Biocompatible material and method for producing biocompatible material

Abstract

To provide a biocompatible material that exhibits sufficient antibacterial properties and a method for producing the biocompatible material.SOLUTION: According to one embodiment of the present invention, a biocompatible material is provided. The biocompatible material comprises a base formed of a metallic material and a porous ceramic layer containing silicon nitride, the porous ceramic layer covering at least part of a surface of the base.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a biocompatible material and a method for producing the biocompatible material. [Background technology]

[0002] Sintered bodies made of hydroxyapatite have been used as bone filling materials (biocompatible materials) for some time (see Patent Document 1). Hydroxyapatite has excellent biocompatibility and high osteoconductivity. However, since hydroxyapatite does not exhibit antibacterial properties, after the bone filling material is implanted into a living body, treatment is carried out to prevent the onset of infection by administering antibacterial agents or the like. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Laid-Open No. 2003-286073 Summary of the Invention [Problem to be solved by the invention]

[0004] In view of the above circumstances, the present invention aims to provide a biocompatible material having sufficient antibacterial properties and a method for producing the biocompatible material. [Means for solving the problem]

[0005] According to one aspect of the present invention, there is provided a biocompatible material comprising a base made of a metal material and a porous ceramic layer containing silicon nitride that covers at least a portion of the surface of the base.

[0006] According to this embodiment, a biocompatible material having sufficient antibacterial properties can be obtained. [Brief explanation of the drawings]

[0007] [Figure 1] 1 is a diagram showing a schematic configuration of a biocompatible material according to an embodiment of the present invention; [Figure 2] 1 is a process diagram showing a method for manufacturing a biocompatible material according to the present embodiment. [Figure 3] FIG. 10 is a schematic diagram showing the state in which the base is embedded in powder during firing. [Figure 4] Photographs of the appearance of samples No. A1 and A2. [Figure 5] This is a scanning electron microscope (SEM) image (10,000x magnification) of a cross section of the ceramic layer of sample No. A1 along the thickness direction. [Figure 6] FIG. 10 is a diagram for explaining a method for testing the adhesion of a ceramic layer. DETAILED DESCRIPTION OF THE INVENTION

[0008] Hereinafter, embodiments of the present disclosure will be described with reference to the drawings. Various features shown in the following embodiments can be combined with each other. First, the biocompatible material of this embodiment will be described. FIG. 1 is a diagram schematically showing the configuration of the biocompatible material of this embodiment. The biocompatible material 1 shown in FIG. 1 includes a base 2 made of a metal material, and a porous ceramic layer 3 that covers at least a part of the surface of the base 2 and contains silicon nitride.

[0009] The metal material that constitutes the base portion 2 is preferably one that is non-toxic or has very little biohazardous properties. Such a metal material preferably contains at least one metal atom belonging to Groups 3 to 12 of the periodic table. By forming the base 2 from a metal material containing these metal atoms, the hardness of the base 2 can be easily increased. Among these, the metallic material preferably contains at least one selected from the group consisting of titanium (Ti), vanadium (V), iron (Fe), chromium (Cr), nickel (Ni), molybdenum (Mo), manganese (Mn), cobalt (Co), niobium (Nb), zirconium (Zr), tantalum (Ta), tungsten (W), copper (Cu), palladium (Pd), iridium (Ir), platinum (Pt), and gold (Au), and more preferably contains titanium (Ti) as the main component, because metallic materials containing these metal atoms (simple metals or alloys) are particularly less harmful to living organisms.

[0010] In this specification, the term "main component" refers to the component that is contained in the largest amount when multiple components are contained. Components other than the "main component" are referred to as "minor components." In a preferred embodiment, the base 2 may consist solely of titanium, which is the main component, or may contain minor components different from the main component.

[0011] The base 2 preferably has a metal nitride layer 21 on the surface facing the ceramic layer 3. The metal nitride layer 21 is formed, for example, by nitriding the surface of the base 2 when manufacturing the biocompatible material 1 (see the manufacturing method of the biocompatible material described below). Note that the metal nitride layer 21 may be formed by separately nitriding the surface of the base 2 and vapor-phase deposition of the metal nitride (evaporation, sputtering, etc.) prior to forming the ceramic layer 3. The base 2 has the metal nitride layer 21 on the surface facing the ceramic layer 3, which improves the wear resistance and reactivity resistance of the base 2. The presence of the metal nitride layer 21 also improves the adhesion between the base 2 and the ceramic layer 3. Therefore, the biocompatible material 1 can exhibit excellent durability over a long period of time.

[0012] The ceramic layer 3 contains silicon nitride. According to the research of the present inventors, when the biocompatible material 1 is implanted in a living body, silicon nitride is found to exhibit high antibacterial properties by eluting ammonia (NH3). In addition, the present inventors have found that ammonia is converted into ammonium ions (NH4 + ), it is believed that excellent osteoconductivity is also exhibited. Therefore, the biocompatible material 1 having the ceramic layer 3 containing silicon nitride can suitably prevent the onset of infections associated with the implantation of the biocompatible material 1. Furthermore, when the biocompatible material 1 is used as a bone filling material, it can quickly fuse with the bone at the implantation site. Furthermore, since the metal nitride layer 21 is an interstitial nitride (i.e., a transition metal nitride), it is thought to be difficult to generate ammonia and ammonium ions, and it is presumed that the antibacterial and osteoconductive properties are effects derived from silicon nitride.

[0013] The porosity of the ceramic layer 3 is preferably about 3% or more and 70% or less, more preferably about 20% or more and 60% or less, and even more preferably about 40% or more and 60% or less. By setting the porosity of the ceramic layer 3 to the above-mentioned lower limit or more, it is possible to ensure a sufficient contact area between the ceramic layer 3 and body fluids (e.g., blood) when the biocompatible material 1 is implanted in a living body. This makes it possible to increase the amount of elution of ammoniacal nitrogen (ammonia or ammonium ions). On the other hand, by setting the porosity of the ceramic layer 3 to the above-mentioned upper limit or less, it is possible to suitably prevent or suppress a decrease in the mechanical strength of the ceramic layer 3.

[0014] The porosity of the ceramic layer 3 can be determined as follows. First, the biocompatible material 1 is embedded in resin and the cross section is polished to prepare a cross section of the ceramic layer 3. The cross section of the ceramic layer 3 is observed by a scanning electron microscope (SEM), and the ceramic layer 3 (including voids) is measured within a field of view to be 5 μm in size. 2A cross-sectional SEM image is acquired so that it contains the above. Note that in order to separate the ceramic from the voids in the binarization process described below, the number of pixels per unit length (resolution) of the cross-sectional SEM image should be 320 pixels / μm or more. Next, the acquired cross-sectional SEM image is binarized using image analysis software by adjusting the brightness threshold so that the ceramics (bright areas) and voids (dark areas) are separated. After that, the ratio (%) of the number of void pixels to the number of pixels of the ceramic layer 3 (ceramics and voids) is calculated. The average value of the ratio (%) of the number of pixels of voids to the number of pixels of the ceramic layer 3 calculated from each of the cross-sectional SEM images of five or more fields of view is defined as the porosity (%).

[0015] Furthermore, the coverage of the surface of the base 2 with the ceramic layer 3 is preferably approximately 30% to 95%, more preferably approximately 40% to 90%, and even more preferably approximately 50% to 85%. By setting the coverage of the surface of the base 2 with the ceramic layer 3 to be equal to or greater than the above-mentioned lower limit, it is possible to ensure a sufficient amount of ammoniacal nitrogen elution from the biocompatible material 1. On the other hand, by setting the coverage of the surface of the base 2 with the ceramic layer 3 to be equal to or less than the above-mentioned upper limit, it is possible to suitably prevent the ceramic layer 3 from peeling off from the base 2 even when the base 2 is deformed, for example, by the application of an external force or thermal expansion.

[0016] The coverage of the surface of the base 2 with the ceramic layer 3 can be determined as follows. First, the surface of the biocompatible material 1 was observed by SEM, and it was found that the ceramic layer 3 and the region (base 2) not covered with the ceramic layer 3 were separated by 42,000 μm. 2 A surface SEM image is acquired so that the above is included. Note that, in order to separate the ceramic layer 3 and the base 2 in the binarization process described below, the number of pixels per unit length (resolution) of the surface SEM image is set to 5.4 pixels / μm or more. In addition, since the contrast between the ceramic layer 3 and the base 2 tends to be clear, a backscattered electron image is acquired as the surface SEM image. Next, the acquired surface SEM image is binarized using image analysis software by adjusting the brightness threshold so as to separate the ceramic layer 3 (dark area) from the base 2 (bright area). After that, the ratio (%) of the number of pixels in the ceramic layer 3 to the total number of pixels in the ceramic layer 3 and the base 2 is calculated. The calculated value is then taken as the coverage rate (%).

[0017] The content of silicon nitride in the ceramic layer 3 is preferably about 30% by mass to 100% by mass, more preferably about 40% by mass to 99% by mass, and even more preferably about 50% by mass to 98% by mass. A ceramic layer 3 containing silicon nitride in such an amount can increase the amount of eluted ammoniacal nitrogen, and therefore tends to have improved antibacterial properties and osteoconductivity. Furthermore, the ceramic layer 3 preferably further contains yttrium (Y) and / or magnesium (Mg) and oxygen (O). Such atoms are likely to be introduced into the ceramic layer 3, for example, from auxiliary particles used in forming the ceramic layer 3 during the production of the biocompatible material 1. When the ceramic layer 3 contains yttrium (Y) and / or magnesium (Mg) and oxygen (O), it appears that differentiation of undifferentiated mesenchymal stem cells into osteoblasts, i.e., osteoconductivity (calcification), can be promoted when the biocompatible material 1 is used as a bone filling material.

[0018] The alpha phase ratio of silicon nitride (the ratio of alpha-Si3N4 to the total Si3N4 phase) is preferably about 50% or more, more preferably about 80% or more, and even more preferably about 90% or more. Increasing the alpha phase ratio tends to improve antibacterial properties, especially against gram-negative bacteria. The gelatinization rate of silicon nitride may be, for example, about 50% or more and 100% or less. The gelatinization rate of silicon nitride can be adjusted, for example, by changing the conditions (e.g., firing temperature and firing time) when firing silicon particles to nitride them.

[0019] The thickness of the ceramic layer 3 is preferably about 20 μm or less, more preferably about 15 μm or less, and even more preferably about 10 μm or less. The lower limit of the thickness of the ceramic layer 3 is not particularly limited, but is usually about 0.1 μm. The thickness of the ceramic layer 3 may be about 0.1 μm or more and 20 μm or less. Such a ceramic layer 3 can have high mechanical strength while maintaining sufficient antibacterial properties and osteoconductivity.

[0020] The biocompatible material 1 as described above can be produced, for example, as follows. FIG. 2 is a process diagram showing the method for producing the biocompatible material of this embodiment. As shown in Figure 2, the manufacturing method of the biocompatible material of this embodiment includes a step (first step) A of preparing a base 2 made of a metal material and a powder 30 containing silicon (Si) particles, a step B of pretreating the base 2, and a step (second step) C of applying the powder 30 to the surface of the base 2, and then firing the base 2 in a state where it is embedded in the powder 30 (i.e., in a state where the base 2 and the powder 30 are in contact) in a nitrogen-containing atmosphere to form a ceramic layer 3 that covers at least a portion of the surface of the base 2. Each step will be explained below in order.

[0021] [Process A] First, the base 2 and the powder 30 are prepared. The shape of the base 2 is not particularly limited and may be appropriately selected depending on the intended use of the biocompatible material 1 . In addition to silicon particles, the powder 30 preferably contains auxiliary particles that function to remove oxide films (SiO2) from the surfaces of the silicon particles. Removal of the oxide films from the silicon particles promotes nitriding of the silicon. As a result, a ceramic layer 3 with a high silicon nitride content is easily formed.

[0022] Such powder 30 can be obtained by mixing silicon particles and auxiliary particles while pulverizing them. Examples of auxiliary particles include yttria (YO) particles, magnesia (MgO) particles, alumina (AlO) particles, silica (SiO), ceria (CeO), ytterbia (YbO), lutetia (LuO), zirconia (ZrO), chromia (CrO), hafnia (HfO), strontia (SrO), lanthania (LaO), neodia (NdO), gadolinia (GdO), and aluminum nitride (AlN) particles. These particles may be used alone or in combination. Among these, at least one of yttria (YO) and magnesia (MgO) particles is preferably used as the auxiliary particles.

[0023] The use of these auxiliary particles can increase the efficiency of removing the oxide film on the surface of the silicon particles, and can also impart the above-mentioned osteoconductivity to the ceramic layer 3. In addition, α-silicon nitride, which is a low-temperature phase, is also easily formed. In addition to the above functions, the auxiliary particles may also have, for example, a function of promoting nitriding of silicon (silicon particles) or a function of promoting sintering of silicon particles. The molar ratio of silicon particles to auxiliary particles is preferably about 85:15 or more and 99:1 or less, more preferably about 88:12 or more and 98.5:1.5 or less, and even more preferably about 91:9 or more and 98:2 or less. By using a powder containing silicon particles and auxiliary particles in such a ratio, the above effects are more likely to be improved.

[0024] The average particle diameter (D50, median diameter) of the silicon particles is preferably about 0.1 μm to 10 μm, more preferably about 0.5 μm to 7.5 μm, and even more preferably about 1 μm to 5 μm. Using silicon particles with an average particle diameter equal to or greater than the lower limit can prevent oxygen atoms from being mixed into the ceramic layer 3 due to their surface oxide coating. Furthermore, the silicon particles are less likely to scatter, improving workability during the formation of the ceramic layer 3. On the other hand, silicon particles with an average particle diameter equal to or less than the upper limit have a sufficiently large specific surface area, allowing rapid nitridation and conversion to silicon nitride. Furthermore, a sufficient contact area with the base 2 can be ensured, facilitating the formation of a ceramic layer 3 with high adhesion to the base 2. Here, the particle size distribution is measured in accordance with the method described in JIS Z 8825:2013 "Particle size analysis - Laser diffraction and scattering method." In the particle size distribution (cumulative distribution) shown with the horizontal axis representing particle size [μm] on a logarithmic scale and the vertical axis representing frequency [volume %], the particle size at which the cumulative value from the smallest particle size reaches 50% of the total is the average particle size (D50).

[0025] The particles can be pulverized and mixed using, for example, a pulverizer, a kneader, or the like. Examples of the grinding machine and kneading machine include a ball mill (rolling ball mill, planetary ball mill), bead mill, hammer mill, sand mill, attritor, vibration mill, cutter mill, stamp mill, pin mill, colloid mill, atomizer, rotoplex, jet mill (fluidized bed jet mill, collision plate jet mill), roll crusher, mortar, crusher, high-pressure disperser, stone mill, kneader, extruder, two-roll mill, three-roll mill, lab blast mill, Banbury mixer, ribbon mixer, Henschel mixer kneading roll, single-screw extruder, twin-screw extruder, and multi-screw extruder having three or more screws. In this manner, the powder 30 is obtained.

[0026] [Process B] Next, the base 2 is subjected to pretreatment. This pretreatment may be, for example, at least one of cleaning treatment, surface roughening treatment, etc. By carrying out these pretreatments, the adhesion between the base 2 and the ceramic layer 3 can be further improved. Examples of the cleaning treatment include water washing, organic solvent washing, ethanol washing, plasma treatment, steam treatment, acid treatment, and alkali treatment. Examples of surface roughening treatments include blasting, etching with an acid solution / alkaline solution / ion / plasma / electrolysis, and the like.

[0027] The surface roughness (arithmetic mean roughness Ra) of the base 2 is preferably about 0.1 μm to 10 μm, more preferably about 0.5 μm to 7.5 μm, and even more preferably about 1 μm to 5 μm. In this case, the adhesion between the base 2 and the ceramic layer 3 can be further improved, and uneven coverage of the ceramic layer 3 can also be reduced. The arithmetic mean roughness Ra is measured in accordance with the method described in JIS B 0601:2013. The surface roughness of the base 2 may be adjusted to fall within the above range by pre-treatment, or if the base 2 already has a surface roughness within the above range before pre-treatment, the pre-treatment may be omitted.

[0028] [Process C] First, the powder 30 prepared in the above step A is applied to the surface of the base 2, for example, by hand or with a brush. Next, the base 2 is fired using the container 10 shown in Fig. 3. Fig. 3 is a schematic diagram showing the state in which the base is embedded in powder during firing. The container 10 has a ceramic container body 11 and a ceramic lid 12 that closes the upper opening of the container body 11. Specifically, the powder 30 prepared in step A above is filled into the container body 11, and the base 2 is embedded in this powder 30. Thereafter, a ceramic plate 20 is placed on the powder 30, and the container body 11 is closed with the lid 12. At this time, in order to achieve a more tight contact between the powder 30 and the base 2, the mass or quantity of the plate 20 may be adjusted as appropriate, or the powder 30 may be pressurized via the plate 20. In this state, the base 2 together with the container 10 is fired in a nitrogen-containing atmosphere. Examples of ceramics that can be used to form the container 10 and the plate 20 include boron nitride and alumina. Finally, the base 2 (biocompatible material 1) on which the ceramic layer 3 is formed may be removed from the powder 30, and the unbonded powder 30 (silicon nitride particles, particles derived from the auxiliary agent, silicon particles, and auxiliary agent particles) adhering to the surface of the biocompatible material 1 may be removed using a blower, brush, ultrasonic cleaning, etc.

[0029] The firing temperature in step (second step) C is preferably about 1100° C. or higher and 1500° C. or lower, more preferably about 1150° C. or higher and 1450° C. or lower, and even more preferably about 1200° C. or higher and 1400° C. By firing at such a firing temperature, silicon can be nitrided while preventing or suppressing a decrease in the mechanical strength of the base 2 due to heating. The firing time in step (second step) C is not particularly limited, as it is set appropriately depending on the firing temperature, but is preferably about 0.5 to 12 hours, more preferably about 1 to 10 hours, and even more preferably about 1 to 8 hours. Firing for such a firing time makes it possible to nitride silicon while preventing or suppressing a decrease in the mechanical strength of the base 2 due to heating. In this specification, the firing temperature is the maximum temperature, and the firing time is the time during which the firing temperature is maintained.

[0030] The nitrogen content in the firing atmosphere (nitrogen-containing atmosphere) is preferably about 85% by volume or more, more preferably about 90% by volume or more, even more preferably about 95% by volume or more, and may be 100% by volume. This allows silicon to be sufficiently nitrided. When the firing atmosphere contains gas components other than nitrogen, examples of the other gas components include hydrogen, oxygen, and rare gases, with hydrogen being preferred. In other words, it is preferable that the nitrogen-containing atmosphere further contains hydrogen. This makes it easier for silicon to be nitrided, and therefore tends to result in more silicon nitride being formed. The pressure of the firing atmosphere in step (second step) C is preferably about 0.01 MPaG or more and 10 MPaG or less, more preferably about 0.02 MPaG or more and 5 MPaG or less, and even more preferably about 0.03 MPaG or more and 1 MPaG or less. When the pressure of the firing atmosphere is above the above lower limit, silicon is more easily nitrided. On the other hand, when the pressure of the firing atmosphere is below the above upper limit, handling of the gas during production of the biocompatible material 1 is easier.

[0031] Instead of embedding the base 2 in the powder 30, a slurry containing the powder 30 can be applied or sprayed onto the surface of the base 2 to bring the base 2 into contact with the powder 30, and then fired in this state. In addition, with the base 2 embedded in the powder 30, pressure can be applied from the surroundings using cold isostatic pressing (CIP) or the like, bringing the base 2 and the powder 30 into contact without using a container 10, and firing can be performed in this state. Through the above steps, silicon particles are nitrided and partially sintered on the surface of the base 2, forming a porous ceramic layer 3 containing silicon nitride on the surface of the base 2. As a result, a biocompatible material 1 is obtained in which at least a portion of the surface of the base 2 is coated with the ceramic layer 3.

[0032] The biocompatible material 1 has a porous ceramic layer 3 containing silicon nitride. Therefore, the biocompatible material 1 can increase the amount of ammoniacal nitrogen eluted into body fluids that come into contact with it, and can therefore fully exhibit antibacterial and osteoconductive properties. Such biocompatible material 1 can be used for components (stems) of artificial joints, bone filling materials (artificial bones) such as intervertebral spacers and vertebral arch spacers, puncture needles, indwelling needles, stents, scissors, clips, scalpels, forceps, screws, bolts, and the like. Furthermore, it may be provided in the following aspects.

[0033] (1) A biocompatible material comprising a base made of a metal material and a porous ceramic layer containing silicon nitride that covers at least a portion of the surface of the base.

[0034] (2) The biocompatible material according to (1) above, wherein the porosity of the ceramic layer is 3% or more and 70% or less.

[0035] (3) The biocompatible material according to (1) or (2) above, wherein the base has a metal nitride layer on the surface on the ceramic layer side.

[0036] (4) A biocompatible material according to any one of (1) to (3) above, wherein the metal material contains at least one metal atom belonging to groups 3 to 12 of the periodic table.

[0037] (5) In the biocompatible material described in (4) above, the metal material contains at least one selected from the group consisting of titanium (Ti), vanadium (V), iron (Fe), chromium (Cr), nickel (Ni), molybdenum (Mo), manganese (Mn), cobalt (Co), niobium (Nb), zirconium (Zr), tantalum (Ta), tungsten (W), copper (Cu), palladium (Pd), iridium (Ir), platinum (Pt), and gold (Au).

[0038] (6) The biocompatible material according to (5) above, wherein the metal material contains titanium (Ti) as a main component.

[0039] (7) The biocompatible material according to any one of (1) to (6) above, wherein the coverage of the surface of the base with the ceramic layer is 30% or more and 95% or less.

[0040] (8) The biocompatible material according to any one of (1) to (7) above, wherein the content of silicon nitride in the ceramic layer is 30% by mass or more and 100% by mass or less.

[0041] (9) A method for producing a biocompatible material, comprising: a first step of preparing a base made of a metal material and a powder containing silicon (Si) particles; and a second step of contacting the base and the powder and firing them in a nitrogen-containing atmosphere to coat at least a portion of the surface of the base and form a porous ceramic layer containing silicon nitride.

[0042] (10) A method for producing a biocompatible material as described in (9) above, wherein in the second step, the powder is applied to the surface of the base, and then the base is embedded in the powder.

[0043] (11) The method for producing a biocompatible material according to (9) or (10) above, wherein in the second step, the nitrogen-containing atmosphere further contains hydrogen.

[0044] (12) The method for producing a biocompatible material according to any one of (9) to (11) above, wherein the silicon particles have an average particle size of 0.1 μm or more and 10 μm or less.

[0045] (13) A method for producing a biocompatible material according to any one of (9) to (12) above, wherein the powder further contains auxiliary particles having the function of removing an oxide coating on the surface of the silicon particles.

[0046] (14) The method for producing a biocompatible material according to any one of (9) to (13) above, wherein the firing temperature in the second step is 1100°C or higher and 1500°C or lower.

[0047] (15) A method for producing a biocompatible material according to any one of (9) to (14) above, wherein the surface roughness (arithmetic mean roughness Ra) of the surface of the base is 0.1 μm or more and 10 μm or less. Of course, this is not the case.

[0048] Finally, while various embodiments of the present disclosure have been described, they are presented as examples and are not intended to limit the scope of the invention. The novel embodiments may be embodied in various other forms, and various omissions, substitutions, and modifications may be made without departing from the spirit of the invention. Such embodiments and modifications are intended to be included within the scope and spirit of the invention, as well as within the scope of the inventions and their equivalents as defined in the claims. [Example]

[0049] The present invention will be described in more detail below using the following examples and comparative examples, but the present invention is not limited to the following examples.

[0050] Example A A-1.Preparing the powder First, a total of 40 g of silicon particles (manufactured by Kojundo Chemical Research Institute, purity 3N, <45 μm), yttria particles (manufactured by Shin-Etsu Chemical Co., Ltd., "UU type"), and magnesia particles (manufactured by Iwatani Chemical Co., Ltd., "MJ-30") were weighed out to a molar ratio of 97.6:0.7:1.7. Next, these particles were placed in a silicon nitride pot (volume 250 mL) together with silicon nitride balls (φ5 mm) and 120 mL of ethanol, and mixed while being pulverized for 3 hours at 250 rpm using a planetary ball mill (Fritsch, "P-5") The pulverized slurry was suction filtered, dried (100°C), and sieved through a nylon sieve #200 to obtain a powder with an average particle size (D50, median size) of 1 µm.

[0051] A-2. Preparation of the base Two types of 1.5 mm thick Ti-6Al-4V plate materials were prepared as bases. The planar shape of one of the plates was a circle with a diameter of 20 mm, and the planar shape of the other plate was a square with sides of 40 mm.

[0052] A-3. Sample production (No. A1) First, a blasting treatment (pretreatment) was performed on a plate material with a circular shape in plan view using alumina-based abrasive grains. After the blasting treatment, the surface roughness (arithmetic mean roughness Ra) of the plate material was 1 μm or more and 2 μm or less. Next, the powder was manually applied to the surface of the plate. Then, the plate material was embedded in the powder filled in the boron nitride container body, as shown in Figure 3. Furthermore, a boron nitride plate was placed on top of the powder, and the container body was closed with a boron nitride lid. Next, this container was placed in a multipurpose high-temperature furnace (Fuji Denpa Kogyo Co., Ltd., "Hi-Multi") and fired in a nitrogen atmosphere (0.03 MPaG) containing 4% by volume of hydrogen at a firing temperature of 1200°C for 1 hour, thereby producing a sample (biocompatible material) with a ceramic layer.

[0053] (No. A2) A sample (biocompatible material) having a ceramic layer was produced in the same manner as No. A1, except that a plate material having a square shape in plan view was used instead of the plate material having a circular shape in plan view. Figure 4 shows photographs of the appearance of samples No. A1 and A2. As shown in FIG. 4, the surfaces of the samples No. A1 and A2 were black or gray.

[0054] A-4. Measurement and evaluation A-4-1. X-ray diffraction (XRD) measurement The surface of the ceramic layer of sample No. A1 was subjected to XRD measurement using an XRD device (Rigaku Corporation, "Ultima IV"), with a focusing optical system and a Cu sealed tube as the X-ray source. In the XRD pattern, peaks of α-silicon nitride (α-Si3N4) and titanium nitride (TiN) were confirmed.

[0055] A-4-2.Scanning electron microscope (SEM) observation - Energy dispersive X-ray spectroscopy (EDX) analysis A cross section of the ceramic layer of Sample No. A1 along its thickness direction was observed using a field emission scanning electron microscope (FE-SEM) (JEOL Ltd., "JSM-7001F / SHL") at an accelerating voltage of 15.0 kV, a working distance (WD) of approximately 10 mm, and a magnification of 10,000. EDX analysis was also performed using an EDX (JEOL Ltd., "JED-2300"). Figure 5 shows an SEM image of a cross section of sample No. A1 along the thickness direction of the ceramic layer. As shown in Figure 5, a porous ceramic layer composed of needle-like or columnar particles was confirmed on the plate. It was also confirmed that there were areas on the plate's surface that were not covered with the ceramic layer. EDX analysis detected Si in the ceramic layer and Ti on the surface of the plate facing the ceramic layer. The results of XRD measurement and SEM observation-EDX analysis confirmed that the ceramic layer is composed of needle-like or columnar Si3N4 particles and has a porous structure, and that the plate has a TiN layer on the surface facing the ceramic layer.

[0056] A-4-3.Porosity of ceramic layer First, sample No. A1 was embedded in resin, and a cross section along the thickness direction of the ceramic layer was polished by mechanical polishing and ion milling to prepare an observation cross section. The cross section was then observed using a field emission scanning electron microscope (FE-SEM) (JEOL Ltd., "JSM-7001F / SHL") at an accelerating voltage of 10.0 kV, a working distance (WD) of approximately 10 mm, and a magnification of 30,000x, to obtain backscattered electron images for five fields of view. The cross-sectional SEM images were then binarized using image analysis software (ImageJ) as described above to determine the porosity (%). The porosity of the ceramic layer of sample No. A1 was 47.1%.

[0057] A-4-4.Ceramic layer coverage The surface of sample No. A1 was observed using a field emission scanning electron microscope (FE-SEM) (JEOL Ltd., "JSM-7001F / SHL") at an accelerating voltage of 10.0 kV, a working distance (WD) of approximately 10 mm, and a magnification of 500x to obtain a backscattered electron image. The surface SEM image was then binarized using image analysis software (ImageJ) as described above to determine the coverage (%). The coverage of the ceramic layer of sample No. A1 was 69.2%.

[0058] A-4-5. Ceramic layer adhesion test Fig. 6 is a diagram for explaining the method of testing the adhesion of the ceramic layer, where the unit of the numerical values ​​is "mm." Two test pieces measuring approximately 10 mm x 40 mm were cut out from the No. A2 sample, and a thermosetting resin cup was formed on the surface of the ceramic layer in the shape and size shown in Figure 6. The resin molding conditions were as follows: Mold clamping pressure: 14t Molding pressure: 9MPa ·Molding time: 120 seconds ·Molding temperature: 175℃ Post cure: 175°C x 6 hours

[0059] Next, a shear load was applied to the cup using a bond tester (Nordson Corporation, "Series 4000") to measure the shear adhesion strength of the ceramic layer. The measurement conditions were as follows: ·Measurement temperature: room temperature Stage speed: 10μm / s Tool height: 100 μm from sample Measurement limit: 0.5 kgf Load direction: Short side of sample Number of measurement points: 8

[0060] The shear bond strength of sample No. A2 was 15 MPa on average at eight locations. In addition, since no sample damage occurred across the entire contact surface of the cup at any of the measurement locations, it can be said that the shear bond strength of sample No. A2 is 15 MPa or more.

[0061] Example B B-1.Preparing the powder Prepared in the same manner as "A-1" above. B-2. Preparation of the base A 1.5 mm thick plate made of Ti-6Al-4V was prepared as the base. The planar shape of this plate was a circle with a diameter of 20 mm.

[0062] B-3. ​​Sample production (No. B1: Example) First, the powder was manually applied to the surface of the plate material. Then, the plate material was embedded in the powder filled in the boron nitride container body, as shown in Figure 3. Furthermore, a boron nitride plate was placed on top of the powder, and the container body was closed with a boron nitride lid. Next, this container was placed in a multipurpose high-temperature furnace (Fuji Denpa Kogyo Co., Ltd., "Hi-Multi") and fired in a pure nitrogen atmosphere (0.03 MPaG) at a firing temperature of 1400°C for 1 hour, thereby producing a sample (biocompatible material) with a ceramic layer.

[0063] (No. B2: Example) A sample (biocompatible material) having a ceramic layer was produced in the same manner as No. B1, except that the firing temperature was changed to 1200°C. (No. B3: Example) First, the plate material was subjected to blasting (pretreatment) using alumina abrasive grains. Using this plate material, a sample (biocompatible material) with a ceramic layer was produced in the same manner as No. B2, except that the firing atmosphere was changed to a nitrogen atmosphere containing 4% by volume of hydrogen. Sample No. B3 is identical to Sample No. A1.

[0064] (No.B4: Comparative example) A silicon nitride sintered plate with a thickness of 0.64 mm was prepared using a molar ratio of Si3N4:Y2O3:MgO = 93:2:5 raw material powders. This silicon nitride sintered plate was cut into a 14 mm x 24 mm piece to prepare sample No. B4. (No. B5: Comparative Example) The plate material prepared in "B-2" above was used as sample No. B5.

[0065] B-4. Measurement and Evaluation B-4-1.Porosity of ceramic layer In the same manner as in "A-4-3" above, the porosity of the ceramic layer was measured for Samples Nos. B1 to B3. For sample No. B4, the bulk density ρ was measured by the Archimedes method, and the t -ρ) / ρ t The value calculated by multiplying the ratio by ρ × 100 was taken as the porosity. t is the theoretical density, 3.23 g / cm 3 It was decided. B-4-2.Ceramic layer coverage The coverage of the ceramic layer was measured in the same manner as in "A-4-4" above.

[0066] B-4-3. Ammonia nitrogen elution test First, two samples each of Nos. B1, B3, B4 and B5 were placed in a 50 mL polypropylene container, and 10 mL of distilled water was added. Next, the container was shaken by hand for 30 seconds and then left to stand for 10 minutes, after which the sample was removed. Next, the concentration of ammoniacal nitrogen in 10 mL of the solution was measured using a coulometric ammonia meter (manufactured by Central Scientific Co., Ltd., "AT-2000 model").

[0067] B-4-4. Antibacterial test For samples No. B3 and B5, the number of remaining bacteria after 24 hours of incubation at 35°C was measured using a method based on JIS Z 2801:2012 "Antibacterial products - Antibacterial test methods, antibacterial effect." Sample No. B3 is the antibacterial treated test piece, and sample No. B5 is the untreated test piece. The measurement was performed twice, and the viable cell count was calculated as the average of the two measurements. The antibacterial activity value R of sample No. B3 was calculated from the viable cell counts of samples No. B3 and B5.

[0068] Other test conditions are as follows: Film type: Polyethylene film Film size: approx. 10mm x 10mm Film thickness: approx. 0.05 mm Inoculation volume of test bacteria solution: 0.1 mL Viable cell count in test solution: 2.4 x 10 5 / mL (Staphylococcus aureus), 1.6 × 10 5 / mL (E. coli)

[0069] The results are shown in Table 1 below. [Table 1]

[0070] As shown in Table 1, sample No. B3 has sufficiently high antibacterial properties. Although the amount of ammonium nitrogen eluted from sample No. B1 was lower than that from sample No. B3, it was still sufficiently high and is thought to have antibacterial properties similar to those of sample No. B3. The difference in the amount of ammonium nitrogen eluted is thought to be due to differences in porosity (see also the data for sample No. B4).

[0071] Furthermore, sample No. B2 has a porosity similar to that of sample No. B3, and is thought to have the same amount of eluted ammoniacal nitrogen and antibacterial properties as sample No. B3. On the other hand, sample No. B5 had a low amount of eluted ammoniacal nitrogen and did not have sufficient antibacterial properties.Sample No. B4 also had a low amount of eluted ammoniacal nitrogen and is therefore considered to have inferior antibacterial properties compared to samples B1, B2, and B3. [Explanation of symbols]

[0072] 1: Biocompatible materials 2: Base 21: Metal nitride layer 3: Ceramic layer 10: Container 11: Container body 12: Lid 20: Board 30: powder

Claims

1. A biocompatible material, a base made of a metal material; a porous ceramic layer containing silicon nitride covering at least a portion of the surface of the base.

2. The biocompatible material according to claim 1, A biocompatible material, wherein the porosity of the ceramic layer is 3% or more and 70% or less.

3. The biocompatible material according to claim 1, The base is a biocompatible material having a metal nitride layer on the surface facing the ceramic layer.

4. The biocompatible material according to claim 1, The metal material is a biocompatible material containing at least one metal atom belonging to groups 3 to 12 of the periodic table.

5. The biocompatible material according to claim 4, The metal material is a biocompatible material containing at least one selected from the group consisting of titanium (Ti), vanadium (V), iron (Fe), chromium (Cr), nickel (Ni), molybdenum (Mo), manganese (Mn), cobalt (Co), niobium (Nb), zirconium (Zr), tantalum (Ta), tungsten (W), copper (Cu), palladium (Pd), iridium (Ir), platinum (Pt), and gold (Au).

6. The biocompatible material according to claim 5, The metal material is a biocompatible material containing titanium (Ti) as its main component.

7. The biocompatible material according to claim 1, A biocompatible material, wherein the coverage of the surface of the base with the ceramic layer is 30% or more and 95% or less.

8. The biocompatible material according to claim 1, A biocompatible material, wherein the content of silicon nitride in the ceramic layer is 30% by mass or more and 100% by mass or less.

9. A method for producing a biocompatible material, comprising: A first step of preparing a base made of a metal material and a powder containing silicon (Si) particles; a second step of firing the base and the powder in a nitrogen-containing atmosphere while they are in contact with each other, thereby coating at least a portion of the surface of the base and forming a porous ceramic layer containing silicon nitride.

10. The method for producing a biocompatible material according to claim 9, In the second step, the powder is applied to the surface of the base, and then the base is embedded in the powder.

11. The method for producing a biocompatible material according to claim 9, A method for producing a biocompatible material, wherein in the second step, the nitrogen-containing atmosphere further contains hydrogen.

12. The method for producing a biocompatible material according to claim 9, A method for producing a biocompatible material, wherein the silicon particles have an average particle size of 0.1 μm or more and 10 μm or less.

13. The method for producing a biocompatible material according to claim 9, A method for producing a biocompatible material, wherein the powder further contains auxiliary particles having the function of removing an oxide coating on the surface of the silicon particles.

14. The method for producing a biocompatible material according to claim 9, A method for producing a biocompatible material, wherein the firing temperature in the second step is 1100°C or higher and 1500°C or lower.

15. The method for producing a biocompatible material according to claim 9, A method for producing a biocompatible material, wherein the surface roughness (arithmetic mean roughness Ra) of the surface of the base is 0.1 μm or more and 10 μm or less.

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