing the zirconia ceramic powder of Examples D, E, and F was pipetted is referred to as the "medium of Example D,” the “medium of Example E,” and the “medium of Example F,” respectively.
• an agar medium onto which the suspension not containing zirconia ceramic powder was applied hereinafter, in this second antibacterial test, this is referred to as the additive-free medium was prepared.
• Figure 7 shows the results of measuring the colony density in the culture medium of Examples D-F and in the additive-free medium. It was confirmed that the colony density in the culture medium of Examples D-F was significantly lower than the colony density in the additive-free medium. In other words, the antibacterial properties of the zirconia ceramic powder of each of Examples D-F against the above-mentioned Staphylococcus aureus were confirmed.
• the above 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.
• suspensions containing the zirconia ceramic powders of Examples D-F were obtained in the same manner as in the second antibacterial test, and the resulting suspensions were diluted and pipetted onto agar medium and cultured overnight at 37°C.
• the agar medium into which the suspension containing the zirconia ceramic powder of Examples D, E, and F was pipetted is referred to as the "medium of Example D,” the “medium of Example E,” and the “medium of Example F,” respectively.
• an agar medium into which the bacterial liquid to which the zirconia ceramic of the comparative example was added instead of the zirconia ceramic powder of Examples D, E, and F was pipetted was prepared (hereinafter, in this third antibacterial test, this will be referred to as the medium of the comparative example).
• Figure 8 shows the results of measuring the colony density in the culture medium of Examples D-F and the culture medium of the Comparative Example. It was confirmed that the colony density in the culture medium of Examples D-F was significantly lower than the colony density in the culture medium of the Comparative Example. In other words, the antibacterial properties of the zirconia ceramic powder of each of Examples D-F against the above-mentioned E. coli were confirmed.
• zirconia ceramic containing tetragonal crystals as the zirconia crystals was exemplified, but the zirconia ceramic does not necessarily have to contain tetragonal crystals.
• the zirconia ceramic may be made of monoclinic crystals as the zirconia crystals.
• the silver ions do not act as a stabilizer, but the inclusion of silver ions in the zirconia crystals provides an antibacterial effect.
• the firing powder used to manufacture the zirconia ceramic is exemplified as containing zirconia powder and silver powder, but a silver compound powder may be used in place of the silver powder or in combination with the silver powder.
• the zirconia ceramic according to the present invention is particularly suitable for use in applications requiring antibacterial properties, specifically in in vivo implants.
• 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 blades and accessories (e.g., rings and earrings), and as a radiosensitizer.

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• 2023
  • 2023-10-16 JP JP2024551792A patent/JPWO2024080382A1/ja active Pending
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