calcium phosphate powder

Abstract

The present application aims to provide a calcium phosphate powder which can produce a slurry for laminated molding having excellent dispersion stability in laminated molding, and can produce a three-dimensional laminated molded article of high strength. A calcium phosphate powder having an average particle diameter (D 50 ) of 0.1 to 5.0 μm, and a fine pore volume of a mesopore (fine pore diameter of 2 to 50 nm) of 0.01 to 0.06 cc / g measured by a gas adsorption method also has excellent dispersion stability in a slurry for laminated molding, and by using a slurry for laminated molding containing the calcium phosphate to perform laminated molding, a three-dimensional laminated molded article of high strength useful for an implant such as artificial bone can be produced.

Description

Technical Field

[0001] This invention relates to calcium phosphate powder capable of preparing laminate shaping slurries with excellent dispersion stability in laminate shaping and capable of producing high-strength three-dimensional laminate shapes. Background Technology

[0002] In recent years, for the treatment of bone diseases such as fractures, artificial bone has been used as a substitute for human bone for bone defects. The raw materials for artificial bone include metals, ceramics, and polymers.

[0003] Although ceramics have lower mechanical strength than metals and polymers, they possess excellent biocompatibility, making them highly useful as raw materials for artificial bone. Among ceramics, calcium phosphates such as hydroxyapatite (HAP) and β-tricalcium phosphate (β-TCP) have compositions similar to human bone and exhibit excellent osteoinductive properties. Therefore, they can directly bind to bone or become components of bone formation, leading to increased research on artificial bone formed from calcium phosphates.

[0004] However, artificial bone formed from calcium phosphate has the same composition as bone, but its treatment speed is not as fast as that of autologous bone. Therefore, in order to make artificial bone formed from calcium phosphate have the same structure as autologous bone, block-shaped and granular artificial bone with porous bodies and interconnected pores has been developed. However, its treatment speed is still not as fast as that of autologous bone. In addition, it needs to be molded to match the defect site during surgery.

[0005] To address this issue, in the formation of calcium phosphate-based artificial bone, attempts have been made to use lamination techniques (3D printing) to create artificial bone that not only matches the shape of the defective area but also reproduces the internal structure of the bone. Among the 3D printers used for artificial bone, known methods include lamination (powder lamination) which involves injecting curing liquid into powder and then curing it, and photofabrication (photoforming) which involves curing a lamination paste (modeling paste) made by mixing ceramic raw materials with photocurable resin by irradiating it with ultraviolet light and then removing the resin from the resulting cured material.

[0006] Non-patent document 1 discloses the fabrication of artificial bone using powders containing α-tricalcium phosphate, tetracalcium phosphate, dicalcium phosphate, and HAP through a powder lamination molding process; however, the compressive strength of the resulting artificial bone is limited to approximately 27 MPa. Furthermore, non-patent document 2 discloses the fabrication of artificial bone using HAP with a particle size of 12 μm through a photolithography process; however, the compressive strength of the resulting artificial bone is only about 15 MPa. Thus, artificial bones fabricated using calcium phosphate through lamination molding techniques have the disadvantages of low compressive strength and inapplicability to areas subjected to strong loads (such as the femur). In patent document 1, alumina and zirconium oxide were investigated as ceramic raw materials for the lamination molding technique; however, while these materials can produce three-dimensional laminations with a certain strength, they suffer from poor osteoinductive properties.

[0007] In addition, the artificial bone produced must exhibit high reproducibility (modeling accuracy) of bone during surgery, without requiring a degree of shaping. To improve the modeling accuracy in photolithography, reducing the particle size of calcium phosphate powder is effective. However, if the average particle size of calcium phosphate powder is reduced to below 1 μm, the calcium phosphate powder tends to agglomerate in the slurry, resulting in a tendency to be unable to disperse evenly.

[0008] Against this backdrop of existing technology, it is desirable to develop a calcium phosphate powder that can be used to prepare a slurry for cascade modeling with excellent dispersion stability, and to use cascade modeling technology to create high-strength three-dimensional cascade models.

[0009] Existing technical documents

[0010] Non-patent literature

[0011] Non-Patent Literature 1: Proposal for an Artificial Bone Molding Method Using Powder Lamination Molding - Porosity of Molded Bone - Biomedical Engineering 47(2): 142-147, 2009

[0012] Non-patent document 2: Additive manufacturing of hydroxyapatite bone scaffolds via digital lightprocessing and in vitro compatibility (CeramicsInternationalVolume 45, Issue 81 June 2019Pages 11079-11086)

[0013] Patent documents

[0014] Patent Document 1: International Publication No. 2016 / 147681 Summary of the Invention

[0015] The problem that the invention aims to solve

[0016] The purpose of this invention is to provide a calcium phosphate powder that can be used to prepare a slurry for layered molding with excellent dispersion stability in layered molding, and can be used to produce high-strength three-dimensional layered molded objects.

[0017] Methods for solving problems

[0018] In order to solve the above-mentioned problems, the inventors conducted in-depth research and found that the average particle size (D) 50 Calcium phosphate powder with a micropore size of 0.1–5.0 μm and a pore volume of 0.01–0.06 cc / g (mesopore diameter 2–50 nm as measured by gas adsorption) exhibits excellent dispersion stability in lamination slurries. By using lamination slurries containing this calcium phosphate, high-strength three-dimensional laminated structures useful for implants such as artificial bones can be fabricated. This invention was completed based on further repeated research based on this insight.

[0019] That is, the present invention provides an invention in the manner described below.

[0020] Item 1. A calcium phosphate powder having an average particle size (D) 50 The micropore size is 0.1–5.0 μm, and the micropore volume of the mesopores (micropore diameter 2–50 nm) determined by gas adsorption method is 0.01–0.06 cc / g.

[0021] 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.

[0022] Item 3. The calcium phosphate powder according to item 1 or 2, having a BET specific surface area of ​​0.1 to 20 m². 2 / g.

[0023] Item 4. The calcium phosphate powder according to any one of items 1 to 3, wherein the pore volume of the macropores (pore diameter 50 to 200 nm) determined by gas adsorption method is 0.02 to 0.10 cc / g.

[0024] Item 5. The calcium phosphate powder according to any one of items 1 to 4, wherein the Dsize measured using a laser diffraction-scattering particle size distribution measuring device... 10 It is below 3.0μm.

[0025] Item 6. The calcium phosphate powder according to any one of items 1 to 5, wherein the above-mentioned D 10 It is below 1.0.

[0026] Item 7. A material for layering and shaping, comprising calcium phosphate powder as described in any one of items 1 to 6.

[0027] Item 8. The material for layered modeling as described in Item 7, used for light modeling.

[0028] Item 9. The material for layering as described in Item 7 or 8, used in the manufacture of implants.

[0029] Item 10. A slurry for layering molding, comprising calcium phosphate powder as described in any one of items 1 to 6 and a light-curing resin.

[0030] Item 11. A method for manufacturing a three-dimensional layered model, comprising the following steps (1) to (4),

[0031] (1) The process of forming a slurry layer using the slurry for layered molding as described in item 10;

[0032] (2) A process of curing the above-mentioned slurry layer by irradiating it with a laser in a specified pattern shape;

[0033] (3) The process of repeating steps (1) and (2) above to form a three-dimensional laminated cured material; and

[0034] (4) The process of removing uncured resin and cured resin from the above three-dimensional laminated cured material.

[0035] Item 12. The method for manufacturing a three-dimensional stacked object according to Item 11, wherein the three-dimensional stacked object is an implant.

[0036] Item 13. Use of calcium phosphate powder as a material for layering molding, as described in any one of items 1 to 6.

[0037] Invention Effects

[0038] The calcium phosphate powder of the present invention can be used to prepare a slurry for laminated molding with excellent dispersion stability. Furthermore, three-dimensional laminated structures prepared using the slurry containing the calcium phosphate powder of the present invention can possess high strength, making them useful as artificial bones for load-bearing areas such as the femur. Attached Figure Description

[0039] Figure 1 The results show the determination of the crystal structure of the calcium phosphate powder in Example 6.

[0040] Figure 2 The results show the determination of the crystal structure of the calcium phosphate powder in Example 7.

[0041] Figure 3 The results show the determination of the crystal structure of the calcium phosphate powder in Example 8.

[0042] Figure 4 The results show the determination of the crystal structure of the calcium phosphate powder in Example 9.

[0043] Figure 5 The images show the surface of three-dimensional stacked models made using calcium phosphate powder from Examples 1, 3 and Comparative Example 2, observed using a field emission scanning electron microscope.

[0044] Figure 6 The results show that the crystal structure of a three-dimensional laminated model obtained by sintering a slurry containing calcium phosphate powder of Example 6 at 1100°C was measured.

[0045] Figure 7 The results show that the crystal structure of a three-dimensional laminated model obtained by sintering a slurry containing calcium phosphate powder of Example 8 at 1100°C was measured. Detailed Implementation

[0046] The calcium phosphate powder of the present invention is characterized by an average particle size (D) 50 The micropore size is 0.1–5.0 μm, and the pore volume of the mesopores (fine pore diameter 2–50 nm) determined by gas adsorption is 0.01–0.06 cc / g. The calcium phosphate of the present invention will be described in detail below.

[0047] Types of calcium phosphate

[0048] Regarding the type of calcium phosphate powder of the present invention, it can be hydroxyapatite (HAP:(Ca5(PO4)3(OH))), β-TCP (β-Ca3(PO4)2), or calcium-deficient hydroxyapatite (Ca... 10-z (HPO4) z (PO4) 6-z (OH) 2-z (Where 0 < Z ≤ 1), any of the following: α-tricalcium phosphate (α-Ca3(PO4)2), tricalcium phosphate (Ca3(PO4)2), octacalcium phosphate (Ca8(PO4)4(HPO4)2(OH)2), etc. Alternatively, it can be a mixture or mixed crystal containing two or more of these. The aforementioned calcium-deficient hydroxyapatite can be any of anhydrous or hydrated forms. For example, the structural formula of a calcium-deficient hydroxyapatite as a hydrated form can be Ca... 10-z (HPO4) z (PO4) 6-z (OH) 2-z ·nH2O (where 0<Z≤1, 0<n≤2.5).

[0049] Among calcium phosphates, HAP and β-TCP exhibit excellent biocompatibility and are useful as raw materials for artificial bone. Therefore, preferred examples of the calcium phosphate powder of the present invention include HAP powder, β-TCP powder, calcium-deficient hydroxyapatite powder, and mixtures or mixed crystal powders thereof. As an example of the aforementioned mixtures or mixed crystal powders, a mixture or mixed crystal powder of β-TCP and calcium-deficient hydroxyapatite can be given. In the mixture or mixed crystal powder of β-TCP and calcium-deficient hydroxyapatite, the content ratio of β-TCP to calcium-deficient hydroxyapatite is not particularly limited. Based on the content determined by the RIR method (Reference Intensity Ratio) based on X-ray diffraction, examples include 2 to 98% by weight of β-TCP and 2 to 98% by weight of calcium-deficient hydroxyapatite, preferably 30 to 98% by weight of β-TCP and 2 to 70% by weight of calcium-deficient hydroxyapatite.

[0050] The calcium phosphate powder of the present invention can be either a sintered body that has undergone sintering treatment or a non-sintered body that has not undergone sintering treatment. When the calcium phosphate powder is HAP powder, it is suitable to have a specified average particle size (D). 50 From the perspective of the range of pore volume of mesopores (fine pore diameter 2-50 nm) and micropore volume, non-sintered bodies are preferred.

[0051] [Physical properties of calcium phosphate powder]

[0052] The average particle size (D) of the calcium phosphate powder of the present invention 50 The average particle size (D) of the calcium phosphate powder of the present invention is 0.1–5.0 μm. By achieving a specified pore volume (pore diameter 2–50 nm) and satisfying this average particle size, the slurry for laminated molding can possess excellent dispersion stability, and the fabricated three-dimensional laminated molded objects can possess high strength. From the viewpoint of further improving the dispersion stability of the slurry for laminated molding and the strength of the fabricated three-dimensional laminated molded objects, the average particle size (D) of the calcium phosphate powder of the present invention is... 50 Preferred examples of the particle size of the calcium phosphate powder of the present invention include 0.1 to 3.0 μm, and more preferably 0.4 to 1.0 μm. Furthermore, the average particle size (D) of the calcium phosphate powder of the present invention... 50 Other preferred examples of the particle size distribution include 0.5–5.0 μm, more preferably 1.0–5.0 μm, and even more preferably 3.0–5.0 μm. It should be noted that in this invention, the "average particle size (D)" of the calcium phosphate powder is... 50 "" is the particle size (median particle size) that reaches 50% accumulation in the volume cumulative reference particle size distribution measured using a laser diffraction-scattering particle size distribution measuring device.

[0053] Regarding the calcium phosphate powder of the present invention, D 10 To meet the above average particle size (D)50 The range of ) is limited and not particularly limited; for example, 3.0 μm or less or 1 μm or less can be cited. D is the calcium phosphate powder of the present invention. 10 Preferably, the micrometer size is 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. This is achieved by adjusting the D-type of the calcium phosphate powder of the present invention. 10 Meeting this range increases the pore volume of each particle, further improving the dispersion stability in the slurry used for layering and molding. It should be noted that in this invention, the "D" of the calcium phosphate powder... 10 "It refers to the particle size that reaches 10% of the cumulative standard particle size distribution in the volume cumulative standard particle size distribution measured using a laser diffraction-scattering particle size distribution measuring device."

[0054] Regarding the calcium phosphate powder of the present invention, D 90 To meet the above average particle size (D) 50 The range of ) is limited and not particularly limited; for example, 1–30 μm is possible, preferably 1–20 μm, and more preferably 2–18 μm. It should be noted that in this invention, the "D" of the calcium phosphate powder... 90 "It refers to the particle size that reaches 90% accumulation in the volume cumulative reference particle size distribution measured using a laser diffraction-scattering particle size distribution measuring device."

[0055] Regarding the average particle size of the calcium phosphate powder of the present invention, it satisfies the above-mentioned average particle size (D). 50 The range of ) is limited and not particularly limited. For example, 0.1 to 3 μm is possible, preferably 0.1 to 2 μm, more preferably 0.1 to 1 μm, and even more preferably 0.1 to 0.6 μm. It should be noted that, in this invention, the "number average particle size" of calcium phosphate powder is the particle size that reaches 50% cumulatively by calculation of the number of particles in the cumulative reference particle size distribution measured using a laser diffraction-scattering particle size distribution measuring device.

[0056] The calcium phosphate powder of the present invention has a mesopore volume (pore diameter 2-50 nm) of 0.01-0.06 cc / g, as determined by gas adsorption. This is achieved by satisfying the above-mentioned average particle size (D... 50While satisfying the requirement of a mesopore volume (fine pore diameter 2-50 nm), the slurry exhibits excellent dispersion stability in laminated molding processes. In this slurry, the resin and particles do not separate, and the resin can form hydrogen bonds, etc., providing the thixotropic properties required for layer fabrication during lamination, such as the separation of these hydrogen bonds and a decrease in viscosity when force is applied during lamination. Furthermore, by satisfying the requirement of a mesopore volume (fine pore diameter 2-50 nm), particle irregularities can be suppressed on the surface of the three-dimensional laminated model, resulting in high-precision three-dimensional laminated models. On the other hand, if the mesopore volume (fine pore diameter 2-50 nm) is less than 0.01 cc / g, the dispersion stability of the lamination slurry decreases, and if force is applied during lamination, an expansion tendency occurs, resulting in denser particles and increased viscosity. From the viewpoint of further improving the dispersion stability in the slurry for layered modeling and the strength of the three-dimensional layered model produced, the pore volume of the mesopore (pore diameter 2-50 nm) of the calcium phosphate powder of the present invention is preferably 0.02-0.06 cc / g, more preferably 0.02-0.05 cc / g.

[0057] In this invention, the "pore volume of mesopores (pore diameter 2-50 nm) determined by gas adsorption" of calcium phosphate powder is measured using a high-speed specific surface area pore distribution measuring device by the following method. First, 0.1 g or 1.0 g of calcium phosphate powder is accurately measured and sealed into an adsorption tube, and degassed at 105 °C for 3 hours. Next, the adsorption isotherm of nitrogen is determined at liquid nitrogen temperature, and the pore volume (cc / g) of mesopores (2-50 nm) is calculated using the BJH method.

[0058] The pore volume of the calcium phosphate powder of the present invention, measured by gas adsorption, is not particularly limited, but examples include 0.02 to 0.10 cc / g, preferably 0.02 to 0.09 cc / g, and more preferably 0.02 to 0.08 cc / g. Having such a large pore volume further improves the dispersion stability in slurries used for layering molding. In the present invention, the "pore volume of the calcium phosphate powder, measured by gas adsorption," is a value measured using a high-speed specific surface area pore distribution measuring device by the following method: First, 0.1 g or 1.0 g of calcium phosphate powder is accurately measured, sealed in an adsorption tube, and degassed at 105°C for 3 hours. Next, the adsorption isotherm of nitrogen is determined at liquid nitrogen temperature, and the pore volume (cc / g) of the large pores (50 to 200 nm) is calculated using the BJH method.

[0059] There is no particular limitation on the BET specific surface area of ​​the calcium phosphate powder of the present invention; for example, 20 m² can be cited. 2 / g or less, preferably 0.1 to 20m 2 / g, more preferably 5-20m 2 / g, more preferably 8-18m 2 / g. By satisfying such a BET specific surface area, the particles can shrink tightly during degreasing and / or sintering of the fabricated three-dimensional laminated models, enabling the production of three-dimensional laminated models with higher strength. In this invention, the "BET specific surface area" of calcium phosphate powder is a value determined using a high-speed specific surface area fine pore distribution measuring device by the following method. First, accurately measure 0.1g or 1.0g of calcium phosphate, seal it in an adsorption tube, and degas it at 105°C for 3 hours. Next, determine the adsorption isotherm of nitrogen at liquid nitrogen temperature, and use this adsorption isotherm to calculate the specific surface area (m²) using the multi-point BET method. 2 / g).

[0060] Furthermore, the average pore size of the calcium phosphate powder of the present invention, as measured by the gas adsorption method, is not particularly limited. For example, 10 to 50 nm is possible, preferably 20 to 40 nm, and more preferably 15 to 35 nm.

[0061] In this invention, the "average pore size of calcium phosphate powder as determined by gas adsorption method" is a value obtained by the following method.

[0062] First, using a high-speed specific surface area fine pore distribution measuring device, the total fine pore volume was determined by gas adsorption under the following operating conditions.

[0063] Pretreatment: Accurately measure 0.1g or 1.0g of calcium phosphate powder, seal it into an adsorption tube, and degas at 105℃ for 3 hours.

[0064] Measurement and analysis: The adsorption isotherm of nitrogen was determined at the temperature of liquid nitrogen, and the total micropore volume (cc / g) was calculated based on the amount of gas adsorbed when the relative pressure P / P0 (P0: saturated vapor pressure) was 0.995.

[0065] Next, using the BET specific surface area and total micropore volume obtained above (gas adsorption method), the average micropore diameter is calculated according to the following formula.

[0066] Average pore size (nm) = 4V / S × 1000

[0067] V: Total micropore volume (gas adsorption method) (cc / g)

[0068] S: BET specific surface area (m²) 2 / g)

[0069] There is no particular limitation on the bulk density of the calcium phosphate powder used in this invention. For example, 0.1 to 1.0 g / mL is possible, preferably 0.1 to 0.5 g / mL, and more preferably 0.1 to 0.3 g / mL.

[0070] In this invention, the "loose bulk density" of calcium phosphate powder is calculated as follows: while vibrating a 710μm mesh sieve with an amplitude of 0.5mm, calcium phosphate powder is allowed to fall from the sieve into a cup (10cm³ capacity). 3 In a cup with an inner diameter of 2.2 cm and a height of 2.6 cm, the falling of calcium phosphate powder is stopped at the moment it overflows from the cup. The powder that has risen on the cup is scraped off. The weight of the empty cup is subtracted from the weight of the cup containing the powder to calculate the weight of the powder per 1 mL. The value obtained from this calculation is as follows.

[0071] The tapped bulk density (tap density) of the calcium phosphate powder used in this invention is not particularly limited, but can 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.

[0072] In this invention, the "tap bulk density" of calcium phosphate powder is determined by the following method: First, while vibrating a 710 μm mesh sieve with an amplitude of 0.5 mm, calcium phosphate powder is dropped from the sieve into a cup (10 cm³ capacity). 3 In a container (2.2cm inner diameter, 2.6cm height), the calcium phosphate powder is allowed to overflow from the cup, at which point the falling powder is stopped, and any raised powder on the cup is scraped off. Next, a cylinder (2.2cm inner diameter, 3.2cm height) is installed on top of the cup. While vibrating a 710μm mesh sieve with an amplitude of 0.5mm, calcium phosphate powder is allowed to fall from the sieve into the cup, filling the cylinder to approximately 80% capacity. At this point, the container is tapped a total of 180 times. During the tapping, when the amount of calcium phosphate powder in the cylinder is compressed to approximately 20% of its capacity, it is again allowed to fall into the cylinder through the 710μm mesh sieve vibrating with an amplitude of 0.5mm, replenishing the cylinder to approximately 80% capacity. After 180 taps, the cylinder is removed, any raised powder on the cup is scraped off, and the weight of the cup containing the powder is measured. Subtract the weight of the empty cup from the total weight to calculate the weight of the powder inside the cup, and then calculate the weight per 1cm. 3 The weight of the powder is used as the tap density (g / mL).

[0073] [Method for manufacturing calcium phosphate powder]

[0074] Regarding the method for manufacturing calcium phosphate powder of the present invention, there are no particular limitations as long as calcium phosphate powder with the above-described properties can be obtained. For example, as a preferred example, a first method including the following steps 1-1 to 1-4, a second method including the following steps 2-1 to 2-4, or a third method including the following steps 3-1 to 3-2 can be cited.

[0075] Law 1

[0076] Step 1-1: A process for generating calcium phosphate by (1) adding phosphoric acid and / or phosphate dropwise to a suspension in which calcium salts are suspended, with a Ca / P molar ratio of 1.40 to 1.80, and reacting at a temperature above 30°C; or (2) adding a suspension in which phosphoric acid and / or phosphates are dissolved in water to an aqueous solution of phosphoric acid, with a Ca / P molar ratio of 1.40 to 1.80, and reacting at a temperature above 30°C.

[0077] Step 1-2: The calcium phosphate obtained in Step 1-1 above is wet-crushed to obtain a slurry;

[0078] Steps 1-3: The process of hydrothermally treating the slurry obtained in steps 1-2 above at 250℃~300℃ to obtain the hydrothermally treated product; and

[0079] Steps 1-4: Drying the hydrothermal treated material obtained in steps 1-3 above to obtain calcium phosphate powder.

[0080] Method 2

[0081] Step 2-1: A wet process for producing calcium phosphate by simultaneously adding a suspension of calcium salts and an aqueous solution of phosphoric acid (made by dissolving phosphoric acid and / or phosphates in water) dropwise into an aqueous medium at a Ca / P molar ratio of 1.40 to 1.80, and reacting at a temperature above 30°C.

[0082] Step 2-2: The calcium phosphate obtained in step 2-1 above is wet-crushed to obtain a slurry;

[0083] Step 2-3: A step of subjecting the slurry obtained in step 2-2 above to hydrothermal treatment at 150℃~300℃ to obtain the hydrothermally treated product; and...

[0084] Steps 2-4: Drying the hydrothermal treated material obtained in steps 2-3 above to obtain calcium phosphate powder.

[0085] Method 3

[0086] Step 3-1: A step of generating calcium phosphate by a wet process, wherein the wet process involves simultaneously adding a suspension of calcium salt at a temperature below 50°C and an aqueous solution of phosphoric acid at a temperature below 50°C (prepared by dissolving phosphoric acid and / or phosphate in water) at a Ca / P molar ratio of 1.40 to 1.80 to an aqueous medium at a temperature above 80°C, and allowing the reaction to proceed. Furthermore, the reaction is carried out under conditions of pH 8.5 to 9.5 or pH 3.5 to 4.5.

[0087] Step 3-2: The process of drying the slurry obtained in step 3-1 above to obtain calcium phosphate powder.

[0088] The first method described above will be explained in detail below.

[0089] In step 1-1, calcium ions react with phosphate ions to carry out the synthesis reaction of calcium phosphate by (1) adding phosphoric acid and / or phosphate dropwise to a suspension in which calcium salt is suspended, with a Ca / P molar ratio of 1.40 to 1.80, or (2) adding a suspension in which calcium salt is suspended dropwise to an aqueous solution of phosphoric acid in which phosphoric acid and / or phosphate is dissolved in water, with a Ca / P molar ratio of 1.40 to 1.80.

[0090] In step 1-1, there are no particular limitations on the types of calcium salts used as raw materials; for example, inorganic salts and organic acid salts can be mentioned. Specifically, inorganic salts include calcium chloride, calcium nitrate, calcium carbonate, calcium oxide, and calcium hydroxide. Specifically, organic acid salts include calcium formate, calcium acetate, calcium lactate, calcium gluconate, and calcium citrate.

[0091] Furthermore, there are no particular limitations on the type of phosphate used as a raw material in step 1-1. Examples include alkali metal salts and ammonium salts of phosphoric acid. Examples of alkali metal salts of phosphoric acid include sodium salts and potassium salts. More specifically, examples include disodium hydrogen phosphate, sodium dihydrogen phosphate, trisodium hydrogen phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, tripotassium hydrogen phosphate, diammonium hydrogen phosphate, ammonium dihydrogen phosphate, and triammonium phosphate.

[0092] In the case of manufacturing HAP powder, in step 1-1, calcium hydroxide is preferably used as the calcium salt, and phosphoric acid is preferably used as the phosphoric acid and / or phosphate. Furthermore, in the case of manufacturing β-TCP powder, or a mixture powder or mixed crystal powder of β-TCP and calcium-deficient hydroxyapatite, in step 1-1, calcium hydroxide or calcium nitrate is preferably used as the calcium salt, and phosphoric acid or diammonium hydrogen phosphate is preferably used as the phosphoric acid and / or phosphate.

[0093] In addition, in step 1-1, the dropping rate of phosphoric acid and / or an aqueous solution of phosphate is appropriately adjusted so that the pH of the reaction solution after dropping is below 9.

[0094] For example, when synthesizing HAP by adding phosphoric acid and / or phosphate to a suspension in which calcium salts are suspended, examples include a phosphorus (P) atom concentration of 0.05 to 0.7 mol / h, preferably 0.1 to 0.6 mol / h, and more preferably 0.2 mol / h, relative to 1 mol of calcium (Ca) atoms. Furthermore, when synthesizing HAP by adding a suspension in which calcium salts are suspended in an aqueous phosphoric acid solution, examples include a calcium (Ca) atom concentration of 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, relative to 1 mol of phosphorus (P) atoms, wherein the aqueous phosphoric acid solution is prepared by dissolving phosphoric acid and / or phosphate in water.

[0095] For example, when synthesizing β-TCP or a mixture or mixed-crystal powder of β-TCP and calcium-deficient hydroxyapatite by adding phosphoric acid and / or phosphate to a suspension containing calcium salts, examples include a phosphorus (P) atom concentration of 0.01 to 0.6 mol / h, preferably 0.1 to 0.4 mol / h, and more preferably 0.2 to 0.3 mol / h, relative to 1 mol of calcium (Ca) atoms. Furthermore, when synthesizing β-TCP by adding a suspension formed by suspending calcium salts in an aqueous phosphoric acid solution, examples include a calcium (Ca) atom concentration of 0.05 to 1.8 mol / h, preferably 0.1 to 1.0 mol / h, and more preferably 0.5 to 0.6 mol / h, relative to 1 mol of phosphorus (P) atoms, wherein the aqueous phosphoric acid solution is prepared by dissolving phosphoric acid and / or phosphate in water.

[0096] Furthermore, in step 1-1, the amount of aqueous solution of phosphoric acid and / or phosphate, or the amount of suspension formed by suspending calcium salt, can be appropriately set according to the type of calcium phosphate to be manufactured, such that the Ca / P molar ratio at the end of the addition is in the range of 1.40 to 1.80. For example, in the case of manufacturing 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 around 1.67. In addition, in the case of manufacturing β-TCP powder or a mixture 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 around 1.50.

[0097] Furthermore, in step 1-1, the temperature (reaction temperature) at which the calcium salt coexists with phosphoric acid and / or phosphate can be appropriately set according to the amount of water added, the dropping rate, etc. For example, 30°C or higher is acceptable, preferably 40-100°C, more preferably 80-100°C, and even more preferably 90-100°C. To further effectively react calcium ions with phosphate ions to generate a reaction solution, it is preferable to allow the calcium salt and total amount of phosphoric acid and / or phosphate to coexist before aging at the above-mentioned temperature conditions. In this invention, aging refers to placing the mixture for a certain period of time under stillness or stirring. Regarding the aging time in step 1-1, it can be appropriately set according to the amount of water added, the dropping rate, the reaction temperature, etc. For example, 10 minutes or higher is acceptable, preferably 10-120 minutes, and even more preferably 30-90 minutes. Here, "maturation time" refers to the time during which the total amount of calcium salt and phosphoric acid and / or phosphate coexisting in water is set to 0 minutes, and the water is left to stand or be stirred. For example, in the case of adding an aqueous solution of phosphoric acid and / or phosphate to a suspension in which calcium salt is suspended, the time is calculated by setting the end of the addition of the aqueous solution of phosphoric acid and / or phosphate to 0 minutes.

[0098] By performing step 1-1 in this way, a reaction solution containing calcium phosphate can be obtained.

[0099] In step 1-2, the calcium phosphate obtained in step 1-1 above is wet-milled to obtain a slurry (wet-milled material).

[0100] In the first and second steps, the reaction liquid after the first step can be directly supplied to wet grinding, or the concentrated liquid obtained by concentrating the reaction liquid after the first step, or the suspension obtained by recovering calcium phosphate from the reaction liquid after the first step through dehydration and washing and resuspending it in organic solvents such as water and alcohol, can be supplied to wet grinding.

[0101] In steps 1 and 2, there are no particular restrictions on the wet grinding method; it can be carried out by any means, such as impact, shearing, grinding, compression, or vibration. Furthermore, there are no particular restrictions on the type of wet grinding equipment; it can be any of the following: high-pressure fluid impact mill, high-speed rotary slot mill, grinding mill, ball mill, bead mill, roller mill, annular grinding media mill, or high-speed rotary thin film mill. These devices themselves can be known or commercially available. Among these wet grinding devices, bead mills are preferred.

[0102] When using a bead mill as a wet grinding device, there are no particular limitations on the type of beads, but beads made of zirconia-based materials are preferred. The size of the beads can be, for example, approximately 0.1 to 3 mm in diameter. The bead filling amount can be appropriately set according to the size of the device used, for example, within a range of approximately 50 to 90% by volume.

[0103] In steps 1 and 2, the degree of wet grinding can be adjusted appropriately. From the viewpoint of efficiently manufacturing the calcium phosphate powder of the present invention, it is preferable to adjust the average particle size of the wet-ground calcium phosphate powder to be 10 μm or less, preferably 0.1 to 5 μm, and the maximum particle size to be 50 μm or less, preferably 0.1 to 30 μm. In the present invention, the "average particle size" and "maximum particle size" of the wet-ground calcium phosphate powder are the particle size (median particle size) and the maximum particle size, respectively, that reaches 50% accumulation in the volumetric cumulative reference particle size distribution as measured by a laser diffraction-scattering particle size distribution measuring device.

[0104] In the first and second steps, there is no particular limitation on the liquid temperature during wet grinding. It can be set appropriately according to the heat resistance of the equipment used. For example, it can be around 0 to 100°C, preferably around 5 to 60°C.

[0105] In steps 1-3, the slurry obtained in steps 1-2 is subjected to hydrothermal treatment (also known as hydrothermal synthesis) to obtain a hydrothermally treated product. The solids concentration of the slurry supplied for hydrothermal treatment is not particularly limited, typically ranging from 1 to 30% by weight, more preferably from about 5 to 20% by weight. To adjust the solids concentration in the slurry supplied for hydrothermal treatment, the slurry obtained in steps 1-2 is dehydrated and washed, and then resuspended to achieve the desired solids concentration.

[0106] The hydrothermal treatment in steps 1-3 can be carried out using known devices such as autoclaves.

[0107] The hydrothermal treatment temperature in steps 1-3 can be 250°C to 300°C, and preferably 260°C to 280°C. If the hydrothermal treatment temperature in steps 1-3 is lower than 250°C, the produced calcium phosphate powder will not meet the above-mentioned physical properties, and the calcium phosphate powder of the present invention cannot be obtained.

[0108] The hydrothermal treatment time in steps 1-3 should be set to be sufficient for the formation of the desired calcium phosphate, typically 1 to 5 hours, preferably about 1 to 3 hours. In this invention, "hydrothermal treatment time" refers to the time during which the hydrothermal treatment temperature is reached, excluding the heating time up to reaching the hydrothermal treatment temperature and the cooling time after the hydrothermal treatment.

[0109] In steps 1-4, the hydrothermal treated material obtained in steps 1-3 above is dried to obtain calcium phosphate powder.

[0110] There are no particular limitations on the drying method used in steps 1-4. Examples include shelf drying, spray drying, box drying, belt drying, vacuum drying, freeze drying, microwave drying, drum drying, and flow drying. Among these, shelf drying is preferred.

[0111] There are no particular limitations on the drying temperature in steps 1-4, but for example, it can be around 30-150°C, and preferably around 80-105°C.

[0112] The calcium phosphate powder obtained after processes 1-4 can be used for calcination treatment as needed. The calcination temperature is not particularly limited, but examples include 200–1300°C, preferably 200–800°C, more preferably 350–750°C, and even more preferably 300–600°C. Regarding the calcination time, it can be appropriately set within the range that yields calcium phosphate powder with the aforementioned properties, taking into account the calcination temperature. Reaching the aforementioned temperature conditions instantaneously is sufficient. The holding time of these temperature conditions is preferably 0.1–10 hours, and even more preferably 1–5 hours.

[0113] Furthermore, after processes 1-4 or after the second firing treatment, the calcium phosphate powder may be subjected to crushing, pulverizing, or other treatments as needed to adjust the particle size. Additionally, for the calcium phosphate powder after processes 1-4 or after firing treatment, it is preferable to use a sieve to pre-remove large-sized calcium phosphate powder that deviates from the aforementioned physical properties. There are no particular limitations on the mesh size of the sieve used; for example, 150 μm or less is acceptable, but 100 to 40 μm is preferred.

[0114] Next, we will explain the second method mentioned above in detail.

[0115] In step 2-1, a wet method is used to simultaneously add a suspension of calcium salt and an aqueous solution of phosphoric acid (made by dissolving phosphoric acid and / or phosphate in water) to an aqueous medium at a Ca / P molar ratio of 1.40 to 1.80, thereby causing calcium ions to react with phosphate ions and carry out the synthesis reaction of calcium phosphate.

[0116] In step 2-1, the types of calcium salts and phosphates used as raw materials, the preferred raw materials for manufacturing HAP powder, and the preferred raw materials for manufacturing β-TCP powder or a mixture of β-TCP and calcium-deficient hydroxyapatite powder or mixed crystal powder are the same as in step 1-1 above.

[0117] In step 2-1, the aqueous medium that is the object to be added is preferably water.

[0118] In step 2-1, the amount of calcium salt suspension and the amount of phosphoric acid aqueous solution dissolved in water are appropriately set according to the type of calcium phosphate to be manufactured, such that the Ca / P molar ratio at the end of the addition is in the range of 1.40 to 1.80. The preferred Ca / P molar ratio when manufacturing HAP powder and the preferred Ca / P molar ratio when manufacturing β-TCP powder or a mixture of β-TCP and calcium-deficient hydroxyapatite powder or mixed crystal powder are the same as those in step 1-1 above.

[0119] Furthermore, in step 2-1, there are no particular limitations on the dropping rates of the suspension formed by suspending calcium salts and the aqueous solution of phosphoric acid formed by dissolving phosphoric acid and / or phosphates in water. For example, the rate can be appropriately adjusted according to the manufacturing scale, such as ensuring the pH of the reaction solution during dropping is between 5 and 9. Additionally, in step 2-1, the dropping amounts of the aqueous solution of phosphoric acid and / or phosphates and the dropping amount of the suspension formed by suspending calcium salts can be appropriately set according to the type of calcium phosphate being manufactured, such that the Ca / P molar ratio at the end of dropping is within the range of 1.40 to 1.80. For example, in the case of manufacturing HAP powder, the Ca / P molar ratio at the end of dropping is preferably set to 1.0 to 2.5, more preferably 1.5 to 1.8, and even more preferably around 1.67. In addition, when manufacturing β-TCP powder or a mixture of β-TCP and calcium-deficient hydroxyapatite powder or mixed crystal powder, the molar ratio of Ca / P at the end of the drop addition is preferably set to 0.5 to 2.0, more preferably to 1.0 to 1.7, and even more preferably to about 1.50.

[0120] In step 2-1, the temperature (reaction temperature) at which calcium salts coexist with phosphoric acid and / or phosphates is the same as in step 1-1 above.

[0121] In step 2-1, it is preferable to perform the curing at a specified reaction temperature. The curing time is the same as in step 1-1 described above.

[0122] In step 2-2, the reaction liquid obtained in step 2-1 is wet-milled to obtain a slurry (wet-milled product). In step 2-2, the method of wet milling, the degree of wet milling, and the liquid temperature during wet milling are the same as in step 1-2.

[0123] In step 2-3, a hydrothermally treated product is obtained by hydrothermally treating the slurry obtained in step 2-2. In step 2-3, the solid content concentration of the slurry used for hydrothermal treatment, the hydrothermal treatment apparatus, etc., are the same as in steps 1-3. The hydrothermal treatment temperature in step 2-3 is 150°C to 300°C, preferably 200°C to 300°C, and more preferably 200°C to 280°C. The hydrothermal treatment time in step 2-3 is the same as in steps 1-3.

[0124] In steps 2-4, the hydrothermal treated material obtained in steps 2-3 above is dried to obtain calcium phosphate powder.

[0125] In steps 2-4, the drying method and drying temperature are the same as in steps 1-4 above.

[0126] The calcium phosphate powder obtained after steps 2-4 can be used for calcination treatment as needed. The temperature conditions for calcination treatment are the same as in method 1 described above. Furthermore, after steps 2-4 or after calcination treatment, the calcium phosphate powder can be subjected to crushing, pulverizing, sieving, or other treatments as needed to adjust the particle size. In the case of sieving, the mesh size of the sieve used is the same as in method 1 described above.

[0127] Next, we will explain the third method mentioned above in detail.

[0128] In step 3-1, a wet method is used to simultaneously add a suspension of calcium salt and an aqueous solution of phosphoric acid (made by dissolving phosphoric acid and / or phosphate in water) to an aqueous medium at a temperature above 80°C, so that calcium ions react with phosphate ions to carry out the synthesis reaction of calcium phosphate.

[0129] In step 3-1, the types of calcium salts and phosphates used as raw materials, the preferred raw materials for manufacturing HAP powder, and the preferred raw materials for manufacturing β-TCP powder or a mixture of β-TCP and calcium-deficient hydroxyapatite powder or mixed crystal powder are the same as in step 1-1 above.

[0130] In step 3-1, the temperature of the suspension formed by suspending the calcium salt used as a raw material and the aqueous solution of phosphoric acid formed by dissolving phosphoric acid and / or phosphate in water should both be 50°C or below, preferably 40°C or below, more preferably 30°C or below, and particularly preferably 1 to 30°C.

[0131] In step 3-1, the aqueous medium that is the object to be added is preferably water.

[0132] In step 3-1, the temperature of the aqueous medium can be 80°C or higher, preferably 90°C or higher, more preferably 95°C or higher, and especially preferably 95°C to 100°C.

[0133] In step 3-1, the amount of calcium salt suspension and the amount of phosphoric acid aqueous solution dissolved in water are appropriately set according to the type of calcium phosphate to be manufactured, such that the Ca / P molar ratio at the end of the addition is in the range of 1.40 to 1.80. The preferred Ca / P molar ratio when manufacturing HAP powder and the preferred Ca / P molar ratio when manufacturing β-TCP powder or a mixture of β-TCP and calcium-deficient hydroxyapatite powder or mixed crystal powder are the same as those in step 1-1 above.

[0134] Furthermore, in step 3-1, the simultaneous dropwise addition rate of the suspension formed by suspending calcium salts and the aqueous solution of phosphoric acid formed by dissolving phosphoric acid and / or phosphates in water can be set such that the pH of the reaction solution being added is 8.5–9.5 or 3.5–4.5. Specifically, in the case of manufacturing HAP powder, the simultaneous dropwise addition rate can be set such that the pH of the reaction solution being added is 8.5–9.5. Additionally, in the case of manufacturing β-TCP powder or a mixture powder or mixed crystal powder of β-TCP and calcium-deficient hydroxyapatite, the simultaneous dropwise addition rate can be set such that the pH of the reaction solution being added is 3.5–4.5.

[0135] Furthermore, in step 3-1, the amount of aqueous solution of phosphoric acid and / or phosphate added, and the amount of suspension added simultaneously to suspend the calcium salt, can be appropriately set according to the type of calcium phosphate to be manufactured, such that the Ca / P molar ratio at the end of the addition is in the range of 1.40 to 1.80. For example, in the case of manufacturing HAP powder, the Ca / P molar ratio at the end of the addition is preferably set to 1.0 to 2.5, more preferably to 1.5 to 1.8, and even more preferably to about 1.67. In addition, in the case of manufacturing β-TCP powder, or 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 to 1.0 to 1.7, and even more preferably to about 1.50.

[0136] In step 3-1, the temperature (reaction temperature) at which calcium salt coexists with phosphoric acid and / or phosphate is 80°C or higher, preferably 90°C or higher, more preferably 95°C or higher, and particularly preferably 95°C to 100°C.

[0137] In step 3-1, it is preferable to perform the curing at a specified reaction temperature. The curing time is the same as in step 1-1 described above.

[0138] In step 3-2, the reaction solution obtained in step 3-1 is dried to obtain calcium phosphate powder. The drying method and temperature in step 3-2 are the same as in steps 1-4.

[0139] The calcium phosphate powder obtained after step 3-2 can be used for calcination treatment as needed. The temperature conditions for calcination treatment are the same as in method 1 described above. Furthermore, after step 3-2 or after calcination treatment, the calcium phosphate powder can be subjected to wet grinding, crushing, pulverizing, sieving, or other treatments as needed for particle size adjustment. In the case of wet grinding, the method, degree of wet grinding, and liquid temperature during wet grinding are the same as in steps 1-2 described above. Similarly, in the case of sieving, the mesh size of the sieve used is the same as in method 1 described above.

[0140] [Uses / Materials for layered designs]

[0141] The use of the calcium phosphate powder of the present invention is not particularly limited, but it is suitable for use as a material for layered molding. In the present invention, "material for layered molding" refers to a substance that serves as the substrate for three-dimensional layered molded objects.

[0142] When using the calcium phosphate powder of the present invention as a material for layered modeling, it can be applied to any of the following methods: light modeling or powder layered modeling, and is suitable as a material for layered modeling for light modeling.

[0143] When using the calcium phosphate powder of the present invention as a layered modeling material for photoforming, it is sufficient to prepare a layered modeling paste (modeling paste) containing the calcium phosphate of the present invention and a photocurable resin (ultraviolet-curable resin) for photoforming.

[0144] Regarding the content of the calcium phosphate powder of the present invention contained in the slurry for layering molding, it is acceptable as long as the slurry for layering molding can exhibit thixotropy, for example, 40 to 90% by weight, preferably 60 to 90% by weight, more preferably 70 to 85% by weight.

[0145] There are no particular limitations on the type of photocurable resin used in the slurry for layering molding; for example, acrylic photocurable resins are also acceptable. Regarding the content of photocurable resin in the slurry for layering molding, examples include 5 to 60% by weight, preferably 5 to 57% by weight, and more preferably 6 to 24% by weight.

[0146] Furthermore, without impairing the effects of the present invention, the slurry for layering molding may contain photopolymerization initiators, dispersants (such as polycarboxylic acids), thickeners, antioxidants, light stabilizers, etc. When the slurry for layering molding contains a photopolymerization initiator, its content is not particularly limited; for example, 0.5 to 15% by weight is possible, preferably 0.5 to 10% by weight. Similarly, when the slurry for layering molding contains a dispersant, its content is not particularly limited; for example, 0.1 to 50% by weight is possible, preferably 8 to 40% by weight.

[0147] In order to manufacture three-dimensional stacked objects by using a slurry containing calcium phosphate powder of the present invention and by photoforming, the following steps (1) to (4) are performed.

[0148] (1) The process of forming a slurry layer using the layered molding slurry;

[0149] (2) A process of curing the above-mentioned slurry layer by irradiating it with a laser in a specified pattern shape;

[0150] (3) The process of repeating steps (1) and (2) above to form a three-dimensional laminated cured material; and

[0151] (4) The process of removing uncured resin and cured resin from the above three-dimensional laminated cured material.

[0152] In step (1) above, the slurry layer can be adjusted to a thickness of, for example, about 5 to 200 μm. In addition, the type of laser used in step (2) above can be any laser that can cure photocurable resin, such as an ultraviolet laser.

[0153] In the above process (4), in order to remove uncured resin, it can be cleaned with ethanol, for example.

[0154] In addition, in the above step (4), in order to remove the cured resin, a degreasing treatment can be performed, for example. "Degreasing treatment" refers to the process of removing the cured resin by heating. A heating furnace or the like can be used for degreasing treatment.

[0155] The temperature conditions for degreasing are not particularly limited, but can be typically 100 to 600°C, preferably 300 to 600°C. As for the degreasing time, it can be appropriately set within a range sufficient to remove the cured resin, such as typically 1 to 100 hours, preferably 10 to 50 hours, and more preferably 10 to 20 hours.

[0156] In addition, for the purpose of improving the strength of the three-dimensional laminated model, sintering can also be performed after the above-mentioned process (4). The sintering process can be performed using the same equipment used in the degreasing process.

[0157] The temperature conditions for sintering are not particularly limited, but can be typically 600–1500°C, preferably 800–1500°C, more preferably 1000–1400°C, and particularly preferably 1100–1300°C. The sintering time can be appropriately set taking into account the degreasing process, and can be typically 1–12 hours, preferably 1–5 hours.

[0158] Alternatively, the three-dimensional laminated cured material can be degreased and sintered through a series of operations. When performing degreasing and sintering through a series of operations, the temperature conditions of the furnace or similar equipment can be set in stages. For example, by setting the temperature conditions and holding time for sintering after the aforementioned degreasing treatment, the degreasing of the cured resin and the sintering of the calcium phosphate powder can be performed through a series of operations.

[0159] Three-dimensional laminated structures made using the calcium phosphate powder of the present invention can be used as implants such as artificial joints, artificial tooth roots, and artificial bones. Furthermore, the three-dimensional structures made using the calcium phosphate powder of the present invention possess high strength, making them suitable for use as artificial bones in areas subject to strong loads, such as the femur.

[0160] Example

[0161] The following examples illustrate the invention in more detail, but the invention is not limited to these examples.

[0162] 1. Manufacturing and evaluation of calcium phosphate powder

[0163] 1-1. Manufacturing of calcium phosphate powder

[0164] Example 1

[0165] A 20% by weight calcium hydroxide suspension (1200.0 g) and a 32% by weight phosphoric acid aqueous solution (742.1 g) were prepared with a Ca / P molar ratio of 1.67. For each liquid, the solution was preheated to 80°C and simultaneously added dropwise over 1 hour to 1785.0 mL of water heated to 98°C while stirring at 300 rpm, maintaining the temperature at 98°C and the pH of the reaction solution within the range of 7.0–7.5. After the addition was complete, the solution was stirred for another 30 minutes to allow it to mature. The precipitated hydroxyapatite crystals were then filtered and washed with water.

[0166] Then, hydroxyapatite was suspended in water at 10% by weight and wet-milled using an Ultra Apex Mill (Kotobukuri Kogyo Co., Ltd., UAM-015) at 41.6 Hz, pump speed 2, zirconia bead diameter 0.3 mm, and bead weight 400 g (64% filling weight). Next, the resulting solution was hydrothermally treated in an autoclave (Pressure Glass Industry Co., Ltd., TAS-09-20-300 type) at 200°C for 3 hours. Furthermore, it was dried on a shelf at 100°C using a blower-controlled thermostat (YamatoScientific Co., Ltd., DKM400) and dry-milled using a micronizer (Hosokawa Micron Co., Ltd., AP-B) to obtain calcium phosphate (HAP) particles.

[0167] Example 2

[0168] A 20% by weight calcium hydroxide suspension (1200.0 g) and a 32% by weight phosphoric acid aqueous solution (742.1 g) were prepared with a Ca / P molar ratio of 1.67. Each liquid was preheated to 80°C and simultaneously added dropwise over 1 hour to 1785.0 mL of water heated to 98°C while stirring at 300 rpm, maintaining the temperature at 98°C and the pH of the reaction solution within the range of 7.0–7.5. After the addition was complete, the mixture was stirred for an additional 30 minutes to allow it to mature.

[0169] Next, hydroxyapatite crystals were wet-milled using an Ultra Apex Mill (Kotobukuri Kogyo Co., Ltd., UAM-015) at 41.6 Hz, pump speed 2, zirconia bead diameter 0.3 mm, and bead weight 400 g (64% filling rate). The resulting solution was then hydrothermally treated in an autoclave (Pressure Glass Industry Co., Ltd., TAS-09-20-300 type) at 280°C for 3 hours. Furthermore, the crystals were dried on shelves at 100°C using a blower-controlled thermostat (Yamato Scientific Co., Ltd., DKM400) and then dry-milled using a micronizer (Hosokawa Micron Co., Ltd., AP-B) to obtain calcium phosphate (HAP) particles.

[0170] Example 3

[0171] 3514.1 g of an 8.4 wt% calcium hydroxide suspension and 464.5 g of a 50 wt% phosphoric acid aqueous solution were prepared with a Ca / P molar ratio of 1.67. Phosphoric acid was added dropwise over 3 hours to the calcium hydroxide suspension, which was heated to 95 °C and stirred at 300 rpm, followed by further stirring for 1 hour to allow it to mature.

[0172] Then, wet grinding was performed using an Ultra Apex Mill (Kotobukuri Kogyo Co., Ltd., UAM-015) at 41.6 Hz, pump speed 2, zirconia bead diameter 0.3 mm, and bead weight 400 g (64% filling rate). Next, the resulting solution was hydrothermally treated in an autoclave (Pressure Glass Industry Co., Ltd., TAS-09-20-300 type) at 280°C for 3 hours. Furthermore, shelf drying was performed using a blower-controlled thermostat (Yamato Scientific Co., Ltd., DKM400) at 100°C, followed by dry grinding using a micronizer (Hosokawa Micron Co., Ltd., AP-B) to obtain calcium phosphate (HAP) particles.

[0173] Example 4

[0174] The HAP particles obtained in Example 2 were calcined at 600°C for 3 hours using an electric furnace (Kusaba Chemical Co., Ltd., KY-5NX) (heating rate 100°C / h) to obtain calcium phosphate (HAP) particles.

[0175] Example 5

[0176] Except for changing the firing temperature to 300°C, calcium phosphate (HAP) particles were obtained under the same conditions as in Example 4.

[0177] Example 6

[0178] A 20 wt% calcium hydroxide suspension (92.5 kg) and a 32 wt% phosphoric acid aqueous solution (45.7 kg) were prepared with a Ca / P molar ratio of 1.67. For each liquid, it was simultaneously added dropwise over 1 hour to 112.5 kg of water heated to 98°C while maintaining the pH of the reaction solution within the range of 8.5–9.5. After the addition was complete, the mixture was stirred for an additional 30 minutes to allow it to mature, then filtered and washed with water.

[0179] Then, using a constant-temperature, air-blown thermostat (Yamato Scientific, DKN812), the calcium phosphate powder was dried on shelves at 100°C. It was then dry-pulverized using a Comil (POWREX, QUADRO COMIL 194) and an ACM PULVERIZER (Hosokawa Micron, 10A) to obtain calcium phosphate powder. The crystal structure of the obtained calcium phosphate powder was analyzed by X-ray diffraction, and the results are as follows: Figure 1 As shown, it has been confirmed to be hydroxyapatite (HAP).

[0180] Example 7

[0181] A 20 wt% calcium hydroxide suspension (92.5 kg) and a 32 wt% phosphoric acid aqueous solution (45.7 kg) were prepared with a Ca / P molar ratio of 1.67. For each liquid, it was simultaneously added dropwise over 1 hour to 112.5 kg of water heated to 98°C while maintaining the pH of the reaction solution within the range of 8.5–9.5. After the addition was complete, the mixture was stirred for an additional 30 minutes to allow it to mature, then filtered and washed with water.

[0182] Then, calcium phosphate powder was suspended in water at 10% by weight and wet-milled using a DYNO-MILL (Shinmaru Enterprises, MULTI LAB type) at 20 rpm, with zirconia beads of 1.0 mm diameter and a bead weight of 4.03 kg (80% filling). Furthermore, it was dried on a shelf at 100°C using a blower-controlled thermostat (Yamato Scientific, DKN812) and dry-milled using a micro-pulverizer (Hosokawa Micron, AP-B) to obtain calcium phosphate powder. The crystal structure of the obtained calcium phosphate powder was analyzed by X-ray diffraction, and the results are as follows: Figure 2 As shown, it has been confirmed to be hydroxyapatite (HAP).

[0183] Example 8

[0184] A 20 wt% calcium hydroxide suspension (90.0 kg) and a 32 wt% phosphoric acid aqueous solution (49.6 kg) were prepared with a Ca / P molar ratio of 1.50. For each liquid, it was simultaneously added dropwise over 1 hour to 111.5 kg of water heated to 98°C while maintaining the pH of the reaction solution within the range of 3.5–4.5. After the addition was complete, the mixture was stirred for another 30 minutes to allow it to mature, then filtered and washed with water.

[0185] Then, shelf drying was performed at 100°C using a blower-controlled thermostat (Yamato Scientific, DKN812), followed by dry pulverization using a Comil (POWREX, QUADRO COMIL 194) and a micronizer (Hosokawa Micron, AP-B). Furthermore, calcination was carried out at 650°C for 3 hours (heating rate 100°C / h) using an electric furnace (Kousumura Electric Furnace Manufacturing Co., Ltd., KSO-40 type, square electric furnace for oxidation calcination). After cooling, dry pulverization was performed using an ACM PULVERIZER (Hosokawa Micron, 10A) to obtain calcium phosphate powder. The crystal structure of the obtained calcium phosphate powder was analyzed by X-ray diffraction, and the results are as follows: Figure 3 As shown, peaks corresponding to hydroxyapatite (49 wt%) and β-TCP (51 wt%) were confirmed. Furthermore, as described later, the crystal structure of the three-dimensional laminated model obtained by sintering the laminated modeling slurry using the obtained calcium phosphate powder at 1100°C was analyzed by X-ray diffraction, and the results are as follows: Figure 7 As shown, only the β-TCP peak was detected, while the hydroxyapatite peak was not detected. Therefore, it can be concluded that... Figure 3 The peaks of hydroxyapatite identified were those of calcium-deficient hydroxyapatite, which underwent structural changes due to heat treatment. Based on these analytical results, it was confirmed that the obtained calcium phosphate powder was a mixed crystal of 49 wt% calcium-deficient hydroxyapatite and 51 wt% β-TCP.

[0186] Example 9

[0187] A 20 wt% calcium hydroxide suspension (90.0 kg) and a 32 wt% phosphoric acid aqueous solution (49.6 kg) were prepared with a Ca / P molar ratio of 1.50. For each liquid, it was simultaneously added dropwise over 1 hour to 111.5 kg of water heated to 98°C while maintaining the pH of the reaction solution within the range of 3.5–4.5. After the addition was complete, the mixture was stirred for another 30 minutes to allow it to mature, then filtered and washed with water.

[0188] Then, shelf drying was performed at 100°C using a blower-controlled thermostat (Yamato Scientific, DKN812), followed by dry pulverization using a Comil (POWREX, QUADRO COMIL 194) and a micro-pulverizer (Hosokawa Micron, AP-B). Additionally, calcination was carried out at 750°C for 3 hours using an electric furnace (Kusaba Chemical, KY-5NX) (heating rate 100°C / h). After cooling, the mixture was suspended in water at 10% by weight and wet pulverized using a DYNO-MILL (Shinmaru Enterprises, MULTI LAB type) at 20 rpm, zirconia bead diameter 1.0 mm, and bead weight 4.03 kg (80% filling). Furthermore, using a constant-temperature, air-blown thermostat (Yamato Scientific, DKN812), the calcium phosphate (β-TCP) particles were obtained by shelf drying at 100°C and then dry pulverization using a micronizer (Hosokawa Micron, AP-B). The crystal structure of the obtained calcium phosphate powder was analyzed by X-ray diffraction, and the results are as follows... Figure 4 As shown, it was confirmed to be β-TCP, with a β-TCP content of 99% by weight.

[0189] Comparative Example 1

[0190] After adding 6L of water and 1kg of calcium oxide to the reaction vessel for hydration, water was added to the suspension to adjust the total volume to 15L. Next, the mixture was heated to 50°C, and an aqueous phosphoric acid solution was added until the pH reached 8. The resulting solution was then heated at 95°C for 2 hours to allow it to mature.

[0191] Next, the obtained reaction solution was spray-dried using a spray dryer equipped with a disc-type spray mechanism, and the dried material was recovered. Furthermore, the obtained dried material was calcined at 1150°C for 3 hours using an electric furnace (Kusaba Chemical Co., Ltd., KY-5NX) (heating rate 65°C / h). After cooling, it was pulverized using an ACM PULVERIZER (Hosokawa Micron Co., Ltd., 10A) to obtain calcium phosphate (HAP) particles.

[0192] Comparative Example 2

[0193] Commercially available HAP particles (Fujifilm and Kojun Pharmaceutical Co., Ltd., apatite HAP, monoclinic crystal).

[0194] Comparative Example 3

[0195] Except for changing the autoclave temperature to 200°C, calcium phosphate (HAP) particles were obtained under the same conditions as in Example 3.

[0196] Comparative Example 4

[0197] 3514.1 g of an 8.4 wt% calcium hydroxide suspension and 464.5 g of a 50 wt% phosphoric acid aqueous solution were prepared with a Ca / P molar ratio of 1.67. Phosphoric acid was added dropwise to the calcium hydroxide suspension at 20 °C with stirring at 300 rpm over 3 hours, followed by further stirring for 1 hour to allow it to mature.

[0198] Then, wet grinding was performed using an Ultra Apex Mill (Kotobukuri Kogyo Co., Ltd., UAM-015) at 41.6 Hz, pump speed 2, zirconia bead diameter 0.3 mm, and bead weight 400 g (64% filling rate). Next, the resulting solution was hydrothermally treated in an autoclave (Pressure Glass Industry Co., Ltd., TAS-09-20-300 type) at 280°C for 3 hours. Furthermore, shelf drying was performed using a blower-controlled thermostat (Yamato Scientific Co., Ltd., DKM400) at 100°C, followed by dry grinding using a micronizer (Hosokawa Micron Co., Ltd., AP-B) to obtain calcium phosphate (HAP) particles.

[0199] Comparative Example 5

[0200] The HAP particles obtained in Comparative Example 3 were calcined at 1000°C for 3 hours using an electric furnace (Kusaba Chemical Co., Ltd., KY-5NX) (heating rate 100°C / h), and then dry-pulverized using a micronizer (Hosokawa Micron Co., Ltd., AP-B) to obtain calcium phosphate (HAP) particles.

[0201] Comparative Example 6

[0202] A 20% by weight calcium hydroxide suspension (1200.0 g) and a 32% by weight phosphoric acid aqueous solution (742.1 g) were prepared with a Ca / P molar ratio of 1.67. Each liquid was preheated to 80°C and simultaneously added dropwise over 1 hour to 1785.0 mL of water heated to 98°C while stirring at 300 rpm, maintaining the temperature at 98°C and the pH of the reaction solution within the range of 7.0–7.5. After the addition was complete, the mixture was stirred for an additional 30 minutes to allow it to mature. Next, the mixture was dried on a shelf at 100°C using a blower-controlled thermostat (Yamato Scientific, DKM400) to obtain calcium phosphate (HAP) particles.

[0203] Comparative Example 7

[0204] A 20% by weight calcium hydroxide suspension (1200.0 g) and a 32% by weight phosphoric acid aqueous solution (742.1 g) were prepared with a Ca / P molar ratio of 1.67. For each liquid, the solution was preheated to 80°C and simultaneously added dropwise over 1 hour in 1785.0 mL of water heated to 98°C with stirring at 300 rpm, maintaining the temperature at 98°C and the pH of the reaction solution within the range of 7.0–7.5. After the addition was complete, the mixture was stirred for an additional 30 minutes. The precipitated hydroxyapatite crystals were then wet-milled using an Ultra Apex Mill (Kotobukuri Kogyo Co., Ltd., UAM-015) at 41.6 Hz, pump speed 2, zirconia bead diameter of 0.3 mm, and bead quantity of 400 g (64% filling weight). Next, the rack drying was carried out at a temperature of 100°C using a constant temperature thermostat (YamatoScientific Co., Ltd., DKM400), and then dry pulverization was performed using a micro pulverizer (Hosokawa Micron Co., Ltd., AP-B) to obtain calcium phosphate (HAP) particles.

[0205] 1-2. Evaluation methods for the physical properties of calcium phosphate powder

[0206] For each calcium phosphate powder obtained, the following methods were used to evaluate the average particle size, particle size distribution, number of particles, average particle size, pore volume (gas adsorption method), BET specific surface area, average pore size (gas adsorption method), loose bulk density, tapped bulk density, crystal structure, and content.

[0207] [Average Particle Size, Particle Size Distribution, Number of Particles]

[0208] A suspension prepared by adding 0.4g of calcium phosphate powder and 0.02g of dispersant (product name "Celuna D-305" (manufactured by Chukyo Oils & Fats Co., Ltd.)) to 5g of water was dispersed in water. The particle size distribution was measured using a laser diffraction and scattering particle size distribution measuring device (MicrotracBEL Co., Ltd., Microtrac MT3300EXII) to determine D10 (particle size at 10% cumulativeity), D50 (average particle size), D90 (particle size at 90% cumulativeity), and number-average particle size (particle size at 50% cumulativeity in the number calculation).

[0209] [Minipore volume of mesopores (2-50 nm) (gas adsorption method)]

[0210] The mesopore volume (2–50 nm) was determined using a high-speed surface area pore size distribution measuring device (Quantachrome Corporation, NOVA-4000) via the following method: First, 0.1 g or 1.0 g of calcium phosphate powder was accurately measured and sealed into an adsorption tube, and degassed at 105 °C for 3 hours. Next, the adsorption isotherm of nitrogen was determined at liquid nitrogen temperature, and the mesopore volume (2–50 nm) (cc / g) was calculated using the BJH method.

[0211] [Pore volume of macropores (50-200 nm) (gas adsorption method)]

[0212] The pore volume of macropores (50–200 nm) was determined using a high-speed surface area pore size distribution measuring device (Quantachrome Corporation, NOVA-4000) via the following method: First, 0.1 g or 1.0 g of calcium phosphate powder was accurately measured and sealed into an adsorption tube, and degassed at 105 °C for 3 hours. Next, the adsorption isotherm of nitrogen was determined at liquid nitrogen temperature, and the pore volume of macropores (50–200 nm) (cc / g) was calculated using the BJH method.

[0213] [BET specific surface area]

[0214] The BET surface area was measured using a high-speed surface area pore distribution measuring device (Quantachrome Corporation, NOVA-4000) under the following operating conditions.

[0215] Pretreatment: Accurately measure 0.1g or 1.0g of calcium phosphate powder, seal it into an adsorption tube, and degas at 105℃ for 3 hours.

[0216] Measurement and Analysis: The adsorption isotherm of nitrogen was determined at the liquid nitrogen temperature. Using this adsorption isotherm, the specific surface area (m²) was calculated using the multi-point BET method. 2 / g).

[0217] [Average pore size]

[0218] First, the total pore volume was determined by gas adsorption under the following operating conditions using a high-speed specific surface area pore distribution measuring device (Quantachrome Corporation, NOVA-4000).

[0219] Pretreatment: Accurately measure 0.1g or 1.0g of calcium phosphate powder, seal it into an adsorption tube, and degas at 105℃ for 3 hours.

[0220] Measurement and analysis: The adsorption isotherm of nitrogen was determined at the temperature of liquid nitrogen, and the total micropore volume (cc / g) was calculated from the amount of gas adsorbed when the relative pressure P / P0 (P0: saturated vapor pressure) was 0.995.

[0221] Using the BET specific surface area and total pore volume obtained above (gas adsorption method), the average pore diameter is calculated according to the following formula (gas adsorption method).

[0222] Average pore size (nm) = 4V / S × 1000

[0223] V: Total micropore volume (gas adsorption method) (cc / g)

[0224] S: BET specific surface area (m²) 2 / g)

[0225] Loose bulk density

[0226] Using a powder analyzer (Hosokawa Micron Co., Ltd., PT-X), select the "loose bulk density" setting on the device, and measure the powder density in a 10cm³ cup. 3 The process was carried out under the conditions of a 710μm mesh sieve, a vibration time of 50 seconds, and an amplitude of 0.5mm. The powder was stopped falling from the cup at the point where it overflowed. The powder bulge on the cup was scraped off, and the weight of the empty cup was subtracted from the weight of the cup containing powder to calculate the powder content per 1cm. 3 The weight of the powder is taken as the bulk density (g / mL).

[0227] [Tap density (vibration density)]

[0228] After determining the loose bulk density, the compacted density measuring cylinder (2.2 cm inner diameter, 3.2 cm height) was installed on top of the cup according to the device's instructions. Next, calcium phosphate powder was passed through a 710 μm mesh sieve vibrating with an amplitude of 0.5 mm to allow it to fall into the cylinder, filling it to approximately 80% capacity. At this point, tapping was initiated, with a total of 180 taps performed. During tapping, when the amount of calcium phosphate powder in the cylinder was compressed to approximately 20% of its capacity, the powder was again passed through a 710 μm mesh sieve vibrating with an amplitude of 0.5 mm to replenish the cylinder to approximately 80% capacity, according to the device's instructions. After tapping, the cylinder was removed, the powder buildup on the cup was leveled, 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, thus determining the density per 1 cm³. 3 The weight of the powder is used as the tapped bulk density (g / mL).

[0229] [Crystal Structure]

[0230] Measurements were performed using an X-ray diffraction apparatus (Rigaku, 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 = 20–40°; Scan speed / counting time: 4.0° / min; Step size: 0.02°; Entrance slit: 2 / 3°; Length limiting slit: 10 mm; Light receiving slit 1: 10 mm; Light receiving slit 2: 10 mm; Detector: D / teX Ultra.

[0231] [content]

[0232] Based on the crystal structure determination results above, the contents of β-TCP and HAP were determined using the Reference Intensity Ratio (RIR) method in the comprehensive powder X-ray analysis software PDXL2. At this time, the DB card number for β-TCP was 2128, and for HAP it was 01-076-0694.

[0233] 2. Preparation and evaluation of slurry for layered molding

[0234] 2-1. Preparation of slurry for layered molding

[0235] Accurately measure 20.0 g of calcium phosphate powder and place it into a container for a stirring and degassing device. Next, add a mixture of UV-curable resin and dispersant, and stir using the stirring and degassing device. It should be noted that for the calcium phosphate particles of Examples 1-5, 7, 9 and Comparative Examples 1-7, a mixture of UV-curable resin (SK FINE Co., Ltd., SZ series acrylic UV-curable resin) and dispersant (SK FINE Co., Ltd., polycarboxylate dispersant) was used; for the calcium phosphate particles of Examples 6 and 8, a mixture of UV-curable resin (SK FINE Co., Ltd., SZ series acrylic UV-curable resin) and dispersant (SK FINE Co., Ltd., polycarboxylate dispersant, fatty acid amide dispersant) was used. Stop adding the mixture when fluidity is achieved, obtaining a slurry for layering. Here, the moment fluidity is achieved refers to the moment when the above mixture is added to form a slurry, and the moment when the agglomeration of the calcium phosphate powder disappears due to the addition of the mixture.

[0236] The concentration (wt%) of calcium phosphate powder in the slurry for layered molding is determined by the ratio of the weight of calcium phosphate powder to the weight of the slurry. The concentration (volume%) of calcium phosphate powder in the slurry is determined by the ratio of the volume of calcium phosphate powder to the volume of the slurry (weight of calcium phosphate powder (g) / true density of HAP powder (3.2 g / cm³)). 3The true density of β-TCP powder (3.1 g / cm³) or β-TCP powder. 3 Find the answer.

[0237] 2-2. Evaluation Methods for the Physical Properties of Slurries Used in Layered Molding

[0238] Take 10-14 mL of the slurry obtained above for layering and place it in a 15 mL centrifuge tube A, and let it stand for 3 days. After standing, transfer the liquid separated in centrifuge tube A to another 15 mL centrifuge tube B, and take this volume as the separation volume X. Furthermore, tilt centrifuge tube A at 45° so that the liquid falling from centrifuge tube A without thixotropy enters centrifuge tube B, where the separation volume has been collected, and let it stand for 2 hours. After standing for 2 hours, confirm that no liquid has fallen, and take the liquid remaining in centrifuge tube A where powder aggregation is observed as the settling volume Y. After this operation, the solid components of the liquid remaining in centrifuge tube A where powder aggregation is observed precipitate and lose fluidity. If used for layering, this could lead to separation within the molding apparatus, potentially causing uneven molding concentration and clogging of the apparatus. Calculate the separation rate and settling rate according to the values ​​of the separation volume X and settling volume Y using the following formula.

[0239] [Mathematical Expression 1]

[0240] Separation rate (%) = {Separation liquid volume × (mL) / Volume of slurry added to centrifuge tube A at the start of the experiment (mL)} × 100

[0241] Settling rate (%) = {Settling liquid volume Y (mL) / Volume of slurry added to centrifuge tube A at the start of the experiment (mL)} × 100

[0242] 3. Fabrication and evaluation of three-dimensional layered structures

[0243] 3-1. Manufacturing of three-dimensional layered structures

[0244] Using the same method as described in "2-1. Manufacturing of the Lamination for Lamination" above, the lamination for lamination was photo-molded using a photo-molding apparatus (Shōshin Kagaku Co., Ltd., SZ series high-precision photo-molding apparatus for ceramics) to form a cylindrical shape with a diameter of 5 mm and a height of 12.5 mm, resulting in a three-dimensional laminated cured product. Next, after removing the uncured resin with ethanol, degreasing and sintering were performed using a warm electric furnace (Advantec Toyo Co., Ltd., FUH732PA) under the conditions described later to obtain a three-dimensional laminated product. In the case of a three-dimensional laminated cured product formed from the lamination for lamination containing calcium phosphate powder of Examples 1-5 and Comparative Examples 1-7, degreasing was performed by heating to 600°C at a heating time (30°C / h), followed by heating to 1300°C at a heating rate of 100°C / h and maintaining at 1300°C for 3 hours, thereby obtaining a three-dimensional laminated product. In the case of a three-dimensional laminated solidified product formed from a slurry for laminating modeling containing calcium phosphate powder of Example 6, the temperature was raised to 500°C at a heating time of 30°C / h, and maintained at 500°C for 6 hours for degreasing treatment. Then, the temperature was raised to 1000°C, 1100°C, and 1300°C respectively at a heating rate of 100°C / h, and maintained at the above heating temperature for 3 hours, thereby performing a sintering treatment to obtain three-dimensional laminated solidified products with different sintering temperatures. In the case of a three-dimensional laminated solidified product formed from a slurry for laminating modeling containing calcium phosphate powder of Example 8, the temperature was raised to 1000°C and 1100°C respectively, and other than that, three-dimensional laminated solidified products were obtained under the same conditions as in Example 6.

[0245] 3-2. Manufacturing adaptability of three-dimensional stacked models and evaluation methods for the physical properties of three-dimensional stacked models

[0246] The following methods are used to evaluate shape, warpage, deformation, breakage, compressive strength, appearance, and crystal structure.

[0247] [Styling]

[0248] The form should be evaluated according to the following criteria.

[0249] A: It can create layered designs with a thickness of 10mm or more.

[0250] B: Cannot perform layered designs with a thickness of more than 10mm.

[0251] C: It can spread the slurry for layering on the layering platform of the modeling device, but unevenness occurs on the coating surface, and the model cannot be formed due to lack of layering.

[0252] D: The solid components of the slurry settle, making it impossible to spread the slurry for layering on the stacking platform of the molding device, thus preventing molding.

[0253] [Warping, Deformation, Destructiveness]

[0254] Visually confirm the appearance of the three-dimensional stacked model and evaluate warping, deformation, and damage according to the following criteria.

[0255] A: Compared to an object from which uncured resin has been removed from a 3D laminated solidified product, a 3D laminated solidified product exhibits no warping, deformation, or breakage.

[0256] B: Compared to an object from which the uncured resin has been removed from a three-dimensional laminated solid, a three-dimensional laminated solid only exhibits warping and deformation.

[0257] C: A three-dimensional laminated object is only damaged compared to an object from which the uncured resin has been removed from a three-dimensional laminated solidified object.

[0258] D: Three-dimensional laminated objects exhibit warping, deformation, and breakage compared to objects from which uncured resin has been removed from three-dimensional laminated solidified objects.

[0259] [Compressive Strength]

[0260] The compressive strength of a three-dimensional laminated model was determined using a precision universal testing machine (Instron Japan Co., Ltd., Model 4507). Specifically, according to JIS R1608 (2003), the compressive strength of the three-dimensional laminated model was determined by compressing it in a direction perpendicular to the laminated surface (bottom surface) of the model under the conditions of a 5 kN force sensor, a φ50 mm indenter, and a test speed of 0.5 mm / min.

[0261] [Appearance]

[0262] The appearance of the three-dimensional stacked model was observed at 100x and 1000x using a field emission scanning electron microscope (Hitachi High-Technologies, SU-8220).

[0263] [Crystal Structure]

[0264] Measurements were performed using an X-ray diffraction apparatus (Rigaku, 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 = 20–40°; Scan speed / counting time: 4.0° / min; Step size: 0.02°; Entrance slit: 2 / 3°; Length limiting slit: 10 mm; Light receiving slit 1: 10 mm; Light receiving slit 2: 10 mm; Detector: D / teX Ultra.

[0265] 4. Results

[0266] The results are shown in Tables 1-4, and Figures 1-7 .exist Figure 1 The results of determining the crystal structure of the calcium phosphate powder in Example 6 are shown in the figure. Figure 2 The results of determining the crystal structure of the calcium phosphate powder in Example 7 are shown in the figure. Figure 3 The results of determining the crystal structure of the calcium phosphate powder of Example 8 are shown, as well as in... Figure 4 The results of determining the crystal structure of the calcium phosphate powder of Example 9 are shown. Additionally, in... Figure 5 The image shown is an image obtained by observing the surface of a three-dimensional laminated model made using calcium phosphate powder from Examples 1, 3, and Comparative Example 2 using a field emission scanning electron microscope. Figure 6 The results shown are obtained by measuring the crystal structure of a three-dimensional laminated model obtained by sintering a lamination containing calcium phosphate powder of Example 6 at 1100°C. Figure 7 The results shown are obtained by measuring the crystal structure of a three-dimensional laminated model obtained by sintering a slurry containing calcium phosphate powder of Example 8 at 1100°C.

[0267] For the calcium phosphate powders of Examples 1 to 9, the average particle size is 0.1 to 5.0 μm, and the pore volume in the mesopores (fine pore diameter 2 to 50 nm) is 0.01 to 0.06 cc / g, which can produce a slurry for layering with excellent dispersion stability that does not separate from the UV-curable resin even when left for a long time.

[0268] Furthermore, by using a slurry for layering molding containing calcium phosphate powder from Examples 1 to 5 for light modeling, it is possible to produce high-strength three-dimensional laminated structures that do not break during debinding and sintering and have a compressive strength of 84 to 195 MPa. Additionally, by using a slurry for layering molding containing calcium phosphate powder from Example 6 for light modeling, even changes in the debinding and sintering temperatures do not cause breakage, and high-strength three-dimensional laminated structures with a compressive strength of approximately 51 to 113 MPa can be produced. Furthermore, in the three-dimensional laminated structures using the calcium phosphate powder from Example 8, similarly, changes in the debinding and sintering temperatures do not cause breakage, and even with β-TCP, which is generally considered to have lower strength than HAP, high-strength three-dimensional laminated structures with a compressive strength of approximately 78 to 221 MPa can be produced. Based on these results, it is evident that by using the calcium phosphate powder of the present invention, the strength of the three-dimensional laminated structure can be arbitrarily varied in high-strength regions, thus enabling the production of high-strength artificial bones suitable for desired locations.

[0269] On the other hand, the calcium phosphate powders in Comparative Examples 1 and 5 had poor dispersibility during the fabrication of the slurry for layering due to their small mesopore (pore diameter 2-50 nm) volume (less than 0.01 cc / g), resulting in sedimentation. While the calcium phosphate powders in Comparative Examples 2 and 6 met the mesopore volume requirements, their average particle size exceeded 5.0 μm, leading to a smaller pore volume per particle. This resulted in a lack of thixotropy required for the slurry, low dispersion stability, uneven coating, and inability to layer or create models, or to achieve layering thicknesses greater than 10 mm. Furthermore, in the calcium phosphate powders of Comparative Examples 3, 4, and 7, the mesopore volume exceeded 0.06 cc / g, resulting in a higher proportion of photocurable resin in the slurry for layering. This led to increased shrinkage of the modeled product after degreasing and sintering during photoforming, causing warping, deformation, breakage, or insufficient strength in the three-dimensional layered model.

[0270] In addition, such as Figure 5 As shown, the three-dimensional stacked models (photoforms) manufactured using the calcium phosphate powder of Examples 1 and 3 have fewer surface irregularities and are smoother compared to Comparative Example 2. That is, this result indicates that by using the calcium phosphate powder of the present invention, even from a microscopic point of view, it is possible to manufacture three-dimensional stacked models with smooth, flat surfaces and high precision.

[0271] like Figure 6 As shown, the calcium phosphate powder of Example 6 maintains the crystal structure of hydroxyapatite even in three-dimensional stacked structures.

[0272] In addition, such as Figure 7 As shown, the three-dimensional stacked model using calcium phosphate powder from Example 8 became a single crystal of β-TCP, but as... Figure 3 As shown, X-ray diffraction of the calcium phosphate powder in Example 8 confirmed the presence of peaks corresponding to hydroxyapatite and β-TCP. That is, Figure 3 The peaks in the image that correspond to hydroxyapatite are peaks of calcium-deficient hydroxyapatite whose structure has changed due to heat treatment. It can be seen that the calcium phosphate powder in Example 8 is a mixed crystal containing calcium-deficient hydroxyapatite and β-TCP crystal structures.

[0273] [Table 1]

[0274]

[0275] [Table 2]

[0276]

[0277] [Table 3]

[0278]

Claims

1. A material for layered molding, comprising calcium phosphate powder, wherein the average particle size D of the calcium phosphate powder is... 50 The range is 0.1–5.0 μm. The calcium phosphate powder, as determined by gas adsorption, has a mesopore volume of 0.01–0.06 cc / g, with a pore size of 2–50 nm. The calcium phosphate powder, as determined by gas adsorption, has a pore size of 50–200 nm and a pore volume of 0.02–0.10 cc / g. The D-value of the calcium phosphate powder was determined using a laser diffraction-scattering particle size distribution analyzer. 10 It is below 1.0μm.

2. The material for layered molding 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. The material for layered molding according to claim 1 or 2, wherein, The BET specific surface area of ​​the calcium phosphate powder is 0.1–20 m². 2 / g.

4. The material for layered molding according to claim 1 or 2, wherein, The calcium phosphate powder, as determined by gas adsorption, has a pore size of 50–200 nm and a pore volume of 0.02–0.09 cc / g.

5. The material for layered molding according to claim 1 or 2, wherein, The D-value of the calcium phosphate powder was determined using a laser diffraction-scattering particle size distribution analyzer. 10 The range is 0.1~0.9μm.

6. The material for layered molding according to claim 1 or 2, wherein, The D-value of the calcium phosphate powder was determined using a laser diffraction-scattering particle size distribution analyzer. 10 The thickness is 0.2~0.8μm.

7. The material for layered modeling according to claim 1 or 2, used for light modeling.

8. The material for layering and shaping according to claim 1 or 2, used in the manufacture of implants.

9. A slurry for layered molding, comprising calcium phosphate powder and a light-curing resin. The average particle size D of the calcium phosphate powder 50 The range is 0.1–5.0 μm. The calcium phosphate powder, as determined by gas adsorption, has a mesopore volume of 0.01–0.06 cc / g, with a pore size of 2–50 nm. The calcium phosphate powder, as determined by gas adsorption, has a pore size of 50–200 nm and a pore volume of 0.02–0.10 cc / g. The D-value of the calcium phosphate powder was determined using a laser diffraction-scattering particle size distribution analyzer. 10 It is below 1.0μm.

10. A method for manufacturing a three-dimensional layered model, comprising the following steps (1) to (4). (1) The process of forming a slurry layer using the slurry for layered molding as described in claim 9; (2) A process of curing the slurry layer by irradiating it with a laser in a specified pattern shape; (3) The process of repeating steps (1) and (2) to form a three-dimensional laminated cured material; and (4) The process of removing uncured resin and cured resin from the three-dimensional laminated cured material.

11. The method for manufacturing a three-dimensional layered model according to claim 10, wherein, The three-dimensional layered structure is an implant.

12. Uses of calcium phosphate powder as a material for layered molding. The average particle size D of the calcium phosphate powder 50 The range is 0.1–5.0 μm. The calcium phosphate powder, as determined by gas adsorption, has a mesopore volume of 0.01–0.06 cc / g, with a pore size of 2–50 nm. The calcium phosphate powder, as determined by gas adsorption, has a pore size of 50–200 nm and a pore volume of 0.02–0.10 cc / g. The D-value of the calcium phosphate powder was determined using a laser diffraction-scattering particle size distribution analyzer. 10 It is below 1.0μm.

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