Method for producing biocompatible material, and biocompatible material

Abstract

[Problem] To provide a biocompatible material having sufficient osteoconductivity and antibacterial properties, and a method for producing the biocompatible material. [Solution] Provided according to one embodiment of the present invention is a method for producing a biocompatible material, the method comprising: a step for preparing a base and particles that contain, as a main component, a compound containing silicon and nitrogen; and a step for causing the particles to collide with the surface of the base by aerosol deposition and forming a coating layer that covers at least part of the base, thus obtaining a biocompatible material.

Description

Biocompatible material manufacturing method and biocompatible material

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

[0002] Sintered bodies made of hydroxyapatite have traditionally been used as biocompatible materials (see Patent Document 1). Hydroxyapatite has excellent biocompatibility and high osteoconductivity. However, because hydroxyapatite does not exhibit antibacterial properties, after implantation of a biocompatible material into a living body, treatment is performed to prevent the onset of infection by administering an antibacterial agent or the like. Meanwhile, biocompatible materials made of titanium or titanium alloys also exist, but they have lower cell proliferation capacity and osteoconductivity than biocompatible materials made of hydroxyapatite.

[0003] Japanese Patent Application Laid-Open No. 2003-286073

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

[0005] According to one aspect of the present invention, there is provided a method for producing a biocompatible material, comprising the steps of: preparing a base and particles containing, as main components, a compound containing silicon and nitrogen; and adhering the particles to the surface of the base by colliding them with the surface using an aerosol deposition method, thereby forming a coating layer that covers at least a portion of the base, thereby obtaining the biocompatible material.

[0006] According to this embodiment, a biocompatible material having sufficient osteoconductivity and antibacterial properties can be obtained.

[0007] FIG. 1 is a front view (partially cut away) showing an embodiment of a biocompatible material. ３ N ４ , SiO ２ and Y ２ O ３1 is a phase diagram of a three-component system of the above. FIG. 1 is a schematic diagram showing an example of an aerosol deposition apparatus. FIG. 2 is a graph showing the results of XRD measurement of a sample. FIG. 3 is a schematic diagram showing a method of adhesion testing of a sample. FIG. 4 is a graph showing the results of adhesion strength measurement of a sample. FIG. 5 is a graph showing the results of an antibacterial test of a sample. FIG. 6 is a diagram showing the results of surface SEM observation and composition analysis of a sample of Example 21. FIG. 7 is a diagram showing the results of surface SEM observation and composition analysis of a sample of Example 22. FIG. 8 is a diagram showing the results of cross-sectional SEM observation and composition analysis of a sample of Example 21. FIG. 9 is a diagram showing the results of cross-sectional SEM observation and composition analysis of a sample of Example 22. FIG. 10 is a schematic diagram showing the configuration of an adhesion strength testing apparatus. FIG. 11 is a graph showing the results of an antibacterial test of samples of Examples 41 and 42. FIG. 12 is a photograph showing the appearance of a screw before and after formation of a coating layer. FIG. 13 is a diagram showing the results of surface SEM observation and composition analysis of a root portion of a coated screw. FIG. 14 is a diagram showing the results of surface SEM observation and composition analysis of a crest portion of a coated screw. FIG. 15 is a diagram showing the results of cross-sectional SEM observation and composition analysis of a root portion of a coated screw.

[0008] Hereinafter, embodiments of the present disclosure will be described with reference to the drawings. The various features shown in the following embodiments can be combined with each other. First, a biocompatible material (implant) manufactured by the manufacturing method of a biocompatible material according to this embodiment will be described. FIG. 1 is a front view (partially cut away) showing an embodiment of the biocompatible material. FIG. 2 is a front view of a Si ３ N ４ , SiO ２ and Y ２ O ３ This is a phase diagram of a three-component system. The biocompatible material 1 shown in Figure 1 is a component (stem) of an artificial joint, and has an insertion portion 11 that is inserted into the femur, and a mounting portion 12 to which an artificial femoral head is attached. This biocompatible material 1 includes a base portion 2 and a coating layer 3 that covers at least a portion of the base portion 2 (in this embodiment, the entire base portion 2). The coating layer 3 is formed using particles containing a compound containing silicon and nitrogen as a main component. Therefore, the coating layer 3 also contains a compound containing silicon and nitrogen as a main component.

[0009] Suitable materials for the base 2 include metals, resins, and the like that are biohazardous or minimally toxic. Metal materials include, for example, titanium, cobalt, chromium, tantalum, iron, nickel, copper, palladium, and platinum. These metals can be used alone or in combination (as alloys). Resin materials include, for example, polyetheretherketone (PEEK), polymethylmethacrylate (PMMA), polyarylamide (PARA), polycarbonate (PC), polyethylene (PE), and polylactic acid (PLA). These metals can be used alone or in combination (as alloys).

[0010] The inventors' studies have revealed that compounds containing silicon and nitrogen have sufficient osteoconductivity and antibacterial properties. Therefore, a biocompatible material 1 having a coating layer 3 containing such a compound as a primary component on its surface can effectively prevent the onset of infection associated with the implantation of the biocompatible material 1 while quickly achieving bone fusion at the application site (e.g., the implantation site). Preferably, such a compound further contains yttrium and oxygen, i.e., is a composite compound (complex oxide) containing yttrium, oxygen, silicon, and nitrogen as constituent elements. The use of such a composite compound further improves the osteoconductivity and antibacterial properties of the biocompatible material 1.

[0011] The composite compound is Si ３ N ４ -SiO ２ -Y ２ O ３ Compounds and Si ３ N ４ -Y ２ O ３ The compound may contain at least one selected from the group consisting of Si-based compounds. ３ N ４ -SiO ２ -Y ２ O ３ The Si-based compounds are shown in FIG. ３ N ４ , SiO ２ and Y ２ O ３The composite compound is preferably a compound included in the phase diagram of the three-component system of Y. The composite compound preferably has a composition within the shaded area (including the boundary line) in FIG. ５ Si ３ O １２ N (N-apatite), Y ２ Si ３ O ３ N ４ (N-Melilite) and Y ４ Si ２ O ７ N ２ It is a triangular area with the three points of (N-YAM) as vertices. The triangular area includes the compositions on the boundary of the area.

[0012] The complex compound is Y on the boundary of this triangular region. ５ Si ３ O １２ N (N-apatite), YSiO ２ N (N-wollastonite), Y ２ Si ３ O ３ N ４ (N-Melilite) and Y ４ Si ２ O ７ N ２ (N-YAM). This can enhance cell proliferation while sufficiently reducing cytotoxicity. It can also promote the differentiation of undifferentiated mesenchymal stem cells into osteoblasts, i.e., osteoconductivity (calcification). For this reason, such a composite compound is suitable as a constituent material for the coating layer 3 (particles).

[0013] As used herein, the term "main component" refers to the component that is most abundant when multiple components are included. Components other than the "main component" are referred to as "secondary components." The coating layer 3 (particle) may consist solely of the complex compound that is the main component, or may contain a secondary component different from the main component. The content of the complex compound in the coating layer 3 may be 90% by mass or more, 95% by mass or more, 98% by mass or more, 99% by mass or more, 99.5% by mass or more, or 99.7% by mass or more. The higher the content of the complex compound in the coating layer 3, the more likely it is to have improved biocompatibility. Examples of secondary components that may be included in the coating layer 3 include silicon nitride, silicon dioxide, and yttrium oxide. The coating layer 3 may also contain a complex oxide in which two of these three components are combined.

[0014] The compound may also contain silicon nitride. The content of silicon nitride in the coating layer 3 may be 90% by mass or more, 95% by mass or more, 98% by mass or more, 99% by mass or more, 99.5% by mass or more, or 99.7% by mass or more. The higher the content of silicon nitride in the coating layer 3, the more improved the antibacterial properties tend to be. Examples of minor components that may be contained in the coating layer 3 include fluorine, chlorine, oxygen, iron, aluminum, and calcium. These may form compounds.

[0015] In this case, the fluorine content in the coating layer 3 is preferably 900 ppm by mass or less. The fluorine content in the coating layer 3 may be 700 ppm by mass or less, 500 ppm by mass or less, 300 ppm by mass or less, 250 ppm by mass or less, 100 ppm by mass or less, or 60 ppm by mass or less. The lower the fluorine content in the coating layer 3, the more likely it is that antibacterial properties will be improved. One of the reasons for this is that when the fluorine content in the coating layer 3 is low, ammonium ions (NH ４ ＋ ) to ammonia (NH ３ ) is likely to increase.

[0016] The fluorine content in the coating layer 3 varies depending on the raw material composition used to produce the particles used to form the coating layer 3 and whether or not the particles are surface-treated. For example, the fluorine content in the particles, and therefore the fluorine content in the coating layer 3, can be reduced by thoroughly washing the particles with a cleaning liquid such as water. The fluorine content in the coating layer 3 may be 10 ppm by mass or more, 20 ppm by mass or more, or 30 ppm by mass or more. This allows for a reduction in the manufacturing cost of the coating layer 3 (biocompatible material 1). The fluorine content in the coating layer 3 may range from 10 ppm by mass to 900 ppm by mass.

[0017] The chlorine content in the coating layer 3 may be 30 ppm by mass or more, 50 ppm by mass or more, 100 ppm by mass or more, 300 ppm by mass or more, 400 ppm by mass or more, or 500 ppm by mass or more. A higher chlorine content in the coating layer 3 tends to improve antibacterial properties, particularly against gram-negative bacteria. The chlorine content in the coating layer 3 varies depending on the raw material composition used in producing the particles used to form the coating layer 3 and whether or not the particles are surface-treated. The chlorine content in the coating layer 3 may be 1000 ppm by mass or less, 800 ppm by mass or less, or 700 ppm by mass or less. This makes it possible to suppress chlorine-induced corrosion. The chlorine content in the coating layer 3 may be in the range of 30 ppm by mass or more to 1000 ppm by mass or less.

[0018] The content of oxygen in the coating layer 3 may be 2% by mass or less, 1.5% by mass or less, or 1% by mass or less. Oxygen may be, for example, silicon dioxide (SiO ２) may be included. The lower the oxygen content in the coating layer 3, the more improved the antibacterial performance. The oxygen content in the coating layer 3 varies depending on the raw material composition and the firing atmosphere used to produce the particles used to form the coating layer 3. For example, if the oxygen concentration in the firing atmosphere is reduced when synthesizing particles (silicon nitride) by direct nitriding, the oxygen content in the particles (coating layer 3) tends to be lower. The oxygen content in the coating layer 3 may be 0.2% by mass or more, 0.4% by mass or more, or 0.5% by mass or more. This makes it possible to use raw materials and gases with lower purity, thereby reducing the production costs of the particles and, ultimately, the biocompatible material 1. The oxygen content in the coating layer 3 may be in the range of 0.2% by mass or more to 2% by mass or less.

[0019] The total content of aluminum, iron, and calcium in the coating layer 3 may be 2000 ppm by mass or less, or 1800 ppm by mass or less. By reducing these total contents, the silicon nitride content in the coating layer 3 increases, and antibacterial properties tend to be improved. The total content of aluminum, iron, and calcium in the coating layer 3 may be 10 ppm by mass or more, 50 ppm by mass or more, 500 ppm by mass or more, or 1000 ppm by mass or more. This makes it possible to use raw materials with lower purity, thereby reducing the production costs of the particles and, ultimately, the biocompatible material 1. The total content of aluminum, iron, and calcium in the coating layer 3 may be in the range of 10 ppm by mass or more to 2000 ppm by mass or less.

[0020] The contents of fluorine, chlorine, oxygen, aluminum, iron and calcium in the particles can be measured by the methods described in Examples. The particles and the coating layer 3 may contain other subcomponents than those described above.

[0021] Alpha conversion rate of silicon nitride (Si ３ N ４ α-Si for the whole ３ N ４The alpha phase ratio of silicon nitride may be 80% or more, 85% or more, 88% or more, or 90% or more. Increasing the alpha phase ratio tends to improve antibacterial activity against gram-negative bacteria. The alpha phase ratio of silicon nitride may be 99% or less, 97% or less, or 96% or less. This reduces the production costs of the particles and, ultimately, the biocompatible material 1. An example of the alpha phase ratio of silicon nitride may be 80% or more and 99% or less. The alpha phase ratio of silicon nitride can be adjusted, for example, by changing the firing conditions (e.g., firing temperature and firing time) when synthesizing silicon nitride (particles) by firing.

[0022] When the arithmetic mean roughness Ra of the surface of the base 2 is RaB [μm] and the arithmetic mean roughness Ra of the surface of the coating layer 3 is RaC [μm], the ratio RaC / RaB is preferably 0.9 to 1.5, more preferably 0.92 to 1.3, and even more preferably 0.94 to 1.1. In this case, the value of RaC can be set large depending on the value of RaB. This facilitates adhesion of undifferentiated mesenchymal stem cells to the coating layer 3 (biocompatible material 1), thereby promoting the differentiation and proliferation of undifferentiated mesenchymal stem cells into osteoblasts. In other words, the osteoconductivity and cell proliferation ability of the biocompatible material 1 can be further improved. Such a coating layer 3 can be formed smoothly and reliably, for example, by the aerosol deposition method (AD method) described below.

[0023] Specifically, the arithmetic mean roughness RaB of the surface of the base 2 is preferably 0.005 μm to 300 μm, more preferably 0.01 μm to 150 μm, and even more preferably 0.05 μm to 50 μm. Meanwhile, the arithmetic mean roughness Ra of the surface of the coating layer 3 is preferably 0.01 μm to 300 μm, more preferably 0.05 μm to 150 μm, and even more preferably 0.1 μm to 50 μm. In this case, osteoconductivity and cell proliferation ability can be further improved. The arithmetic mean roughness Ra is measured in accordance with the method described in JIS B 0601:2001 (ISO 4287:1997).

[0024] In this case, the antibacterial properties also tend to improve as the specific surface area of ​​the surface of the coating layer 3 increases. The reason for the improvement in osteoconductivity and cell proliferation ability is thought to be that the larger the specific surface area of ​​the surface of the coating layer 3, the greater the amount of ammonium ions produced when the layer comes into contact with water (e.g., blood). On the other hand, the reason for the improvement in antibacterial properties is thought to be that the larger the specific surface area of ​​the surface of the coating layer 3, the greater the amount of ammonia produced when the layer comes into contact with water. In particular, the antibacterial properties against gram-positive bacteria tend to improve.

[0025] The maximum height Rz of the base 2 is preferably 0.5 μm or more and 1000 μm or less, more preferably 1 μm or more and 750 μm or less, and even more preferably 1.5 μm or more and 500 μm or less. On the other hand, the maximum height Rz of the coating layer 3 is preferably 0.5 μm or more and 1000 μm or less, more preferably 1 μm or more and 750 μm or less, and even more preferably 1.5 μm or more and 500 μm or less. The maximum height Rz is also measured in accordance with the method described in JIS B 0601:2001 (ISO 4287:1997).

[0026] The thickness of the coating layer 3 is preferably 50 μm or less, more preferably 30 μm or less, even more preferably 15 μm or less, and particularly preferably 10 μm or less. The thickness of the coating layer 3 is preferably 0.5 μm or more, more preferably 0.75 μm or more, and even more preferably 1 μm or more. The thickness of the coating layer 3 can be, for example, 0.5 μm or more and 30 μm or less. Such a coating layer 3 can have high mechanical strength while exhibiting sufficient osteoconductivity and antibacterial properties. When the aerosol deposition method described below is used to form the coating layer 3, the thickness of the coating layer 3 can be adjusted by setting the film formation time in the aerosol deposition method, the composition, shape, size, etc. of the particles P.

[0027] The adhesion strength of the coating layer 3 to the base 2 is preferably 15 MPa or more, more preferably 20 MPa to 100 MPa, and even more preferably 25 MPa to 50 MPa. A coating layer 3 having such adhesion strength can be formed relatively easily by using the aerosol deposition method described below. Furthermore, it is preferable that the base 2 has an uneven structure at least in the area to be covered by the coating layer 3. Even with such a base 2, it is easy to form a homogeneous coating layer 3 with a relatively uniform thickness by using the aerosol deposition method described below. The biocompatible material 1 as described above can be manufactured, for example, as follows. A method for manufacturing the biocompatible material of this embodiment will now be described.

[0028] The method for producing a biocompatible material of this embodiment includes the steps of preparing a base 2 and particles containing a silicon- and nitrogen-containing compound as a main component, and adhering the particles to the surface of the base 2 by colliding them with the surface using an aerosol deposition method, thereby forming a coating layer 3 that covers at least a portion of the base 2, thereby obtaining a biocompatible material 1. Such an aerosol deposition method is performed, for example, using an aerosol deposition apparatus shown in Figure 3. Figure 3 is a schematic diagram showing an example of an aerosol deposition apparatus. The aerosol deposition apparatus 10 shown in Figure 3 mainly includes an aerosol chamber 20, a film formation chamber 30, a support mechanism 40, an aerosol supply mechanism 50, and a carrier gas supply mechanism 60.

[0029] The aerosol chamber 20 contains particles P containing a silicon- and nitrogen-containing compound as its main component. The average particle size (D50, median diameter) of the particles P is preferably 10 μm or less, more preferably 0.1 μm to 7.5 μm, and even more preferably 0.5 μm to 5 μm. This allows the particles P to be ejected from the aerosol supply mechanism 50 at a higher speed. This facilitates the formation of a coating layer 3 having the above-mentioned surface roughness (arithmetic mean roughness Ra). 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 a 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).

[0030] The BET specific surface area of ​​the particles P is 0.3 m ２ / g or more, 0.4m ２ / g or more, 0.5m ２ / g or more, 2m ２ / g or more, 4m ２ / g or more, 5m ２ / g or more, or 7m ２ / g or more. By increasing the BET specific surface area, it is easy to form a coating layer 3 having the above surface roughness (arithmetic mean roughness Ra). The BET specific surface area can be adjusted by changing the firing conditions (e.g., firing temperature and firing time) when synthesizing the compound (producing the particles P) and the size of the raw material powder. The BET specific surface area of ​​the particles P is 20 m ２ / g or less, 15m ２ / g or less, 10m ２ / g or less, or 6m ２ The BET specific surface area ranges from 0.3 m ２ / g or more 20m ２ The BET specific surface area of ​​the particles P can be measured by a single-point BET method using nitrogen gas in accordance with JIS Z 8830:2013 "Method for measuring specific surface area of ​​powder (solid) by gas adsorption."

[0031] Particles P containing the above-mentioned composite compound as a main component can be produced, for example, by the following procedure. First, silicon nitride powder, yttria powder, and silica powder are prepared as raw material powders. Next, at least two of these are blended to obtain a mixed powder with the target crystal composition. The raw material powders may be mixed, for example, using a ball mill or the like. The raw material powders may also be mixed by wet mixing using a solvent. The mixed powder is then sieved to remove coarse particles, and then fired in a nitrogen atmosphere at a temperature of 1500°C to 1600°C. The firing time may be, for example, 2 hours to 20 hours. Next, the obtained fired product is crushed using a ball mill or the like to obtain particles P. The crystalline phase contained in particles P can be analyzed by X-ray diffraction.

[0032] On the other hand, particles P containing silicon nitride as a main component can be produced by, for example, surface treating silicon nitride powder obtained by a known method such as direct nitridation, imide pyrolysis, or combustion synthesis, and washing it with water, as necessary. A heating unit 201 for heating particles P is provided on the outer periphery of aerosol chamber 20. The heating temperature of aerosol chamber 20 is not particularly limited, but is preferably 100°C or higher and 300°C or lower, and more preferably 150°C or higher and 250°C or lower.

[0033] The support mechanism 40 is provided in the film formation chamber 30 and is configured to support the film formation target (in this embodiment, the base 2). The support mechanism 40 includes a fixing unit 401 for fixing the base 2 and a driving unit (not shown) for rotating the fixing unit 401 around its central axis and tilting the fixing unit 401. This configuration facilitates the formation of a uniform and homogeneous coating layer 3 on the surface of the base 2. The aerosol supply mechanism 50 connects the aerosol chamber 20 and the film formation chamber 30 and includes a nozzle 501 for ejecting particles P. The aerosol supply mechanism 50 also includes a moving mechanism (not shown) for moving the nozzle 501 in the in-plane direction of the base 2. This configuration facilitates the formation of a uniform and homogeneous coating layer 3 on the surface of the base 2. An exhaust device (decompression device) 70 is also connected to the film formation chamber 30.

[0034] The degree of pressure reduction in the aerosol chamber 20 and the deposition chamber 30 is preferably 10 kPa or more and 100 kPa or less, and more preferably 20 kPa or more and 70 kPa or less. The movement speed of the nozzle 501 (base 2) is preferably approximately 1 mm / s or more and 30 mm / s or less, and more preferably approximately 5 mm / s or more and 20 mm / s or less. Moving the nozzle 501 at such a movement speed facilitates improving the uniformity and homogeneity of the coating layer 3. The distance between the nozzle 501 and the base 2 is preferably 5 mm or more and 30 mm or less, and more preferably 10 mm or more and 20 mm or less. The angle between the normal NL at the position of the base 2 where the particles P collide and the central axis O of the nozzle 501 is preferably 10° or more and 50° or less, and more preferably 20° or more and 40° or less.

[0035] In the aerosol deposition apparatus 10, a carrier gas is supplied from the carrier gas supply mechanism 60 to the aerosol chamber 20. As a result, particles P are dispersed in the carrier gas supplied to the aerosol chamber 20 to generate an aerosol, which is then ejected from the nozzle 501 of the aerosol supply mechanism 50 toward the base 2. The ejection speed of the particles P is preferably set to 1 L / min or more and 25 L / min or less, and more preferably set to 5 L / min or more and 15 L / min or less. The flow rate and flow rate of the carrier gas may be set appropriately depending on the ejection amount of the aerosol, the constituent material of the particles P ejected from the nozzle 501, and the average particle diameter. The carrier gas may be separated into two systems: a carrier gas that originally transports the particles P, and a lift-up gas that lifts up the particles P, and then supplied to the aerosol chamber 20. As the carrier gas, for example, O ２ , N ２ Gases such as Ar, He or air can be used.

[0036] When manufacturing a biocompatible material 1 using the aerosol deposition apparatus 10, first, the base 2 is fixed to the fixing portion 401 of the support mechanism 40. The aerosol chamber 20 and the deposition chamber 30 are then depressurized. This suppresses convection within the deposition chamber 30, making it easier for particles P to collide with the surface of the base 2. In this state, the drive unit is activated to start rotating and / or tilting the base 2. Next, a carrier gas is supplied from the carrier gas supply mechanism 60 to the aerosol chamber 20. This disperses and accelerates the particles P in the carrier gas, generating an aerosol. The aerosol (particles P) is then sprayed from the nozzle 501 of the aerosol supply mechanism 50 toward the surface of the base 2. At this time, the nozzle 501 may be moved in an in-plane direction, if necessary.

[0037] The particles P collide with the base 2, whereby they are crushed (pulverized) and deposited on the surface of the base 2. Through the above steps, a coating layer 3 of a predetermined thickness is formed. The above steps may be repeated multiple times. According to the aerosol deposition method described above, it is possible to form the coating layer 3 that coats the surface of the base 2 while preventing or suppressing alteration (e.g., oxidation, composition change, etc.) and deterioration of the compounds contained in the particles P. Therefore, the biocompatible material 1 can fully exhibit the osteoconductivity and antibacterial properties derived from the properties of the above compounds.

[0038] The biocompatible material 1 described above has excellent osteoconductivity and is therefore used for bones, teeth, etc., and is particularly preferably used for bones. By filling, embedding, screwing, piercing, etc., the biocompatible material 1 can be used in bone to quickly fuse with the bone. Examples of the base 2 having the above-mentioned uneven structure include medical devices such as screws, bolts, nuts, and screws. A uniform coating layer 3 can be formed even on surfaces having such uneven structures (irregular shapes) by the aerosol deposition method. Furthermore, the biocompatible material 1 may be provided in each of the following forms.

[0039] (1) A method for producing a biocompatible material, comprising the steps of: preparing a base and particles containing, as main components, a compound containing silicon and nitrogen; and adhering the particles to the surface of the base by colliding them with the surface using an aerosol deposition method, thereby forming a coating layer that covers at least a portion of the base, thereby obtaining the biocompatible material.

[0040] (2) The method for producing a biocompatible material according to (1) above, wherein the compound further contains yttrium and oxygen.

[0041] (3) In the method for producing a biocompatible material according to (2) above, the compound is Si ３ N ４ -SiO ２ -Y ２ O ３ Compounds and Si ３ N ４ -Y ２ O ３A method for producing a biocompatible material containing at least one compound selected from the group consisting of hydroxybenzoates, hydroxybenzoates, and hydroxybenzoates.

[0042] (4) In the method for producing a biocompatible material according to (2) or (3), the compound is Si ３ N ４ , SiO ２ and Y ２ O ３ In the phase diagram of the three-component system, Y ５ Si ３ O １２ N.Y. ２ Si ３ O ３ N ４ and Y ４ Si ２ O ７ N ２ A method for producing a biocompatible material having a composition within a triangular area with the three points as vertices.

[0043] (5) In the method for producing a biocompatible material according to any one of (2) to (4) above, the compound is Y ５ Si ３ O １２ N, YSiO ２ N.Y. ４ Si ２ O ７ N ２ and Y ２ Si ３ O ３ N ４ A method for producing a biocompatible material, comprising:

[0044] (6) The method for producing a biocompatible material according to (1) above, wherein the compound contains silicon nitride and has a fluorine content of 900 mass ppm or less.

[0045] (7) In the method for producing a biocompatible material described in any one of (1) to (6) above, when the arithmetic mean roughness Ra of the surface of the base is RaB and the arithmetic mean roughness Ra of the surface of the coating layer is RaC, RaC / RaB is 0.9 or more and 1.5 or less.

[0046] (8) A method for producing a biocompatible material described in any one of (1) to (7) above, wherein the arithmetic mean roughness Ra of the surface of the coating layer is 0.01 μm or more and 300 μm or less.

[0047] (9) The method for producing a biocompatible material according to any one of (1) to (8) above, wherein the thickness of the coating layer is 50 μm or less.

[0048] (10) The method for producing a biocompatible material according to any one of (1) to (9) above, wherein the particles have an average particle size of 10 μm or less.

[0049] (11) In the method for producing a biocompatible material according to any one of (1) to (10) above, the BET specific surface area of ​​the particles is 0.3 m ２ / g or more.

[0050] (12) A biocompatible material comprising a base and a coating layer that covers at least a portion of the base and contains a compound containing silicon and nitrogen as a main component.

[0051] (13) The biocompatible material according to (12) above, wherein the adhesive strength of the coating layer to the base is 15 MPa or more.

[0052] (14) The biocompatible material according to (12) or (13) above, wherein the base has an uneven structure at least in the area covered with the covering layer.

[0053] (15) The biocompatible material according to any one of (12) to (14) above, wherein the biocompatible material is used for bones. Of course, this is not a limitation.

[0054] Finally, while various embodiments of the present disclosure have been described, these 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. These embodiments and their modifications are within the scope and spirit of the invention, and are encompassed by the claims and their equivalents. The biocompatible material can be used not only for artificial joint components (stems), but also for bone prosthesis materials (artificial bone or bone substitutes) such as intervertebral spacers and vertebral arch spacers, puncture needles, indwelling needles, stents, scissors, clips, scalpels, forceps, screws, bolts, and other medical devices. The biocompatible material may also be a component to be filled in a bone defect.

[0055] 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.

[0056] 11. Preparation of Particles 11-1. Silicon Nitride Particles A raw material was prepared by blending silicon powder and calcium fluoride. At this time, calcium fluoride was blended at a ratio of 1.5 mass% relative to the silicon powder. A compact (bulk density: 1.4 g / cm3) was produced using this raw material, and then fired in an electric furnace at 1400°C for 60 hours to produce a silicon nitride ingot. The firing atmosphere was a mixed atmosphere of nitrogen and hydrogen (N ２ : H ２ The ratio was 80:20 (volume basis). The obtained ingot was coarsely crushed and then wet-pulverized in a ball mill. The silicon nitride powder obtained by wet-pulverization was subjected to post-treatment by immersing it in hydrofluoric acid (concentration: 10 mass%) at a temperature of 60°C for 2 hours. The silicon nitride powder was then removed from the hydrofluoric acid, washed with water, and dried under a nitrogen atmosphere. In this manner, silicon nitride particles were obtained.

[0057] <Fluorine and Chlorine Content> The fluorine and chlorine contents of the silicon nitride particles were measured by the following procedure. First, silicon nitride powder was heated using an automatic sample combustion apparatus (manufactured by Mitsubishi Chemical Corporation, apparatus name: AQF-2100H type), and the generated gas was dissolved in water. Next, the fluorine and chlorine dissolved in water were measured using an ion chromatograph (manufactured by Thermo Fisher Scientific, apparatus name: ICS-2100) in accordance with JIS R 1603:2007. Based on these measurements, the fluorine and chlorine contents in the silicon nitride particles were 36 ppm by mass and 680 ppm by mass, respectively.

[0058] <Fe, Al, and Ca Contents> The Fe (iron), Al (aluminum), and Ca (calcium) contents of the silicon nitride particles were measured using an X-ray fluorescence analyzer (manufactured by Rigaku Corporation, device name: ZSX-Primus II). The respective contents were 380 ppm by mass, 160 ppm by mass, and 1000 ppm by mass.

[0059] <Oxygen Content> 0.01 g of silicon nitride particles and 0.01 g of carbon powder were placed in an oxygen / nitrogen analyzer (manufactured by Horiba, Ltd., device name: EMGA-920). In a helium gas atmosphere, the temperature was increased from 20°C to 2400°C at a rate of 8°C / sec. The oxygen and nitrogen generated with the temperature increase were detected. The surface oxygen amount and the internal oxygen amount were determined from the peak areas resulting from the desorption of surface oxygen and internal oxygen, respectively. The oxygen content calculated based on the sum of these values ​​was 0.94 mass%.

[0060] <α-phase ratio> The α-phase ratio of silicon nitride was measured by the following procedure. That is, X-ray diffraction of silicon nitride was performed with CuKα radiation using an X-ray diffractometer (manufactured by Rigaku, device name: Ultima IV). The α-phase was determined by a diffraction intensity of I ａ１０２ and the diffraction intensity I of the (210) plane. ａ２１０ , the β phase has a diffraction intensity of I ｂ１０１ and the diffraction intensity I of the (210) plane. ｂ２１０ The degree of gelatinization calculated using these diffraction line intensities according to the following formula was 91.0%. Degree of gelatinization (%) = (Iａ１０２ +I ａ２１０ ) / (I ａ１０２ +I ａ２１０ +I ｂ１０１ +I ｂ２１０ ) x 100

[0061] <BET specific surface area> The BET specific surface area of ​​the silicon nitride particles measured by the BET single-point method using nitrogen gas in accordance with JIS Z 8830:2013 "Method for measuring the specific surface area of ​​powders (solids) by gas adsorption" was 8.04 m ２ / g.

[0062] <Particle size distribution> The particle size distribution of silicon nitride particles was measured by laser diffraction / scattering. The measurement was performed in accordance with the method described in JIS Z 8825:2013 "Particle size analysis - Laser diffraction / scattering method." In the particle size distribution (cumulative distribution) shown with particle size [μm] on a logarithmic scale on the horizontal axis and frequency [volume %] on the vertical axis, the particle size D50, when the cumulative value from the smallest particle size reached 50% of the total, was 0.72 μm.

[0063] 11-2. N-apatite (Y ５ Si ３ O １２ N) Particles First, 0.7 g of silicon nitride powder (manufactured by UBE Corporation, trade name: E10), 11.5 g of yttria powder (manufactured by Shin-Etsu Chemical Co., Ltd., trade name: UUHP), and 2.8 g of silica powder (manufactured by Kojundo Chemical Laboratory Co., Ltd.) were weighed out as raw material powders. Next, the weighed raw material powders, 350 g of silicon nitride balls with a diameter of 16 mm, and 150 mL of ethanol were placed in a container (Nalgene plastic bottle, capacity: 500 mL). The container sealed with a lid was placed on a benchtop ball mill (manufactured by Eishin Co., Ltd., trade name: BM-15), the rotation speed was set to 82 rpm, and pre-mixing was carried out under these conditions for 1 hour to obtain a mixed slurry.

[0064] Next, only the powder was collected from the resulting mixed slurry using a membrane filter. The collected particles were dried at 120°C for 3 hours. The dried particles were then sieved using a nylon sieve (#100). The particles that passed through the sieve were then packed into a boron nitride molding container. This molding container was fired for 6 hours using an electric furnace (manufactured by Fuji Denpa Kogyo Co., Ltd., product name: Hi-Multi 500) under conditions of 1550°C, a nitrogen atmosphere, and 0.85 MPa (gauge pressure).

[0065] Next, the particles obtained by firing were placed in a container (Nalgene plastic bottle, capacity: 500 mL). 375 g of silicon nitride balls with a diameter of 5 mm and 150 mL of ethanol were then placed in the container, and the container was then sealed with a lid. The sealed container was placed on the above-mentioned benchtop ball mill, and the rotation speed was set to 82 rpm. A crushing treatment was carried out under these conditions for 30 hours. Then, particles were collected from the slurry after the crushing treatment using a membrane filter. The collected particles were dried at 110°C for 3 hours.

[0066] Next, the dried particles were sieved using a nylon sieve (#330). The particles that fell below the sieve were classified as Si ３ N ４ -SiO ２ -Y ２ O ３ The particles were collected as particles of a Y-based compound. The components of the particles were then examined using an X-ray diffraction device (manufactured by Rigaku Corporation, device name: Ultima IV). As a result, the particles were found to be composed of N-apatite (Y ５ Si ３ O １２ It was confirmed that the powder contained N-apatite as the main component. On the other hand, no components other than N-apatite were detected. The average particle diameter D50 was 1.2 μm, and the BET specific surface area was 4.36 m. ２ / g.

[0067] 11-3. N-wollastonite (YSiO ２First, 3.2 g of silicon nitride powder (manufactured by UBE Corporation, product name: E10), 10.4 g of yttria powder (manufactured by Shin-Etsu Chemical Co., Ltd., product name: UUHP), and 1.4 g of silica powder (manufactured by Kojundo Chemical Laboratory Co., Ltd.) were weighed as raw material powders. Except for using these raw material powders, the same procedure as for the N-apatite particles was followed to produce Si ３ N ４ -SiO ２ -Y ２ O ３ Particles of the YSiO2-based compound were obtained. The components of the particles were then examined in the same manner as above. As a result, it was found that the particles were composed of N-wollastonite (YSiO ２ It was confirmed that the powder contained N-wollastonite as the main component. On the other hand, no components other than N-wollastonite were detected. The average particle diameter D50 was 1.2 μm, and the BET specific surface area was 4.26 m. ２ / g.

[0068] 11-4. N-YAM(Y ４ Si ２ O ７ N ２ ) particles First, as raw material powders, 1.9 g of silicon nitride powder (manufactured by UBE Corporation, product name: E10), 12.3 g of yttria powder (manufactured by Shin-Etsu Chemical Co., Ltd., product name: UUHP), and 0.8 g of silica powder (manufactured by Kojundo Chemical Laboratory Co., Ltd.) were weighed out. Except for using these raw material powders, the same procedure as for the N-apatite particles was followed to produce Si ３ N ４ -SiO ２ -Y ２ O ３ Particles of the N-YAM (Y)-based compound were obtained. The components of the particles were then examined in the same manner as above. ４ Si ２ O ７ N ２ ) as the main component. On the other hand, no components other than N-YAM were detected. The average particle diameter D50 was 23.83 μm, and the BET specific surface area was 0.34 m ２ / g.

[0069] 11-5. N-Merilite (Y ２ Si ３O ３ N ４ ) particles First, 5.7 g of silicon nitride powder (manufactured by UBE Corporation, product name: E10) and 9.3 g of yttria powder (manufactured by Shin-Etsu Chemical Co., Ltd., product name: UUHP) were weighed out as raw material powders. Except for using these raw material powders, the same procedure as for the N-apatite particles was followed to produce Si ３ N ４ -Y ２ O ３ The particles of the compound were obtained. The components of the powder were examined in the same manner as above. As a result, the particles were found to be N-melilite (Y ２ Si ３ O ３ N ４ ) as the main component. On the other hand, no components other than N-melite were detected. The average particle diameter D50 was 17.74 μm, and the BET specific surface area was 0.49 m. ２ / g.

[0070] 12. Preparation of Sample (Biocompatible Material) (Example 11) First, a disk-shaped titanium alloy base A measuring 20 mm in diameter and 2 mm in thickness and a rectangular titanium base B measuring 10 mm in width and 40 mm in length were prepared. Using the aerosol deposition apparatus 10 shown in Figure 3, a coating layer of silicon nitride particles was formed on the surfaces of base A and base B. The aerosol deposition apparatus 10 was designed to supply carrier gas and lift-up gas separately into two systems. The nozzle was fixed, and the X-Y stage (support mechanism 40) supporting base A and base B was movable in the in-plane direction.

[0071] The film formation conditions were as follows: Degree of pressure reduction in the aerosol chamber 20 and the film formation chamber 30: 31 kPa Gas species of carrier gas and lift-up gas: N ２ Flow rate of the winding gas: 5 L / min Flow rate of the carrier gas: 8 L / min Heating temperature of the aerosol chamber 20: 150°C Number of stacks: 20 times Moving speed of the base: 5 mm / s Angle between the nozzle and the normal to the surface of the base: 30° Distance between the nozzle and the surface of the base: 10 mm

[0072] As a result, a coating layer having a thickness of 4 μm was formed on each of the surfaces of the base A and the base B.

[0073] (Example 12) N-apatite (Y ５ Si ３ O １２ A coating layer having a thickness of 4 μm was formed on each of the surfaces of the base A and the base B in the same manner as in Example 11, except that N) particles were used.

[0074] 13. Measurement and Evaluation 13-1. Surface Roughness (Arithmetic Mean Roughness Ra, Maximum Height Rz) The surface roughness (arithmetic mean roughness Ra, maximum height Rz) of the surface of the base A and the surface of the coating layer in Example 11 was measured in accordance with the method described in JIS B 0601:2001. As a result, the arithmetic mean roughness Ra and maximum height Rz of the surface of the base A were 0.25 μm and 1.53 μm, respectively, and the arithmetic mean roughness Ra and maximum height Rz of the surface of the coating layer in Example 11 were 0.33 μm and 1.86 μm, respectively.

[0075] 13-2. XRD Measurement XRD measurement was performed on the surface of the base A and the surface of the coating layer in Example 11 using an XRD measurement device (Rigaku Corporation, "Ulitima IV"). The results are shown in Figure 4. As shown in Figure 4, it was confirmed that silicon nitride was present in the coating layer without being altered.

[0076] 13-3. Coating layer adhesion test Cups made of epoxy thermosetting resin (glass transition temperature 200°C, linear expansion coefficient (α1) 15 ppm / °C, linear expansion coefficient (α2) 55 ppm / °C, hot hardness 85, flexural modulus 13 GPa, flexural strength 100 MPa) were formed on the surface of base B and the surface of the coating layer in Examples 11 and 12, in the shape and size shown in Figure 5. The units of values ​​in Figure 5 are "mm". The resin molding conditions were as follows: Mold clamp pressure: 14t Molding pressure: 9 MPa Molding time: 120 seconds Molding temperature: 175°C Post cure: 175°C x 6 hours

[0077] Next, a bond tester ("Bond Tester 4000" manufactured by Nordson) was used to peel off the cup. The conditions for this operation were as follows: Shear temperature: room temperature, speed: 10 μm / s, test height: 100 μm, measurement lower limit: 0.5 kgf, and shear direction: short side direction of the base.

[0078] The results are shown in Figure 6. Peeling occurred at the interface between the cup and the coating layer, but was not observed at the interface between the base B and the coating layer. It is believed that the adhesive strength between the base B and the coating layer is greater than the measured value shown in Figure 6.

[0079] 13-4. Antibacterial Test of Samples The antibacterial properties of the sample of Example 1 were evaluated according to JIS Z 2801:2010, "Antibacterial Test by Film Adhesion Method." Specifically, 0.1 mL of test bacteria solution was dropped onto the sample placed in a petri dish, and a film (1 cm square) was placed over the sample, after which the petri dish was capped. Next, the petri dish was placed in an environment of 35°C and 90% RH or higher and cultured for 24 hours. After 24 hours, 10 mL of SCDLP medium was added to wash out the test bacteria from the film and sample. The number of test bacteria in the washout solution was then measured using the agar plate culture method. The results are shown in Figure 7. As shown in Figure 7, the sample of Example 11 exhibited high antibacterial properties against both Staphylococcus aureus and Escherichia coli.

[0080] Furthermore, as confirmed by XRD measurement, silicon nitride is present in the coating layer without being altered. In other words, the excellent antibacterial properties are the result of the silicon nitride itself. Therefore, in the following, we will discuss the use of N-apatite (Y) in addition to silicon nitride particles. ５ Si ３ O １２ N) particles, N-wollastonite (YSiO ２ N) particles, N-YAM(Y ４ Si ２ O ７ N ２ ) particles, and N-melite (Y ２ Si ３ O ３ N ４The particles were evaluated for antibacterial properties, cell proliferation ability, and osteoconductivity.

[0081] 14-1. Antibacterial test of particles First, bacteria (Staphylococcus aureus) were pre-cultured in BHI liquid medium to prepare a bacterial suspension (1 x 10 ５ ~1 x 10 ６ CFU / mL) was prepared. Next, 0.15 g of each particle and 1 mL of distilled water were placed in a microtube to obtain a 15 w / v% dispersion. After sterilization with ultraviolet light, 1 mL of the bacterial suspension was added to the microtube. After mixing for 5 minutes with a tube rotator at room temperature (approximately 20°C), the supernatant was collected and the bacterial viability was measured by WST-8 assay and fluorescent imaging (Live & Dead staining: CFDA PI DAPI). The viability was also measured in the same manner when Staphylococcus epidermidis was used as the bacteria. The results are shown in Table 1. In Table 1, the viability results when no particles were used are shown in the "ref." column.

[0082] 14-2. Cell proliferation and osteoconductivity (mineralization) tests for particles. First, the particles were crushed using a pestle and mortar, then sieved to a size of 75 μm or less. Then, using ultrapure water, suspensions with particle concentrations of 1 mg / mL and 10 mg / mL were prepared. Next, the suspensions were added dropwise to tissue culture microplates [Iwaki 3820-024 (24 wells) or MatTek P06G-0-20-F / H (6 wells)] to achieve concentrations of 0.1 mg / well and 1 mg / well. After addition, the microplates were dried in a dry heat sterilizer (TABAI LC-122) at 50°C for 24 hours and sterilized with ultraviolet light. This prepared a cell culture bed. Growth medium and osteoconductivity medium were prepared on the beds thus prepared. The preparation method for each medium was as follows.

[0083] The growth medium was prepared by adding 4.5 g / L glucose-containing DMEM (Nacalai tesque), 10% fetal bovine serum, and 1% PS. The osteoconductive medium was prepared by adding 10 mM β-glycerophosphate, 50 μg / mL (L+) ascorbic acid, and 100 nM texamethasone to the growth medium. The mouse bone marrow-derived KUSA-A1 cell line (JCRB) was used as the first choice. The KUSA-A1 cell line was cultured at a cell count of 5 x 10 cells in both the growth medium and the osteoconductive medium. ４ / cm ２ After a predetermined number of days had passed, the cell proliferation ability and osteoconductivity were evaluated.

[0084] WST-8 (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., product name: Dojindo 341-07761) was used to evaluate cell proliferation ability. The WST-8 measurement method followed the instructions attached to the product. The absorbance of the medium after 14 days was measured (manufactured by Hitachi High-Tech Corporation, product name: Spectrophotometer U-3900) to quantify the cell proliferation ability. The results are shown in Table 1. Note that a higher absorbance indicates a superior cell proliferation ability. In addition, in Table 1, the absorbance results when no particles were used are shown in the "ref." column.

[0085] Osteoconductivity (calcification) was estimated and evaluated by Alizarin Red S staining of the medium after 7 days. The Raman spectrum of the stained medium was measured, and the degree of staining was evaluated according to the following criteria: A: The proportion of stained areas is greater than when particles are not used. B: The proportion of stained areas is the same as when particles are not used. C: The proportion of stained areas is less than when particles are not used. The results are also shown in Table 1.

[0086]

[0087] As shown in Table 1, each particle has sufficient osteoconductivity and antibacterial properties. Therefore, when a biocompatible material is manufactured by forming a coating layer primarily composed of a silicon- and nitrogen-containing compound using the aerosol deposition method to cover the base, it is believed that sufficient osteoconductivity and antibacterial properties will be exhibited even in the living body after implantation. This allows for safe treatment of patients. Furthermore, it is believed that the same effects as those described above can be obtained even if the type of base or the thickness of the coating layer is changed.

[0088] 21. Preparation of bases Titanium alloy powder was molded to prepare disk-shaped bases C and D with a diameter of 14 mm and a thickness of 2 mm.

[0089] 22. Preparation of Samples (Biocompatible Materials) Example 21 A coating layer was formed on the surface of base C in the same manner as in Example 11, except that the angle between the nozzle and the normal to the surface of the base was set to 0°. Example 22 A coating layer was formed on the surface of base D in the same manner as in Example 11, except that the angle between the nozzle and the normal to the surface of the base was set to 15°.

[0090] 23. Measurement and Evaluation 23-1. Surface Roughness (Arithmetic Mean Roughness Ra, Maximum Height Rz) The surface roughness (arithmetic mean roughness Ra, maximum height Rz) of the surface of the coating layer in base C and Example 21, and the surface of the coating layer in base D and Example 22 was measured in the same manner as in "13-1. Surface Roughness." As a result, the arithmetic mean roughness Ra and maximum height Rz of the surface of base C were 150 μm and 778 μm, respectively, and the arithmetic mean roughness Ra and maximum height Rz of the surface of the coating layer in Example 21 were 149 μm and 752 μm, respectively. Meanwhile, the arithmetic mean roughness Ra and maximum height Rz of the surface of base D were 20.2 μm and 109 μm, respectively, and the arithmetic mean roughness Ra and maximum height Rz of the surface of the coating layer in Example 22 were 20.6 μm and 122 μm, respectively.

[0091] 23-2. Surface SEM Observation and Composition Analysis The surfaces of the sample of Example 21 and the sample of Example 22 were observed using a field emission scanning electron microscope (FE-SEM) (manufactured by JEOL Ltd., "JSM-7001F / SHL") at an acceleration voltage of 15.0 kV, a working distance (WD) of approximately 10 mm, and a magnification of 10,000 times. EDX analysis was also performed using an EDX (manufactured by JEOL Ltd., "JED-2300"). The results are shown in Figure 8 (Example 21) and Figure 9 (Example 22).

[0092] Fig. 8 shows the results of surface SEM observation and composition analysis of the sample of Example 21. Fig. 9 shows the results of surface SEM observation and composition analysis of the sample of Example 22. As shown in Fig. 8, in the sample of Example 21, components derived from the film-forming particles (Si and N) were strongly observed in the convex portions, but the detection sensitivity of components derived from the film-forming particles was reduced in the concave portions. On the other hand, as shown in Fig. 9, in the sample of Example 22, components derived from the base portion (Ti and Al) were observed in addition to the components derived from the film-forming particles.

[0093] 23-3. Cross-sectional SEM Observation and Composition Analysis The cross sections of the sample of Example 21 and the sample of Example 22 were observed using a field emission scanning electron microscope (FE-SEM) (manufactured by JEOL Ltd., "JSM-7001F / SHL") at an acceleration voltage of 15.0 kV, a working distance (WD) of approximately 10 mm, and a magnification of 10,000 times. EDX analysis was also performed using an EDX (manufactured by JEOL Ltd., "JED-2300"). The results are shown in Figure 10 (Example 21) and Figure 11 (Example 22).

[0094] Fig. 10 shows the results of cross-sectional SEM observation and composition analysis of the sample of Example 21. Fig. 11 shows the results of cross-sectional SEM observation and composition analysis of the sample of Example 22. As shown in Fig. 10, it was confirmed that a homogeneous and dense coating layer having a thickness of about 1 µm was formed in the sample of Example 21. Furthermore, as shown in Fig. 11, it was confirmed that a homogeneous and dense coating layer having a thickness of about 1 µm was also formed in the sample of Example 22.

[0095] 31. Preparation of Bases Ten bases D and ten bases E having a smooth surface (arithmetic mean roughness Ra: 0.25 μm, maximum height Rz: 1.57 μm) were prepared.

[0096] 32. Preparation of Samples (Biocompatible Materials) (Example 31-1) Coating layers were formed on the surfaces of five bases D in the same manner as in Example 11, except that the angle between the nozzle and the normal to the base surface was set to 15°. (Example 31-2) Coating layers were formed on the surfaces of five bases D in the same manner as in Example 12, except that the angle between the nozzle and the normal to the base surface was set to 15°. (Example 32-1) Coating layers were formed on the surfaces of five bases E in the same manner as in Example 11. (Example 32-2) Coating layers were formed on the surfaces of five bases E in the same manner as in Example 12.

[0097] 33. Measurement 33-1. Coating Layer Adhesion Strength Test An adhesion strength test was performed on each of the samples of Example 31-1, Example 31-2, Example 32-1, and Example 32-2. The adhesion strength test was performed using the apparatus shown in FIG. 12. FIG. 12 is a schematic diagram showing the configuration of the adhesion strength test apparatus. As shown in FIG. 12, the sample was placed in the adhesion strength test apparatus 100 so that the coating layer 3 was in contact with the support table 102. The support table 102 was a cylinder with an inner diameter of 4 mm and an outer diameter of 6 mm. In addition, a reinforcing plate 101 was placed on the base 2.

[0098] The bottom surface 103a of the stud pin 103 was adhered to the coating layer 3 with an adhesive 105. At this time, the adhesive strength was 700 kg / cm. ２This was the case. A load was gradually applied downward (in the direction of the arrow in Figure 12) via a gripper 104 fixed to the end of the stud pin 103 opposite the bottom surface 103a. The load was increased at a rate of 3 kg / sec, and the adhesion strength (MPa) was calculated from the load at which the stud pin 103 peeled off from the sample. It was also visually confirmed which layer had peeled off. The location where this peeling occurred can be considered to be the location with the weakest adhesion in the thickness direction of the sample. In the samples of Examples 31-1 and 31-2, Hardlock C-355-20 (manufactured by Denka Co., Ltd.) was used as the adhesive 105, while in the samples of Examples 32-1 and 32-2, the device manufacturer's standard epoxy adhesive was used as the adhesive 105.

[0099] The average adhesion strength measured for the samples of Example 31-1 was 30.3 MPa, and the average adhesion strength measured for the samples of Example 31-2 was 28.4 MPa. It was also confirmed that the peeling mode was material failure of the adhesive 105, and that the adhesion strength of the coating layer 3 to the base 2 was 15 MPa or more. Meanwhile, the average adhesion strength measured for the samples of Example 32-1 was 89.1 MPa, and the average adhesion strength measured for the samples of Example 32-2 was 87.4 MPa. It was also confirmed that the peeling mode was material failure of the adhesive 105, and that the adhesion strength of the coating layer 3 to the base 2 was 15 MPa or more.

[0100] 41. Preparation of base Two bases C were prepared.

[0101] 42. Preparation of Sample (Biocompatible Material) Example 41 A coating layer was formed on the surface of the base C in the same manner as in Example 11, except that the angle between the nozzle and the normal to the surface of the base was set to 0°. Example 42 A coating layer was formed on the surface of the base C in the same manner as in Example 12, except that the angle between the nozzle and the normal to the surface of the base was set to 0°.

[0102] 43. Antibacterial Test on Samples The antibacterial properties of the sample of Example 41 and the sample of Example 42 were evaluated in the same manner as in "13-4. Antibacterial Test on Samples" above. The results are shown in Figure 13. Figure 13 is a graph showing the results of the antibacterial test on the samples of Examples 41 and 42.

[0103] The antibacterial activity value (R) is calculated as follows: R = (U １ -U ０ ) - (A ｔ -U ０ ) where U ０ is the average logarithm of the number of viable bacteria immediately after inoculation of the untreated test piece, U １ is the average logarithm of the number of viable bacteria on the untreated test piece after 24 hours, A ｔ is the average logarithm of the viable cell count on the antibacterial treated test piece after 24 hours. As shown in Figure 13, the sample of Example 41 exhibited antibacterial activity exceeding the target value (antibacterial activity value: 2 or more).

[0104] 51. Preparation of the base The screw shown in Figure 14(b) (Misumi Corporation, "Phillips Recessed Pan Head A Tapping Screw") was prepared. The material of this screw was stainless steel, and the dimensions were 8 mm in diameter and 100 mm in length.

[0105] 52. Preparation of Sample (Biocompatible Material) A coating layer was formed in the same manner as in Example 11, except that the screw was not surface-treated and rotated around its central axis at 10 rpm, the base was moved at a speed of 1 mm / s, the angle between the nozzle and the normal to the base surface was 0°, and the distance between the nozzle and the base surface was 15 mm. The results are shown in Figure 14. Figure 14 is a photograph showing the appearance of the screw before and after coating layer formation. As shown in Figure 14(a), a coating layer appears to have been formed uniformly on the surface of the screw.

[0106] 53. Measurement and Evaluation 53-2. Surface SEM Observation and Composition Analysis The surfaces of the valleys and peaks of the coated screw (sample) were observed using a field emission scanning electron microscope (FE-SEM) (manufactured by JEOL Ltd., "JSM-7001F / SHL") at an acceleration voltage of 15.0 kV, a working distance (WD) of approximately 10 mm, and a magnification of 10,000 times. EDX analysis was also performed using an EDX (manufactured by JEOL Ltd., "JED-2300").

[0107] The results are shown in Figure 15 (valley portion) and Figure 16 (crown portion). Figure 15 shows the results of surface SEM observation and composition analysis of the valley portion of a coated screw. Figure 17 shows the results of surface SEM observation and composition analysis of the crest portion of a coated screw. As shown in Figure 15, it was confirmed that a coating layer was formed in the valley portion of the screw. As shown in Figure 16, it was confirmed that a coating layer was also formed on the crest portion of the screw, but there seemed to be some variation in the degree of coating.

[0108] 53-3. Cross-sectional SEM observation and composition analysis The cross section of the valley of the coated screw (sample) was observed using a field emission scanning electron microscope (FE-SEM) (manufactured by JEOL Ltd., "JSM-7001F / SHL") at an acceleration voltage of 15.0 kV, a working distance (WD) of approximately 10 mm, and a magnification of 10,000x. EDX analysis was also performed using an EDX (manufactured by JEOL Ltd., "JED-2300"). The results are shown in Figure 17. Figure 17 shows the results of cross-sectional SEM observation and composition analysis of the valley of the coated screw. As shown in Figure 17, it was confirmed that a homogeneous and dense coating layer with a thickness of approximately 3 μm to 3.5 μm was formed.

[0109] 1: Biocompatible material, 11: Insertion part, 12: Mounting part, 2: Base part, 3: Coating layer, 10: Aerosol deposition device, 20: Aerosol chamber, 201: Heating part, 30: Film deposition chamber, 40: Support mechanism, 401: Fixing part, 50: Aerosol supply mechanism, 501: Nozzle, 60: Carrier gas supply mechanism, 70: Exhaust device, 100: Adhesion strength test device, 101: Reinforcing plate, 102: Support base, 103: Stud pin, 103a: Bottom surface, 104: Gripper, 105: Adhesive, A: Base part, B: Base part, P: Particle, NL: Normal line, O: Central axis

Claims

1. A method for producing a biocompatible material, comprising the steps of: preparing a base and particles containing, as main components, a compound containing silicon and nitrogen; and adhering the particles to the surface of the base by colliding them with an aerosol deposition method, thereby forming a coating layer that covers at least a portion of the base, thereby obtaining the biocompatible material.

2. The method for producing a biocompatible material according to claim 1, wherein the compound further contains yttrium and oxygen.

3. In the method for producing a biocompatible material according to claim 2, the compound is Si ３ N ４ -SiO ２ -Y ２ O ３ Compounds and Si ３ N ４ -Y ２ O ３ A method for producing a biocompatible material containing at least one compound selected from the group consisting of .

4. In the method for producing a biocompatible material according to claim 2 or 3, the compound is Si ３ N ４ , SiO ２ and Y ２ O ３ In the phase diagram of the three-component system, Y ５ S ３ O １２ N.Y. ２ S ３ O ３ N ４ and Y ４ S ２ O ７ N ２ A method for producing a biocompatible material having a composition within a triangular area defined by the three vertices.

5. In the method for producing a biocompatible material according to any one of claims 2 to 4, the compound is Y ５ S ３ O １２ N, YSiO ２ N.Y. ４ S ２ O ７ N ２ and Y ２ S ３ O ３ N ４ A method for producing a biocompatible material, comprising:

6. The method for producing a biocompatible material according to claim 1, wherein the compound contains silicon nitride and has a fluorine content of 900 ppm by mass or less.

7. A method for producing a biocompatible material according to any one of claims 1 to 6, wherein, when the arithmetic mean roughness Ra of the surface of the base is RaB and the arithmetic mean roughness Ra of the surface of the coating layer is RaC, RaC / RaB is 0.9 or more and 1.5 or less.

8. A method for producing a biocompatible material according to any one of claims 1 to 7, wherein the arithmetic mean roughness Ra of the surface of the coating layer is 0.01 μm or more and 300 μm or less.

9. A method for producing a biocompatible material according to any one of claims 1 to 8, wherein the coating layer has a thickness of 50 μm or less.

10. A method for producing a biocompatible material according to any one of claims 1 to 9, wherein the particles have an average particle size of 10 μm or less.

11. The method for producing a biocompatible material according to any one of claims 1 to 10, wherein the particles have a BET specific surface area of ​​0.3 m ２ / g or more.

12. A biocompatible material comprising: a base; and a coating layer covering at least a portion of the base and containing a compound containing silicon and nitrogen as a main component.

13. The biocompatible material according to claim 12, wherein the adhesive strength of the coating layer to the base is 15 MPa or more.

14. A biocompatible material according to claim 12 or 13, wherein the base has an uneven structure at least in the area covered with the covering layer.

15. The biocompatible material according to any one of claims 12 to 14, wherein the biocompatible material is used for bone.

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