JP2018016523A - Apatite ceramic and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an apatite ceramic which prevents an increase in the size of a grain aggregate of metallic silver even when fired and is excellent in homogeneous antifungal properties and durability, and to provide a method for producing the same.SOLUTION: There are provided an apatite ceramic and a method for producing the same which includes: a step of adding ethanol to a mixture of powder of carbonic acid-containing apatite hydroxide containing a carbonate group in crystal and silver oxide and kneading the mixture to prepare a slurry-like apatite composition; a step of evaporating and removing the ethanol from the slurry-like apatite composition to obtain a powdery apatite composition; a step of placing the powdery apatite composition into a mold vessel, pressurizing the composition to prepare an apatite composition body having a predetermined shape; and a step of heating and firing the apatite composite body to a setting temperature in a range of 900-1,200°C to obtain apatite ceramic which precipitates silver dissolved as a solid solution once in ceramic as particulate metallic silver.SELECTED DRAWING: Figure 5

Description

  The present invention relates to apatite ceramics containing silver and a method for producing the same.

Hydroxyapatite [composition formula: Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ] and carbonate apatite [composition formula: Ca ₁₀ (PO ₄ ) ₆ CO ₃ ] are excellent in biocompatibility and directly bind to bone in the body. Therefore, it has been widely clinically applied as a bioactive coating material for artificial bone filling materials and artificial joints. In particular, antibacterial apatite in which silver or silver ions are supported on hydroxyapatite (hereinafter also referred to as hydroxyapatite) has a wide antibacterial spectrum, so in fields such as implants for living body implants, It is expected that bacterial infections can be prevented or suppressed, and many reports on it have been made (see Non-Patent Documents 1 to 3, etc.).

These reports are all about the synthesis and crystal structure of silver-substituted hydroxyapatite (silver-substituted hydroxyapatite) in which silver ions (Ag ⁺ ) are replaced with calcium ions (Ca ²⁺ ) of hydroxyapatite. For example, Non-Patent Document 1 reports that when silver-substituted hydroxyapatite was synthesized by wet synthesis, silver was replaced with CaI sites of hydroxyapatite as the a-axis and c-axis increased. Non-Patent Document 2 reports that when the silver-substituted hydroxyapatite produced by the microwave method is heated, the structure is maintained up to a temperature of 700 ° C. Furthermore, Non-Patent Document 3 reports changes in the crystal phase when silver-substituted hydroxyapatite with various Ca / P ratios prepared by wet synthesis is heat-treated.

In these studies, the hydroxyl group (OH ⁻ ) of the aforementioned hydroxyapatite and silver-substituted hydroxyapatite [compositional formula: Ca _10-x Ag _x (PO ₄ ) ₆ (OH) ₂ ] is replaced with the A site (A type). ), The phosphate group (PO ₄ ³⁻ ) may be referred to as a B site (B type). Further, the bottom surface (end surface) of the hexagonal columnar (needle-shaped) crystal of hydroxyapatite (hexagonal system) is the c-plane, the side surface (wall surface) is the a-plane, and the growth direction of the columnar crystal perpendicular to the bottom surface (c-plane) Is the c-axis, the diameter (radius) direction around the c-axis parallel to the bottom surface (c-plane) is called the a-axis, and the nine-coordinate calci arranged in a columnar shape (chain) in the c-axis direction is CaI (columnar The 7-coordinate calcium (Ca ²⁺ ) surrounding the oxygen of the hydroxyl group and the hydroxyl group is called a CaII (screw axis Ca) site.

L. Badrour, A. Sadel, M. Zahir, L. Kimakh, AE. Hajbi, “Synthesis and physical and chemical characterization of Ca10-xAgx (PO4) 6 (OH) 2-x × apatite” Annales de Chimie Science des Materiaux , Vol.23, Issue 1-2, (1998), P61-64 N. Rameshbabu, TS. Sampath Kumar, TG. Prabhakar, VS. Sastry, KV. Murty, K. Prasad Rao, “Antibacterial nanosized silver substituted: Synthesis and characterization”, Journal of Biomedical Materials Research Part A, Vol. 80, Issue 3, (2007), P581-591 O. Gokcekaya, K. Ueda, T. Narushima, C. Ergun, “Synthesis and characterization of Ag-containing calcium phosphates with various Ca / P ratios”, Materials Science and Engineering: C, Vol. 53, (2015), P111 -119

  As described above, hydroxyapatite has an advantage that it can easily give antibacterial properties by easily replacing calcium with silver by a wet synthesis method or the like. However, silver-substituted hydroxyapatite produced by a wet synthesis method has low crystallinity, and when heat treatment (firing) is performed thereafter, the crystallization or sintering of hydroxyapatite accompanying the temperature rise Therefore, there is a problem that precipitation of tricalcium phosphate β-phase (β-TCP) and calcium oxide (CaO), precipitation of metal silver, and grain growth (enlargement) occur.

  Therefore, the apatite ceramics fired from silver-substituted hydroxyapatite used for antibacterial implants and the like have non-uniformity that antibacterial properties are unevenly developed only in the vicinity of metallic silver that has precipitated and grown during molding and firing. Could have occurred. Moreover, there is a possibility that metallic silver is detached and the required antibacterial property cannot be maintained. Furthermore, when this apatite ceramic is to be applied in the vicinity of a sliding portion such as an artificial joint, the fallen silver may enter the joint sliding portion and cause wear of the sliding member.

  An object of the present invention is to provide an apatite ceramic having excellent homogeneous antibacterial properties and durability, and a method for producing the same, in which a metallic silver agglomerate does not increase in size even when fired.

  The present invention is composed of a molded body obtained by firing a mixture of a carbonate-containing hydroxyapatite containing a carbonate group in a crystal and silver or silver oxide, and among the metal silver particles observed by a scanning electron microscope, the particle diameter Is apatite ceramics characterized in that the ratio of the number of metallic silver particles of 0.1 to 2.0 μm is 95% or more based on the number of all metallic silver particles observed.

  The apatite ceramic of the present invention is characterized in that the silver content is 0.093 wt% or more and less than 9.3 wt% with respect to the entire apatite ceramic.

  Furthermore, the apatite ceramic of the present invention is characterized in that the carbonate group content in the carbonate-containing hydroxyapatite is 0.1 wt% or more and 6.0 wt% or less.

  The apatite ceramic according to the present invention suitably employs a configuration comprising a molded body obtained by firing the mixture for a predetermined time within a temperature range of 900 to 1200 ° C.

  On the other hand, in the method for producing an apatite ceramic of the present invention, a mixture of a carbonate-containing hydroxyapatite powder containing a carbonate group in a crystal and silver or silver oxide is kneaded by adding ethanol to form a slurry-like apatite composition. A step of producing a product, a step of evaporating and removing the ethanol from the slurry-like apatite composition to obtain a powdery apatite composition, and a step of putting the powdery apatite composition in a mold container and pressurizing And a step of producing an apatite composition object having a predetermined shape, and the apatite composition object is heated to a set temperature within a range of 900 to 1200 ° C. and fired, and the silver once solid-solved in the ceramic is particulate metal silver And a step of obtaining an apatite ceramic that precipitates as follows.

  Further, the method for producing an apatite ceramic of the present invention is such that the number of metal silver particles having a particle diameter of 0.1 to 2.0 μm among the metal silver precipitated in the ceramic is observed by a scanning electron microscope. It occupies 95% or more of the number of metallic silver particles.

  Furthermore, the method for producing an apatite ceramic of the present invention is characterized in that the silver content is 0.093 wt% or more and less than 9.3 wt% with respect to the entire apatite ceramic, and the carbonic acid-containing hydroxide The carbonate group content in the apatite is from 0.1% by weight to 6.0% by weight.

The composition formula of “carbonate-containing hydroxyapatite” (carbonated hydroxyapatite) used as a raw material for the apatite ceramic of the present invention is, for example, Ca _10-y [(PO ₄ ) _6-y (CO ₃ ) _y ] [( OH) _2-2z (CO ₃ ) _z ], and the composition formula of apatite ceramics in which a part of the calcium is substituted with silver is, for example, Ca _10-xy Ag _x [(PO ₄ ) _6-y ( CO ₃ ) _y ] [(OH) _2-2z (CO ₃ ) _z ].

  ADVANTAGE OF THE INVENTION According to this invention, the apatite ceramics which are excellent in antibacterial property and durability can be manufactured efficiently. That is, in the obtained apatite ceramic, the ratio of the number of metal silver particles having a particle diameter of 0.1 to 2.0 μm among the metal silver particles observed by a scanning electron microscope after firing is all observed. It is 95% or more based on the number of metallic silver particles. Therefore, in the apatite ceramic (molded article) of the present invention, the silver particles present in the ceramic are uniformly and evenly distributed, and further, there is no large silver particle lump, so the antibacterial dew is not uneven. It is like that.

Furthermore, among the low-temperature fired apatite ceramics of the present invention, those whose carbonate group content in the carbonate-containing hydroxyapatite is 0.1 wt% or more and 6.0 wt% or less are being fired (temperature rise). The carbonate group is efficiently substituted with a hydroxyl group (OH ⁻ : A site) in the carbonate-containing hydroxyapatite, whereby the a-axis of the hexagonal columnar crystal of hydroxyapatite [parallel to the bottom surface (c-plane), The length in the diameter (radius) direction around the c-axis] increases. Therefore, this configuration facilitates the replacement of silver ions (Ag ⁺ ) with calcium ions (Ca ²⁺ ) of hydroxyapatite, resulting in an increase in the amount of silver (silver ions) dissolved in the apatite crystal. Thus, the amount of silver deposited can be controlled.

  And when the apatite ceramic of this invention is a molded object obtained by baking the said mixture in the temperature range of 900-1200 degreeC, it heated up to 500-900 degreeC until it reaches predetermined temperature from normal temperature. At this stage, the silver once dissolved and dissolved in the apatite crystal is slowly and slowly released as the ceramic temperature rises, and only metallic silver with a small particle size is uniformly dispersed in the apatite ceramic. Will be present. Thereby, the growth (enlargement) and the production | generation of a silver grain lump can be suppressed.

  On the other hand, according to the method for producing an apatite ceramic of the present invention, it is possible to efficiently produce the apatite ceramic having no large silver particle agglomerates and excellent in antibacterial properties and durability as described above. Moreover, the apatite ceramic can be manufactured with good reproducibility.

(A) to (e) are, in order, heat-treated carbonic acid-containing hydroxyapatite (HAP-100) containing 0.93% by weight of silver at 400 ° C., 600 ° C., 800 ° C., 1000 ° C., and 1200 ° C. It is an electron micrograph which shows the state of the obtained apatite ceramics. (A) to (e) are, in order, heat-treated carbonic acid-containing hydroxyapatite (HAP-200) containing 0.93% by weight of silver at 400 ° C., 600 ° C., 800 ° C., 1000 ° C., and 1200 ° C. It is an electron micrograph which shows the state of the obtained apatite ceramics. (A)-(e) heat-treat carbonic acid containing hydroxyapatite (HAP-300) which contains 0.93 weight% of silver in order at 400 degreeC, 600 degreeC, 800 degreeC, 1000 degreeC, and 1200 degreeC in order. It is an electron micrograph which shows the state of the obtained apatite ceramics. It is a graph which shows the particle size distribution of the metal silver particle which exists in the apatite ceramic obtained by baking the carbonic acid containing hydroxyapatite (HAP-100) containing 0.93 weight% of silver at 1000 degreeC. It is a graph which shows the particle size distribution of the metallic silver particle which exists in the apatite ceramic obtained by baking the carbonic acid containing hydroxyapatite (HAP-200) containing 0.93 weight% of silver at 1000 degreeC. It is a graph which shows the particle size distribution of the metal silver particle which exists in the apatite ceramic obtained by baking the carbonic acid containing hydroxyapatite (HAP-300) containing 0.93 weight% of silver at 1000 degreeC. It is a chart figure which shows the X-ray-diffraction pattern of the apatite ceramic containing 0.93 weight% of silver heat-processed at 400-1200 degreeC.

Hereinafter, embodiments of the present invention will be described.
The apatite ceramic according to the present embodiment uses, as raw materials, a carbonate-containing hydroxyapatite powder (carbonated hydroxyapatite: CO ₃ HAp) containing carbonate groups in apatite crystals, and silver oxide (Ag ₂ O). After being sufficiently kneaded with a mill or the like, it is pressure-molded to form a molded body, and this molded body does not exceed 1200 ° C at which apatite sintering starts, usually 900 to 1200 ° C, preferably 1000 to 1200 ° C. It is fired in a temperature range within the range of ° C., and silver (metal silver) having a small particle size derived from the silver oxide is uniformly deposited in the ceramic. In the present invention, “precipitating silver” means that it first reaches a predetermined temperature (about 600 to 800 ° C.) by heating and cannot be observed as being dispersed and dissolved as silver ions in a hydroxyapatite crystal. The silver particles are released from the crystal lattice of hydroxyapatite by subsequent further temperature rise, and manifest as single metallic silver.

  In the manufacturing method, first, a carbonate-containing hydroxyapatite powder containing a carbonate group in a raw material apatite crystal and silver oxide are prepared. There is no restriction | limiting in particular in the silver oxide to be used, A powdery commercial item is used.

Carbonic acid-containing hydroxyapatite is, for example, a compound represented by the composition formula Ca _10-y [(PO ₄ ) _6-y (CO ₃ ) _y ] [(OH) _2-2z (CO ₃ ) _z ], In the hydroxyapatite (crystal), usually 0.1 wt% or more and 6.0 wt% or less, preferably 0.5 wt% or more and 5.5 wt% or less, more preferably 1.0 wt% or more and 5.0 wt% or less. It contains no more than wt% carbonate groups.

In general, when hydroxyapatite (hydroxyapatite) is artificially synthesized, A type in which carbonate ion (CO ₃ ²⁻ ) is substituted with hydroxyl (OH) A site in the dry synthesis method is used in the wet synthesis method. It is known that carbonate-containing hydroxyapatite called B-type in which carbonate ions are substituted at phosphate B (PO ₄ ) group B sites is produced preferentially. In the case of this embodiment, hydroxyapatite produced by wet synthesis is suitably employed. Specifically, carbonic acid-containing hydroxyapatite powder having high crystallinity, for example, high-purity calcium phosphate HAP series, HPA-100, HPA-200, HPA-300 (grade name) manufactured by Taihei Chemical Sangyo Co., Ltd., is prepared.

Next, silver is added to the prepared carbonate-containing hydroxyapatite powder (mixed type A and B), and the silver content relative to the total is usually 0.093 wt% or more and 9.3 wt%. The silver is added and mixed so that it is less than, preferably 0.093 wt% or more and 5.58 wt% or less, more preferably 0.093 wt% or more and 1.86 wt% or less. Furthermore, ethanol is added as a solvent for dispersion and mixing, and the mixture is sufficiently mixed and dispersed by kneading. As described above, silver is added as silver oxide (Ag ₂ O), and the number of added parts (parts by weight) is, for example, about silver oxide in the form of silver oxide when the weight of the carbonate-containing hydroxyapatite powder is 100. 1.01 to 11.1 parts by weight are added. This is an addition of about 0.094 to 10.3 parts by weight in terms of metallic silver (Ag).

  In addition, when content with respect to the whole carbonic acid containing hydroxyapatite mixture of silver derived from silver oxide is less than 0.093 weight%, there exists a possibility that the antibacterial performance of the apatite ceramics derived from silver may not fully be exhibited. On the other hand, when the silver content is 9.3 wt% or more, all the silver cannot be once dissolved in the apatite ceramics, and the residual agglomerates may remain in the ceramics. There is.

  Mixing and kneading of the mixture is performed using a ball mill or the like. For example, zirconia balls or the like are added as a kneading medium to a mixture of carbonic acid-containing hydroxyapatite and silver oxide to which ethanol is added as a solvent. For example, the weight ratio is powder (mixture): solvent: media = 1: 2: 6 and put into a kneading polyethylene container, and ball mill mixing is carried out for 24 hours at a rotational speed of 50 revolutions / minute to produce a slurry-like apatite composition.

Subsequently, ethanol was removed from the slurry apatite by evaporating using a suction means such as an evaporator to obtain a powdery apatite composition. Incidentally, in this state, the peak of the raw material silver oxide (Ag ₂ O) was not confirmed by analysis, but the peak of silver (Ag) was confirmed instead. This is presumably because silver oxide was reduced to silver during ball mill mixing with ethanol.

  Next, the powdery apatite composition is put into a mold container or the like and subjected to pressure molding to produce an apatite composition object having a predetermined shape. Although a shaping | molding method is not specifically limited, It is preferable to carry out using a die press, cold isostatic pressing (CIP), etc. Depending on the shape of the target implant or the like, the formed body (apatite composition object) such as CIP may be subjected to cutting or grinding.

  Next, the apatite composition body formed into a desired shape is fired by using an electric furnace or the like to a set temperature in the range of usually 900 to 1200 ° C., preferably 1000 to 1200 ° C. An apatite ceramic (product) with a uniform deposition of is produced.

  The heating (temperature) profile by an electric furnace or the like can be set as appropriate. For example, when the maximum temperature is set to 1000 ± 10 ° C., this maximum temperature state is maintained for about 1 to 3 hours. The heating profile is set so that is kept for about 1 to 3 hours. In addition, in order to give the time for the silver ion mentioned above to disperse-solid-dissolve in an apatite crystal, you may provide about 1 to 3 hours to maintain at 600-800 degreeC in the middle of temperature rising.

  As described above, in the method for producing an apatite ceramic according to the present embodiment, the firing temperature is in the range of 900 to 1200 ° C., preferably 1000 to 1200 ° C., so that the silver particles present after firing are uniform in the ceramic. Are distributed evenly, and there is no large silver particle lump, and only metallic silver having a small particle diameter is evenly dispersed and arranged.

  Next, the state of the obtained molded body of the silver-containing apatite ceramic will be described in the following examples.

In Examples, as a raw material, carbonate-containing hydroxyapatite containing carbonate groups in apatite crystals (carbonate-containing hydroxyapatite: CO ₃ HAp), high-purity calcium phosphate HAP-100 (white powder: particle size) manufactured by Taihei Chemical Industry Co., Ltd. 1.7 mm or less), HAP-200 (white powder: average particle size 5 to 20 μm), HAP-300 (white powder), and silver oxide (Ag ₂ O), silver oxide powder (average grain) manufactured by Kanto Chemical Co., Inc. Are mixed with the carbonate-containing hydroxyapatite powder so that the mixing ratio of silver derived from the silver oxide powder is 1% by weight, and a part of calcium in the apatite crystal is silver. Example 1 (Ag-HAP-100) group, Example 2 (Ag-HAP-200) group and Example 3 (Ag-HAP-300) To prepare a group.

[Preparation of Example Sample]
Carbonate-containing hydroxyapatite powder and a predetermined amount (1% by weight) of silver oxide powder are mixed, anhydrous ethanol is added as a solvent, and 5 mmφ zirconia balls are added as a kneading medium, and powder (mixture) in a weight ratio: solvent : The composition is 1: 2: 6 in media, and these are stored in a kneading polyethylene container and rotated at 50 revolutions / minute × 24 hours in a ball mill to fully mix and disperse the slurry-like apatite composition. A product was made.

  After mixing, the slurry was taken out and absolute ethanol was evaporated using an evaporator to obtain a mixed powder. Next, the mixed powder of each silver concentration is accommodated in a mold having a diameter of 24 mmφ and a mold having a diameter of 80 mmφ for an antibacterial test, and is temporarily formed by a uniaxial press, followed by cold isostatic pressing (CIP ) To prepare a tablet-like apatite composition object for heat treatment.

  Next, each sample was heated and fired in an electric furnace (under atmospheric pressure). Heating conditions were 400 ° C., 600 ° C., 800 ° C., 1000 ° C., and 1200 ° C. for 2 hours, respectively.

  An electron micrograph of the obtained silver-containing hydroxyapatite is shown in FIGS. Note that a scanning electron microscope (SEM: SN-3400N, manufactured by Hitachi, Ltd.) was used as the electron microscope.

  FIG. 1 shows a first embodiment in which HAP-100 is used as a raw material carbonic acid-containing hydroxyapatite. In (d) 1000 ° C. fired product and (e) 1200 ° C. fired product, large metallic silver agglomerates are shown. There are several.

  FIG. 2 shows a second embodiment in which HAP-200 is used as a raw material carbonic acid-containing hydroxyapatite. In (b) 600 ° C. calcined product and (c) 800 ° C. calcined product, metallic silver particles are completely absent. I couldn't see it. Moreover, in (d) 1000 degreeC baked goods and (e) 1200 degreeC baked goods, although the particle | grains of metallic silver were scattered, the big lump was not observed.

  FIG. 3 shows Embodiment 3 in which HAP-300 is used for the raw material carbonate-containing hydroxyapatite, and (d) 1000 ° C. calcined product and (e) 1200 ° C. calcined product, similar to HAP-100 (FIG. 1). In, a plurality of large metallic silver agglomerates were observed.

  Next, among the obtained samples, the 1000 ° C. baked product of Example 1 (Ag-HAP-100) (corresponding to FIG. 1 (d)), and the baked 1000 ° C. of Example 2 (Ag-HAP-200). Product (corresponding to FIG. 2 (d)), 1000 ° C. baked product of Example 3 (Ag-HAP-300) (corresponding to FIG. 3 (d)), ) Was measured by the following method. The results are shown in the particle size distribution diagrams of FIGS.

[Measuring method of silver particle size distribution]
A cross-sectional photograph of each sintered body was obtained as a reflected electron image with a scanning electron microscope (SEM) under the conditions of acceleration voltage: 15 kV and observation magnification: 2000 times. 10 backscattered electron images are obtained for each sample, and binarization processing is performed on silver particle portions and other hydroxyapatite portions on each SEM photograph using image analysis software (Win ROOF). Then, the equivalent circle diameter of each silver particle was measured, and the result of silver particle size distribution was obtained.

From the graph shown in FIG. 4, in the 1000 ° C. fired product of Example 1 (containing 1% by weight of silver and using HAP-100 as a raw material), silver particles having a maximum transverse diameter of 0.1 to 4.4 μm after the firing. It was found that the number of metal silver particles having a particle diameter of 0.1 to 2.0 μm accounted for 96% of the total number of metal silver particles observed. In actual measurement,
Number of particles having a maximum transverse diameter of 0.1 to 2.0 μm: 153 Number of particles having a maximum transverse diameter exceeding 2.0 μm: 6.

From the graph shown in FIG. 5, in the 1000 ° C. fired product of Example 2 (containing 1 wt% silver and using HAP-200 as a raw material), silver particles having a maximum transverse diameter of 0.1 to 1.4 μm after firing. It was found that the number of metallic silver particles having a particle diameter of 0.1 to 2.0 μm accounted for 100% of the number of all metallic silver particles observed. In actual measurement,
Number of particles having a maximum transverse diameter of 0.1 to 2.0 μm: 182 Number of particles having a maximum transverse diameter exceeding 2.0 μm: 0, which is the most homogeneous as compared with Example 1 and Example 3. Apatite ceramics could be obtained.

From the graph shown in FIG. 6, in the 1000 ° C. fired product of Example 3 (containing 1 wt% silver, using HAP-300 as a raw material), the silver particles having a maximum transverse diameter of 0.1 to 4.4 μm after the firing. It was found that the number of metal silver particles having a particle diameter of 0.1 to 2.0 μm accounted for 96% of the total number of metal silver particles observed. In actual measurement,
Number of particles having a maximum transverse diameter of 0.1 to 2.0 μm: 196 Number of particles having a maximum transverse diameter exceeding 2.0 μm: 8

  Next, among the obtained samples, the 800 ° C. baked product of Example 2 (Ag-HAP-200) [FIG. 2 (c)], the 1000 ° C. baked product [FIG. 2 (d)], and the 1200 ° C. baked product [FIG. 2 (e)] was used to evaluate antibacterial properties.

[Evaluation of antibacterial properties]
Antibacterial tests were performed using methicillin resistant Staphylococcus aureus (MRSA, UOEH6). Using inactivated bovine serum (manufactured by Invitrogen) medium, the number of bacteria was adjusted to 6.9 × 10 ⁵ cells / mL per mL, and used as a test bacterial solution. On each sterilized sample of Example 2 placed in a petri dish, 0.4 mL of the test bacterial solution was dropped, covered with a 40 mm × 40 mm square polyethylene film, and then cured. Then, after culturing at 35 ° C. and atmospheric pressure for 24 hours, the number of viable bacteria was counted. In the test, n = 3 was set for each sample, and apatite ceramics to which silver was not added was prepared and used as a control (blank).

<Results of antibacterial test>
Viable count (CFU) 24 hours after starting the test Example 2 800 ° C. baked product 2.1 × 10 ⁵ <10
1000 ° C. fired product 2.1 × 10 ⁵ <10
1200 x baked product 2.1 x 10 ⁵ 4.6 x 10 ³
Control 800 calcined product 2.1 × 10 ⁵ 4.3 × 10 ⁶
1000 calcined product 2.1 × 10 ⁵ 1.7 × 10 ⁷
1200 calcined product 2.1 × 10 ⁵ 1.5 × 10 ⁷

From the results of the “antibacterial test”, it was observed that the number of viable bacteria increased from 2.1 × 10 ⁵ CFU in all of the control samples not containing silver. On the other hand, in Example 2 (using HAP-200, containing 1% by weight of silver), the 800 ° C. and 1000 ° C. baked products were killed until <10 CFU (below the measurement limit) after 24 hours. It was confirmed to show high antibacterial properties.

  Moreover, the 1200 degreeC baked product of Example 2 did not show remarkable antibacterial properties as the above-mentioned 800 ° C baked product and 1000 ° C baked product, but showed sufficient antibacterial properties compared to the control. The reason why the antibacterial property was relatively low is that at a firing temperature of 1200 ° C., the apatite crystals were densified (sintered), and the silver particles were thought to have grown (granulated). The 800 ° C. and 1000 ° C. fired products have a large specific surface area due to their low bulk density and a large number of pores. In addition, the silver particles are fine and many silvers are replaced with calcium (solid solution). Therefore, it is considered that the silver ions that exhibit antibacterial activity were more eluted than the 1200 ° C. baked product.

  Next, the reason why the precipitated silver particles are miniaturized in the apatite ceramic of the present invention will be described.

FIG. 7 shows the crystal structure analysis by X-ray diffraction on the unfired product and the 400-1200 ° C. fired product of Example 2 (containing 1% by weight of silver, and HAP-200 is used for the raw material carbonate-containing hydroxyapatite). It is the result of having gone. X-ray diffraction (XRD) measurement was performed using an X-ray diffractometer (PW6003 / 00, manufactured by Spectris) using CuKα rays and obtaining an XRD pattern under the following measurement conditions.
Tube voltage: 45 kV Tube current: 40 mA Scan speed: 2.2 ° / min

According to the XRD pattern of Example 2 group in FIG. 7, the peak of the raw material silver oxide (Ag ₂ O) was not confirmed in the state of the molded body (after CIP pressing) before the heat treatment (baking), instead of A silver (Ag) peak was observed. This is probably because silver oxide was reduced to silver during ball mill mixing.

  In Example 2 group, diffraction peaks attributed to silver (indicated by black circles ● Ag (cubic) in FIG. 7) were observed in the unfired product and the 400 ° C. fired product, but the 600 ° C. fired product and 800 ° C. In the baked product at 0 ° C., the silver peak disappeared. And in the 1000 degreeC baked product and the 1200 degreeC baked product, the said silver peak appeared again and silver precipitation was estimated. In the 1000 ° C. and 1200 ° C. fired products, calcium oxide (CaO) precipitation peaks (indicated by white triangles Δ) were simultaneously confirmed. This series of silver-related phenomena is consistent with the results of the SEM observation described above (FIG. 2 (b) 600 ° C. fired product, (c) 800 ° C. fired product).

That is, from the XRD pattern and the IR spectrum measurement of Example 2 group performed separately from this, “a-axis expansion and c-axis contraction” and “carbonate ions to the A site” in the vicinity of 600 to 800 ° C. "Increased replacement". This phenomenon is considered to be caused by replacing a large planar carbonate group (CO ₃ ²⁻ ) group with a small linear hydroxyl group (OH ⁻ ).

Here, the ionic radius (1.28 angstroms) of silver ions (Ag ⁺ ) is larger than the ionic radius (0.99 angstroms) of calcium ions (Ca ²⁺ ), and the HAP-200 ( Hydroxyapatite) is very high in crystallinity, and therefore silver ions are usually difficult to replace with calcium ions in the hydroxyapatite crystals. ) Or silver phosphate (Ag ₃ PO ₄ ).

Then, the a-axis of the hydroxyapatite crystal rapidly spreads by heat treatment at 600 ° C. to 800 ° C., so that silver ions having a large ionic radius can be easily penetrated, and calcium ions (Ca ²⁺ ) and silver in the crystal structure can be obtained. It is considered that substitution with ions (Ag ⁺ ) has progressed. However, when the temperature is further raised to 1000 ° C. or more, the carbonate group is eliminated from both the A site and the B site, the expansion of the a-axis is restored, and some silver ions are produced from hydroxyapatite crystals. It is thought that it was detached from the lattice and precipitated as silver. Further, since the carbonate group disappeared from the phosphate group site, crystallization of stoichiometric hydroxyapatite progressed, and excess calcium ions seem to have precipitated as calcium oxide.

  For the reasons described above, in the apatite ceramic and the manufacturing method thereof according to the present embodiment, the firing temperature of the ceramic does not exceed 1200 ° C. at which apatite sintering starts, that is, 900 to 1200 ° C., preferably 1000 to 1200. The temperature is within the range of ° C. As a result, the silver in the raw material first reaches about 600 to 800 ° C. by heating, and is dispersed and dissolved as silver ions in the hydroxyapatite crystal. It seems that it was deposited evenly and uniformly.

  In the present embodiment, Taihei Chemical Industry is suitable as a carbonate-containing hydroxyapatite powder containing 0.1% by weight or more and 6.0% by weight or less of a carbonate group suitable for the present invention and having high crystallinity. HAP-100, HAP-200, and HAP-300 (grade name) were used in the high purity calcium phosphate HAP series manufactured by the company. As the carbonate-containing hydroxyapatite powder used in the present invention, other carbonate-containing hydroxides are used. Apatite can also be used.

As a preferred specification of the carbonate-containing hydroxyapatite powder that can be used, it is desirable to use sodium hydrogen phosphate (DCPA, monetite) capable of growing hexagonal columnar crystals as a starting material. Hydroxyapatite of the type in which (CO ₃ ²⁻ ) is preferentially substituted at phosphate group sites (B sites) is preferred. As an example, the carbonate group content is about 2.8 to 4.8% by weight, but “B site (phosphate group) substituted carbonate group / A site (hydroxyl group) substituted carbonate before heating (firing)”. The ratio of the “group” is about “½” or less, and the crystal structure allows the carbonate group to be introduced into the A site at the same time as the carbonate group is discharged from the B site by heating at 800 ° C. It is preferable. The specific surface area of the carbonate-containing hydroxyapatite alone is 10 m ² · g ⁻¹ or less, preferably 5 m ² · g ⁻¹ or less. The pore distribution is preferably one having a distribution with few pores exceeding 5 nm.

Claims (8)

  It is composed of a molded body obtained by firing a mixture of a carbonate-containing hydroxyapatite containing a carbonate group in the crystal and silver or silver oxide, and among the metallic silver particles observed by a scanning electron microscope, the particle diameter is 0.1. An apatite ceramic characterized in that the ratio of the number of metallic silver particles of ˜2.0 μm is 95% or more with respect to the number of all metallic silver particles observed.   2. The apatite ceramic according to claim 1, wherein a content of the silver is 0.093 wt% or more and less than 9.3 wt% with respect to the entire apatite ceramic.   3. The apatite ceramic according to claim 1, wherein the carbonate group content in the carbonate-containing hydroxyapatite is 0.1 wt% or more and 6.0 wt% or less.   The apatite ceramic according to any one of claims 1 to 3, wherein the apatite ceramic is composed of a molded body obtained by firing the mixture within a temperature range of 900 to 1200 ° C for a predetermined time. A step of preparing a slurry-like apatite composition by adding ethanol to a mixture of a carbonate-containing hydroxyapatite powder containing a carbonate group in the crystal and silver or silver oxide;
Evaporating and removing the ethanol from the slurry apatite composition to obtain a powdery apatite composition;
Putting the powdery apatite composition into a mold container and pressurizing it to produce an apatite composition object of a predetermined shape;
The apatite composition body is heated to a set temperature in the range of 900 to 1200 ° C. and fired to obtain apatite ceramics in which silver once dissolved in the ceramics is precipitated as particulate metallic silver;
A method for producing an apatite ceramic, comprising:   Among the metallic silver precipitated in the ceramics, the number of metallic silver particles having a particle diameter of 0.1 to 2.0 μm accounts for 95% or more of the total number of metallic silver particles observed by a scanning electron microscope. The method for producing an apatite ceramic according to claim 5.   The method for producing an apatite ceramic according to claim 5 or 6, wherein the silver content is 0.093 wt% or more and less than 9.3 wt% with respect to the entire apatite ceramic.   The apatite ceramic according to any one of claims 5 to 7, wherein the carbonate content of the carbonate-containing hydroxyapatite powder is 0.1 wt% or more and 6.0 wt% or less. Production method.