Bioceramic and method for producing the same

Abstract

To provide a bioceramic that is suitable for artificial bone materials and exhibits superior bioabsorbability.SOLUTION: A bioceramic material comprises: a plurality of bioceramic particles; and a bonding phase that binds the plurality of bioceramic particles to each other, wherein the bonding phase contains Ca and P and is constituted by a matrix phase composed of a first phase and a second phase dispersed within the matrix phase, and a halo pattern is observed in an electron diffraction pattern.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to bioceramics and methods for producing the same. [Background technology]

[0002] Bone grafting is one of the treatments for bone tumors, osteoarthritis, fractures, and other conditions. Autologous bone is often used as a material for bone grafts, but this has disadvantages, such as limited amounts that can be harvested. For this reason, various artificial bones have been developed. Common artificial bone materials include bioceramics such as hydroxyapatite and beta-tricalcium phosphate (β-TCP). Artificial bones must be bioabsorbable, meaning they are absorbed in the body and replaced with autologous bone over time, and have the mechanical strength to support loads.

[0003] Patent Document 1 discloses an artificial bone using hydroxyapatite. When the artificial bone using hydroxyapatite is implanted in a living body, a strong bond is formed between the artificial bone and the patient's own bone, resulting in bone fusion. Patent Document 2 discloses an artificial bone using β-TCP. Unlike artificial bone using hydroxyapatite, artificial bone using β-TCP is gradually absorbed in the body and is simultaneously replaced by the patient's own bone. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 60-021763 [Patent Document 2] Japanese Patent Application Laid-Open No. 2013-184878 Summary of the Invention [Problem to be solved by the invention]

[0005] The artificial bone disclosed in Patent Document 1 exhibits excellent bone bonding properties, but is not absorbed by the body once implanted, causing problems with fractures due to remaining artificial bone portions. The artificial bone disclosed in Patent Document 2 exhibits superior bioabsorbability compared to Patent Document 1, but is inferior to autogenous bone in bioabsorbability, and some artificial bone material may remain. For this reason, there is a demand for artificial bone with excellent bioabsorbability.

[0006] Therefore, an object of the present invention is to provide a bioceramic that is excellent in bioabsorbability and mechanical strength and is suitable for use as an artificial bone material. [Means for solving the problem]

[0007] The present invention relates to a bioceramic comprising a plurality of bioceramic particles and a binder phase that bonds the plurality of bioceramic particles to one another, the binder phase containing Ca and P, a matrix phase consisting of a first phase, and a second phase dispersed within the matrix phase, and in which a halo pattern is observed in an electron diffraction pattern.

[0008] Furthermore, the present invention has been reported to reduce the Ca concentration within 3 hours when immersed in Tris-buffered saline with a salt concentration of 150 mmol / L at 37±0.5°C. 2+ The amount of ions dissolved is 30 x 10 -6 (g / m 2 ) Bioceramics is.

[0009] Furthermore, it is preferable that the area ratio of the binder phase in which no crystal orientation is detected is 20% or more and 80% or less in a band contrast image obtained by electron backscatter diffraction.

[0010] Furthermore, it is preferable that the X-ray diffraction pattern using CuKα rays contains a peak of calcium hydrogen phosphate.

[0011] Furthermore, in an X-ray diffraction pattern using CuKα rays, the half width of the peak of the calcium hydrogen phosphate is preferably 0.10° or more and 1.0° or less.

[0012] Furthermore, the bioceramic particles are preferably calcium phosphate or calcium carbonate.

[0013] Furthermore, the bioceramic particles are preferably bioabsorbable β-tricalcium phosphate.

[0014] The present invention also provides a method for producing bioceramics, comprising a mixture preparation step of mixing a plurality of bioceramic particles, at least one dissolution / precipitation promoter that dissolves the plurality of bioceramic particles, and a solvent that can ionize the dissolution / precipitation promoter to prepare a mixture; a filling step of filling the mixture into a mold; and a solidification step of solidifying the mixture by heating the mold at 200°C or less while applying pressure to the mold.

[0015] Furthermore, the bioceramic particles are preferably bioabsorbable β-tricalcium phosphate.

[0016] Furthermore, in the solidification step, it is preferable to heat the mold to a temperature equal to or lower than the boiling point of the solvent.

[0017] Furthermore, in the solidification step, the mold is preferably pressed at a pressure of 375 to 625 MPa. [Effects of the Invention]

[0018] According to the present invention, it is possible to provide a bioceramic that is suitable for use as an artificial bone material, having both excellent bioabsorbability and mechanical strength. [Brief explanation of the drawings]

[0019] [Figure 1] 1A is a schematic diagram showing an example of a cross-sectional structure of the present embodiment, and FIG. 1B is a schematic diagram showing an enlarged portion of FIG. [Figure 2]FIG. 1 is a flow chart showing an example of a method for producing bioceramics in the present embodiment. [Figure 3] Photographs of cross sections of bioceramics of the example. (a) is a backscattered electron image observed with a scanning electron microscope. (b) is a dark-field image observed with a scanning transmission electron microscope. [Figure 4] Photographs of the cross section of the bioceramic of the comparative example. (a) is a backscattered electron image observed with a scanning electron microscope. (b) is a dark-field image observed with a scanning transmission electron microscope. [Figure 5] 1 is an electron diffraction image of a binder phase of an example. [Figure 6] 1 is a graph showing an X-ray diffraction pattern measured with CuKα radiation of a bioceramic of an example, and a plot of the diffraction angle of monetite (calcium hydrogen phosphate, CaHPO4). [Figure 7] (a-1) is a scanning electron microscope image of the bioceramic of the example. (a-2) is a binary image obtained by image processing of (a-1). (b-1) is a band contrast image obtained by backscattered electron diffraction of the bioceramic of the example. (b-2) is a binary image obtained by image processing of (b-1). [Figure 8] 1 is a graph showing the time dependence of the amount of Ca 2+ ion elution when bioceramics of an example and a comparative example are immersed in Tris-buffered saline. DETAILED DESCRIPTION OF THE INVENTION

[0020] Hereinafter, an embodiment of the present invention will be described with reference to the drawings.

[0021] <Bioceramics> As shown in Figure 1(a), the bioceramic of this embodiment contains a plurality of biocompatible bioceramic particles 1, which are bound to one another by a binder phase 2 to form the bioceramic. The bioceramic of this embodiment may contain pores 3.

[0022] [Bioceramic particles] The material of the bioceramic particles 1 is not particularly limited as long as it is biocompatible. For example, calcium phosphates such as hydroxyapatite, β-tricalcium phosphate, and calcium hydrogen phosphate, carbonate apatite, calcium carbonate, etc. may be used. The bioceramic particles 1 may also be a combination of two or more of the above ceramic materials. The bioceramic particles 1 may also use a crystalline phase in which some sites in the crystal structure are substituted with other ions. Bioabsorbable β-tricalcium phosphate is particularly preferred for the bioceramic particles 1.

[0023] The bioceramic particles 1 preferably have an equivalent circle diameter of 50 μm or less, more preferably 10 μm or less. Within this range, the particles are easily taken up by osteoclasts and have improved bioabsorbability. The equivalent circle diameter of the bioceramic particles 1 can be determined by image processing or the like from photographs taken using a scanning electron microscope or a transmission electron microscope.

[0024] [Binded phase] In the bioceramic, a plurality of bioceramic particles 1 are arranged via a binder phase 2. As will be described later, the binder phase 2 is formed by filling a mixture of bioceramic particles, a dissolution / precipitation accelerator, and a solvent into a mold and applying pressure while heating.

[0025] The binder phase 2 exists at the grain boundary between one bioceramic particle 1 and another bioceramic particle 1. The binder phase 2 may be formed so as to cover the entire surface of the bioceramic particle 1, or may be in contact with only a portion of the surface of the bioceramic particle 1, with pores 3 existing therein. The binder phase 2 is a phase containing Ca and P. The presence of Ca and P can be confirmed using, for example, a scanning transmission electron microscope and energy dispersive X-ray analysis (STEM-EDX).

[0026] As shown in FIG. 1( b ), the binder phase 2 includes a matrix phase 4 (first phase) and a second phase 5 that is dispersed in the matrix phase 4 in the form of particles. The composition of the matrix phase 4 is different from that of the second phase 5. For example, compared to the matrix phase 4, the second phase 5 dispersed and arranged within the matrix phase 4 may have a smaller Ca / P ratio.

[0027] The second phase 5 dispersed and arranged within the matrix phase 4 preferably has an equivalent circle diameter of 10 nm to 500 nm. When the equivalent circle diameter of the second phase 5 is within this range, the mechanical strength of the bioceramic is improved due to the particle dispersion effect. The equivalent circle diameter of the second phase 5 can be determined by image processing or the like from photographs observed with a scanning electron microscope or a transmission electron microscope. The binder phase 2 has the second phase 5 dispersed in the matrix phase at a density of 10 particles / μm 2 It is preferable that the above-mentioned components are contained. This improves the mechanical strength of the bioceramic due to the particle dispersion effect.

[0028] A halo pattern is observed in the electron diffraction image of the binder phase 2 obtained by selected area electron diffraction using a transmission electron microscope. In addition to the halo pattern, the binder phase 2 may contain spotted diffraction spots or concentric patterns (Debye-Scherrer rings). The halo pattern is observed in amorphous materials. Amorphous materials have higher solubility than crystalline materials composed of similar elements, which improves bioabsorption.

[0029] When observed by electron backscattering diffraction (EBSD), the binder phase 2 does not show a pseudo-Kikuchi pattern and is not detected in a band contrast image, appearing as a black region. In the bioceramics of this embodiment, the area ratio of the black region is preferably 20% or more and 80% or less when viewed in a band contrast image. This allows for the production of bioceramics that combine bioabsorbability and mechanical strength. The area ratio of the black region in the band contrast image can be obtained, for example, by binarizing the band contrast image and then calculating the area ratio. The calculation of the area ratio may be performed using image analysis software or programming.

[0030] [Ca 2+ Ion elution amount] When the bioceramic of this embodiment is immersed in Tris-buffered saline with a salt concentration of 150 mmol / L at 37±0.5°C, it shows a Ca 2+ The amount of ions dissolved is 30 x 10 -6 (g / m 2 When artificial bone is implanted, the Ca 2+ It is known that the release of Ca ions activates osteoclasts and osteoblasts. 2+ The elution of ions is thought to promote bioabsorption. 2+ The bioceramics of this embodiment, which have a high ion elution rate, are considered to have excellent bioabsorbability. 2+ The amount of ions dissolved is 30 x 10 -6 (g / m 2 ), the bioabsorbability of the bioceramics is considered to be poor.

[0031] The dissolution rate of bioceramics varies depending on the specific surface area of ​​the material, so it is normalized by the specific surface area, which can be measured by, for example, mercury intrusion porosimetry or gas adsorption method. The solvent used in the dissolution rate test is Tris-buffered saline with a salt concentration of 150 mmol / L, and the pH of Tris-buffered saline is 7.4.

[0032] [X-ray diffraction pattern] The bioceramics preferably contain a peak of calcium monohydrogen phosphate in the X-ray diffraction pattern measured with CuKα radiation. When this peak is present, it is considered that the bioceramics contain calcium monohydrogen phosphate, which has high solubility. 2+The elution rate of ions is improved, and the bioabsorbability of the bioceramics can be increased.

[0033] The half-width of the peak in the X-ray diffraction pattern of the calcium hydrogen phosphate is preferably 0.10° or more and 1.0° or less. The larger the half-width, the smaller the crystallite size. For the same crystalline phase, the smaller the crystallite size, the lower the crystallinity and therefore the higher the solubility. Therefore, it is thought that the smaller the crystallite size, the higher the bioabsorbability. If the half-width is less than 0.10°, the crystallinity of calcium hydrogen phosphate is high and the bioabsorbability is poor. If the half-width is more than 1.0°, it becomes difficult to detect the peak.

[0034] The half-width of the peak in the X-ray diffraction pattern of calcium hydrogen phosphate can be calculated, for example, by the following procedure. First, a 2θ range is specified to extract peaks that do not overlap with diffraction peaks of other crystalline phases, and the peaks are fitted with a Gaussian function. For example, the 10-3 peak of calcium hydrogen phosphate may be extracted. The intersection point between y=(half the peak intensity) and the fitted Gaussian function is calculated, and the absolute value of the difference between the two intersection points is calculated.

[0035] To improve bioabsorbability, the bioceramic of this embodiment may be added with or processed to contain components other than the bioceramic particles 1 and the binder phase 2. For example, bone formation promoters such as bone morphogenetic proteins (BMPs), antibacterial agents such as Ag ions or Ag nanoparticles, or antibiotics such as vancomycin may be added.

[0036] <Method for manufacturing bioceramics> Next, an embodiment of the manufacturing method will be described. As shown in Figure 2, the manufacturing method of this embodiment includes a mixture preparation step S1, a filling step S2, and a solidification step S3. Each step will be described below.

[0037] [Mixture preparation process S1] First, in the mixture preparation step S1, a mixture is prepared by mixing a plurality of bioceramic particles, at least one dissolution / precipitation accelerator that dissolves the plurality of bioceramic particles, and a solvent that can ionize the dissolution / precipitation accelerator. The dissolution / precipitation accelerator and the ionizable solvent may be mixed in advance, and then the bioceramic particles are mixed. The mixing method is not particularly limited, but examples include mortar mixing using a grinder, or mixing using a mixer or kneader.

[0038] (bioceramic particles) The material of the bioceramic particles is not particularly limited as long as it is biocompatible. For example, hydroxyapatite, calcium phosphate such as β-tricalcium phosphate and calcium hydrogen phosphate, carbonate apatite, calcium carbonate, etc. are usable. Bioabsorbable β-tricalcium phosphate is particularly preferred. The method for preparing bioceramic particles is not particularly limited. The raw material particles may be used as they are, or may be used after being pulverized in a mortar or ball mill. The raw material powder may also be used after being granulated or granulated.

[0039] The particle size of the bioceramic particles is preferably 50 μm or less (D50), more preferably 10 μm or less. Within this range, the particles are easily taken up by osteoclasts and have improved bioabsorption. The particle size of the bioceramic particles can be measured, for example, by laser diffraction / scattering or dynamic light scattering. The shape of the bioceramic particles is not particularly limited, but may be, for example, spherical or plate-like. The blending ratio of bioceramic particles can be in the range of 20% to 80% by mass, which allows for both bioabsorbability and mechanical strength.

[0040] (Dissolution and precipitation accelerator) The dissolution / precipitation promoter can be selected from chemical species that promote dissolution of bioceramic particles, chemical species that promote reprecipitation, or both. Examples of the promoter for dissolution of bioceramic particles include acids such as hydrochloric acid and phosphoric acid, and bases such as sodium hydroxide. Examples of the promoter for particle precipitation can include one or more calcium compounds and phosphate compounds that are soluble in the selected solvent. Examples of the calcium compound include calcium chloride and calcium nitrate, and examples of the phosphate compound include sodium dihydrogen phosphate and disodium hydrogen phosphate.

[0041] (solvent) The ionizable solvent may be any solvent that ionizes the dissolution / precipitation accelerator, such as water, alcohol, acetic acid, etc. As the water, for example, industrial purified water may be used.

[0042] [Filling process S2] Next, in the filling step S2, the mixture prepared in the mixture preparation step S1 is filled into a mold for solidification. The mold used is not particularly limited as long as it has a shape and material that can withstand pressure and heat. It may be a metal mold or a resin mold. Materials that can be used for the mold include, for example, cemented carbide, SUS, and SKD11. Materials that can be used for the resin mold include, for example, silicone and acrylic. The surface of the mold may be subjected to a surface treatment for corrosion resistance or the like. The method for producing the mold is not particularly limited. For example, it may be produced by machining, three-dimensional additive manufacturing, or injection molding. The method for filling the mold is not particularly limited. In consideration of ease of filling, the mixture can be diluted with a liquid before being filled into the mold.

[0043] [Solidification process S3] In the solidification step S3, the mold filled with the mixture is heated and pressurized to solidify the bioceramic. The heating temperature should be 200°C or lower, preferably 70 to 90°C. Since the ions dissolved in the solvent diffuse through the solvent and re-precipitate, it is better for the liquid phase to remain during the reaction. For this reason, the heating temperature is preferably below the boiling point of the solvent. The heating method is not particularly limited as long as the sample can be heated to the desired temperature. For example, a press equipped with a heating mechanism may be used, or the mold may be heated using heating equipment such as a band heater. The mold may also be heated via gas or liquid such as water or oil. The pressure during pressing should be 50 MPa or higher, preferably 375 MPa to 625 MPa. This allows for the production of bioceramics with superior mechanical strength. The pressing method may be uniaxial pressing or isotropic pressing. The pressing device may be a manual press or an inverter press. The mold may be pressurized using gas or liquid such as water or oil. The heating and pressing time is preferably 1 minute or more in order to obtain sufficient mechanical strength.

[0044] When the bioceramic of this embodiment is to be implanted in a living body, it is preferable to carry out a sterilization treatment after the mixture preparation step S1 to the solidification step S3. Examples of the sterilization treatment include gamma ray irradiation and sterilization using a gas such as ethylene oxide.

[0045] The method for producing bioceramics according to this embodiment may include a step of adding components other than the bioceramic particles, dissolution / precipitation promoter, and solvent to improve bioabsorption. It may also include a step of processing the formed bioceramics. For example, it may include a step of adding a bone formation promoter such as bone morphogenetic proteins (BMPs), an antibacterial agent such as Ag ions or Ag nanoparticles, or an antibiotic such as vancomycin. [Example]

[0046] The bioceramics of this embodiment will be described in more detail below with reference to examples and comparative examples. (Example) In this example, β-tricalcium phosphate (β-TCP) particles (D50: 1 μm) were used as the bioceramic particles. Calcium chloride (CaCl2) and sodium dihydrogen phosphate (NaH2PO4) were used as dissolution and deposition accelerators. Industrial purified water was used as the ionizable solvent. Calcium chloride and sodium dihydrogen phosphate were dissolved in industrial purified water in advance to prepare saturated aqueous solutions.

[0047] The β-TCP particles and the saturated aqueous solution were weighed out so that the ratio was 60% by mass and 20% by mass, respectively, and mixed in a mortar for 5 minutes to obtain a mixture. The mixture was filled into a round mold with a hole diameter of 10 mm. The mold filled with the mixture was pressed using a press equipped with heating mechanisms on the top and bottom plates. A band heater was attached to the mold, and the die was also heated from the side (80°C, 500 MPa, maintained for 3 hours). After heating, the mold was removed from the press and the frame was removed to obtain a cylindrical bioceramic.

[0048] (Comparative Example) In the comparative example, 0.5 g of β-TCP particles (D50: 1 μm) was used, as in the examples. The β-TCP particles were filled into a mold, and 50 μL of industrial purified water was added dropwise. Pressurization (50 MPa, held for 1 minute) was performed using a press machine to obtain a cylindrical molded body. The molded body was fired in an electric furnace (1100°C, held for 2 hours, heating rate 200°C / h) to obtain a sintered β-TCP body.

[0049] <Cross-sectional structure observation of bioceramics> The bioceramics of the Examples and Comparative Examples were embedded in resin and then processed into rectangular parallelepiped shapes of 8 mm x 7 mm x 3 mm or less using sandpaper or similar. The surfaces of the bioceramics of the Examples and Comparative Examples were processed using ion milling (IM: manufactured by JEOL Ltd.). These were observed using a field emission scanning electron microscope (FE-SEM) (accelerating voltage 5 kV, backscattered electron image).

[0050] Figure 3 shows cross-sectional photographs of the bioceramics of the example. (a) shows a backscattered electron image observed with a scanning electron microscope, and (b) shows a dark-field image observed with a scanning transmission electron microscope. Figure 4 shows cross-sectional photographs of the bioceramics of the comparative example. (a) shows a backscattered electron image observed with a scanning electron microscope, and (b) shows a dark-field image observed with a scanning transmission electron microscope.

[0051] As shown in Figure 3(a), in the example, it was confirmed that a plurality of bioceramic particles 1 were bonded via a binder phase 2. Furthermore, the example contained pores 3. As shown in Figure 3(b), it was confirmed that the binder phase 2 in the example is arranged so as to be in contact with the surface of the bioceramic particle 1, and contains a matrix phase 4 and a second phase 5 dispersed in particulate form within the matrix phase. In contrast, as shown in Figure 4(a), in the comparative example, it was confirmed that multiple bioceramic particles 1 were bonded to each other without the intervention of a binder phase 2. It was also confirmed that the comparative example contained pores 3. As shown in FIG. 4(b), in the comparative example, even when observed under magnification, it was confirmed that there was no phase binding the plurality of bioceramic particles 1, which corresponds to the binding phase 2 in the example.

[0052] Elemental analysis by STEM-EDX revealed that the binder phase 2 was a phase containing Ca and P. Furthermore, the composition of the matrix phase 4 was different from that of the second phase 5. Compared to the matrix phase 4, the Ca / P ratio of the second phase 5 dispersed within the matrix phase 4 was smaller.

[0053] <Evaluation of electron diffraction patterns of bioceramics> The bioceramics of the examples were embedded in resin and then processed into rectangular parallelepiped shapes of 8 mm x 7 mm x 3 mm or less using sandpaper or the like. The bioceramics were dried overnight in a vacuum at 80°C, and the surface was processed using ion milling (IM: manufactured by JEOL). Samples were processed for observation with a scanning transmission electron microscope (STEM) using a focused ion beam (FIB: manufactured by JEOL), and STEM observation was performed. During observation with a scanning transmission electron microscope (STEM) (accelerating voltage 80 kV, dark-field image), an electron diffraction image of the bioceramics was obtained. The field of view was a diameter of 500 nm in the bonding phase.

[0054] Figure 5 shows an electron diffraction image of the binder phase of the example. No diffraction spots were observed, but a halo pattern was observed. A halo pattern is observed when the sample is amorphous. Therefore, it is assumed that the binder phase of the example is mainly amorphous.

[0055] <Evaluation of the crystalline phase of bioceramics> The obtained bioceramics were analyzed using an X-ray diffractometer (PANalytical, X'pert Pro) under the following conditions: tube voltage 45 kV, tube current 40 mA, Cu-Kα diffraction angle 2θ = 25° to 50°, step size 0.0084°, mask 5 mm, divergence slit 1 / 4°, anti-scatter slit 1 / 2°. Figure 6 shows the X-ray diffraction pattern of the example measured with CuKα radiation, and a plot of calcium hydrogen phosphate. As shown in Figure 6, in addition to the peak of β-TCP, which is the main phase (bioceramic particles), a calcium hydrogen phosphate peak was also observed in the example. This indicates that the example contains calcium hydrogen phosphate.

[0056] <Evaluation of half-width of bioceramics> The half-width was calculated from the diffraction peak of calcium hydrogen phosphate in the X-ray diffraction pattern obtained in Figure 6. The calculation of the half-width was performed using the 10-3 peak, which does not overlap with the diffraction peaks of other crystalline phases in Figure 6. The detailed calculation procedure is as follows.

[0057] First, the 2θ range was specified as 38.78° to 39.35°, and the 10-3 peak was extracted. Next, the peak was fitted with a Gaussian function to obtain an approximate curve function. Then, the half-peak intensity was calculated, and the intersection point between y = (half-peak intensity) and the fitted Gaussian function was determined. Furthermore, the absolute value of the difference between the two intersection points was calculated to obtain the half-width. The peak intensity obtained was 170, and the half-width obtained therefrom was 0.39.

[0058] <Structural evaluation of bioceramics using EBSD> The bioceramics of the examples were embedded in resin and then processed into rectangular parallelepiped shapes of 8 mm x 7 mm x 3 mm or less using sandpaper or the like. The surfaces of the bioceramics of the examples were processed using ion milling (IM: manufactured by JEOL Ltd.). These were observed and measured using a scanning electron microscope and electron backscatter diffraction (SEM-EBSD).

[0059] As shown in Figure 7, an SEM image and a band contrast image of electron backscatter diffraction were obtained for this example. Each image was binarized to calculate the area ratio of the black region in the band contrast image, which indicates the bonded phase. ImageJ, an image processing software, was used for binarization and calculation of the area ratio. The detailed procedure is explained below.

[0060] First, the SEM image in Figure 7(a-1) was binarized and the area ratio of the black area was calculated. The binarized image is shown in Figure 7(a-2). The area ratio of the black area in Figure 7(a-2) was 17.4%. The white areas in Figure 7(a-2) correspond to the bioceramic particles β-TCP or the binder phase, and the black areas correspond to the pores. Next, the band contrast image in Figure 7(b-1) was binarized and the area ratio of the black area was calculated. The binarized image is shown in Figure 7(b-2). The area ratio of the black area in Figure 7(b-2) was 61.4%. The white areas in Figure 7(b-2) correspond to the bioceramic particles β-TCP or the binder phase, and the black areas correspond to the pores. The difference in the area ratio of the black regions in Figure 7(b-2) and Figure 7(a-2) was then calculated. The obtained difference was 44.0%. This is the difference between the area of ​​the black regions corresponding to the binder phase and pores and the area of ​​the black regions corresponding to the pores, and therefore corresponds to the area ratio of the binder phase.

[0061] The black areas in the band contrast image are areas where a pseudo-Kikuchi pattern was not obtained and no crystal orientation was detected. The example is thought to contain approximately 44% amorphous phase. The black areas, which are thought to represent the amorphous phase, are thought to increase the solubility of the bioceramics, and it is estimated that the more black areas there are, the better the bioabsorbability of the bioceramics.

[0062] <Ca 2+ Ion elution amount evaluation> Bioceramics produced in the examples and bioceramics produced in the comparative examples were prepared. 0.5 g of each sample was immersed in 5.0 g of Tris-buffered saline (salt concentration 150 mmol / L, trisaminoethane concentration 20 mmol / L, pH 7.4, 37.0±0.5°C) and shaken at 200 rpm. After a predetermined time (10 min, 30 min, 1 h, 2 h, 3 h, 10 h, 1 day) had elapsed since the start of immersion, the sample was removed and the solution was recovered. The Ca content in the recovered solution was 2+ The amount of ions (unit: mass ppm) was measured by inductively coupled plasma mass spectrometry (ICP-MS).

[0063] Ca 2+ The amount of ion elution will be explained using an example after 3 hours from the start of immersion. In the example, it was 171 ppm, and in the comparative example, it was 11.4 ppm. To normalize the elution rate, the specific surface area of ​​each of the example and comparative example was determined by mercury porosimetry (evaluation device: Autopore V 9620, manufactured by Micromeritics). The measurement conditions were a 5 cc large piece cell, an initial pressure of 3 kPa, a mercury contact angle of 130 degrees, and a mercury surface tension of 485 dynes / cm. The specific surface area of ​​the example was 4.3 m 2 / g, and the specific surface area of ​​the comparative example is 0.5m 2 / g. The Ca concentration normalized by the specific surface area for 3 hours after immersion was 2+The amount of ion elution in this example is 39.5 × 10 -6 (g / m 2 ), and 22.8 × 10 -6 (g / m 2 ) became.

[0064] FIG. 8 shows the Ca 2+ The time dependence of the amount of ion elution is shown. In the example, Ca 2+ The amount of ions dissolved is 30 x 10 -6 (g / m 2 ) and, as mentioned above, Ca 2+ The elution of ions is expected to activate osteoclasts and osteoblasts, which contribute to bioabsorption.

[0065] Although the present invention has been described using the above-mentioned embodiment, the present invention is not limited to the above-mentioned embodiment and can be modified within the technical scope of the present invention as defined in the claims. [Explanation of symbols]

[0066] 1: Bioceramic particles 2: Bonded phase 3: Stoma 4: Matrix phase consisting of the first phase 5: Second phase dispersed within the matrix phase

Claims

1. a plurality of bioceramic particles and a binder phase that bonds the plurality of bioceramic particles together; The binder phase contains Ca and P, and the bioceramic contains a matrix phase consisting of a first phase and a second phase dispersed within the matrix phase, and a halo pattern is observed in the electron diffraction pattern.

2. When immersed in Tris-buffered saline with a salt concentration of 150 mmol / L at 37±0.5°C, Within 3 hours, Ca ２＋ The amount of ions eluted is 30 x 10 －６ (g / m ２ ) Bioceramics that reach

3. 2. The bioceramic according to claim 1, wherein the area ratio of the region in which no crystal orientation is detected in the binder phase is 20% or more and 80% or less in a band contrast image obtained by electron backscatter diffraction.

4. 4. The bioceramic according to claim 1, wherein the X-ray diffraction pattern using CuKα radiation contains a peak of calcium hydrogen phosphate.

5. 5. The bioceramic according to claim 4, wherein the half-width of the calcium hydrogen phosphate peak in an X-ray diffraction pattern using CuKα rays is 0.10° or more and 1.0° or less.

6. 5. The bioceramic of claim 4, wherein the bioceramic particles are calcium phosphate or calcium carbonate.

7. 5. The bioceramic of claim 4, wherein the bioceramic particles are bioabsorbable β-tricalcium phosphate.

8. a mixture preparation step of preparing a mixture by mixing a plurality of bioceramic particles, at least one dissolution / precipitation accelerator capable of dissolving the plurality of bioceramic particles, and a solvent capable of ionizing the dissolution / precipitation accelerator; a filling step of filling the mixture into a mold; a solidification step of solidifying the mixture by heating at 200°C or less while applying pressure to the mold; A method for producing bioceramics comprising the steps of:

9. 9. The method for producing bioceramics according to claim 8, wherein the bioceramic particles are bioabsorbable β-tricalcium phosphate.

10. 10. The method for producing bioceramics according to claim 8, wherein the mold is heated at a temperature equal to or lower than the boiling point of the solvent in the solidification step.

11. The method for producing bioceramics according to claim 8 or 9, wherein the mold is pressurized at a pressure of 375 to 625 MPa in the solidification step.

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