calcium phosphate powder

Abstract

An object of the present invention is to provide a calcium phosphate powder that can be used to prepare a slurry for additive manufacturing that has excellent dispersion stability and can be used to produce a high-strength three-dimensional additive manufacturing object. [Solution] Average particle diameter (D 50 ) of 0.1 to 5.0 μm and a pore volume of mesopores (pore diameter of 2 to 50 nm) of 0.01 to 0.06 cc / g measured by gas adsorption method has excellent dispersion stability even in an additive manufacturing slurry, and by additive manufacturing using an additive manufacturing slurry containing this calcium phosphate, it is possible to produce high-strength three-dimensional additive manufactured objects useful for implants such as artificial bones.

Description

[Technical Field]

[0001] The present invention relates to a calcium phosphate powder that can be used to prepare a slurry for additive manufacturing that has excellent dispersion stability and that can be used to produce a high-strength three-dimensional additive manufacturing object. [Background technology]

[0002] In recent years, artificial bones have been used as substitutes for human bones in bone defects for the treatment of bone diseases such as fractures. Materials used for artificial bones include metals, ceramics, and polymeric materials.

[0003] Although ceramics are inferior to metals and polymeric materials in terms of mechanical strength, they have excellent biocompatibility and are highly useful as materials for artificial bones. Among ceramics, calcium phosphates such as hydroxyapatite (HAP) and beta-tricalcium phosphate (beta-TCP) have compositions similar to those of human bones and have excellent osteoinductivity, allowing them to bond directly with bone and become a component in bone formation. Therefore, much research has been conducted on artificial bones made from calcium phosphates.

[0004] However, although artificial bones made from calcium phosphate have a composition similar to that of natural bone, their healing speed is slower than that of autologous bone. Therefore, block or granular artificial bones made from calcium phosphate with porous or interconnected pores have been developed to have a structure similar to that of autologous bone, but their healing speed is still slower than that of autologous bone, and they must be shaped to fit the defect site during surgery.

[0005] To solve these problems, attempts are being made to create artificial bones using calcium phosphate using additive manufacturing technology (3D printers) that not only conform to the shape of the missing part, but also replicate the internal structure of the bone.Known 3D printers used for artificial bones include a manufacturing method in which a hardening liquid is injected into powder and hardened (powder additive manufacturing), and a manufacturing method in which an additive manufacturing slurry (modeling paste) made by kneading ceramic raw materials with a photocurable resin is irradiated with ultraviolet light to harden it, and the resin is then removed from the hardened product (stereolithography).

[0006] Non-Patent Document 1 discloses the production of artificial bone by powder additive manufacturing using powders containing α-tricalcium phosphate, tetracalcium phosphate, calcium hydrogen phosphate, and HAP, but the compressive strength of the resulting artificial bone was only about 27 MPa. Non-Patent Document 2 also discloses the production of artificial bone by stereolithography using HAP with a particle size of 12 μm, but the compressive strength of the resulting artificial bone was only about 15 MPa. Thus, conventional artificial bones produced by additive manufacturing using calcium phosphate have the disadvantage of low compressive strength and being unsuitable for use in areas subject to heavy loads (such as the femur). Patent Document 1 examines alumina, zirconia, and other ceramic materials for use in additive manufacturing. While these materials produce three-dimensional additively manufactured objects with a certain level of strength, they suffer from the problem of poor osteoinductivity.

[0007] Furthermore, the artificial bones produced must be reproducible enough to avoid the need for shaping during surgery (modeling precision). Reducing the particle size of the calcium phosphate powder is an effective way to increase the modeling precision in stereolithography, but when the average particle size of the calcium phosphate powder is reduced to 1 μm or less, the calcium phosphate powder tends to aggregate easily in the slurry, making it difficult to achieve uniform dispersion.

[0008] Against this background of conventional technology, there is a need for the development of calcium phosphate powder that can be used to prepare slurries for additive manufacturing with excellent dispersion stability and that can be used to produce high-strength three-dimensional additive manufacturing objects using additive manufacturing techniques. [Prior art documents] [Non-patent literature]

[0009] [Non-Patent Document 1] Proposal of a method for forming artificial bone using powder additive manufacturing - Porosity of formed bone - Biomedical Engineering 47(2):142-147,2009 [Non-patent document 2] Additive manufacturing of hydroxyapatite bone scaffolds via digital lightprocessing and in vitro compatibility(Ceramics InternationalVolume 45, Issue 81 June 2019Pages 11079-11086) [Patent documents]

[0010] [Patent Document 1] International Publication No. 2016 / 147681 Summary of the Invention [Problem to be solved by the invention]

[0011] An object of the present invention is to provide a calcium phosphate powder that can be used to prepare a slurry for additive manufacturing that has excellent dispersion stability and can be used to produce a high-strength three-dimensional additive manufacturing object. [Means for solving the problem]

[0012] The present inventors have conducted extensive research to solve the above problems, and have found that the average particle diameter (D 50It has been found that calcium phosphate powder having a particle size distribution of 0.1 to 5.0 μm and a mesopore volume (pore diameter of 2 to 50 nm) of 0.01 to 0.06 cc / g as measured by gas adsorption has excellent dispersion stability even in an additive manufacturing slurry, and that high-strength three-dimensional additive manufacturing objects useful for implants such as artificial bones can be produced by additive manufacturing using an additive manufacturing slurry containing this calcium phosphate. The present invention was completed based on this finding and through further investigation.

[0013] That is, the present invention provides the following aspects. Item 1. Average particle diameter (D 50 ) is 0.1 to 5.0 μm, and the pore volume of mesopores (pore diameter 2 to 50 nm) measured by gas adsorption method is 0.01 to 0.06 cc / g. Item 2. The calcium phosphate powder according to Item 1, wherein the calcium phosphate comprises at least one of hydroxyapatite, tricalcium phosphate, α-TCP, calcium-deficient hydroxyapatite, and β-TCP. Item 3. BET specific surface area is 0.1 to 20 m 2 Item 3. The calcium phosphate powder according to Item 1 or 2, wherein the calcium phosphate content is 1 / g. Item 4. The calcium phosphate powder according to any one of Items 1 to 3, wherein the pore volume of macropores (pore diameter 50 to 200 nm) measured by gas adsorption method is 0.02 to 0.10 cc / g. Item 5. D measured using a laser diffraction / scattering particle size distribution analyzer 10 Item 5. The calcium phosphate powder according to any one of Items 1 to 4, wherein the particle size is 3.0 μm or less. Section 6. D above 10 Item 6. The calcium phosphate powder according to any one of Items 1 to 5, wherein the value is 1.0 or less. Item 7. A material for additive manufacturing, comprising the calcium phosphate powder according to any one of Items 1 to 6. Item 8. The additive manufacturing material according to Item 7, which is used for stereolithography. Item 9. The additive manufacturing material according to Item 7 or 8, which is used to manufacture an implant. Item 10. A slurry for additive manufacturing, comprising the calcium phosphate powder according to any one of Items 1 to 6 and a photocurable resin. Item 11. A method for producing a three-dimensional layered object, comprising the following steps (1) to (4): (1) A step of forming a slurry layer using the slurry for additive manufacturing according to item 10; (2) a step of irradiating the slurry layer with laser light in a predetermined pattern to harden it; (3) repeating the steps (1) and (2) to form a three-dimensional laminated cured product; and (4) removing the uncured resin and the cured resin from the three-dimensional laminated cured product. A method for manufacturing a three-dimensional additively manufactured object, comprising: Item 12. The method for producing a three-dimensionally laminated object according to Item 11, wherein the three-dimensionally laminated object is an implant. Item 13. Use of the calcium phosphate powder according to any one of Items 1 to 6 as a material for additive manufacturing. [Effects of the Invention]

[0014] The calcium phosphate powder of the present invention can be used to prepare a slurry for additive manufacturing with excellent dispersion stability. Furthermore, a three-dimensional additive manufacturing object produced using the slurry for additive manufacturing containing the calcium phosphate powder of the present invention has high strength and is useful as an artificial bone for use in weight-bearing parts such as the femur. [Brief explanation of the drawings]

[0015] [Figure 1] 1 shows the results of measuring the crystal structure of the calcium phosphate powder of Example 6. [Figure 2] 1 shows the results of measuring the crystal structure of the calcium phosphate powder of Example 7. [Figure 3] 1 shows the results of measuring the crystal structure of the calcium phosphate powder of Example 8. [Figure 4] 1 shows the results of measuring the crystal structure of the calcium phosphate powder of Example 9. [Figure 5]Images showing the surfaces of three-dimensional laminated objects produced using the calcium phosphate powders of Example 1, Example 3, and Comparative Example 2 observed with a field emission scanning electron microscope are shown. [Figure 6] Results of measuring the crystal structure of a three-dimensional laminated object obtained by sintering a lamination molding slurry containing the calcium phosphate powder of Example 6 at 1100 °C are shown. [Figure 7] Results of measuring the crystal structure of a three-dimensional laminated object obtained by sintering a lamination molding slurry containing the calcium phosphate powder of Example 8 at 1100 °C are shown.

Embodiments for Carrying Out the Invention

[0016] The calcium phosphate powder of the present invention has an average particle diameter (D 50 ) of 0.1 to 5.0 μm, and is characterized in that the pore volume of mesopores (pore diameter 2 to 50 nm) measured by the gas adsorption method is 0.01 to 0.06 cc / g. Hereinafter, the calcium phosphate of the present invention will be described in detail.

[0017] [Types of Calcium Phosphate] Regarding the type of the calcium phosphate powder of the present invention, any of hydroxyapatite (HAP: (Ca5(PO4)3(OH))), β-TCP (β-Ca3(PO4)2), calcium-deficient hydroxyapatite (Ca 10-z (HPO4) z (PO4) 6-z (OH) 2-z (where 0 < Z ≦ 1), α-tricalcium phosphate (α-Ca3(PO4)2), tricalcium phosphate (Ca3(PO4)2), octacalcium phosphate (Ca8(PO4)4(HPO4)2(OH)2), etc. may be used, or a mixture or mixed crystal containing two or more of these may be used. The calcium-deficient hydroxyapatite may be either an anhydride or a hydrate, and as the structural formula of the hydrate calcium-deficient hydroxyapatite, for example, Ca 10-z (HPO4) z (PO4) 6-z (OH)2-z ·nH2O (where 0 < Z ≤ 1, 0 < n ≤ 2.5) can be mentioned.

[0018] Among calcium phosphates, HAP and β-TCP are excellent in biocompatibility and useful as materials for artificial bone. Therefore, as suitable examples of the calcium phosphate powder of the present invention, HAP powder, β-TCP powder, calcium-deficient hydroxyapatite powder, and a mixed powder or mixed crystal powder thereof can be mentioned. As an example of the mixed powder or mixed crystal powder, a mixed powder or mixed crystal powder of β-TCP and calcium-deficient hydroxyapatite can be mentioned. In the mixed powder or mixed crystal powder of β-TCP and calcium-deficient hydroxyapatite, the content ratio of β-TCP and calcium-deficient hydroxyapatite is not particularly limited, but is a content measured according to the RIR method (Reference Intensity Ratio) by X-ray diffraction measurement, and β-TCP is 2 to 98% by weight and calcium-deficient hydroxyapatite is 2 to 98% by weight, preferably β-TCP is 30 to 98% by weight and calcium-deficient hydroxyapatite is 2 to 70% by weight.

[0019] The calcium phosphate powder of the present invention may be either a sintered body subjected to firing treatment or a non-sintered body not subjected to firing treatment. However, when the calcium phosphate powder is HAP powder, from the viewpoint of preferably having a predetermined average particle diameter (D 50 ) and a pore volume of mesopores (pore diameter 2 to 50 nm), it is preferably a non-sintered body.

[0020] [Physical properties of calcium phosphate powder] The calcium phosphate powder of the present invention has an average particle diameter (D 50) is 0.1 to 5.0 μm. By satisfying this average particle diameter while setting the pore volume of mesopores (pore diameter 2 to 50 nm) to a predetermined value, it is possible to provide excellent dispersion stability in the slurry for additive manufacturing and to provide high strength to the produced three-dimensional additive manufacturing object. From the viewpoint of further improving the dispersion stability in the slurry for additive manufacturing and the strength of the produced three-dimensional additive manufacturing object, the average particle diameter (D 50 ) is preferably 0.1 to 3.0 μm, more preferably 0.4 to 1.0 μm. 50 Other preferred examples of the "average particle diameter (D)" of the calcium phosphate powder include 0.5 to 5.0 μm, more preferably 1.0 to 5.0 μm, and even more preferably 3.0 to 5.0 μm. 50 ) is the particle size (median diameter) at which the cumulative degree is 50% in the volume cumulative standard particle size distribution measured using a laser diffraction / scattering particle size distribution analyzer.

[0021] D of the calcium phosphate powder of the present invention 10 Regarding the average particle diameter (D 50 The D of the calcium phosphate powder of the present invention is not particularly limited as long as it satisfies the range of 3.0 μm or less, or 1 μm or less, for example. 10 The particle size of the calcium phosphate powder of the present invention is preferably 0.1 μm to 2.5 μm, more preferably 0.1 to 0.9 μm, and even more preferably 0.2 to 0.8 μm. 10 However, by satisfying this range, the pore volume per particle increases, and the dispersion stability in the slurry for additive manufacturing can be further improved. 10 " is the particle size at which the cumulative percentage is 10% in the volume cumulative particle size distribution measured using a laser diffraction / scattering particle size distribution analyzer.

[0022] D of the calcium phosphate powder of the present invention 90 Regarding the average particle diameter (D 50) is not particularly limited as long as it satisfies the range, but examples include 1 to 30 μm, preferably 1 to 20 μm, and more preferably 2 to 18 μm. In the present invention, the "D 90 " is the particle size at which the cumulative percentage is 90% in the volume cumulative particle size distribution measured using a laser diffraction / scattering particle size distribution analyzer.

[0023] The number-average particle diameter of the calcium phosphate powder of the present invention is determined by the above-mentioned average particle diameter (D 50 ) is not particularly limited as long as it satisfies the range, but examples include 0.1 to 3 μm, preferably 0.1 to 2 μm, more preferably 0.1 to 1 μm, and even more preferably 0.1 to 0.6 μm. In the present invention, the "number average diameter" of the calcium phosphate powder is the particle diameter at a cumulative degree of 50% by number calculation in a number-cumulative standard particle size distribution measured using a laser diffraction / scattering particle size distribution analyzer.

[0024] The pore volume of mesopores (pore diameter: 2 to 50 nm) of the calcium phosphate powder of the present invention measured by gas adsorption method is 0.01 to 0.06 cc / g. 50By satisfying the above requirements while also satisfying the pore volume of mesopores (pore diameter 2-50 nm), the additive manufacturing slurry has excellent dispersion stability. The resin and particles do not separate in the additive manufacturing slurry, allowing the resins to form hydrogen bonds. When force is applied during additive manufacturing, these hydrogen bonds separate, reducing viscosity, providing the thixotropy necessary for layer formation during additive manufacturing. Furthermore, by satisfying the pore volume of mesopores (pore diameter 2-50 nm), particle irregularities on the surface of three-dimensional additive manufacturing objects are reduced, enabling the production of highly accurate three-dimensional additive manufacturing objects. On the other hand, if the pore volume of mesopores (pore diameter 2-50 nm) is less than 0.01 cc / g, the additive manufacturing slurry's dispersion stability decreases, and when force is applied during additive manufacturing, particles tend to crowd together, increasing viscosity, resulting in dilatancy. From the viewpoint of further improving the dispersion stability in the slurry for additive manufacturing and the strength of the produced three-dimensional additive manufacturing object, the pore volume of the mesopores (pore diameter 2 to 50 nm) of the calcium phosphate powder of the present invention is preferably 0.02 to 0.06 cc / g, more preferably 0.02 to 0.05 cc / g.

[0025] In the present invention, the "pore volume of mesopores (pore diameter 2 to 50 nm) measured by gas adsorption" of calcium phosphate powder is a value measured by the following method using a high-speed specific surface area pore distribution analyzer. First, 0.1 g or 1.0 g of calcium phosphate powder is accurately weighed, sealed in an adsorption tube, and degassed at 105°C for 3 hours. Next, the nitrogen gas adsorption isotherm is determined at the temperature of liquid nitrogen gas, and the pore volume (cc / g) of mesopores (2 to 50 nm) is calculated by the BJH method.

[0026] The pore volume of macropores (50-200 nm) of the calcium phosphate powder of the present invention measured by gas adsorption is not particularly limited, but may be, for example, 0.02-0.10 cc / g, preferably 0.02-0.09 cc / g, and more preferably 0.02-0.08 cc / g. Having such a macropore volume can further improve the dispersion stability of the slurry for additive manufacturing. In the present invention, the "pore volume of macropores (50-200 nm) measured by gas adsorption" of the calcium phosphate powder is a value measured using a high-speed specific surface area pore distribution analyzer as follows: First, 0.1 g or 1.0 g of calcium phosphate powder is accurately weighed, sealed in an adsorption tube, and degassed at 105°C for 3 hours. Next, the nitrogen gas adsorption isotherm is determined at the temperature of liquid nitrogen gas, and the pore volume (cc / g) of the macropores (50-200 nm) is calculated by the BJH method.

[0027] The BET specific surface area of ​​the calcium phosphate powder of the present invention is not particularly limited, but may be, for example, 20 m 2 / g or less, preferably 0.1 to 20m 2 / g, more preferably 5 to 20m 2 / g, more preferably 8 to 18m 2 / g. By satisfying this BET specific surface area, the particles can shrink densely during debinding and / or sintering of the fabricated three-dimensional additive manufacturing object, making it possible to fabricate three-dimensional additive manufacturing objects with even higher strength. In the present invention, the "BET specific surface area" of calcium phosphate powder is a value measured by the following method using a high-speed specific surface area pore distribution measuring device. First, 0.1 g or 1.0 g of calcium phosphate is accurately weighed, sealed in an adsorption tube, and degassed at 105°C for 3 hours. Next, the adsorption isotherm of nitrogen gas is determined at the temperature of liquid nitrogen gas, and the specific surface area (m ) is measured by the multipoint BET method using the adsorption isotherm. 2 / g) is calculated.

[0028] In the calcium phosphate powder of the present invention, the average pore size measured by gas adsorption is not particularly limited, but may be, for example, 10 to 50 nm, preferably 20 to 40 nm, and more preferably 15 to 35 nm.

[0029] In the present invention, the "average pore diameter measured by gas adsorption method" of the calcium phosphate powder is a value determined by the following method. First, the total pore volume is measured by a gas adsorption method using a high-speed specific surface area pore distribution measuring device under the following operating conditions. Pretreatment: Accurately weigh 0.1 g or 1.0 g of calcium phosphate powder, seal it in an adsorption tube, and degas it at 105°C for 3 hours. Measurement and analysis: The adsorption isotherm of nitrogen gas is determined at the temperature of liquid nitrogen gas, and the total pore volume (cc / g) is calculated from the amount of gas adsorbed at a relative pressure P / P0 (P0: saturated vapor pressure) of 0.995. Next, the average pore diameter is calculated according to the following formula using the BET specific surface area and total pore volume (gas adsorption method) obtained above. Average pore diameter (nm)=4V / S×1000 V: Total pore volume (gas adsorption method) (cc / g) S:BET specific surface area (m 2 / g)

[0030] The loose bulk density of the calcium phosphate powder used in the present invention is not particularly limited, and may be, for example, 0.1 to 1.0 g / mL, preferably 0.1 to 0.5 g / mL, and more preferably 0.1 to 0.3 g / mL.

[0031] In the present invention, the "loose bulk density" of calcium phosphate powder is measured by vibrating a sieve with 710 μm openings at an amplitude of 0.5 mm while pouring calcium phosphate powder into a cup (capacity 10 cm) from above the sieve. 3The calcium phosphate powder is dropped into a cup (2.2 cm inner diameter, 2.6 cm height), and when the calcium phosphate powder overflows from the cup, the drop is stopped, the mound of powder on the cup is scraped off, and the weight of the empty cup is subtracted from the weight of the cup containing the powder to calculate the powder weight per 1 mL.

[0032] The tapped density (tap density) of the calcium phosphate powder used in the present invention is not particularly limited, and may be, for example, 0.2 to 1.5 g / mL, preferably 0.3 to 1.0 g / mL, and more preferably 0.4 to 0.8 g / mL.

[0033] In the present invention, the "packed bulk density" of calcium phosphate powder is a value determined by the following method. First, while a sieve with 710 μm openings is vibrated at an amplitude of 0.5 mm, calcium phosphate powder is poured onto a cup (capacity 10 cm) from above the sieve. 3 The calcium phosphate powder was dropped into a sieve (2.2 cm inner diameter, 2.6 cm height). When the calcium phosphate powder overflowed the cup, the drop was stopped and the raised powder on top of the cup was scraped off. Next, a cylinder (2.2 cm inner diameter, 3.2 cm height) was attached to the top of the cup. The calcium phosphate powder was dropped from above the sieve with a 710 μm mesh size while vibrating it at an amplitude of 0.5 mm into the cup, filling the cylinder to approximately 80% of its capacity. Tapping was started in this state, and a total of 180 tappings were performed. During tapping, when the amount of calcium phosphate powder in the cylinder was compressed to approximately 20% of its capacity, the calcium phosphate powder was dropped into the cylinder again through the 710 μm mesh size sieve, which was vibrating at an amplitude of 0.5 mm, to replenish the cylinder to approximately 80% of its capacity. After 180 tappings, the cylinder was removed, the raised powder on top of the cup was scraped off, and the weight of the cup containing the powder was measured. Subtract the weight of the empty cup from this weight to calculate the weight of the powder in the cup. 3 The powder weight per unit is calculated and used as the compact density (g / mL).

[0034] [Method of manufacturing calcium phosphate powder] The method for producing the calcium phosphate powder of the present invention is not particularly limited as long as it can produce a calcium phosphate powder having the physical properties described above. For example, suitable examples include Method 1 including the following steps 1-1 to 1-4, Method 2 including the following steps 2-1 to 2-4, and Method 3 including the following steps 3-1 to 3-2.

[0035] Law 1 Step 1-1: (1) a wet method of adding phosphoric acid and / or a phosphate to a suspension of a calcium salt so that the molar ratio of Ca / P becomes 1.40 to 1.80, and reacting at 30°C or higher, or (2) a wet method of adding a suspension of a calcium salt to an aqueous phosphoric acid solution prepared by dissolving phosphoric acid and / or a phosphate in water so that the molar ratio of Ca / P becomes 1.40 to 1.80, and reacting at 30°C or higher, to produce calcium phosphate; Step 1-2: wet-pulverizing the calcium phosphate obtained in Step 1-1 to obtain a slurry; Step 1-3: A step of hydrothermally treating the slurry obtained in Step 1-2 at 250°C to 300°C to obtain a hydrothermally treated product; and Step 1-4: A step of drying the hydrothermally treated product obtained in Step 1-3 to obtain calcium phosphate powder.

[0036] Law 2 Step 2-1: A step of producing calcium phosphate by a wet method in which a suspension of a calcium salt and an aqueous phosphoric acid solution in which phosphoric acid and / or a phosphate salt is dissolved in water are simultaneously dropped into an aqueous medium so that the Ca / P molar ratio is 1.40 to 1.80, and the reaction is carried out at 30°C or higher; Step 2-2: wet-pulverizing the calcium phosphate obtained in Step 2-1 to obtain a slurry; Step 2-3: A step of hydrothermally treating the slurry obtained in Step 2-2 at 150°C to 300°C to obtain a hydrothermally treated product; and Step 2-4: A step of drying the hydrothermally treated product obtained in Step 2-3 to obtain calcium phosphate powder.

[0037] Third law Step 3-1: A step of producing calcium phosphate by a wet method in which a suspension of a calcium salt at 50°C or less and an aqueous phosphoric acid solution in which phosphoric acid and / or a phosphate salt is dissolved in water and at 50°C or less are simultaneously dropped into an aqueous medium at 80°C or more so that the Ca / P molar ratio becomes 1.40 to 1.80, and the reaction is carried out under conditions of pH 8.5 to 9.5 or pH 3.5 to 4.5; Step 3-2: A step of drying the slurry obtained in Step 3-1 to obtain calcium phosphate powder.

[0038] The first method will now be described in detail.

[0039] In step 1-1, calcium ions and phosphate ions are reacted to synthesize calcium phosphate by either (1) a wet method in which phosphoric acid and / or a phosphate salt is added dropwise to a suspension of a calcium salt so that the molar ratio of Ca / P becomes 1.40 to 1.80, or (2) a wet method in which a suspension of a calcium salt is added dropwise to an aqueous phosphoric acid solution in which phosphoric acid and / or a phosphate salt is dissolved in water so that the molar ratio of Ca / P becomes 1.40 to 1.80.

[0040] In Step 1-1, the type of calcium salt used as a raw material is not particularly limited, and examples thereof include inorganic salts and organic acid salts. Specific examples of inorganic salts include calcium chloride, calcium nitrate, calcium carbonate, calcium oxide, and calcium hydroxide. Specific examples of organic acid salts include calcium formate, calcium acetate, calcium lactate, calcium gluconate, and calcium citrate.

[0041] Furthermore, in Step 1-1, the type of phosphate used as a raw material is not particularly limited, and examples thereof include alkali metal salts of phosphoric acid, ammonium salts, etc. Examples of alkali metal salts of phosphoric acid include sodium salts and potassium salts, and more specific examples include disodium hydrogen phosphate, sodium dihydrogen phosphate, trisodium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, tripotassium phosphate, diammonium hydrogen phosphate, ammonium dihydrogen phosphate, triammonium phosphate, etc.

[0042] When producing HAP powder, it is preferable to use calcium hydroxide as the calcium salt and phosphoric acid as the phosphoric acid and / or phosphate salt in step 1-1.Also, when producing β-TCP powder, or a mixed powder or mixed crystal powder of β-TCP and calcium-deficient hydroxyapatite, it is preferable to use calcium hydroxide or calcium nitrate as the calcium salt and phosphoric acid or diammonium hydrogen phosphate as the phosphoric acid and / or phosphate salt in step 1-1.

[0043] In addition, in Step 1-1, the dropping rate when the aqueous solution of phosphoric acid and / or phosphate salt is dropped into the suspension of the calcium salt may be appropriately adjusted so that the pH of the reaction solution after dropping is 9 or less.

[0044] For example, when HAP is synthesized by adding phosphoric acid and / or a phosphate to a suspension of a calcium salt, the range of phosphorus (P) atoms per mole of calcium (Ca) atoms is 0.05 to 0.7 mol / h, preferably 0.1 to 0.6 mol / h, and more preferably 0.2 mol / h. When HAP is synthesized by adding a suspension of a calcium salt to an aqueous phosphoric acid solution prepared by dissolving phosphoric acid and / or a phosphate in water, the range of calcium (Ca) atoms per mole of phosphorus (P) atoms is 0.05 to 2.0 mol / h, preferably 0.1 to 1.0 mol / h, and more preferably 0.5 to 0.6 mol / h.

[0045] For example, when phosphoric acid and / or a phosphate is added to a suspension of a calcium salt to synthesize a powder or a mixed crystal powder of β-TCP or β-TCP and calcium-deficient hydroxyapatite, the range of phosphorus (P) atoms per mole of calcium (Ca) atoms is 0.01 to 0.6 mol / h, preferably 0.1 to 0.4 mol / h, more preferably 0.2 to 0.3 mol / h. When a suspension of a calcium salt is added to an aqueous phosphoric acid solution in which phosphoric acid and / or a phosphate is dissolved in water to synthesize β-TCP, the range of calcium (Ca) atoms per mole of phosphorus (P) atoms is 0.05 to 1.8 mol / h, preferably 0.1 to 1.0 mol / h, more preferably 0.5 to 0.6 mol / h.

[0046] In step 1-1, the amount of aqueous solution of phosphoric acid and / or phosphate salt or suspension of calcium salt added can be appropriately determined depending on the type of calcium phosphate to be produced so that the Ca / P molar ratio at the end of the addition is within the range of 1.40 to 1.80. For example, when producing HAP powder, the Ca / P molar ratio at the end of the addition is preferably set to 1.0 to 2.5, more preferably 1.5 to 1.8, and even more preferably about 1.67. When producing β-TCP powder or a mixed powder or mixed crystal powder of β-TCP and calcium-deficient hydroxyapatite, the Ca / P molar ratio at the end of the addition is preferably set to 0.5 to 2.0, more preferably 1.0 to 1.7, and even more preferably about 1.50.

[0047] In Step 1-1, the temperature (reaction temperature) at which the calcium salt and phosphoric acid and / or phosphate salt are allowed to coexist may be appropriately set depending on the drop amount, drop rate, etc., and may be, for example, 30°C or higher, preferably 40 to 100°C, more preferably 80 to 100°C, and even more preferably 90 to 100°C. To more efficiently react the calcium ions and phosphate ions and generate a reaction solution, it is desirable to allow the entire amount of the calcium salt and phosphoric acid and / or phosphate salt to coexist and then age the solution under the above-mentioned temperature conditions. In the present invention, "aging" refers to leaving the solution standing or under stirring for a certain period of time. The ageing time in Step 1-1 may be appropriately set depending on the drop amount, drop rate, reaction temperature, etc., and may be, for example, 10 minutes or more, preferably 10 to 120 minutes, and even more preferably 30 to 90 minutes. Here, the "aging time" refers to the time during which the solution is left standing or under stirring, with the time when the calcium salt and the total amounts of phosphoric acid and / or phosphate salts coexist in water being designated as 0 minutes. For example, in the case of adding an aqueous solution of phosphoric acid and / or phosphate salts dropwise to a suspension of a calcium salt, the time is calculated with the time when the dropwise addition of the aqueous solution of phosphoric acid and / or phosphate salts is completed designated as 0 minutes.

[0048] By carrying out step 1-1 in this manner, a reaction liquid in which calcium phosphate is produced is obtained.

[0049] In step 1-2, the calcium phosphate obtained in step 1-1 is wet-pulverized to obtain a slurry (wet-pulverized product).

[0050] In step 1-2, the reaction solution after step 1-1 may be subjected to wet pulverization as it is, or a concentrated solution obtained by concentrating the reaction solution after step 1-1, or a suspension obtained by recovering calcium phosphate from the reaction solution after step 1-1 by dehydration, washing with water, or the like and suspending it in an organic solvent such as water or alcohol, may also be subjected to wet pulverization.

[0051] In Step 1-2, the wet-pulverization method is not particularly limited, and may be any of impact, shear, grinding, compression, vibration, etc. The type of wet-pulverization apparatus is also not particularly limited, and may be any of high-pressure fluid impingement mills, high-speed rotary slit mills, attritors, ball mills, bead mills, roll mills, ring-shaped grinding media mills, and high-speed rotating thin film mills. These apparatuses themselves may be publicly known or commercially available. Among these wet-pulverization apparatuses, a bead mill is preferably used.

[0052] When a bead mill is used as the wet-pulverizing device, the type of beads is not particularly limited, but beads made of a zirconia-based material are preferred. The size of the beads may be, for example, about 0.1 to 3 mm in diameter. The amount of beads to be packed may be appropriately set depending on the size of the device used, and may be appropriately adjusted, for example, within the range of about 50 to 90% by volume.

[0053] In step 1-2, the degree of wet-milling may be adjusted as appropriate, but from the viewpoint of efficiently producing the calcium phosphate powder of the present invention, it is desirable to adjust the degree of wet-milling so that the calcium phosphate powder after wet-milling has an average particle size of 10 μm or less, preferably 0.1 to 5 μm, and a maximum particle size of 50 μm or less, preferably 0.1 to 30 μm. In the present invention, the "average particle size" and "maximum particle size" of the calcium phosphate powder after wet-milling are the particle size (median size) and maximum particle size, respectively, at which the cumulative degree is 50% in a volume-accumulated particle size distribution measured using a laser diffraction / scattering particle size distribution analyzer.

[0054] In Step 1-2, the liquid temperature during wet grinding is not particularly limited and may be appropriately set depending on the heat resistance of the equipment used, but may be, for example, about 0 to 100°C, preferably about 5 to 60°C.

[0055] In step 1-3, the slurry obtained in step 1-2 is subjected to hydrothermal treatment (also referred to as hydrothermal synthesis) to obtain a hydrothermal treated product. The solids concentration of the slurry to be subjected to hydrothermal treatment is not particularly limited, but is usually about 1 to 30% by weight, more preferably about 5 to 20% by weight. When adjusting the solids concentration in the slurry to be subjected to hydrothermal treatment, the slurry obtained in step 1-2 can be dehydrated and washed with water, and then resuspended to the desired solids concentration.

[0056] The hydrothermal treatment in step 1-3 can be carried out using a known apparatus such as an autoclave.

[0057] The temperature for the hydrothermal treatment in step 1-3 may be 250° C. to 300° C., preferably 260 to 280° C. If the temperature for the hydrothermal treatment in step 1-3 is below 250° C., the calcium phosphate powder produced will not satisfy the above-mentioned physical properties, and the calcium phosphate powder of the present invention will not be obtained.

[0058] The time for the hydrothermal treatment in step 1-3 may be a time sufficient for producing the desired calcium phosphate, and is usually about 1 to 5 hours, preferably about 1 to 3 hours. In the present invention, the "time for the hydrothermal treatment" refers to the time required to reach the temperature for the hydrothermal treatment, and does not include the time required for heating up to the temperature for the hydrothermal treatment or the time required for cooling down after the hydrothermal treatment.

[0059] In step 1-4, the hydrothermally treated product obtained in step 1-3 is dried to obtain calcium phosphate powder.

[0060] The drying method used in Step 1-4 is not particularly limited, and examples thereof include tray drying, spray drying, box drying, band drying, vacuum drying, freeze drying, microwave drying, drum dryer, fluidized bed drying, etc. Among these, tray drying is preferred.

[0061] The drying temperature in Step 1-4 is not particularly limited, but may be, for example, about 30 to 150°C, and preferably about 80 to 105°C.

[0062] The calcium phosphate powder obtained after step 1-4 may be subjected to a calcination treatment, if necessary. The temperature conditions for the calcination treatment are not particularly limited, but are usually 200 to 1300°C, preferably 200 to 800°C, more preferably 350 to 750°C, and even more preferably 300 to 600°C. The calcination treatment time may be appropriately set in consideration of the calcination temperature within a range that allows calcium phosphate powder having the above-mentioned physical properties to be obtained. It is sufficient that the above temperature conditions are reached even for a moment, but the time for which the above temperature conditions are maintained is preferably 0.1 to 10 hours, and more preferably 1 to 5 hours.

[0063] Furthermore, after step 1-4 or the firing treatment, the calcium phosphate powder may be subjected to treatment such as crushing or pulverization, if necessary, for the purpose of adjusting the particle size. Furthermore, it is desirable to use a sieve to remove particles with large particle sizes that do not meet the physical properties described above from the calcium phosphate powder after step 1-4 or the firing treatment. The mesh size of the sieve used is not particularly limited, but may be, for example, 150 μm or less, preferably 100 to 40 μm.

[0064] Next, the second method will be specifically described.

[0065] In step 2-1, a calcium phosphate synthesis reaction is carried out by reacting calcium ions with phosphate ions using a wet method in which a suspension of a calcium salt and an aqueous phosphoric acid solution in which phosphoric acid and / or a phosphate salt is dissolved in water are simultaneously added dropwise to an aqueous medium so that the Ca / P molar ratio becomes 1.40 to 1.80.

[0066] In step 2-1, the types of calcium salts and phosphates used as raw materials, the preferred raw materials when producing HAP powder, and the preferred raw materials when producing β-TCP powder or a mixed powder or mixed crystal powder of β-TCP and calcium-deficient hydroxyapatite are the same as those in step 1-1.

[0067] In the step 2-1, the aqueous medium to be dropped is preferably water.

[0068] In step 2-1, the amounts of the suspension of calcium salt and the aqueous phosphoric acid solution in which phosphoric acid and / or a phosphate salt is dissolved in water to be added dropwise may be appropriately set depending on the type of calcium phosphate to be produced so that the Ca / P molar ratio at the end of the addition is within the range of 1.40 to 1.80. The preferred Ca / P molar ratios for producing HAP powder and for producing β-TCP powder or a mixed powder or mixed crystal powder of β-TCP and calcium-deficient hydroxyapatite are the same as those in step 1-1.

[0069] In step 2-1, the dropwise addition rates of the calcium salt suspension and the phosphoric acid aqueous solution in which phosphoric acid and / or a phosphate salt is dissolved in water are not particularly limited and may be adjusted appropriately depending on the scale of production, for example, so that the pH of the reaction solution during dropwise addition is 5 to 9. In step 2-1, the dropwise addition rates of the phosphoric acid and / or a phosphate salt aqueous solution and the calcium salt suspension may be appropriately set depending on the type of calcium phosphate to be produced so that the Ca / P molar ratio at the end of dropwise addition is within the range of 1.40 to 1.80. For example, in the case of producing HAP powder, the Ca / P molar ratio at the end of dropwise addition is preferably set to 1.0 to 2.5, more preferably 1.5 to 1.8, and even more preferably about 1.67. Furthermore, when producing β-TCP powder or a mixed powder or mixed crystal powder of β-TCP and calcium-deficient hydroxyapatite, the Ca / P molar ratio at the end of the dropping is preferably set to 0.5 to 2.0, more preferably 1.0 to 1.7, and even more preferably about 1.50.

[0070] In step 2-1, the temperature (reaction temperature) when the calcium salt and phosphoric acid and / or phosphate salt are allowed to coexist is the same as in step 1-1.

[0071] In step 2-1, it is preferable to carry out aging at a predetermined reaction temperature. The aging time is the same as in step 1-1.

[0072] In step 2-2, the reaction solution obtained in step 2-1 is wet-pulverized to obtain a slurry (wet-pulverized product). In step 2-2, the wet-pulverization method, the degree of wet-pulverization, the liquid temperature during wet-pulverization, etc. are the same as in step 1-2.

[0073] In step 2-3, the slurry obtained in step 2-2 is hydrothermally treated to obtain a hydrothermal treated product. In step 2-3, the solids concentration of the slurry to be subjected to the hydrothermal treatment, the hydrothermal treatment equipment, etc. are the same as in step 1-3. The temperature of the hydrothermal treatment in step 2-3 may be 150°C to 300°C, preferably 200 to 300°C, and more preferably 200 to 280°C. The time of the hydrothermal treatment in step 2-3 is the same as in step 1-3.

[0074] In step 2-4, the hydrothermally treated product obtained in step 2-3 is dried to obtain calcium phosphate powder.

[0075] In step 2-4, the drying method, drying temperature, etc. are the same as in step 1-4.

[0076] The calcium phosphate powder obtained after step 2-4 may be subjected to a calcination treatment, if necessary. The temperature conditions for the calcination treatment are the same as in the first method. Furthermore, after step 2-4 or the calcination treatment, the calcium phosphate powder may be subjected to treatments such as crushing, pulverization, or sieving, if necessary, for the purpose of adjusting the particle size. In the case of sieving, the mesh size of the sieve used is the same as in the first method.

[0077] Next, the third method will be specifically described.

[0078] In step 3-1, a calcium phosphate synthesis reaction is carried out by reacting calcium ions with phosphate ions using a wet method in which a suspension of a calcium salt and an aqueous phosphoric acid solution in which phosphoric acid and / or a phosphate salt is dissolved in water are simultaneously added dropwise to an aqueous medium at 80°C or higher so that the Ca / P molar ratio becomes 1.40 to 1.80.

[0079] In step 3-1, the types of calcium salts and phosphates used as raw materials, the preferred raw materials when producing HAP powder, and the preferred raw materials when producing β-TCP powder or a mixed powder or mixed crystal powder of β-TCP and calcium-deficient hydroxyapatite are the same as those in step 1-1.

[0080] In step 3-1, the temperatures of the suspension of calcium salt used as a raw material and the aqueous phosphoric acid solution prepared by dissolving phosphoric acid and / or a phosphate salt in water may both be set to 50°C or lower, preferably 40°C or lower, more preferably 30°C or lower, and particularly preferably 1 to 30°C.

[0081] In the step 3-1, the aqueous medium to be dropped is preferably water.

[0082] In the step 3-1, the temperature of the aqueous medium may be set to 80°C or higher, preferably 90°C or higher, more preferably 95°C or higher, and particularly preferably 95°C to 100°C.

[0083] In step 3-1, the amounts of the suspension of calcium salt and the aqueous phosphoric acid solution in which phosphoric acid and / or a phosphate salt is dissolved in water to be added can be appropriately set depending on the type of calcium phosphate to be produced so that the Ca / P molar ratio at the end of the addition is within the range of 1.40 to 1.80. The preferred Ca / P molar ratios for producing HAP powder and for producing β-TCP powder or a mixed powder or mixed crystal powder of β-TCP and calcium-deficient hydroxyapatite are the same as those in step 1-1.

[0084] In step 3-1, the rate of simultaneous dropwise addition of the calcium salt suspension and the phosphoric acid aqueous solution in which phosphoric acid and / or a phosphate salt is dissolved in water may be set so that the pH of the reaction solution during dropwise addition is 8.5 to 9.5 or 3.5 to 4.5. Specifically, when producing HAP powder, the rate of simultaneous dropwise addition may be set so that the pH of the reaction solution during dropwise addition is 8.5 to 9.5. Furthermore, when producing β-TCP powder or a mixed powder or mixed crystal powder of β-TCP and calcium-deficient hydroxyapatite, the rate of simultaneous dropwise addition may be set so that the pH of the reaction solution during dropwise addition is 3.5 to 4.5.

[0085] In step 3-1, the amount of aqueous solution of phosphoric acid and / or phosphate salt added and the amount of suspension containing a calcium salt added simultaneously may be appropriately determined depending on the type of calcium phosphate to be produced so that the Ca / P molar ratio at the end of the addition is within the range of 1.40 to 1.80. For example, when producing HAP powder, the Ca / P molar ratio at the end of the addition is preferably set to 1.0 to 2.5, more preferably 1.5 to 1.8, and even more preferably about 1.67. When producing β-TCP powder, or a mixed powder or mixed crystal powder of β-TCP and calcium-deficient hydroxyapatite, the Ca / P molar ratio at the end of the addition is preferably set to 0.5 to 2.0, more preferably 1.0 to 1.7, and even more preferably about 1.50.

[0086] In step 3-1, the temperature (reaction temperature) when the calcium salt and phosphoric acid and / or phosphate salt are allowed to coexist should be 80°C or higher, preferably 90°C or higher, more preferably 95°C or higher, and particularly preferably 95°C to 100°C.

[0087] In step 3-1, it is preferable to carry out aging at a predetermined reaction temperature. The aging time is the same as in step 1-1.

[0088] In step 3-2, the reaction solution obtained in step 3-1 is dried to obtain calcium phosphate powder. In step 3-2, the drying method, drying temperature, etc. are the same as in step 1-4.

[0089] The calcium phosphate powder obtained after step 3-2 may be subjected to a calcination treatment, if necessary. The temperature conditions for the calcination treatment are the same as in the case of the first method. Furthermore, after step 3-2 or the calcination treatment, the calcium phosphate powder may be subjected to treatments such as wet grinding, crushing or pulverization, sieving, etc., if necessary, for the purpose of adjusting the particle size. In the case of wet grinding, the wet grinding method, the degree of wet grinding, the liquid temperature during wet grinding, etc. are the same as in the case of step 1-2. In the case of sieving, the mesh size of the sieve used is the same as in the case of the first method.

[0090] [Applications / Additive Manufacturing Materials] The calcium phosphate powder of the present invention is not particularly limited in its use, but is preferably used as a material for additive manufacturing. In the present invention, the term "material for additive manufacturing" refers to a substance that serves as a base material for a three-dimensional additive manufacturing product.

[0091] When the calcium phosphate powder of the present invention is used as a material for additive manufacturing, it may be applied to either a stereolithography method or a powder additive manufacturing method, but is suitable as an additive manufacturing material for stereolithography.

[0092] When the calcium phosphate powder of the present invention is used as an additive manufacturing material for stereolithography, a slurry for additive manufacturing (modeling paste) containing the calcium phosphate of the present invention and a photocurable resin (ultraviolet curable resin) can be prepared and subjected to stereolithography.

[0093] The content of the calcium phosphate powder of the present invention contained in the slurry for additive manufacturing may be within a range that allows the slurry for additive manufacturing to exhibit thixotropy, and may be, for example, 40 to 90% by weight, preferably 60 to 90% by weight, and more preferably 70 to 85% by weight.

[0094] The type of photocurable resin used in the slurry for additive manufacturing is not particularly limited, but examples thereof include acrylic photocurable resins, etc. The content of the photocurable resin in the slurry for additive manufacturing is 5 to 60% by weight, preferably 5 to 57% by weight, and more preferably 6 to 24% by weight.

[0095] The additive manufacturing slurry may also contain a photopolymerization initiator, a dispersant (such as a polycarboxylic acid), a thickener, an antioxidant, a light stabilizer, and the like, as long as the effects of the present invention are not impaired. When the additive manufacturing slurry contains a photopolymerization initiator, the content is not particularly limited, but may be, for example, 0.5 to 15% by weight, and preferably 0.5 to 10% by weight. When the additive manufacturing slurry contains a dispersant, the content is not particularly limited, but may be, for example, 0.1 to 50% by weight, and preferably 8 to 40% by weight.

[0096] To produce a three-dimensional layered object by stereolithography using a slurry for layered manufacturing containing the calcium phosphate powder of the present invention, the following steps (1) to (4) may be carried out. (1) forming a slurry layer using the additive manufacturing slurry; (2) a step of irradiating the slurry layer with laser light in a predetermined pattern to harden it; (3) repeating the steps (1) and (2) to form a three-dimensional laminated cured product; and (4) removing the uncured resin and the cured resin from the three-dimensional laminated cured product.

[0097] In the step (1), the thickness of the slurry layer may be adjusted to, for example, about 5 to 200 μm. The type of laser light used in the step (2) may be any type that can cure the photocurable resin, such as an ultraviolet laser.

[0098] In the step (4) above, the uncured resin can be removed by washing with, for example, ethanol.

[0099] In the step (4), the cured resin can be removed by, for example, degreasing. The "degreasing" is a process for removing the cured resin by heating. The degreasing process can be performed using an electric furnace or the like that can be heated.

[0100] The temperature conditions for the degreasing treatment are not particularly limited, but are usually 100 to 600° C., and preferably 300 to 600° C. The degreasing treatment time may be appropriately set within a range that allows removal of the cured resin, but is usually in the range of 1 to 100 hours, preferably 10 to 50 hours, and more preferably 10 to 20 hours.

[0101] Furthermore, in order to increase the strength of the three-dimensional additive manufacturing product, a sintering process may be carried out after the step (4) above. The same equipment as used in the degreasing process can be used for the sintering process. The temperature conditions for the sintering treatment are not particularly limited, but are usually 600 to 1500° C., preferably 800 to 1500° C., more preferably 1000 to 1400° C., and particularly preferably 1100 to 1300° C. The sintering treatment time may be appropriately set taking into consideration the degreasing treatment, and is usually 1 to 12 hours, preferably 1 to 5 hours.

[0102] Furthermore, the three-dimensional laminated cured product may be subjected to a debinding treatment and a sintering treatment in a series of operations. When the debinding treatment and the sintering treatment are performed in a series of operations, the temperature conditions of the electric furnace or the like may be set in stages. For example, by setting the temperature conditions and holding time of the debinding treatment to be met, followed by raising the temperature and maintaining the temperature conditions and holding time of the sintering treatment, the debinding of the cured resin and the sintering of the calcium phosphate powder can be performed in a series of operations.

[0103] Three-dimensional additive manufacturing products produced using the calcium phosphate powder of the present invention are used as implants such as artificial joints, artificial tooth roots, and artificial bones. Furthermore, because the three-dimensional objects produced using the calcium phosphate powder of the present invention have high strength, they can be suitably used as artificial bones for sites that are subject to heavy loads, such as the femur. [Example]

[0104] The present invention will be explained in more detail below by showing examples, but the present invention is not limited to these examples.

[0105] 1. Preparation and evaluation of calcium phosphate powder 1-1. Manufacturing of calcium phosphate powder Example 1 1200.0 g of a 20 wt% calcium hydroxide suspension and 742.1 g of a 32 wt% aqueous phosphoric acid solution were prepared so that the Ca / P molar ratio was 1.67. Each solution was preheated to 80°C and added dropwise simultaneously over 1 hour to 1785.0 mL of water preheated to 98°C and stirred at 300 rpm, while maintaining the temperature at 98°C and the pH of the reaction solution in the range of 7.0 to 7.5. After the addition was completed, the mixture was stirred for an additional 30 minutes to mature, and the precipitated hydroxyapatite crystals were filtered and washed with water.

[0106] The hydroxyapatite was then suspended in water to a concentration of 10 wt% and wet-pulverized using an Ultra Apex Mill (Kotobuki Industries Co., Ltd., UAM-015) at 41.6 Hz, a pump speed of 2, zirconia bead diameter of 0.3 mm, and a bead amount of 400 g (64% loading). The resulting solution was then hydrothermally treated in an autoclave (Taiatsu Glass Industries Co., Ltd., TAS-09-20-300) at 200 °C for 3 hours. The solution was then tray-dried at 100 °C using a constant-temperature incubator (Yamato Scientific Co., Ltd., DKM400), and dry-pulverized using a micropulverizer (Hosokawa Micron Corporation, AP-B) to obtain calcium phosphate (HAP) particles.

[0107] Example 2 1200.0 g of a 20 wt% calcium hydroxide suspension and 742.1 g of a 32 wt% aqueous phosphoric acid solution were prepared so that the Ca / P molar ratio was 1.67. Each solution was preheated to 80°C and added dropwise over 1 hour to 1785.0 mL of water preheated to 98°C and stirred at 300 rpm, while maintaining the temperature at 98°C and the pH of the reaction solution in the range of 7.0 to 7.5. After the addition was completed, the mixture was stirred for an additional 30 minutes to mature.

[0108] The precipitated hydroxyapatite crystals were then wet-pulverized using an Ultra Apex Mill (Kotobuki Industries Co., Ltd., UAM-015) at 41.6 Hz, a pump speed of 2, zirconia bead diameter of 0.3 mm, and a bead amount of 400 g (64% loading). The resulting solution was then hydrothermally treated in an autoclave (Taiatsu Glass Industries Co., Ltd., TAS-09-20-300) at 280 °C for 3 hours. The solution was then dried on trays at 100 °C using a constant-temperature incubator (Yamato Scientific Co., Ltd., DKM400), followed by dry-pulverization using a micropulverizer (Hosokawa Micron Corporation, AP-B) to obtain calcium phosphate (HAP) particles.

[0109] Example 3 3514.1 g of an 8.4 wt% calcium hydroxide suspension and 464.5 g of a 50 wt% aqueous phosphoric acid solution were prepared so that the Ca / P molar ratio was 1.67. Phosphoric acid was added dropwise over 3 hours to the calcium hydroxide suspension heated to 95°C and stirred at 300 rpm, and then the suspension was aged for an additional 1 hour with stirring.

[0110] The mixture was then wet-pulverized using an Ultra Apex Mill (Kotobuki Industries Co., Ltd., UAM-015) at 41.6 Hz, a pump speed of 2, a zirconia bead diameter of 0.3 mm, and a bead amount of 400 g (64% loading). The resulting solution was then hydrothermally treated in an autoclave (Taiatsu Glass Industries Co., Ltd., TAS-09-20-300) at 280 °C for 3 hours. The mixture was then tray-dried at 100 °C using a constant-temperature incubator (Yamato Scientific Co., Ltd., DKM400), and dry-pulverized using a micropulverizer (Hosokawa Micron Corporation, AP-B) to obtain calcium phosphate (HAP) particles.

[0111] Example 4 The HAP particles obtained in Example 2 were fired at 600°C for 3 hours (heating rate 100°C / h) using an electric furnace (Kusaba Chemical Co., Ltd., KY-5NX) to obtain calcium phosphate (HAP) particles.

[0112] Example 5 Calcium phosphate (HAP) particles were obtained under the same conditions as in Example 4, except that the firing temperature was changed to 300°C.

[0113] Example 6 92.5 kg of a 20 wt % calcium hydroxide suspension and 45.7 kg of a 32 wt % aqueous phosphoric acid solution were prepared so that the Ca / P molar ratio was 1.67. Each solution was simultaneously added dropwise over 1 hour to 112.5 kg of water heated to 98°C, while adjusting the pH of the reaction solution to maintain it in the range of 8.5 to 9.5. After the addition was completed, the mixture was stirred for an additional 30 minutes to age, then filtered and washed with water.

[0114] The resulting powder was then dried on trays at 100°C using a constant temperature incubator (Yamato Scientific Co., Ltd., DKN812) and dry-pulverized using a Comil (Powrex Corporation, QUADRO COMIL 194) and an ACM pulverizer (Hosokawa Micron Corporation, 10A) to obtain calcium phosphate powder. The crystal structure of the resulting calcium phosphate powder was analyzed by X-ray diffraction, and it was confirmed to be hydroxyapatite (HAP), as shown in Figure 1.

[0115] Example 7 92.5 kg of a 20 wt % calcium hydroxide suspension and 45.7 kg of a 32 wt % aqueous phosphoric acid solution were prepared so that the Ca / P molar ratio was 1.67. Each solution was simultaneously added dropwise over 1 hour to 112.5 kg of water heated to 98°C, while adjusting the pH of the reaction solution to maintain it in the range of 8.5 to 9.5. After the addition was completed, the mixture was stirred for an additional 30 minutes to mature, then filtered and washed with water.

[0116] The calcium phosphate powder was then suspended in water to a concentration of 10% by weight and wet-milled using a Dynomill (Shinmaru Enterprises, MULTI LAB model) at 20 rpm with 1.0 mm zirconia bead diameter and 4.03 kg bead weight (80% loading). The suspension was then shelf-dried at 100°C using a constant-temperature incubator (Yamato Scientific, DKN812) and dry-milled using a micropulverizer (Hosokawa Micron, AP-B) to obtain calcium phosphate powder. The crystal structure of the resulting calcium phosphate powder was analyzed by X-ray diffraction, confirming its identity as hydroxyapatite (HAP), as shown in Figure 2.

[0117] Example 8 90.0 kg of a 20 wt % calcium hydroxide suspension and 49.6 kg of a 32 wt % aqueous phosphoric acid solution were prepared so that the Ca / P molar ratio was 1.50. Each solution was simultaneously added dropwise over 1 hour to 111.5 kg of water heated to 98°C, while adjusting the pH of the reaction solution to maintain it in the range of 3.5 to 4.5. After the addition was completed, the mixture was stirred for an additional 30 minutes to mature, then filtered and washed with water.

[0118] The mixture was then tray-dried at 100°C using a constant-temperature incubator (Yamato Scientific Co., Ltd., DKN812) and dry-pulverized using a Comil (Powrex Corporation, QUADRO COMIL 194) and a micropulverizer (Hosokawa Micron Corporation, AP-B). It was then fired at 650°C for 3 hours (heating rate: 100°C / h) using an electric furnace (Kitamura Electric Furnace Manufacturing Co., Ltd., rectangular electric furnace for oxidation firing, KSO-40 type, top lid lift-up type). After cooling, it was dry-pulverized using an ACM pulverizer (Hosokawa Micron Corporation, 10A) to obtain calcium phosphate powder. The crystal structure of the resulting calcium phosphate powder was analyzed by X-ray diffraction, revealing peaks corresponding to hydroxyapatite (49 wt%) and β-TCP (51 wt%), as shown in Figure 3. Furthermore, as described below, when the crystalline structure of a 3D additive manufacturing object obtained by sintering an additive manufacturing slurry using the obtained calcium phosphate powder at 1100°C was analyzed by X-ray diffraction, only a β-TCP peak was observed, and no hydroxyapatite peak was observed, as shown in Figure 7. This indicates that the hydroxyapatite peak observed in Figure 3 is the peak of calcium-deficient hydroxyapatite, which undergoes a structural change upon heat treatment. These analysis results confirmed that the obtained calcium phosphate powder was a mixed crystal consisting of 49% by weight of calcium-deficient hydroxyapatite and 51% by weight of β-TCP.

[0119] Example 9 90.0 kg of a 20 wt % calcium hydroxide suspension and 49.6 kg of a 32 wt % aqueous phosphoric acid solution were prepared so that the Ca / P molar ratio was 1.50. Each solution was simultaneously added dropwise over 1 hour to 111.5 kg of water heated to 98°C, while adjusting the pH of the reaction solution to maintain it in the range of 3.5 to 4.5. After the addition was completed, the mixture was stirred for an additional 30 minutes to mature, then filtered and washed with water.

[0120] The mixture was then tray-dried at 100°C using a constant-temperature incubator (Yamato Scientific Co., Ltd., DKN812) and dry-ground using a Comil (Powrex Corporation, QUADRO COMIL 194) and a micropulverizer (Hosokawa Micron Corporation, AP-B). It was then calcined at 750°C for 3 hours (heating rate: 100°C / h) using an electric furnace (Kusaba Chemical Co., Ltd., KY-5NX). After cooling, the mixture was suspended in water to a concentration of 10 wt % and wet-ground using a Dynomill (Shinmaru Enterprises Co., Ltd., MULTI LAB type) at 20 rpm with zirconia beads of 1.0 mm diameter and 4.03 kg of beads (80% loading). The resulting powder was then dried on trays at 100°C using a constant temperature incubator (Yamato Scientific Co., Ltd., DKN812) and dry-pulverized using a micropulverizer (Hosokawa Micron Co., Ltd., AP-B) to obtain calcium phosphate (β-TCP) particles. The crystal structure of the resulting calcium phosphate powder was analyzed by X-ray diffraction, and it was confirmed to be β-TCP with a β-TCP content of 99% by weight, as shown in Figure 4.

[0121] Comparative Example 1 After 6 L of water and 1 kg of calcium oxide were added to a reaction vessel and a hydration reaction was carried out, water was added to the suspension to make a total volume of 15 L. The suspension was then heated to 50°C, and an aqueous solution of phosphoric acid was added until the pH reached 8. The resulting solution was heated at 95°C for 2 hours and aged.

[0122] The resulting reaction solution was then spray-dried using a spray dryer equipped with a disk-type atomizer, and the dried product was collected. The resulting dried product was then fired at 1,150°C for 3 hours (heating rate: 65°C / h) using an electric furnace (Kusaba Chemical Co., Ltd., KY-5NX). After cooling, the product was pulverized using an ACM pulverizer (Hosokawa Micron Corporation, 10A) to obtain calcium phosphate (HAP) particles.

[0123] Comparative Example 2 Commercially available HAP particles (Fujifilm Wako Pure Chemical Industries, Ltd., apatite HAP, monoclinic crystals) were used.

[0124] Comparative Example 3 Calcium phosphate (HAP) particles were obtained under the same conditions as in Example 3, except that the autoclave temperature was changed to 200°C.

[0125] Comparative Example 4 3514.1 g of an 8.4 wt % calcium hydroxide suspension and 464.5 g of a 50 wt % aqueous phosphoric acid solution were prepared so that the Ca / P molar ratio was 1.67. Phosphoric acid was added dropwise to the calcium hydroxide suspension at 20°C while stirring at 300 rpm over 3 hours, and the suspension was then aged with further stirring for 1 hour.

[0126] The mixture was then wet-pulverized using an Ultra Apex Mill (Kotobuki Industries Co., Ltd., UAM-015) at 41.6 Hz, a pump speed of 2, a zirconia bead diameter of 0.3 mm, and a bead amount of 400 g (64% loading). The resulting solution was then hydrothermally treated in an autoclave (Taiatsu Glass Industries Co., Ltd., TAS-09-20-300) at 280 °C for 3 hours. The mixture was then tray-dried at 100 °C using a constant-temperature incubator (Yamato Scientific Co., Ltd., DKM400), and dry-pulverized using a micropulverizer (Hosokawa Micron Corporation, AP-B) to obtain calcium phosphate (HAP) particles.

[0127] Comparative Example 5 The HAP particles obtained in Comparative Example 3 were fired at 1000°C for 3 hours (heating rate 100°C / h) using an electric furnace (Kusaba Chemical Co., Ltd., KY-5NX) and then dry-pulverized using a micropulverizer (Hosokawa Micron Corporation, AP-B) to obtain calcium phosphate (HAP) particles.

[0128] Comparative Example 6 1200.0 g of a 20 wt% calcium hydroxide suspension and 742.1 g of a 32 wt% aqueous phosphoric acid solution were prepared so that the Ca / P molar ratio was 1.67. Each solution was preheated to 80°C and added dropwise to 1785.0 mL of water preheated to 98°C and stirred at 300 rpm over 1 hour, while maintaining the temperature at 98°C and the pH of the reaction solution in the range of 7.0 to 7.5. After the addition was completed, the mixture was stirred for an additional 30 minutes for aging. The mixture was then dried on trays at 100°C using a constant-temperature incubator (Yamato Scientific Co., Ltd., DKM400) to obtain calcium phosphate (HAP) particles.

[0129] Comparative Example 7 1200.0 g of a 20 wt% calcium hydroxide suspension and 742.1 g of a 32 wt% aqueous phosphoric acid solution were prepared to a Ca / P molar ratio of 1.67. Each solution was preheated to 80°C and added dropwise over 1 hour to 1785.0 mL of water preheated to 98°C and stirred at 300 rpm, while maintaining the temperature at 98°C and the pH of the reaction solution in the range of 7.0 to 7.5. After the addition, the mixture was stirred for an additional 30 minutes. The precipitated hydroxyapatite crystals were wet-milled using an Ultra Apex Mill (Kotobuki Industries Co., Ltd., UAM-015) at 41.6 Hz, a pump speed of 2, zirconia bead diameter of 0.3 mm, and 400 g of bead weight (64% loading). Next, the mixture was dried on trays at a temperature of 100°C using a constant temperature incubator (Yamato Scientific Co., Ltd., DKM400), and then dry-pulverized using a micropulverizer (Hosokawa Micron Co., Ltd., AP-B) to obtain calcium phosphate (HAP) particles.

[0130] 1-2. Method for evaluating the physical properties of calcium phosphate powder The average particle size, particle size distribution, number-average particle size, pore volume (gas adsorption method), BET specific surface area, average pore size (gas adsorption method), loose bulk density, compacted bulk density, crystalline structure, and content of each calcium phosphate powder were evaluated using the following methods.

[0131] [Average particle size, particle size distribution, number average diameter] A suspension was prepared by adding 0.4 g of calcium phosphate powder and 0.02 g of a dispersant (product name "Cerna D-305" (manufactured by Chukyo Yushi Co., Ltd.)) to 5 g of water, and the suspension was dispersed in water. The particle size distribution was measured using a laser diffraction / scattering particle size distribution analyzer (Microtrac-Bell Corporation, Microtrac MT3300EXII), and the D10 (particle size at which the cumulative degree is 10%), D50 (average particle size), D90 (particle size at which the cumulative degree is 90%), and number-average particle size (particle size at which the cumulative degree is 50% by number calculation) were determined.

[0132] [Mesopore (2-50 nm) pore volume (gas adsorption method)] The pore volume of mesopores (2-50 nm) was determined using a high-speed specific surface area pore distribution analyzer (Quantachrome Corporation, NOVA-4000) as follows: First, 0.1 g or 1.0 g of calcium phosphate powder was accurately weighed, sealed in an adsorption tube, and degassed at 105°C for 3 hours. Next, the nitrogen gas adsorption isotherm was determined at liquid nitrogen gas temperature, and the pore volume (cc / g) of mesopores (2-50 nm) was calculated using the BJH method.

[0133] [Macropore (50-200 nm) pore volume (gas adsorption method)] The macropore volume (50-200 nm) was determined using a high-speed specific surface area pore distribution analyzer (Quantachrome Corporation, NOVA-4000) as follows: First, 0.1 g or 1.0 g of calcium phosphate powder was accurately weighed, sealed in an adsorption tube, and degassed at 105°C for 3 hours. Next, the nitrogen gas adsorption isotherm was determined at liquid nitrogen gas temperature, and the macropore volume (cc / g) of the macropores (50-200 nm) was calculated using the BJH method.

[0134] [BET specific surface area] The BET specific surface area was measured using a high-speed specific surface area pore distribution analyzer (Quantachrome Corporation, NOVA-4000) under the following operating conditions. Pretreatment: 0.1 g or 1.0 g of calcium phosphate powder was accurately weighed, sealed in an adsorption tube, and degassed at 105°C for 3 hours. Measurement and analysis: The adsorption isotherm of nitrogen gas was determined at the temperature of liquid nitrogen gas, and the specific surface area (m 2 / g) was calculated.

[0135] [Average pore diameter] First, the total pore volume was measured by gas adsorption method using a high-speed specific surface area pore distribution analyzer (Quantachrome Corporation, NOVA-4000) under the following operating conditions. Pretreatment: 0.1 g or 1.0 g of calcium phosphate powder was accurately weighed, sealed in an adsorption tube, and degassed at 105°C for 3 hours. Measurement and analysis: The adsorption isotherm of nitrogen gas was determined at liquid nitrogen gas temperature, and the total pore volume (cc / g) was calculated from the amount of gas adsorbed at a relative pressure P / P0 (P0: saturated vapor pressure) of 0.995.

[0136] Using the BET specific surface area and total pore volume (gas adsorption method) obtained above, the average pore diameter (gas adsorption method) was calculated according to the following formula. Average pore diameter (nm)=4V / S×1000 V: Total pore volume (gas adsorption method) (cc / g) S:BET specific surface area (m 2 / g)

[0137] [Loose bulk density] Using a powder tester (Hosokawa Micron Corporation, PT-X), select the "loose bulk density" of the device and measure the volume of the cup with a capacity of 10 cm. 3The conditions were a sieve with a mesh size of 710 μm, a vibration time of 50 seconds, and an amplitude of 0.5 mm. The powder was stopped from falling when it overflowed from the cup. The powder piled up on the cup was scraped off, and the weight of the empty cup was subtracted from the weight of the cup containing the powder to determine the weight of 1 cm. 3 The weight of the powder per unit area was determined and used as the loose bulk density (g / mL).

[0138] [Tapped density (tapped density)] After measuring the loose bulk density, a cylinder (inner diameter 2.2 cm, height 3.2 cm) for measuring tap density was attached to the top of the cup according to the instructions on the apparatus. Next, calcium phosphate powder was dropped into the cylinder through a sieve with a mesh size of 710 μm, vibrating at an amplitude of 0.5 mm, and the cylinder was filled with calcium phosphate powder up to about 80% of its capacity. Tapping was started in this state, and a total of 180 tappings were performed. During tapping, when the amount of calcium phosphate powder in the cylinder was compressed to about 20% of its capacity, calcium phosphate powder was dropped into the cylinder again through a sieve with a mesh size of 710 μm, vibrating at an amplitude of 0.5 mm, according to the instructions on the apparatus, to replenish the cylinder with calcium phosphate powder up to about 80% of its capacity. After tapping was completed, the cylinder was removed, the powder piled up on the cup was leveled off, and the weight of the cup containing the powder was measured. The weight of the empty cup was subtracted from this weight to calculate the weight of the powder in the cup, and the weight of the powder in the cup was calculated. 3 The powder weight per unit was determined and used as the compacted bulk density (g / mL).

[0139] [Crystal structure] Measurements were performed using an X-ray diffraction apparatus (Rigaku Corporation, SmartLab) under the following conditions: tube: Cu, tube voltage: 40 kV, tube current: 30 mA, scan axis 2θ / θ, scan mode: continuous, range specification: absolute, scan range: 2θ = 20 to 40°, scan speed / counting time: 4.0° / min, step width: 0.02°, entrance slit: 2 / 3°, longitudinal limiting slit: 10 mm, receiving slit 1: 10 mm, receiving slit 2: 10 mm, detector: D / teX Ultra).

[0140] [content] The contents of β-TCP and HAP were measured based on the crystal structure measurement results using the RIR method (Reference Intensity Ratio) of the integrated powder X-ray analysis software PDXL2. The DB card numbers used were 2128 for β-TCP and 01-076-0694 for HAP.

[0141] 2. Production and evaluation of slurry for additive manufacturing 2-1. Manufacturing slurry for additive manufacturing 20.0 g of calcium phosphate powder was accurately weighed and placed in a container for agitation and degassing equipment. Next, a mixed solution of ultraviolet-curable resin and dispersant was added and stirred using a stirrer and degassing equipment. For the calcium phosphate particles in Examples 1 to 5, 7, and 9 and Comparative Examples 1 to 7, a mixed solution of ultraviolet-curable resin (SK Fine Corporation, acrylic photocurable resin for the SZ series) and dispersant (SK Fine Corporation, polycarboxylic acid-based dispersant) was used. For the calcium phosphate particles in Examples 6 and 8, a mixed solution of ultraviolet-curable resin (SK Fine Corporation, acrylic photocurable resin for the SZ series) and dispersant (SK Fine Corporation, polycarboxylic acid-based dispersant, fatty acid amide-based dispersant) was used. The addition of the mixed solution was stopped when fluidity was achieved, and a slurry for additive manufacturing was obtained. The point at which fluidity was achieved refers to the point at which the mixed solution was added to form a slurry, and the point at which the aggregation of the calcium phosphate powder ceased due to the addition of the mixed solution.

[0142] The concentration (wt%) of calcium phosphate powder in the additive manufacturing slurry was calculated from the ratio of the weight of calcium phosphate powder to the weight of the additive manufacturing slurry, and the concentration (volume%) of calcium phosphate powder in the additive manufacturing slurry was calculated by dividing the volume of calcium phosphate powder by the volume of the additive manufacturing slurry (weight (g) of calcium phosphate powder / true density of HAP powder (3.2 g / cm 3 ) or the true density of β-TCP powder (3.1 g / cm 3 )) was obtained.

[0143] 2-2. Evaluation method for the physical properties of slurry for additive manufacturing A 10-14 mL aliquot was taken from the obtained AM slurry and placed in a 15 mL centrifuge tube A. The aliquot was then placed in a 15 mL centrifuge tube B and allowed to stand for three days. After the aliquot was placed in the centrifuge tube A, the separated liquid was transferred to another 15 mL centrifuge tube B. The resulting volume was designated as the separated liquid volume X. Then, the centrifuge tube A was tilted 45°, and the non-thixotropic liquid that had fallen from the centrifuge tube A was placed in the separated tube B. The aliquot was then allowed to stand for two hours. After two hours of standing, no further liquid was confirmed to have fallen, and the remaining liquid in the centrifuge tube A, which exhibited powder agglomeration, was designated as the sedimentation liquid volume Y. After this operation, the remaining liquid in the centrifuge tube A, which exhibited powder agglomeration, lost its fluidity due to the solids settling. If used in AM, this liquid may separate within the AM machine, potentially resulting in uneven build density and clogging. The separation rate and sedimentation rate were calculated from the values ​​of the separated liquid volume X and the sedimentation liquid volume Y according to the following equations.

number

[0144] 3. Manufacturing and evaluation of 3D additive manufacturing objects 3-1. Manufacturing of 3D additive manufacturing objects Using the additive manufacturing slurry obtained in the same manner as in "2-1. Production of additive manufacturing slurry," stereolithography was performed using a stereolithography device (SZ Series high-definition ceramic stereolithography device, Photo Chemical Co., Ltd.) to obtain a cylindrical 3D additive manufacturing object with a diameter of 5 mm and a height of 12.5 mm. This resulted in a cured 3D additive manufacturing object. After removing uncured resin with ethanol, the object was degreased and sintered using a thermal electric furnace (FUH732PA, Advantec Toyo Co., Ltd.) under the conditions described below to obtain a 3D additive manufacturing object. In the case of the 3D additive manufacturing objects formed with the additive manufacturing slurry containing calcium phosphate powder in Examples 1 to 5 and Comparative Examples 1 to 7, the object was degreased by increasing the temperature to 600°C at a rate of 30°C / h, followed by increasing the temperature to 1300°C at a rate of 100°C / h and maintaining the temperature at 1300°C for 3 hours to obtain a 3D additive manufacturing object. In the case of the three-dimensional laminated hardened product formed with the additive manufacturing slurry containing calcium phosphate powder of Example 6, the temperature was raised to 500°C at a heating rate of 30°C / h, maintained at 500°C for 6 hours for degreasing, and then the temperature was raised to 1000°C, 1100°C, and 1300°C at a heating rate of 100°C / h, respectively, and sintered by maintaining these elevated temperatures for 3 hours to obtain three-dimensional laminated products with different sintering temperatures.In the case of the three-dimensional laminated hardened product formed with the additive manufacturing slurry containing calcium phosphate powder of Example 8, three-dimensional laminated products were obtained under the same conditions as Example 6, except that the temperature was raised to 1000°C and 1100°C, respectively.

[0145] 3-2. Methods for evaluating the manufacturability of 3D additive manufacturing objects and the physical properties of 3D additive manufacturing objects The moldability, warpage, deformation, breakage, compressive strength, appearance, and crystalline structure were evaluated using the following methods.

[0146] [Formability] The formability was evaluated according to the following criteria. A: It is possible to create additive manufacturing of 10mm or more. B: It is not possible to perform additive manufacturing of more than 10 mm. C: The additive manufacturing slurry can be spread on the stacking table of the modeling device, but unevenness occurs on the applied surface, and the slurry is not stacked and modeling is not possible. D: The solid content of the slurry settles, making it impossible to spread the additive manufacturing slurry on the stacking table of the modeling device, and modeling is not possible.

[0147] [Warping, deformation, breakage] The appearance of the three-dimensional additive manufacturing product was visually inspected, and the warpage, deformation, and breakage were evaluated according to the following criteria. A: The 3D additive manufacturing object showed no warping, deformation or breakage compared to an object in which the uncured resin was removed from the 3D laminated cured object. B: The 3D additively manufactured object only had warping and deformation compared to the object in which the uncured resin was removed from the 3D laminated cured object. C: The 3D additively manufactured object only had damage compared to the object in which the uncured resin was removed from the 3D laminated cured object. D: The 3D additive manufacturing object had warpage, deformation, and damage compared to an object in which the uncured resin was removed from the 3D laminated cured object.

[0148] [Compression strength] The compressive strength of the 3D additive manufacturing object was measured using a precision universal material testing machine (Instron Japan Co., Ltd., Model 4507). Specifically, in accordance with JIS R1608 (2003), the compressive strength of the 3D additive manufacturing object was measured by compressing it perpendicular to the laminated surface (bottom surface) of the 3D additive manufacturing object under the conditions of a 5 kN load cell, an indenter φ50 mm, and a test speed of 0.5 mm / min.

[0149] [exterior] The appearance of the three-dimensional additive manufacturing object was observed at 100x and 1000x magnifications using a field emission scanning electron microscope (Hitachi High-Technologies Corporation, SU-8220).

[0150] [Crystal structure] Measurements were performed using an X-ray diffraction apparatus (Rigaku Corporation, SmartLab) under the following conditions: tube: Cu, tube voltage: 40 kV, tube current: 30 mA, scan axis 2θ / θ, scan mode: continuous, range specification: absolute, scan range: 2θ = 20 to 40°, scan speed / counting time: 4.0° / min, step width: 0.02°, entrance slit: 2 / 3°, longitudinal limiting slit: 10 mm, receiving slit 1: 10 mm, receiving slit 2: 10 mm, detector: D / teX Ultra).

[0151] 4.Results The results are shown in Tables 1 to 4 and Figures 1 to 7. Figure 1 shows the results of measuring the crystalline structure of the calcium phosphate powder of Example 6, Figure 2 shows the results of measuring the crystalline structure of the calcium phosphate powder of Example 7, Figure 3 shows the results of measuring the crystalline structure of the calcium phosphate powder of Example 8, and Figure 4 shows the results of measuring the crystalline structure of the calcium phosphate powder of Example 9. Figure 5 shows images of the surfaces of three-dimensional additive manufacturing objects produced using the calcium phosphate powders of Examples 1 and 3 and Comparative Example 2, observed with a field emission scanning electron microscope. Figure 6 shows the results of measuring the crystalline structure of a three-dimensional additive manufacturing object obtained by sintering an additive manufacturing slurry containing the calcium phosphate powder of Example 6 at 1100°C. Figure 7 shows the results of measuring the crystalline structure of a three-dimensional additive manufacturing object obtained by sintering an additive manufacturing slurry containing the calcium phosphate powder of Example 8 at 1100°C.

[0152] The calcium phosphate powders of Examples 1 to 9 had an average particle size of 0.1 to 5.0 μm and a pore volume of 0.01 to 0.06 cc / g in the mesopores (pore diameter 2 to 50 nm), and it was possible to prepare slurries for additive manufacturing with excellent dispersion stability that did not separate from the UV-curable resin even when left for a long period of time.

[0153] Furthermore, by performing stereolithography using the additive manufacturing slurries containing the calcium phosphate powders of Examples 1 to 5, high-strength 3D additive manufacturing objects were produced without breakage during debinding and sintering, with compressive strengths of 84 to 195 MPa. Furthermore, by performing stereolithography using the additive manufacturing slurries containing the calcium phosphate powder of Example 6, high-strength 3D additive manufacturing objects were produced without breakage even when the debinding and sintering temperatures were varied, with compressive strengths of approximately 51 to 113 MPa. Furthermore, the 3D additive manufacturing objects using the calcium phosphate powder of Example 8 also did not break even when the debinding and sintering temperatures were varied, and high-strength 3D additive manufacturing objects with compressive strengths of approximately 78 to 221 MPa were produced, despite the use of β-TCP, which is generally considered to have lower strength than HAP. These results demonstrate that the use of the calcium phosphate powder of the present invention allows the strength of the 3D additive manufacturing object to be varied arbitrarily within the high-strength range, thereby enabling the production of high-strength artificial bones suitable for desired sites.

[0154] On the other hand, the calcium phosphate powders of Comparative Examples 1 and 5 had a small mesopore volume (pore diameter 2-50 nm) of less than 0.01 cc / g, resulting in poor dispersibility during the production of an additive manufacturing slurry, and sedimentation was observed. The calcium phosphate powders of Comparative Examples 2 and 6 met the mesopore volume requirement, but had a large average particle diameter of over 5.0 μm, resulting in a small pore volume per particle. This resulted in the lack of thixotropy required for additive manufacturing slurries, poor dispersion stability, and uneven coating surfaces, leading to failure to build and additive manufacturing of 10 mm or greater. Furthermore, the calcium phosphate powders of Comparative Examples 3, 4, and 7 had a large mesopore volume of over 0.06 cc / g, resulting in a high proportion of photocurable resin in the additive manufacturing slurry. When subjected to stereolithography, the resulting objects shrank significantly after debinding and sintering, leading to warping, deformation, breakage, or insufficient strength of the 3D additive manufacturing objects.

[0155] 5, the three-dimensional additive manufacturing (stereolithography) objects produced using the calcium phosphate powders of Examples 1 and 3 had smoother, less irregular surfaces than the object produced in Comparative Example 2. In other words, this result indicates that by using the calcium phosphate powder of the present invention, it is possible to produce high-precision three-dimensional additive manufacturing objects that are flat and free of irregularities even from a microscopic perspective.

[0156] As shown in FIG. 6, it can be seen that the calcium phosphate powder of Example 6 maintains the hydroxyapatite crystal structure even in the three-dimensional additive manufacturing product.

[0157] Furthermore, as shown in Figure 7, the 3D additive manufacturing product using the calcium phosphate powder of Example 8 was a single crystal of β-TCP, but as shown in Figure 3, the calcium phosphate powder of Example 8 showed a peak corresponding to hydroxyapatite and a peak corresponding to β-TCP by X-ray diffraction. In other words, the peak corresponding to hydroxyapatite in Figure 3 is the peak of calcium-deficient hydroxyapatite, which undergoes a structural change upon heat treatment, and it can be seen that the calcium phosphate powder of Example 8 is a mixed crystal in which the crystal structures of calcium-deficient hydroxyapatite and β-TCP are present.

[0158] [Table 1]

[0159] [Table 2]

[0160] [Table 3]

Claims

1. Average particle diameter (D 50 ) is 0.1 to 5.0 μm, the pore volume of mesopores (pore diameter 2 to 50 nm) measured by gas adsorption method is 0.01 to 0.06 cc / g, and D 10 measured using a laser diffraction / scattering particle size distribution analyzer is 1.0 μm or less.

2. 2. The calcium phosphate powder according to claim 1, wherein the calcium phosphate comprises at least one of hydroxyapatite, tricalcium phosphate, α-TCP, calcium-deficient hydroxyapatite, and β-TCP.

3. BET specific surface area: 0.1 to 20 m 2 3. The calcium phosphate powder according to claim 1, wherein the calcium phosphate content is 1 / g.

4. 4. The calcium phosphate powder according to claim 1, wherein the pore volume of macropores (pore diameter: 50 to 200 nm) measured by gas adsorption method is 0.02 to 0.10 cc / g.

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