JP6476709B2 - Additive manufacturing powder material, additive manufacturing set, and manufacturing method of additive manufacturing - Google Patents

Description

  The present invention relates to an additive manufacturing powder material, an additive manufacturing set, and an additive manufacturing method.

  Conventionally, artificial bones are made of metal materials such as stainless steel and titanium alloy, wear-resistant plastics, etc., and used for bone replacement. These artificial bones act as dysfunctional joint functions, but metal materials and wear-resistant plastics cause changes over time such as wear, corrosion, and swelling, so they cannot be used for a long time. there were. An alternative material is ceramics based on calcium phosphate. Currently, there are known ones that provide a scaffold for bone formation, and those that themselves are resorbed by bone over time, while promoting the formation of new bone and being replaced in the future.

  As a bone prosthetic material that provides a scaffold for bone formation, for example, a material that is excellent in affinity with a bone tissue such as hydroxyapatite and is directly bonded without a bone structure and inclusions is used. By implanting such a bone grafting material in the bone defect, bone repair is performed quickly using the bone grafting material as a scaffold. However, since hydroxyapatite alone does not cause bone replacement, the remaining hydroxyapatite remains in vivo. There is also a possibility of causing a malfunction. On the other hand, the bone replacement material to be bone-replaced can be implanted in the bone structure to promote the bone-forming action of the bone tissue, and to make the bone repair easier and faster.

  For example, tricalcium phosphate is known as a material for such a bone substitute material for bone replacement. The degree to which the tricalcium phosphate is absorbed by the bone tissue depends on the shape and form of the molded body of the tricalcium phosphate. That is, the porous body has a large surface area in terms of morphology, is easily absorbed by bone tissue, and is easily phagocytosed by phagocytic cells. In contrast, dense bodies are very slow to absorb and are not phagocytosed by phagocytic cells. It is expected that desired biocompatibility can be expressed by combining the porous portion and the dense portion by utilizing the difference in properties depending on these forms (see Patent Document 1). It does not have an applicable level of strength, and it takes not only a long time to mold into the desired shape, but it is also impossible to perform delicate processing with an internal structure, especially in the case of cutting. is there.

  Techniques for producing real solids using solid shape data created by three-dimensional CAD or the like are collectively referred to as rapid prototyping techniques (Rapid Prototyping). Among the rapid prototyping techniques, if a molding technique using high heat-resistant powder is used, molds and cores can be manufactured without using models or wooden molds, so an extremely rapid casting manufacturing process can be achieved. It becomes feasible.

  The rapid prototyping technique is also referred to as additive manufacturing, and creates a three-dimensional object by laminating cross-sectional shapes of objects. Moreover, it is a kind of the rapid prototyping technique, and various lamination methods (powder fixing method) using powder as a material have been proposed (for example, refer to Patent Documents 2 to 6).

For example, in the “artificial bone molding method using a powder lamination method”, a technique for molding artificial bone with higher strength by laminating powder using a powder aggregate that hardens by a hydration reaction has been proposed ( (See Patent Document 7). However, it is difficult to obtain sufficient strength by the hardening by the proposed hydration reaction, and it is difficult to apply it particularly to a site where a load such as a femur is applied.
The powder additive manufacturing method is advantageous in performing the fine processing as described above. However, as described in Patent Document 7, in the case of calcium phosphate that reacts with water, it is non-absorbed by being transplanted in vivo. It is easy to transfer to natural hydroxyapatite. As a result, as described above, the implant may remain in the body for a long period of time, and a problem may occur.

Therefore, it is desired that the implant does not undergo crystal transition in the body as it is and remains in a state where it is replaced with bone.
Therefore, the present invention aims to solve the above-described problems and achieve the following object. In other words, the present invention has a simple and efficient, high-strength, dimensional accuracy, and a complex three-dimensional shaped product that has little transfer to non-absorbable hydroxyapatite even when transplanted in vivo, has no cytotoxicity. It aims at providing the powder material for additive manufacturing which can be manufactured well.

The additive manufacturing powder material of the present invention as a means for solving the above problems is an additive manufacturing powder material containing calcium phosphate powder,
Satisfy A) or B) below,
And the hydroxyapatite (HAp) transition rate of the hardened | cured material formed by hardening | curing the said additive manufacturing powder material is 1% or less, It is characterized by the above-mentioned.
A) An organic compound having a phosphate group or a carboxyl group is applied to the surface of the calcium phosphate powder, and the applied amount of the organic compound is 10,000 ppm or less.
B) It further includes a powder made of an organic compound having a phosphate group or a carboxyl group, and the mixing amount of the organic compound with respect to the calcium phosphate powder is 50% by mass or less.

  According to the present invention, the above-mentioned problems can be solved and the above-mentioned object can be achieved, and there is little transfer to non-absorbable hydroxyapatite even when transplanted in vivo, there is no cytotoxicity, and there is a complicated solid It is possible to provide an additive manufacturing powder material that can manufacture an additive manufacturing object in a simple and efficient manner with high strength and high dimensional accuracy.

FIG. 1 is a schematic view showing an example of a powder additive manufacturing apparatus used in the present invention. FIG. 2 is a schematic view showing another example of the powder additive manufacturing apparatus used in the present invention.

(Powder material for additive manufacturing)
The additive manufacturing powder material of the present invention contains calcium phosphate powder, and the surface of the calcium phosphate has an organic compound having a phosphate group or a carboxyl group, or contains calcium phosphate powder and powder. The powder is an organic compound having a phosphate group or a carboxyl group, and further contains other components as necessary.

<Calcium phosphate powder>
Examples of the calcium phosphate powder is not particularly limited as long as having the form of powder or particles, can be appropriately selected depending on the purpose, as the material thereof, for example, carbonated apatite, fluorinated apatite, beta-tricalcium phosphate Examples include calcium (β-TCP), α-tricalcium phosphate (α-TCP), tetracalcium phosphate, and octacalcium phosphate (OCP). These may be used individually by 1 type and may use 2 or more types together.
Among these, β-tricalcium phosphate (β-TCP), α-tricalcium phosphate (α-TCP), and octacalcium phosphate (OCP) are preferable from the viewpoint of obtaining a layered product to be bone-replaced.
Commercially available particles or powders formed of these materials can be used as the calcium phosphate. As said commercial item, (beta) -TCP (made by Taihei Chemical Industrial Co., Ltd.), (alpha) -TCP (made by Taihei Chemical Industrial Co., Ltd.) etc. are mentioned, for example. The calcium phosphate may be subjected to a known surface (modification) treatment for the purpose of improving cohesion.

  There is no restriction | limiting in particular as a manufacturing method of the said calcium phosphate powder, According to the objective, it can select suitably, For example, the precipitation method etc. which are used suitably by a hydroxyapatite (HAp) synthesis | combination etc. are mentioned.

<Granting of organic compound having phosphoric acid group or carboxyl group>
An organic compound having a phosphate group or a carboxyl group is imparted to the surface of the calcium phosphate powder. As a result, even when calcium phosphate that reacts with water is transplanted into a living body, the organic compound that has been imparted has little transfer to non-absorbable hydroxyapatite, has no cytotoxicity, and has a complicated three-dimensional shape. An additive manufacturing powder material that can manufacture an additive manufacturing object simply and efficiently, with high strength and with high dimensional accuracy is obtained.
The application may be performed by providing the organic compound on the surface of the calcium phosphate powder, and includes various modes such as adsorption, coating, support, and inclusion.
The organic compound is preferably a chelate material that has the ability to capture calcium ions in calcium phosphate, is non-toxic to the human body, and is easily excreted.
The organic compound having a phosphate group includes β-tricalcium phosphate (β-TCP), α-tricalcium phosphate (α-TCP), tetracalcium phosphate, and octacalcium phosphate (OCP) that are subjected to bone replacement. ) And the like. Among these, materials such as α-tricalcium phosphate and octacalcium phosphate that are transferred to hydroxyapatite by reacting with water are particularly preferable. In this case, if the calcium ion capturing ability of the organic compound is weak, it may be transferred to non-absorbable hydroxyapatite when placed in the living body, and the bone replacement ability may be lost.

As the organic compound having a phosphoric acid group, those having two or more phosphoric acid groups per molecule are preferable, and examples thereof include alendronic acid, etidronic acid, and phytic acid. Among these, phytic acid is more preferable because it has many phosphate groups per molecule in order to increase the calcium ion capturing ability.
As the organic compound having a carboxyl group, those having two or more carboxyl groups per molecule are preferable, and examples thereof include citric acid.

The amount of the organic compound applied to the calcium phosphate powder is 10,000 ppm or less, preferably 1,000 ppm to 10,000 ppm, more preferably 3,000 ppm to 10,000 ppm, and more preferably 3,000 ppm to 8,000 ppm. The following is more preferable. When the applied amount is 1,000 ppm or more, it is possible to prevent calcium ions not chelated by the organic compound from transferring to hydroxyapatite when transplanted into a living body. On the other hand, when the applied amount is 10,000 ppm or less, cytotoxicity does not appear when transplanted into a living body, and it is safe.
The application amount (abundance) of the organic compound having a phosphate group can be measured according to a known method using a known elemental analyzer, for example, ICPE-9000 (manufactured by Shimadzu Corporation).
The application amount (abundance) of the organic compound having a carboxyl group can be measured using, for example, NMR, GC-MS, LC-MS, or the like.

  The method for applying the organic compound to the calcium phosphate powder is not particularly limited and may be appropriately selected depending on the purpose. For example, a rolling fluid coating method, a spray drying method, a stirring and mixing addition method, a dipping method, Preferable examples include a kneader coating method. Moreover, the said provision method can be implemented using a well-known commercially available various coating apparatus, granulation apparatus, etc., for example.

<Mixing of powder made of organic compound having phosphoric acid group or carboxyl group>
In the case of using the calcium phosphate powder mixed with a powder made of an organic compound having a phosphate group or a carboxyl group as the layered modeling powder material, for example, the layered modeling powder material is water or water containing a curing agent. When the curable liquid is discharged from the inkjet head and landed, the phosphate group or carboxyl group constituting the additive manufacturing powder material dissolved in water reacts with calcium ions in the calcium phosphate powder, and calcium in the calcium phosphate powder Ions can be sequestered. Even when such end-capped calcium phosphates are transplanted in vivo, there are few transitions to non-absorbable hydroxyapatite due to the action of the phosphate group or carboxyl group provided, there is no cytotoxicity, and a complicated three-dimensional shape Thus, a layered modeling powder material can be obtained that can be manufactured easily and efficiently, with high strength and with high dimensional accuracy.
As the powder composed of an organic compound having a phosphate group or a carboxyl group, the above-mentioned organic compound having a phosphate group or a carboxyl group can be used, and has a calcium ion capturing ability in the calcium phosphate powder. It is preferably a chelate material that is non-toxic to the human body and easily excreted, and phytic acid, etidronic acid, and citric acid are particularly preferable.
The powder made of an organic compound having a phosphate group or a carboxyl group is preferably a water-soluble powder, and since it does not exhibit sufficient chelating ability in a salt state such as a sodium salt, it is not in a salt state. preferable.
Here, “water-soluble” in the “water-soluble powder” means that the solute dissolves in water at 50% by mass or more at room temperature.
In addition, since phytic acid and etidronic acid are liquid at normal temperature, it is preferable to use those pulverized by freeze drying or spray drying.

  The mixing amount of the powder composed of the organic compound having a phosphate group or a carboxyl group with respect to the calcium phosphate powder is 50% by mass or less, preferably 10% by mass to 50% by mass, and more preferably 10% by mass to 30% by mass. More preferred. When the mixing amount is 10% by mass or more, there is no possibility that calcium ions not chelated by the organic compound become nuclei and transfer to hydroxyapatite when transplanted into a living body. On the other hand, when the mixing amount is 50% by mass or less, cytotoxicity does not appear when transplanted into a living body, and it is safe.

  The mixing method of the powder composed of the organic compound having a phosphate group or a carboxyl group into the calcium phosphate powder is not particularly limited and may be appropriately selected depending on the purpose. For example, a stirring and mixing addition method is preferable. It is mentioned in.

<Other ingredients>
The other known components that can be included in the additive manufacturing powder material are not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include a fluidizing agent, a filler, a leveling agent, and a sintering aid. Is mentioned.
When the layered modeling powder material contains the fluidizing agent, it is preferable in that a layer of the layered modeling powder material can be easily and efficiently formed, and when the filler is included, a cured product (layered modeled product) is obtained. , A cured product for sintering) is preferable in that voids are less likely to be generated, and the inclusion of the leveling agent is preferable in that the wettability of the powder material for layered modeling is improved and handling is facilitated. When an auxiliary agent is included, the obtained cured product (laminated shaped product, cured product for sintering) is preferable in that sintering at a lower temperature is possible when performing a sintering treatment.

-Physical properties of powder materials for additive manufacturing-
The volume average particle diameter Dv of the layered modeling powder material is preferably 1.5 μm or more and 10.0 μm or less, and more preferably 3.0 μm or more and 7.0 μm or less. When the volume average particle diameter Dv is 1.5 μm or more, the self-cohesion force of the calcium phosphate powder is appropriate, the production efficiency of the layered object is improved, and the handleability and handling properties may be improved. On the other hand, when the volume average particle diameter Dv is 10.0 μm or less, when the thin layer is formed using the layered modeling powder material, the filling rate of the layered modeling powder material in the thin layer is appropriate. It is difficult to generate voids, and it is possible to prevent voids and the like from being generated in the obtained layered product.
The volume average particle size of the additive manufacturing powder material is determined according to a known method using a known particle size measuring device such as Multisizer III (manufactured by Coulter Counter) or FPIA-3000 (manufactured by Sysmex Corporation). Can be measured.

The particle size distribution Dv / Dn, which is the ratio of the volume average particle diameter Dv to the number average particle diameter Dn of the additive manufacturing powder material, is preferably 1.10 or more and 1.80 or less, and 1.10 or more and 1.40 or less. More preferred. When the particle size distribution Dv / Dn is 1.10 or more, when a thin layer is formed using the layered modeling powder material, the filling rate of the layered modeling powder material in the thin layer is appropriate. In addition, it is difficult for voids to occur, and voids and the like can be prevented from occurring in the obtained layered product. On the other hand, when the particle size distribution Dv / Dn is 1.80 or less, coarse particles do not cause noise in forming a thin layered powder material layer, and there are few fine powders, and self-aggregation is promoted. There is nothing.
The particle size distribution Dv / Dn of the powder material for layered modeling is a known method using a known particle size measuring device such as Multisizer III (manufactured by Coulter Counter), FPIA-3000 (manufactured by Sysmex Corporation), or the like. Can be measured according to.

The average circularity represented by the following formula of the layered modeling powder material is preferably 0.70 or more and 0.80 or less, and more preferably 0.72 or more and 0.78 or less.
Average circularity = (peripheral length of a circle having the same area as the projected area of the additive manufacturing powder material / perimeter of the projected image of the additive manufacturing powder material) × 100
When the average circularity is 0.70 or more, when the layered modeling powder material does not aggregate and a thin layer is formed, the filling rate of the layered modeling powder material in the thin layer is appropriate. In addition, it is difficult for voids to occur, and voids and the like can be prevented from occurring in the obtained layered product. On the other hand, when the average circularity is 0.80 or less, the packing property is appropriate, and the uncured powder existing inside can be easily removed at the time of air blowing after modeling.
The average circularity can be measured according to a known method using a known circularity measuring device such as FPIA-3000 (manufactured by Sysmex Corporation).

  The powder material for additive manufacturing of the present invention can be suitably used for simple and efficient production of various molded bodies and structures. The additive manufacturing set of the present invention described later, and the manufacturing method of the additive manufacturing object of the present invention And it can use especially suitably for the manufacturing apparatus of a laminate-molded article.

(Laminated modeling set)
The additive manufacturing set of the present invention includes the additive manufacturing powder material of the present invention, a curing liquid, and other components as necessary.

<Curing liquid>
As said hardening liquid, the hardening | curing agent containing water containing water or a hardening | curing agent is preferable.

-Water-
Examples of the water include pure water such as ion exchange water, ultrafiltration water, reverse osmosis water, and distilled water, or ultrapure water.
The water can contain other components as necessary. Examples of the other components include surfactants, preservatives, preservatives, stabilizers, pH adjusters, and the like.

-Hardener-containing water-
As said hardening | curing agent containing water, a hardening | curing agent is contained in an aqueous medium, and also other components are contained as needed.

--Aqueous medium--
Examples of the aqueous medium include water, alcohols such as ethanol, ethers, ketones, and the like, and water is preferable. In the aqueous medium, the water may contain some amount of components other than water such as the alcohol.

--Curing agent--
The curing agent is not particularly limited as long as it has the property of curing the calcium phosphate, and can be appropriately selected according to the purpose. For example, citric acid, malic acid, edetic acid, succinic acid, phytin Examples include acids, alendronic acid, etidronic acid and the like. These may be used individually by 1 type and may use 2 or more types together.

  There is no restriction | limiting in particular as content (concentration) of the said hardening | curing agent in the said hardening | curing agent containing water, Although it can select suitably according to the objective, The viscosity of the said hardening | curing agent containing water is 7 mPa * at 20 degreeC. The concentration is s or more and 20 mPa · s or less, and more preferably 9 mPa · s or more and 15 mPa · s or less. When the viscosity is in the range of 7 mPa · s to 20 mPa · s, the hardener-containing water can be satisfactorily applied to the powder material for additive manufacturing, and the dimensional accuracy of the additive manufacturing object is sufficient. can get.

-Other ingredients-
The other components can be appropriately selected in consideration of various conditions such as the kind of means for applying the curing agent-containing water, the usage frequency, and the amount thereof. For example, the curing agent-containing water is imparted by an ink jet method. In this case, the selection can be made in consideration of the influence of clogging on the nozzle head in an inkjet printer or the like. Examples of the other components include preservatives, preservatives, stabilizers, pH adjusters, and the like.

  There is no restriction | limiting in particular as a manufacturing method of the said hardening | curing agent containing water, According to the objective, it can select suitably, For example, the said hardening | curing agent and the said other component as needed are added and mixed in the said aqueous medium. And a method of dissolving them.

  The additive manufacturing kit of the present invention can be suitably used for simple and efficient manufacture of various molded bodies and structures, and is used in the manufacturing method of the additive manufacturing object of the present invention and the manufacturing apparatus of additive manufacturing objects described later. It can be particularly preferably used.

(Manufacturing method of layered object and apparatus for manufacturing layered object)
The manufacturing method of the layered object of the present invention includes at least a layered powder material layer forming step, preferably includes a layer curing step and a sintering step, and further includes other steps as necessary.
The manufacturing apparatus of the layered object used in the present invention preferably includes at least a layered powder material layer forming unit, preferably includes a layer curing unit and a sintering unit, and further includes other units as necessary. It becomes.
The method for manufacturing a layered object according to the present invention can be preferably implemented using the apparatus for manufacturing a layered object used in the present invention, and the step of forming a powder material layer for layered object includes the powder material for layered object. The layer forming means can be preferably carried out, the layer curing step can be suitably carried out by the layer curing means, the sintering step can be suitably carried out by the sintering means, The other steps can be preferably performed by the other means.

<Laminated modeling powder material layer forming step and additive manufacturing powder material layer forming means>
The additive manufacturing powder material layer forming step is a step of forming an additive manufacturing powder material layer having a predetermined thickness on the support using the additive manufacturing powder material of the present invention.
The additive manufacturing powder material layer forming means is means for forming an additive manufacturing powder material layer having a predetermined thickness on the support using the additive manufacturing powder material of the present invention.

-Support-
The support is not particularly limited as long as the layered modeling powder material can be placed thereon, can be appropriately selected according to the purpose, and has a mounting surface on which the layered modeling powder material is placed. Examples thereof include a base plate in the apparatus shown in FIG. 1 of Japanese Utility Model Publication No. 2000-328106. The surface of the support, that is, the placement surface on which the additive manufacturing powder material is placed may be, for example, a smooth surface, a rough surface, or a flat surface. It may be a curved surface.

-Formation of powder material layer for additive manufacturing-
There is no restriction | limiting in particular as a method of arrange | positioning the said powder material for layered modeling on the said support body, Although it can select suitably according to the objective, For example, as a method of arrange | positioning in a thin layer, patent 3607300 A method using a known counter rotation mechanism (counter roller) or the like used in the selective laser sintering method described in the official gazette, and the layered modeling powder material is spread into a thin layer using a member such as a brush, roller, or blade. Preferred examples include a method, a method of pressing the surface of the layered powder material layer using a pressing member to expand it into a thin layer, a method of using a known powdered layered manufacturing apparatus, and the like.

  In order to place the layered modeling powder material in a thin layer on the support using the counter rotating mechanism (counter roller), the brush or blade, the pressing member, etc., for example, as follows: It can be carried out. That is, for example, it is disposed in an outer frame (sometimes referred to as “mold”, “hollow cylinder”, “tubular structure”, etc.) so as to be movable up and down while sliding on the inner wall of the outer frame. The powder material for additive manufacturing is placed on the support using the counter rotating mechanism (counter roller), the brush, a roller or a blade, the pressing member, and the like. At this time, when using the support that can move up and down in the outer frame, the support is arranged at a position slightly lower than the upper end opening of the outer frame, that is, the additive manufacturing is performed. The powder material layer is placed below the thickness of the powder material layer for use, and the powder material for additive manufacturing is placed on the support. As described above, the additive manufacturing powder material can be placed in a thin layer on the support.

  In addition, hardening will arise when the hardening liquid by a laser, an electron beam, or the inkjet method is made to act on the said powder material for layered modeling mounted in the thin layer in this way. The layered modeling powder material (layer) placed on the thin layer is placed on the thin layer of the cured product obtained in the same manner as described above. On the other hand, curing occurs when the laser, electron beam, or curable liquid is applied. The curing at this time is not only in the layered modeling powder material (layer) placed on the thin layer, but also with the thin layer cured product obtained by curing first, which exists under the layered powder material (layer). It also occurs between. As a result, a cured product (laminated modeled product, cured product for sintering) having a thickness of about two layers of the layered modeling powder material (layer) placed on the thin layer is obtained.

  Moreover, in order to mount the powder material for additive manufacturing in a thin layer on the support, it can be automatically and simply performed using the known powder additive manufacturing apparatus. The powder additive manufacturing apparatus generally includes a recoater for stacking the additive manufacturing powder material, a movable supply tank for supplying the additive manufacturing powder material onto the support, and the additive manufacturing powder. A movable molding tank for placing and laminating materials in a thin layer. In the powder additive manufacturing apparatus, the surface of the supply tank can always be slightly raised from the surface of the molding tank by raising the supply tank, lowering the molding tank, or both. The layered powder material can be arranged in a thin layer using the recoater from the supply tank side, and the layered powder material for layered modeling can be laminated by repeatedly moving the recoater. it can.

The thickness of the layered modeling powder material layer is not particularly limited and may be appropriately selected depending on the intended purpose. For example, the average thickness per layer is preferably 3 μm to 200 μm, and preferably 10 μm to 100 μm. More preferred. When the average thickness is 3 μm or more, the time until a layered product is obtained is appropriate, and problems such as loss of shape do not occur during processing such as sintering or handling. On the other hand, when the average thickness is 200 μm or less, the dimensional accuracy of the layered object can be sufficiently obtained.
The average thickness can be measured according to a known method.

<Layer curing step and layer curing means>
The layer curing step is a step of applying a curable liquid to the layered modeling powder material layer by an inkjet method to cure a predetermined region of the layered modeling powder material layer.
The layer curing unit is a unit that applies a curable liquid to the layered modeling powder material layer by an inkjet method and cures a predetermined region of the layered modeling powder material layer.

  The method for applying the curable liquid to the additive manufacturing powder material layer is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include a dispenser method, a spray method, and an inkjet method. In order to carry out these methods, a known apparatus can be suitably used as the layer curing means. Among these, the dispenser method is excellent in droplet quantification, but the application area is narrow, and the spray method can easily form a fine discharge, the application area is wide, and the application property is excellent. The quantitative property of the droplets is poor, and powder scattering occurs due to the spray flow. For this reason, in the present invention, the ink jet method is particularly preferable. The ink jet method is advantageous in that the quantitative property of droplets is better than the spray method, and there is an advantage that the application area can be widened compared with the dispenser method, and a complicated three-dimensional shape can be formed accurately and efficiently. .

  In the case of the ink jet method, the layer curing means has a nozzle capable of applying the curing liquid to the layered modeling powder material layer by the ink jet method. In addition, as a nozzle, the nozzle in a well-known inkjet printer can be used conveniently, and the said inkjet printer can be used conveniently as said layer hardening means. In addition, as said inkjet printer, SG7100 by Ricoh Co., Ltd. etc. are mentioned suitably, for example. The inkjet printer is preferable in that it can increase the speed of coating because it has a large amount of curable liquid that can be dropped from the head portion at a time and has a large coating area. In the present invention, even when the ink jet printer capable of applying the curable liquid with high accuracy and high efficiency is used, the curable liquid is a solid material such as particles or a high-viscosity material such as a resin. Since it does not contain, clogging or the like does not occur in the nozzle or its head, and it does not cause corrosion or the like, so that it is excellent in the production efficiency of the layered product, and a polymer component such as a resin is added. Therefore, it is advantageous in that a hardened product with good dimensional accuracy can be obtained easily and efficiently in a short time without causing an unscheduled increase in volume.

<Sintering process and sintering means>
The sintering step is a step of sintering a laminated cured product formed by sequentially repeating the layer forming step and the layer curing step, and is performed by a sintering means. By performing the sintering step, the cured product can be formed into an integrated molded body (sintered body). Examples of the sintering means include a known sintering furnace.

In addition to the method of sintering after obtaining the cured product as described above, the sintering step includes a method of sintering at the stage of laminating the additive manufacturing powder material.
The method of sintering in the step of laminating the additive manufacturing powder material is a method of sintering the additive manufacturing powder material layer by performing either laser irradiation or electron beam irradiation on the additive manufacturing powder material layer. .

-Laser irradiation-
Examples laser in the laser irradiation is not particularly limited as long as the laser of the absorption wavelength region included in the calcium phosphate powder, can be appropriately selected depending on the intended purpose, for example, CO ₂ lasers, Nd-YAG lasers, fiber lasers, Examples include semiconductor lasers.
The laser irradiation conditions are not particularly limited and can be appropriately selected according to the purpose. For example, when a small laser is used, the calcium phosphate powder cannot be melted, and therefore, an adhesive (for example, (Polyester adhesive) is mixed, and the adhesive is preferably melted by laser irradiation for shaping. In that case, it is preferable to use a CO ₂ laser. As irradiation conditions, for example, a laser output of 15 W, a wavelength of 10.6 μm, and a beam diameter of about 0.4 mm are preferable.

-Electron beam irradiation-
There is no restriction | limiting other than irradiating the electron beam of the energy which a calcium phosphate powder fuse | melts as said electron beam, According to the objective, it can select suitably. When irradiating an electron beam, the additive manufacturing powder material needs to be handled in a vacuum environment.
The conditions for the electron beam irradiation are not particularly limited and can be appropriately selected according to the purpose. For example, the output is 1,500 W, the beam diameter is 0.1 mm, and the degree of vacuum is about 1.0 × 10 ⁻⁵ mbar. Is preferred.

<Other processes and other means>
Examples of the other steps include a drying step, a surface protection treatment step, and a painting step.
Examples of the other means include drying means, surface protection processing means, and painting means.

-Drying process and drying means-
The drying step is a step of drying the cured product obtained in the layer curing step, and is performed by a drying means. In the drying step, not only moisture contained in the cured product but also organic matter may be removed (degreasing). Examples of the drying means include known dryers.

-Surface protection treatment process and surface protection treatment means-
The surface protection treatment step is a step of forming a protective layer on the shaped article formed in the layer curing step or the sintering step. By performing the surface protection treatment step, it is possible to provide the surface of the layered object with durability or the like that allows the modeled object to be used as it is, for example. Specific examples of the protective layer include a water resistant layer, a weather resistant layer, a light resistant layer, a heat insulating layer, and a glossy layer. Examples of the surface protection treatment means include known surface protection treatment devices such as a spray device and a coating device.

-Painting process and painting means-
The painting step is a step of painting the shaped object. By performing this coating process, the shaped article can be colored in a desired color. Examples of the coating means include known coating apparatuses, such as a coating apparatus using a spray, a roller, a brush, and the like.

Here, FIG. 1 shows an example of a powder additive manufacturing apparatus used in the present invention. 1 has a modeling-side powder storage tank 1 and a supply-side powder storage tank 2, and each of these powder storage tanks has a stage 3 that can move up and down. A layer made of the additive manufacturing powder material is formed.
On the modeling side powder storage tank 1, it has the inkjet head 5 which discharges the hardening liquid 4 toward the powder material for lamination modeling in this powder storage tank, and also the modeling side powder from the supply side powder storage tank 2 While supplying the layered modeling powder material to the storage tank 1, the leveling mechanism 6 (hereinafter also referred to as a recoater) is provided to level the surface of the layered modeling powder material layer of the modeling side powder storage tank 1.

The curable liquid 4 is dropped from the inkjet head 5 onto the layered modeling powder material in the modeling-side powder storage tank 1. At this time, the position where the curable liquid 4 is dropped is determined by two-dimensional image data (slice data) obtained by slicing a three-dimensional shape to be finally modeled into a plurality of plane layers.
After the drawing for one layer is completed, the stage 3 of the supply-side powder storage tank 2 is raised, and the stage 3 of the modeling-side powder storage tank 1 is lowered. The layered modeling powder material of the difference is moved to the modeling side powder storage tank 1 by the leveling mechanism 6.

Thus, a new layered modeling powder material layer is formed on the surface of the layered modeling powder material layer previously drawn. The thickness of the layered powder material layer at this time is about several tens μm to 100 μm.
By performing drawing based on the slice data of the second layer on the newly formed powder material layer for layered modeling, and repeating this series of processes to obtain a modeled object, and heating and drying by a heating means (not shown) A layered object is obtained.

FIG. 2 shows another example of the powder additive manufacturing apparatus used in the present invention. The powder additive manufacturing apparatus in FIG. 2 is the same as that in FIG. 1 in principle, but the supply mechanism of the additive manufacturing powder material is different. That is, the supply side powder storage tank 2 is arranged above the modeling side powder storage tank 1. When the drawing of the first layer is completed, the stage 3 of the modeling-side powder storage tank 1 is lowered by a predetermined amount, and the supply-side powder storage tank 2 is moved, while a predetermined amount of the powder material for additive manufacturing is transferred to the modeling-side powder storage tank 1. Drop and form a new layered powder material layer. After that, the leveling mechanism 6 compresses the layered powder material layer to increase the bulk density and uniformly level the height of the layered powder material layer.
According to the powder additive manufacturing apparatus having the configuration shown in FIG. 2, the apparatus can be made compact compared to the configuration of FIG. 1 in which two powder storage tanks are arranged in a plane.

<Hardened product (layered product)>
In a cured product (laminated model) obtained by curing the powder material for layered modeling, the transition rate of calcium phosphate to hydroxyapatite (HAp) is 1% or less, preferably 0.5% or less. When the transfer rate is 1% or less, the calcium phosphate can be prevented from remaining in the living body as hydroxyapatite when transplanted into the living body.
The HAp transition rate can be measured according to a known method using a known X-ray powder diffractometer. Specifically, the crystal phase is identified before and after being immersed in SBF (pseudo body fluid) for 2 weeks, and the transition rate can be measured by the difference in the area ratio of the hydroxyapatite-specific peak appearing in the vicinity of 2θ = 30.

The cytotoxicity of the cured product (layered product) is determined by the following in vitro test: (i) tetrazolium salt 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT). A colorimetric MTT assay that measures the activity of the mitochondrial reductase used; (ii) similar assays using other tetrazolium salts and formazan dyes such as XTT and WST assays; (iii) trypan blue (TB) Iv) assay; (iv) sulforhodamine B (SRB) assay; and (v) clonogenic assay.
In addition, methods known to those skilled in the art for measuring the level of cellular necrosis and apoptosis can be used to determine whether a cationic lipid or agent has cytotoxic activity.
Such methods for measuring apoptosis include, for example, TUNEL assay, caspase activity measurement, DNA fragmentation, poly (ADP-ribose) polymerase (PARP) activation, mitochondrial cytochrome C efflux, apoptosis-inducing factor (AIF) migration, and Annexin-V staining are included, but are not limited to these.

  According to the method and apparatus for manufacturing a layered object of the present invention, a complex three-dimensional layered object can be easily and efficiently produced using the layered modeling powder material of the present invention and the layered model set of the present invention. It can be manufactured with good dimensional accuracy without causing deformation before sintering or the like. The layered product (cured product) obtained in this way has little transfer to non-absorbable hydroxyapatite even when transplanted in vivo, has no cytotoxicity, has sufficient strength, has excellent dimensional accuracy, is fine Since it can reproduce irregularities and curved surfaces, it has excellent aesthetic appearance, high quality, and can be suitably used for various applications.

  Examples of the present invention will be described below, but the present invention is not limited to these examples.

(Preparation Example 1)
<Preparation of additive manufacturing powder material 1>
-Synthesis of α-tricalcium phosphate (α-TCP)-
A 0.342 mol / dm ³ phosphoric acid aqueous solution was fed at a rate of 6 mL / min into a 0.513 mol / dm ³ calcium hydroxide suspension stirred at 160 rpm using a commercially available paddle. The pH was stabilized at around 8.7. Next, it was aged for 72 hours in a 37 ° C. incubator, filtered and dried to obtain a powder. Subsequently, after baking for 1 hour in 800 degreeC environment, it ball-milled using the zirconia bead of diameter 3mm. At that time, ball milling was performed by Glen Creston Ltd. This was carried out using a BM-6 type roller ball mill manufactured, and after 30 minutes of pulverization, fine powder was obtained by passing through a 75 μm mesh and sieving. Next, after baking at 1,400 ° C. for 5 hours and then rapidly cooling, α-tricalcium phosphate (α-TCP) powder was obtained.
When the obtained α-TCP powder was measured as follows, the volume average particle diameter Dv was 9 μm, the particle size distribution Dv / Dn was 1.68, and the average circularity was 0.77.

<Volume average particle diameter Dv and ratio Dv / Dn of volume average particle diameter Dv and number average particle diameter Dn>
Using Coulter Multisizer III (manufactured by Coulter Counter) as a measuring device, an interface for outputting the number distribution and volume distribution (manufactured by Nikkaki Co., Ltd.) and a personal computer are connected. 1 mass% NaCl aqueous solution was prepared using it. As a measuring method, 0.1 mL to 5 mL of a surfactant (alkylbenzene sulfonate) as a dispersant is added to 100 mL to 150 mL of the aqueous solution as the electrolytic solution, and 2 mg to 20 mg of α-TCP powder is added. The dispersion treatment was performed for 1 minute to 3 minutes. Further, 100 mL to 200 mL of an electrolytic aqueous solution is put into another beaker, and the sample dispersion is added to a predetermined concentration therein, and 50,000 particles are used by the Coulter Multisizer III using a 100 μm aperture as an aperture. The average of was measured. The measurement was performed by dropping the dispersion liquid of the α-TCP powder so that the concentration indicated by the apparatus was 8% ± 2%. The ratio Dv / Dn was determined from the obtained volume average particle diameter Dv and number average particle diameter Dn.

<Average circularity>
The average circularity was measured using a flow type particle image analyzer (“FPIA-3000”; manufactured by Sysmex Corporation), and measured using analysis software (FPIA-3000 Data Processing Program For FPIA Version 00-10). . More specifically, 0.1% to 0.5 mL of 10% by weight surfactant (alkylbenzene sulfonate Neogen SC-A; manufactured by Daiichi Kogyo Seiyaku Co., Ltd.) is added to a 100 mL glass beaker, and α- 0.1 g to 0.5 g of TCP powder was added and stirred with a micropartel, and then 80 mL of ion-exchanged water was added. The obtained dispersion is subjected to a dispersion treatment for 3 minutes with an ultrasonic disperser (Honda Electronics Co., Ltd.). About this dispersion liquid, the shape and distribution of the α-TCP powder were measured using the FPIA-3000 until the concentration reached 5,000 / μL to 15,000 / μL.

When the crystal phase of the prepared α-TCP powder was identified using the X-ray powder diffractometer (RINT1100, manufactured by Rigaku Electric Co., Ltd.) under the following conditions, it was found that the crystal phase was α.
[Measurement condition]
・ Tube: Cu
・ Voltage: 40kV
・ Current: 40 mA
・ Starting angle: 3 °
・ End angle: 80 °
・ Scanning speed: 0.5 ° / min

-Treatment of applying an organic compound having a phosphate group or a carboxyl group to calcium phosphate powder-
30 g of the α-TCP powder, 0.2 g of 50 mass% phytic acid (manufactured by Wako Pure Chemical Industries, Ltd., number of phosphate groups: 6) as an organic compound having a phosphate group, 120 g of ion-exchanged water, and a diameter of 3 mm 540 g of zirconia beads were placed in a 500 mL wide-mouthed bottle and wet-ground by a ball mill for 2 hours. Next, the mixture was filtered and dried, and the resulting powder was dry-pulverized to obtain a powder material 1 for additive manufacturing, which is an α-TCP powder provided with phytic acid on the surface.
About the obtained additive manufacturing powder material 1, the application amount (abundance) of phytic acid as an organic compound having a phosphate group on the surface of the α-TCP powder was measured using an elemental analyzer (ICPE-9000, manufactured by Shimadzu Corporation). ) And was 5,000 ppm.

(Preparation Example 2)
<Preparation of additive manufacturing powder material 2>
-Synthesis of tricalcium phosphate (β-TCP)-
A 0.342 mol / dm ³ phosphoric acid aqueous solution was fed at a rate of 6 mL / min into a 0.513 mol / dm ³ calcium hydroxide suspension stirred at 160 rpm using a commercially available paddle. The pH was stabilized at around 8.7. Next, it was aged for 72 hours in a 37 ° C. incubator, filtered and dried to obtain a powder. Next, after firing in an 800 ° C. environment for 1 hour, ball milling was performed using zirconia beads having a diameter of 3 mm.
At that time, ball milling was performed by Glen Creston Ltd. This was carried out using a BM-6 type roller ball mill manufactured, and after 30 minutes of pulverization, fine powder was obtained by passing through a 75 μm mesh and sieving. Next, after baking at 1,100 ° C. for 5 hours and then rapidly cooling, β-tricalcium phosphate (β-TCP) powder was obtained.
The obtained β-TCP powder was measured in the same manner as in Preparation Example 1. The volume average particle diameter Dv was 5 μm, the particle size distribution Dv / Dn was 1.45, and the average circularity was 0.78.
Moreover, when the crystal phase of the obtained calcium phosphate was identified in the same manner as in Preparation Example 1, it was found that the crystal phase was β.

-Treatment of applying an organic compound having a phosphate group or a carboxyl group to calcium phosphate powder-
30 g of the β-TCP powder, 0.2 g of 50 mass% phytic acid (manufactured by Wako Pure Chemical Industries, Ltd., phosphate group number: 6) as an organic compound having a phosphate group, 120 g of ion-exchanged water, and a diameter of 3 mm 540 g of zirconia beads were placed in a 500 mL wide-mouthed bottle and wet-ground by a ball mill for 2 hours. Next, the mixture was filtered and dried, and the powder obtained was dry-pulverized to obtain a powder material 2 for additive manufacturing that was β-TCP powder having phytic acid added to the surface.
When the amount of phytic acid applied (abundance) as an organic compound having a phosphate group on the surface of the β-TCP powder was measured in the same manner as in Preparation Example 1 for the obtained additive manufacturing powder material 2, it was 5,000 ppm. Met.

(Preparation Example 3)
<Preparation of additive manufacturing powder material 3>
-Synthesis of octacalcium phosphate (OCP)-
A 0.342 mol / dm ³ phosphoric acid aqueous solution was fed at a rate of 6 mL / min into a 0.455 mol / dm ³ calcium hydroxide suspension stirred at 160 rpm using a commercially available paddle. The pH was stabilized at around 8.7. Next, it was aged for 72 hours in a 37 ° C. incubator, filtered and dried to obtain a powder. Next, after firing in an 800 ° C. environment for 1 hour, ball milling was performed using zirconia beads having a diameter of 3 mm.
At that time, ball milling was performed by Glen Creston Ltd. This was carried out using a BM-6 type roller ball mill manufactured, and after 30 minutes of pulverization, fine powder was obtained by passing through a 75 μm mesh and sieving. Next, after calcining at 1,100 ° C. for 5 hours and then rapidly cooling, octacalcium phosphate (OCP) powder was obtained.
When the obtained OCP powder was measured in the same manner as in Preparation Example 1, the volume average particle diameter Dv was 7 μm, the particle size distribution Dv / Dn was 1.73, and the average circularity was 0.78.

-Treatment of applying an organic compound having a phosphate group or a carboxyl group to calcium phosphate powder-
30 g of the OCP powder, 0.2 g of 50 mass% phytic acid (manufactured by Wako Pure Chemical Industries, Ltd., number of phosphate groups: 6) as an organic compound having a phosphate group, 120 g of ion-exchanged water, and zirconia beads having a diameter of 3 mm 540 g was put into a 500 mL wide-mouth bottle and wet-ground by a ball mill for 2 hours. Next, the mixture was filtered and dried, and the powder obtained was dry-pulverized to obtain an additive manufacturing powder material 3 which is an OCP powder provided with phytic acid on the surface.
About the obtained additive manufacturing powder material 3, it was 5,000 ppm when the application amount (abundance) of phytic acid which is an organic compound having a phosphate group was measured in the same manner as in Preparation Example 1.

(Preparation Example 4)
-Preparation of curable liquid 1-
60 parts by mass of water, 40 parts by mass of citric acid (manufactured by Wako Pure Chemical Industries, Ltd.) as a curing agent, and 0.5 parts by mass of Triton X-100 (manufactured by Tokyo Chemical Industry Co., Ltd.) as a surfactant are mixed. The curable liquid 1 was prepared by dispersing for 5 minutes using a homomixer.

(Example 1-1)
Using the obtained powder material 1 for additive manufacturing and the curable liquid 1, an additive manufacturing object 1-1 was manufactured as follows using a shape printing pattern of size (length 70 mm × width 12 mm). .

(1) First, using a known powder additive manufacturing apparatus as shown in FIG. 1, the additive manufacturing powder material 1 is transferred from the supply-side powder storage tank to the modeling-side powder storage tank, and then on the support. A thin layer made of additive manufacturing powder material 1 having an average thickness of 100 μm was formed.

(2) Next, the curable liquid 1 is applied (discharged) from a nozzle to the surface of the thin layer made of the layered modeling powder material 1 using an ink jet printer (manufactured by Ricoh Co., Ltd., SG7100). The calcium phosphate was cured by curing the powder material 1 for additive manufacturing.

(3) Next, the operations of (1) and (2) are repeated until a total average thickness of 3 mm is obtained, and the cured thin layer made of the additive manufacturing powder material 1 is sequentially laminated, The layered object 1-1 was manufactured. When the excess layered modeling powder material was removed by air blowing from the obtained layered product 1-1, there was no loss of shape. The layered object 1-1 was excellent in strength and dimensional accuracy.

  About the obtained laminate-molded article 1-1, the hydroxyapatite transition rate (HAp transition rate), cytotoxicity, strength (hardness), and dimensional accuracy were evaluated according to the following criteria. The results are shown in Table 2.

<Hydroxyapatite (HAp) transition rate>
Using an X-ray powder diffractometer (RINT1100, manufactured by Rigaku Electric Co., Ltd.), the crystallographic phase of the layered object 1-1 is identified before and after being immersed in SBF (pseudo body fluid) for 2 weeks, and appears around 2θ = 30. The HAp transition rate (%) was measured from the difference in the area ratio of the hydroxyapatite-specific peak. In the present invention, the HAp transition rate is 1% or less.

<Cytotoxicity>
About 100 V79 cells (Chinese hamster lung-derived fibroblasts) are seeded in a cell culture medium (MEM medium supplemented with 5 vol% fetal calf serum) contained in a well, and allowed to stand for 4 hours. -1 was placed in the well. After culturing in that state for 1 week, the number of colonies was measured, and the average value of the number of colonies was determined. Similarly, the control well without the layered object was cultured for 1 week, the number of colonies was measured, and the average value of the number of colonies was obtained. From these values, the colony formation rate (%) was calculated according to the following formula.
Colony formation rate (%) = (Average value of the number of colonies in the culture solution in which the layered product is immersed) / (Average value of the number of colonies in the culture solution without the layered product) × 100
From the obtained colony formation rate, it was judged that there was no cytotoxicity if it was 60% or more.

<Strength (hardness)>
The strength (hardness) of the layered object 1-1 was evaluated according to the following criteria.
X: The powder material for layered modeling is not sufficiently cured, the layered model cannot be taken out, and a predetermined shape cannot be maintained when the layered model is taken out. In addition to unnecessary additive manufacturing powder material, the additive manufacturing object itself is slightly removed, but the extracted additive object itself maintains its shape. ○: Air blow is applied to the additive object. However, only the unnecessary additive manufacturing powder material is removed, and the removed additive object itself maintains its shape. ◎: The additive object is sufficiently cured and not easily broken.

<Dimensional accuracy>
The dimensional accuracy of the layered object 1-1 was evaluated according to the following criteria.
X: The surface of the obtained layered product is distorted, and when the surface is observed, the uneven distribution of the powder material for layered modeling and the curable liquid is observed. Δ: On the surface of the obtained layered product State where slight distortion and unevenness are generated. ○: The surface state of the obtained layered product is good, but slightly warped. ◎: The surface of the obtained layered product is smooth and beautiful. Yes, no warping

(4) The layered product 1-1 obtained in (3) was sintered in a sintering furnace at 1,300 ° C. under vacuum conditions. The sintered body of the layered object 1-1 was a completely integrated calcium phosphate structure, and no damage or the like occurred even when it was hit against a hard floor.

(Example 2-1)
In Example 1-1, the layered product 2-1 was obtained in the same manner as in Example 1-1 except that the treatment for applying the organic compound having a phosphate group or a carboxyl group to the calcium phosphate powder was changed as follows. Manufactured.
About the obtained laminate-molded article 2-1, the same evaluation as Example 1-1 was performed. The results are shown in Table 2.

-Treatment of applying an organic compound having a phosphate group or a carboxyl group to calcium phosphate powder-
30 g of the α-TCP powder, 0.05 g of 50 mass% phytic acid as an organic compound having a phosphate group (manufactured by Wako Pure Chemical Industries, Ltd., number of phosphate groups: 6), 120 g of ion-exchanged water, and a diameter of 3 mm 540 g of zirconia beads were placed in a 500 mL wide-mouthed bottle and wet-ground by a ball mill for 2 hours. Next, filtration and drying were performed, and the powder obtained was dry pulverized to obtain powder material 4 for additive manufacturing that was α-TCP powder having phytic acid added to the surface.
About the obtained additive manufacturing powder material 4, when the application amount (abundance) of phytic acid which is an organic compound having a phosphate group on the surface of the α-TCP powder was measured in the same manner as in Preparation Example 1, 000 ppm.

(Example 3-1)
In Example 1-1, the layered object 3-1 was obtained in the same manner as in Example 1-1 except that the treatment for applying the organic compound having a phosphate group or a carboxyl group to the calcium phosphate powder was changed as follows. Manufactured.
About the obtained laminate-molded article 3-1, the same evaluation as Example 1-1 was performed. The results are shown in Table 2.

-Treatment of applying an organic compound having a phosphate group or a carboxyl group to calcium phosphate powder-
30 g of the α-TCP powder, 50% by mass of phytic acid as an organic compound having a phosphate group (manufactured by Wako Pure Chemical Industries, Ltd., 6 phosphoric acid groups: 6), 120 g of ion-exchanged water, and a diameter of 3 mm 540 g of zirconia beads were placed in a 500 mL wide-mouthed bottle and wet-ground by a ball mill for 2 hours. Next, filtration and drying were performed, and the resulting powder was dry-pulverized to obtain a layered modeling powder material 5 which was an α-TCP powder provided with phytic acid on the surface.
When the amount of phytic acid (abundance), which is an organic compound having a phosphate group, on the surface of the α-TCP powder was measured in the same manner as in Preparation Example 1, the obtained additive manufacturing powder material 5 was 10, 000 ppm.

(Example 4-1)
In Example 1-1, the same procedure as in Example 1-1 was performed except that α-TCP powder was changed to additive manufacturing powder material 2 in which phytic acid was added to the surface of β-TCP powder prepared in Preparation Example 2. Then, the layered object 4-1 was manufactured.
About the obtained laminate-molded article 4-1, the same evaluation as Example 1-1 was performed. The results are shown in Table 2.

(Example 5-1)
In Example 1-1, except that the α-TCP powder was changed to the additive manufacturing powder material 3 in which phytic acid was added to the OCP powder surface prepared in Preparation Example 3, in the same manner as in Example 1-1, The layered object 5-1 was manufactured.
About the obtained laminate-molded article 5-1, evaluation similar to Example 1-1 was performed. The results are shown in Table 2.

(Example 6-1)
In Example 1-1, the layered object 6-1 was obtained in the same manner as in Example 1-1 except that the treatment for applying the organic compound having a phosphate group or a carboxyl group to the calcium phosphate powder was changed as follows. Manufactured.
About the obtained laminate-molded article 6-1, the same evaluation as Example 1-1 was performed. The results are shown in Table 2.

-Treatment of applying an organic compound having a phosphate group or a carboxyl group to calcium phosphate powder-
30 g of the α-TCP powder, 0.5 g of citric acid as an organic compound having a carboxyl group (manufactured by Wako Pure Chemical Industries, Ltd., number of carboxyl groups: 3), 120 g of ion-exchanged water, and 540 g of zirconia beads having a diameter of 3 mm It put into a 500 mL wide-mouth bottle, and wet-pulverized for 2 hours with the ball mill. Next, filtration and drying were performed, and the obtained powder was dry-pulverized to obtain a powder material 6 for additive manufacturing that is α-TCP powder having citric acid applied to the surface.
In the obtained additive manufacturing powder material 6, the amount of citric acid, which is an organic compound having a carboxyl group on the surface of the α-TCP powder, was measured by LC-MS and found to be 6,000 ppm. .

(Example 7-1)
In Example 1-1, the layered product 7-1 was made in the same manner as in Example 1-1 except that the application treatment of the organic compound having a phosphate group or a carboxyl group to the calcium phosphate powder was changed as follows. Manufactured. About the obtained laminate-molded article 7-1, the same evaluation as Example 1-1 was performed. The results are shown in Table 2.

-Treatment of applying an organic compound having a phosphate group or a carboxyl group to calcium phosphate powder-
30 g of the α-TCP powder, 35% by mass of etidronic acid (manufactured by Dojindo Laboratories, Inc., number of phosphate groups: 2) as an organic compound having a phosphate group, 120 g of ion-exchanged water, and 3 mm in diameter 540 g of zirconia beads were placed in a 500 mL wide-mouthed bottle and wet-ground by a ball mill for 2 hours. Next, filtration and drying were performed, and the powder obtained was dry pulverized to obtain a powder material 7 for layered modeling that was α-TCP powder provided with etidronic acid on the surface.
In the obtained additive manufacturing powder material 7, the amount of etidronic acid that is an organic compound having a phosphate group on the surface of the α-TCP powder was measured in the same manner as in Preparation Example 1. It was 400 ppm.

(Example 8-1)
In Example 1-1, the layered product 8-1 was manufactured as follows instead of the ink jet method instead of the ink jet method. The electron beam irradiation method (EBM) was performed using a self-made electron beam irradiation apparatus.
(1) First, using a known powder additive manufacturing apparatus as shown in FIG. 1, the additive manufacturing powder material 1 is transferred from the supply-side powder storage tank to the modeling-side powder storage tank, and then on the support. A thin layer made of additive manufacturing powder material 1 having an average thickness of 100 μm was formed.
(2) Next, the surface of the thin layer made of the additive manufacturing powder material 1 was irradiated with an electron beam to sinter the additive powder 1 for sintering, thereby sintering the calcium phosphate.
(3) Next, the operations of (1) and (2) are repeated until a total average thickness of 3 mm is reached, and the thin layer made of the additive manufacturing powder material 1 is sequentially laminated, and additive manufacturing is performed. Product 8-1 was produced.
When the excess layered modeling powder material 1 was removed by air blowing from the layered product 8-1 obtained, the mold was not deformed. The obtained sintered body of the layered object 8-1 was excellent in strength and dimensional accuracy.
About the obtained laminate-molded article 8-1, evaluation similar to Example 1-1 was performed. The results are shown in Table 2.

(Example 9-1)
In Example 1-1, the layered object 9-1 was manufactured by the laser irradiation method instead of the ink jet method as follows. The laser was a CO ₂ laser (manufactured by SUNX, LP-400).
(1) First, using a known powder additive manufacturing apparatus as shown in FIG. 1, the additive manufacturing powder material 1 is transferred from the supply-side powder storage tank to the modeling-side powder storage tank, and then on the support. A thin layer made of additive manufacturing powder material 1 having an average thickness of 100 μm was formed.
(2) Next, the surface of the thin layer made of the additive manufacturing powder material 1 is irradiated with the CO ₂ laser to sinter the additive powder 1 to sinter the calcium phosphate. It was.
(3) Next, the operations of (1) and (2) are repeated until a total average thickness of 3 mm is reached, and the thin layer made of the additive manufacturing powder material 1 is sequentially laminated, and additive manufacturing is performed. Product 9-1 was produced.
When the excess layered modeling powder material was removed by air blowing on the obtained layered model 9-1, the mold was not deformed. The sintered body of the obtained layered object 9-1 was excellent in strength and dimensional accuracy.
About the obtained laminate-molded article 9-1, evaluation similar to Example 1-1 was performed. The results are shown in Table 2.

(Comparative Example 1-1)
In Example 1-1, the laminate-molded article 10-1 is the same as Example 1-1 except that the application treatment of the organic compound having a phosphate group or a carboxyl group to the calcium phosphate powder is changed as follows. Manufactured.
About the obtained laminate-molded article 10-1, the same evaluation as Example 1-1 was performed. The results are shown in Table 2.

-Treatment of applying an organic compound having a phosphate group or a carboxyl group to calcium phosphate powder-
30 g of the α-TCP powder, 0.04 g of 50 mass% phytic acid as an organic compound having a phosphate group (manufactured by Wako Pure Chemical Industries, Ltd., number of phosphate groups: 6), 120 g of ion-exchanged water, and a diameter of 3 mm 540 g of zirconia beads were placed in a 500 mL wide-mouthed bottle and wet-ground by a ball mill for 2 hours. Next, the mixture was filtered and dried, and the resulting powder was dry-pulverized to obtain a powder material 8 for additive manufacturing, which is an α-TCP powder provided with phytic acid on the surface.
In the obtained additive manufacturing powder material 8, when the amount of phytic acid (abundance), which is an organic compound having a phosphate group, on the surface of the α-TCP powder was measured in the same manner as in Preparation Example 1, it was 800 ppm. there were.

(Comparative Example 2-1)
In Example 1-1, the laminate-molded article 11-1 was made in the same manner as in Example 1-1 except that the treatment for applying the organic compound having a phosphate group or a carboxyl group to the calcium phosphate powder was changed as follows. Manufactured.
About the obtained laminate-molded article 11-1, the same evaluation as Example 1-1 was performed. The results are shown in Table 2.

-Treatment of applying an organic compound having a phosphate group or a carboxyl group to calcium phosphate powder-
30 g of the α-TCP powder, 0.6 g of 50 mass% phytic acid (manufactured by Wako Pure Chemical Industries, Ltd., number of phosphate groups: 6) as an organic compound having a phosphate group, 120 g of ion-exchanged water, and a diameter of 3 mm 540 g of zirconia beads were placed in a 500 mL wide-mouthed bottle and wet-ground by a ball mill for 2 hours. Next, filtration and drying were performed, and the powder obtained was dry-pulverized to obtain a powder material 9 for layered modeling that was α-TCP powder provided with phytic acid on the surface.
About the obtained additive manufacturing powder material 9, when the application amount (abundance) of phytic acid which is an organic compound having a phosphate group on the surface of the α-TCP powder was measured in the same manner as in Preparation Example 1, 000 ppm.

(Comparative Example 3-1)
In Example 1-1, the laminate-molded article 12-1 was made in the same manner as in Example 1-1 except that the treatment for applying the organic compound having a phosphate group or a carboxyl group to the calcium phosphate powder was changed as follows. Manufactured.
About the obtained laminate-molded article 12-1, the same evaluation as Example 1-1 was performed. The results are shown in Table 2.

-Treatment of applying an organic compound having a phosphate group or a carboxyl group to calcium phosphate powder-
30 g of the α-TCP powder, 0.4 g of polyphosphoric acid (manufactured by Tokyo Chemical Industry Co., Ltd., number of phosphoric acid groups: 15, weight average molecular weight: 1,200) as an organic compound having a phosphoric acid group, 120 g of ion-exchanged water, In addition, 540 g of zirconia beads having a diameter of 3 mm were placed in a 500 mL wide-mouth bottle, and wet-ground by a ball mill for 2 hours. Next, the mixture was filtered and dried, and the resulting powder was dry-pulverized to obtain a powder material 10 for layered modeling that was α-TCP powder with polyphosphoric acid applied to the surface.
In the obtained additive manufacturing powder material 10, the amount (abundance) of polyphosphoric acid, which is an organic compound having a phosphate group, on the surface of the α-TCP powder was measured in the same manner as in Preparation Example 1. there were.

(Comparative Example 4-1)
In Example 1-1, the laminate-molded article 13-1 was made in the same manner as in Example 1-1 except that the treatment for applying the organic compound having a phosphate group or a carboxyl group to the calcium phosphate powder was changed as follows. Manufactured.
About the obtained laminate-molded article 13-1, the same evaluation as Example 1-1 was performed. The results are shown in Table 2.

-Treatment of applying an organic compound having a phosphate group or a carboxyl group to calcium phosphate powder-
30 g of the α-TCP powder, 0.4 g of inositol triphosphate as an organic compound having a phosphate group (manufactured by Dojin Chemical Laboratory Co., Ltd., number of phosphate groups: 3), 120 g of ion-exchanged water, and a diameter of 3 mm 540 g of zirconia beads were placed in a 500 mL wide-mouthed bottle and wet-ground by a ball mill for 2 hours. Next, filtration and drying were performed, and the obtained powder was dry-pulverized to obtain a layered molding powder material 11 which was an α-TCP powder provided with inositol triphosphate on the surface.
In the obtained additive manufacturing powder material 11, when the amount of inositol triphosphate that is an organic compound having a phosphate group on the surface of the α-TCP powder was measured in the same manner as in Preparation Example 1, It was 300 ppm.

(Comparative Example 5-1)
In Example 1-1, the laminate-molded article 14-1 is the same as Example 1-1 except that the treatment for applying the organic compound having a phosphate group or a carboxyl group to the calcium phosphate powder is changed as follows. Manufactured.
About the obtained laminate-molded article 14-1, the same evaluation as Example 1-1 was performed. The results are shown in Table 2.

-Treatment of applying an organic compound having a phosphate group or a carboxyl group to calcium phosphate powder-
30 g of the α-TCP powder, 0.04 g of citric acid as an organic compound having a carboxyl group (manufactured by Wako Pure Chemical Industries, Ltd., number of carboxyl groups: 3), 120 g of ion-exchanged water, and 540 g of zirconia beads having a diameter of 3 mm It put into a 500 mL wide-mouth bottle, and wet-pulverized for 2 hours with the ball mill. Next, the mixture was filtered and dried, and the resulting powder was dry-pulverized to obtain a powder material 12 for additive manufacturing that is an α-TCP powder provided with citric acid on the surface.
About the obtained additive manufacturing powder material 12, when the application amount (abundance) of citric acid, which is an organic compound having a carboxyl group, on the surface of the α-TCP powder was measured in the same manner as in Example 6-1, 400 ppm. Met.

(Comparative Example 6-1)
In Example 1-1, the application treatment of the organic compound having a phosphate group or a carboxyl group to the calcium phosphate powder is not performed, that is, the α-TCP powder prepared in Preparation Example 1 is used as the powder material 13 for additive manufacturing. A layered object 15-1 was produced in the same manner as Example 1-1 except that.
The obtained layered object 15-1 was evaluated in the same manner as in Example 1-1. The results are shown in Table 2.

(Comparative Example 7-1)
In Example 8-1, a layered object 16-1 was produced in the same manner as in Example 8-1, except that the layered powder material 8 was used instead of the layered powder material 1.
The obtained layered product 16-1 was evaluated in the same manner as in Example 1-1. The results are shown in Table 2.

(Comparative Example 8-1)
In Example 8-1, a layered object 17-1 was manufactured in the same manner as in Example 8-1, except that the layered powder material 9 was used instead of the layered powder material 1.
About the obtained layered product 17-1, evaluation similar to Example 1-1 was performed. The results are shown in Table 2.

(Comparative Example 9-1)
In Example 9-1, a layered object 18-1 was manufactured in the same manner as Example 9-1 except that the layered powder material 8 was used instead of the layered powder material 1.
The obtained layered product 18-1 was evaluated in the same manner as in Example 1-1. The results are shown in Table 2.

(Comparative Example 9-1)
In Example 9-1, a layered object 19-1 was produced in the same manner as Example 9-1 except that the layered powder material 9 was used instead of the layered powder material 1.
About the obtained layered product 19-1, evaluation similar to Example 1-1 was performed. The results are shown in Table 2.

From the results of Tables 1 and 2, Comparative Examples 2-1, 8-1 and 10-1 have good strength and dimensional accuracy results, but the amount of phytic acid applied is too large, so that the cytotoxicity is high. There is a possibility that cytotoxicity will be manifested when transplanted in vivo.
Moreover, all of Comparative Examples 1-1, 3-1 to 7-1, and 9-1 have a HAp transfer rate of over 1%, and transfer to hydroxyapatite (HAp) when transplanted in vivo. There is a problem that it remains in the living body.

(Preparation Example 5)
<Preparation of powder material 101 for additive manufacturing>
-Preparation of powder composed of organic compound having phosphate group or carboxyl group-
50 mass% phytic acid (Wako Pure Chemical Industries, Ltd., phosphate group number: 6) was freeze-dried at minus 40 ° C. and 0.1 Torr reduced pressure, pulverized under cooling, and then freeze-pulverized on a 75 μm mesh sieve. A powder made of an organic compound having a phosphoric acid group was passed through the phytic acid and vibrated.

-Mixing of calcium phosphate powder and powder made of organic compound having phosphate group or carboxyl group-
By mixing so that the powder which consists of the said organic compound which has the said phosphate group with respect to 100-g of (alpha) -TCP powder prepared in the said preparation example 1 may be 15 mass%, it carries out an aster blend under cooling, and is for additive manufacturing. A powder material 101 was obtained.

(Preparation Example 6)
-Preparation of curable liquid 2-
100 parts by mass of water and 0.5 parts by mass of Triton X-100 (manufactured by Tokyo Chemical Industry Co., Ltd.) as a surfactant were mixed and dispersed for 5 minutes using a homomixer to prepare a curable liquid 2.

(Example 1-2)
Using the obtained layered modeling powder material 101 and the curable liquid 2, a layered product 1-2 was manufactured as follows using a shape printing pattern of size (length 70 mm × width 12 mm).

(1) First, using a known powder additive manufacturing apparatus as shown in FIG. 1, the additive manufacturing powder material 101 is transferred from the supply-side powder storage tank to the modeling-side powder storage tank, and then on the support. A thin layer made of the additive manufacturing powder material 101 having an average thickness of 100 μm was formed.

(2) Next, the curable liquid 2 is applied (discharged) from a nozzle to the surface of the thin layer formed of the layered modeling powder material 101 using an inkjet printer (manufactured by Ricoh Co., Ltd., SG7100). The calcium phosphate was cured by curing the additive manufacturing powder material 101.

(3) Next, the operations of (1) and (2) are repeated until a total average thickness of 3 mm is reached, and the cured thin layer made of the additive manufacturing powder material 101 is sequentially laminated, The layered object 1-2 was manufactured. When the excess layered modeling powder material was removed by air blowing from the obtained layered product 1-2, the mold was not deformed. The layered object 1-2 was excellent in strength and dimensional accuracy.

  About the obtained layered product 1-2, the hydroxyapatite transition rate (HAp transition rate), cytotoxicity, strength (hardness), and dimensional accuracy were evaluated in the same manner as in Example 1-1. The results are shown in Table 4.

(4) The layered product 1-2 obtained in (3) was sintered in a sintering furnace at 1,300 ° C. under vacuum conditions. The sintered body of the layered object 1-2 was a completely integrated calcium phosphate structure, and no damage or the like occurred even when it was hit against a hard floor.

(Example 2-2)
In Example 1-2, the additive manufacturing object 2- is changed in the same manner as in Example 1-2, except that the additive manufacturing powder material 101 is changed to the additive manufacturing powder material 102 prepared as follows. 2 was produced.
The obtained layered product 2-2 was evaluated in the same manner as in Example 1-1. The results are shown in Table 4.

<Preparation of additive manufacturing powder material 102>
-Preparation of powder composed of organic compound having phosphate group or carboxyl group-
Etidronic acid (manufactured by Dojindo Laboratories, Inc .; number of phosphate groups: 2) was freeze-dried at minus 40 ° C. and 0.1 Torr reduced pressure, ground under cooling, and then freeze-ground Etidronic acid on a 75 μm mesh sieve A powder made of an organic compound having a phosphoric acid group was passed through the plate and vibrated.

-Mixing of calcium phosphate powder and powder made of organic compound having phosphate group or carboxyl group-
By mixing so that the powder which consists of the said organic compound which has the said phosphate group with respect to 100-g of (alpha) -TCP powder prepared in the said preparation example 1 may be 15 mass%, it carries out an aster blend under cooling, and is for additive manufacturing. A powder material 102 was obtained.

(Example 3-2)
In Example 1-2, the additive manufacturing object 3- is manufactured in the same manner as in Example 1-2 except that the additive manufacturing powder material 101 is changed to the additive manufacturing powder material 103 prepared as follows. 2 was produced.
The obtained layered product 3-2 was evaluated in the same manner as in Example 1-1. The results are shown in Table 4.

<Preparation of additive manufacturing powder material 103>
-Preparation of powder composed of organic compound having phosphate group or carboxyl group-
Citric acid (manufactured by Wako Pure Chemical Industries, Ltd., number of carboxyl groups: 3) was freeze-dried at minus 40 ° C. under a reduced pressure of 0.1 Torr, pulverized under cooling, and then freeze-pulverized phytic acid was applied to a 75 μm mesh sieve. The powder that was placed and vibrated and passed was made into a powder made of an organic compound having a carboxyl group.

-Mixing of calcium phosphate powder and powder made of organic compound having phosphate group or carboxyl group-
The powder for additive manufacturing is prepared by mixing 100 g of the α-TCP powder prepared in Preparation Example 1 so that the powder composed of the organic compound having a carboxyl group is 15% by mass, and auster blending under cooling. Material 103 was obtained.

(Example 4-2)
In Example 1-2, except that the additive manufacturing powder material 101 was changed to the additive manufacturing powder material 104 prepared as follows, the additive manufacturing product 4- 2 was produced.
The obtained layered product 4-2 was evaluated in the same manner as in Example 1-1. The results are shown in Table 4.

<Preparation of powder material 104 for additive manufacturing>
-Preparation of powder composed of organic compound having phosphate group or carboxyl group-
50 mass% phytic acid (Wako Pure Chemical Industries, Ltd., phosphate group number: 6) was freeze-dried at minus 40 ° C. and 0.1 Torr reduced pressure, pulverized under cooling, and then freeze-pulverized on a 75 μm mesh sieve. A powder made of an organic compound having a phosphoric acid group was passed through the phytic acid and vibrated.

-Mixing of calcium phosphate powder and powder made of organic compound having phosphate group or carboxyl group-
By mixing so that the powder which consists of the said organic compound which has the said phosphoric acid group with respect to 100g of (beta) -TCP powder prepared in the said preparation example 2 may be 15 mass%, it is auster-blended under cooling, for additive manufacturing A powder material 104 was obtained.

(Example 5-2)
In Example 1-2, the additive manufacturing object 5 was changed in the same manner as in Example 1-2 except that the additive manufacturing powder material 101 was changed to the additive manufacturing powder material 105 prepared as follows. 2 was produced.
The obtained layered product 5-2 was evaluated in the same manner as in Example 1-1. The results are shown in Table 4.

<Preparation of additive manufacturing powder material 105>
-Preparation of powder composed of organic compound having phosphate group or carboxyl group-
50 mass% phytic acid (Wako Pure Chemical Industries, Ltd., phosphate group number: 6) was freeze-dried at minus 40 ° C. and 0.1 Torr reduced pressure, pulverized under cooling, and then freeze-pulverized on a 75 μm mesh sieve. A powder made of an organic compound having a phosphoric acid group was passed through the phytic acid and vibrated.

-Mixing of calcium phosphate powder and powder made of organic compound having phosphate group or carboxyl group-
The powder material for additive manufacturing is prepared by mixing 100 g of the OCP powder prepared in Preparation Example 3 so that the powder composed of the organic compound having a phosphoric acid group is 15% by mass, and auster blending under cooling. 105 was obtained.

(Example 6-2)
In Example 1-2, the additive manufacturing object 6- was manufactured in the same manner as in Example 1-2, except that the additive manufacturing powder material 101 was changed to the additive manufacturing powder material 106 prepared as follows. 2 was produced.
The obtained layered product 6-2 was evaluated in the same manner as in Example 1-1. The results are shown in Table 4.

<Preparation of additive manufacturing powder material 106>
-Preparation of powder composed of organic compound having phosphate group or carboxyl group-
50 mass% phytic acid (Wako Pure Chemical Industries, Ltd., phosphate group number: 6) was freeze-dried at minus 40 ° C. and 0.1 Torr reduced pressure, pulverized under cooling, and then freeze-pulverized on a 75 μm mesh sieve. A powder made of an organic compound having a phosphoric acid group was passed through the phytic acid and vibrated.

-Mixing of calcium phosphate powder and powder made of organic compound having phosphate group or carboxyl group-
By mixing so that the powder which consists of the said organic compound which has the said phosphate group with respect to 100-g of (alpha) -TCP powder prepared in the said preparation example 1 may be 10 mass%, it carries out an aster blend under cooling, and is for additive manufacturing. A powder material 106 was obtained.

(Example 7-2)
In Example 1-2, the additive manufacturing object 7- was prepared in the same manner as in Example 1-2, except that the additive manufacturing powder material 101 was changed to the additive manufacturing powder material 107 prepared as follows. 2 was produced.
The obtained layered product 7-2 was evaluated in the same manner as in Example 1-1. The results are shown in Table 4.

<Preparation of additive manufacturing powder material 107>
-Preparation of powder composed of organic compound having phosphate group or carboxyl group-
50 mass% phytic acid (Wako Pure Chemical Industries, Ltd., phosphate group number: 6) was freeze-dried at minus 40 ° C. and 0.1 Torr reduced pressure, pulverized under cooling, and then freeze-pulverized on a 75 μm mesh sieve. A powder made of an organic compound having a phosphoric acid group was passed through the phytic acid and vibrated.

-Mixing of calcium phosphate powder and powder made of organic compound having phosphate group or carboxyl group-
Mixing so that the powder which consists of the said organic compound which has the said phosphate group with respect to 100 g of (alpha) -TCP powder prepared in the said preparation example 1 may be 50 mass%, and for austenitic mixing by auster blending under cooling. A powder material 107 was obtained.

(Example 8-2)
In Example 1-2, the layered object 8-2 was manufactured by the laser irradiation method instead of the ink jet method as follows. The laser was a CO ₂ laser (manufactured by SUNX, LP-400).
(1) First, using a known powder additive manufacturing apparatus as shown in FIG. 1, the additive manufacturing powder material 101 is transferred from the supply-side powder storage tank to the modeling-side powder storage tank, and then on the support. A thin layer made of the additive manufacturing powder material 101 having an average thickness of 100 μm was formed.
(2) Next, the surface of a thin layer made of the layered modeling powder material 101 is irradiated with the CO ₂ laser to sinter the layered modeling powder material 101, thereby sintering the calcium phosphate. It was.
(3) Next, the operations of (1) and (2) are repeated until a total average thickness of 3 mm is obtained, and the thin layer made of the powder material for additive manufacturing 101 is sequentially stacked, and additive manufacturing is performed. Product 8-2 was produced.
When the excess layered modeling powder material was removed by air blowing from the obtained layered product 8-2, the mold was not deformed. The sintered body of the obtained layered product 8-2 was excellent in strength and dimensional accuracy.
The obtained layered product 8-2 was evaluated in the same manner as in Example 1-1. The results are shown in Table 4.

(Example 9-2)
In Example 1-2, instead of the inkjet method, the layered product 9-2 was manufactured as follows instead of the electron beam irradiation method (EBM). The electron beam irradiation method (EBM) was performed using a self-made electron beam irradiation apparatus.
(1) First, using a known powder additive manufacturing apparatus as shown in FIG. 1, the additive manufacturing powder material 101 is transferred from the supply-side powder storage tank to the modeling-side powder storage tank, and then on the support. A thin layer made of the additive manufacturing powder material 101 having an average thickness of 100 μm was formed.
(2) Next, the surface of the thin layer made of the layered modeling powder material 101 was irradiated with an electron beam to sinter the layered modeling powder material 101, thereby sintering the calcium phosphate.
(3) Next, the operations of (1) and (2) are repeated until a total average thickness of 3 mm is obtained, and the thin layer made of the powder material for additive manufacturing 101 is sequentially stacked, and additive manufacturing is performed. Product 9-2 was produced.
When the excess layered modeling powder material was removed by air blowing on the obtained layered product 9-2, there was no loss of shape. The sintered body of the obtained layered product 9-2 was excellent in strength and dimensional accuracy.
Evaluation similar to Example 1-1 was performed about the obtained layered product 9-2. The results are shown in Table 4.

(Comparative Example 1-2)
In Example 1-2, the additive manufacturing object 10- was prepared in the same manner as in Example 1-2, except that the additive manufacturing powder material 101 was changed to the additive manufacturing powder material 108 prepared as follows. 2 was produced.
The obtained layered object 10-2 was evaluated in the same manner as in Example 1-1. The results are shown in Table 4.

<Preparation of additive manufacturing powder material 108>
-Preparation of powders composed of organic compounds-
Inositol (manufactured by Shikishima Starch Co., Ltd., phosphoric acid group or carboxyl group number: 0) was passed through a 75 μm mesh sieve, and the powder passed through it was made into a powder composed of an organic compound.

-Mixing of calcium phosphate powder and organic compound powder-
The powder material 108 for additive manufacturing is obtained by mixing so that the powder which consists of the said organic compound may be 15 mass% with respect to 100 g of (alpha) -TCP powder prepared in the said preparation example 1, and auster blending under cooling. It was.

(Comparative Example 2-2)
In Example 1-2, the additive manufacturing object 11- was prepared in the same manner as in Example 1-2, except that the additive manufacturing powder material 101 was changed to the additive manufacturing powder material 109 prepared as follows. 2 was produced.
The obtained layered product 11-2 was evaluated in the same manner as in Example 1-1. The results are shown in Table 4.

<Preparation of additive manufacturing powder material 109>
-Preparation of powder composed of organic compound having phosphate group or carboxyl group-
50 mass% phytic acid (Wako Pure Chemical Industries, Ltd., phosphate group number: 6) was freeze-dried at minus 40 ° C. and 0.1 Torr reduced pressure, pulverized under cooling, and then freeze-pulverized on a 75 μm mesh sieve. A powder made of an organic compound having a phosphoric acid group was passed through the phytic acid and vibrated.

-Mixing of calcium phosphate powder and powder made of organic compound having phosphate group or carboxyl group-
By mixing so that the powder which consists of the said organic compound which has the said phosphoric acid group may become 9 mass% with respect to the alpha-TCP powder 100g prepared in the said preparation example 1, it is an auster-blending under cooling, for additive manufacturing A powder material 109 was obtained.

(Comparative Example 3-2)
In Example 1-2, the additive manufacturing object 12- was prepared in the same manner as in Example 1-2, except that the additive manufacturing powder material 101 was changed to the additive manufacturing powder material 110 prepared as follows. 2 was produced.
The obtained layered product 12-2 was evaluated in the same manner as in Example 1-1. The results are shown in Table 4.

<Preparation of powder material 110 for additive manufacturing>
-Preparation of powder composed of organic compound having phosphate group or carboxyl group-
50 mass% phytic acid (Wako Pure Chemical Industries, Ltd., phosphate group number: 6) was freeze-dried at minus 40 ° C. and 0.1 Torr reduced pressure, pulverized under cooling, and then freeze-pulverized on a 75 μm mesh sieve. A powder made of an organic compound having a phosphoric acid group was passed through the phytic acid and vibrated.

-Mixing of calcium phosphate powder and powder made of organic compound having phosphate group or carboxyl group-
By mixing so that the powder which consists of the said organic compound which has the said phosphate group with respect to 100-g of alpha-TCP powder prepared in the said preparation example 1 may be 51 mass%, it carries out an aster blend under cooling, and is for additive manufacturing. A powder material 110 was obtained.

(Comparative Example 4-2)
In Example 1-2, the additive manufacturing object 13- was prepared in the same manner as in Example 1-2, except that the additive manufacturing powder material 101 was changed to the additive manufacturing powder material 111 prepared as follows. 2 was produced.
The obtained layered product 13-2 was evaluated in the same manner as in Example 1-1. The results are shown in Table 4.

<Preparation of additive manufacturing powder material 111>
-Preparation of powder composed of organic compound having phosphate group or carboxyl group-
A freeze-dried product of acetic acid (manufactured by Aszac Foods Co., Ltd., number of carboxyl groups: 1) was passed through a 75 μm mesh sieve, and the passed product was made into a powder composed of an organic compound having a carboxyl group.

-Mixing of calcium phosphate powder and powder made of organic compound having phosphate group or carboxyl group-
The powder for additive manufacturing is prepared by mixing 100 g of the α-TCP powder prepared in Preparation Example 1 so that the powder composed of the organic compound having a carboxyl group is 15% by mass, and auster blending under cooling. Material 111 was obtained.

(Comparative Example 5-2)
In Example 1-2, except that the powder made of an organic compound having a phosphate group or a carboxyl group was not used, that is, the α-TCP powder of Preparation Example 1 was used as the additive manufacturing powder material 112. A layered object 14-2 was produced in the same manner as Example 1-2.
The obtained layered product 14-2 was evaluated in the same manner as in Example 1-1. The results are shown in Table 4.

From the results of Tables 3 and 4, Comparative Example 3-2 has a cytotoxicity of 51% by mass because phytic acid is mixed too much, and may be cytotoxic when transplanted in vivo. There is.
In addition, Comparative Examples 1-2, 2-2, 4-2, and 5-2 have an HAp transfer rate of more than 1%, and when transplanted in vivo, transfer to hydroxyapatite in vivo. There is a problem of remaining.

As an aspect of this invention, it is as follows, for example.
<1> A powder material for additive manufacturing comprising calcium phosphate powder,
Satisfy A) or B) below,
And the hydroxyapatite (HAp) transition rate of the hardened | cured material which hardens the said powder material for layered modeling is 1% or less, It is a powder material for layered modeling characterized by the above-mentioned.
A) An organic compound having a phosphate group or a carboxyl group is applied to the surface of the calcium phosphate powder, and the applied amount of the organic compound is 10,000 ppm or less.
B) It further includes a powder made of an organic compound having a phosphate group or a carboxyl group, and the mixing amount of the organic compound with respect to the calcium phosphate powder is 50% by mass or less.
<2> The additive manufacturing powder material according to <1>, wherein an application amount of the organic compound having a phosphate group or a carboxyl group is 1,000 ppm or more and 10,000 ppm or less.
<3> The additive manufacturing powder material according to any one of <1> to <2>, wherein the organic compound has two or more phosphate groups per molecule or two or more carboxyl groups per molecule. It is.
<4> The additive manufacturing powder material according to any one of <1> to <3>, wherein the organic compound is a monomer.
<5> The additive manufacturing powder material according to any one of <1> to <4>, wherein the organic compound is at least one selected from phytic acid, etidronic acid, and citric acid.
<6> The additive manufacturing powder material according to any one of <1> to <5>, wherein the powder made of the organic compound is a water-soluble powder, and the water-soluble powder is not in a salt state.
<7> The above calcium phosphate is at least one selected from β-tricalcium phosphate (β-TCP), α-tricalcium phosphate (α-TCP), and octacalcium phosphate (OCP) < The powder material for additive manufacturing according to any one of <1> to <6>.
<8> Laminate modeling powder material layer formation in which a layered modeling powder material layer having a predetermined thickness is formed on the support using the additive manufacturing powder material according to any one of <1> to <7>. It is a manufacturing method of a layered product characterized by including at least a process.
<9> The layered product according to <8>, including a layer curing step in which a curing liquid is applied to the layered modeling powder material layer by an inkjet method to cure a predetermined region of the layered modeling powder material layer. It is a manufacturing method.
<10> The method for producing a layered object according to <9>, further including a sintering step of sintering a layered cured product formed by sequentially repeating the layer forming step and the layer curing step.
<11> The layered product according to <8>, including a sintering step in which either the laser irradiation or the electron beam irradiation is performed on the layered powder material layer to sinter the layered powder material layer. It is a manufacturing method.
<12> A layered modeling set comprising: the layered modeling powder material according to any one of <1> to <7>, and a curable liquid.

DESCRIPTION OF SYMBOLS 1 Modeling side powder storage tank 2 Supply side powder storage tank 3 Stage 4 Hardening liquid 5 Inkjet head 6 Leveling mechanism

JP-A-5-237278 US Pat. No. 5,204,055 US Pat. No. 5,902,441 US Pat. No. 6,375,874 JP-A-9-324203 JP 2004-42546 A Japanese Patent No. 4575295

Claims (14)

A powder material for additive manufacturing comprising calcium phosphate powder,
Satisfy A) or B) below,
And the hydroxyapatite (HAp) transition rate of the hardened | cured material formed by hardening | curing the said powder material for layered modeling is 1% or less, The powder material for layered modeling characterized by the above-mentioned.
A) An organic compound having a phosphate group or a carboxyl group is provided on the surface of the calcium phosphate powder, the applied amount of the organic compound is 10,000 ppm or less, and the organic compound is etidronic acid.
B) Including a powder composed of an organic compound having a phosphate group or a carboxyl group, the mixing amount of the organic compound with respect to the calcium phosphate powder is 50% by mass or less, and the organic compound is etidronic acid.   2. The additive manufacturing powder material according to claim 1, wherein an applied amount of the organic compound having a phosphate group or a carboxyl group is 1,000 ppm or more and 5,000 ppm or less.   3. The additive manufacturing powder material according to claim 1, wherein the organic compound has two or more phosphate groups per molecule or two or more carboxyl groups per molecule.   The layered modeling powder material according to any one of claims 1 to 3, wherein the organic compound is a chelate material. A powder material for additive manufacturing comprising calcium phosphate powder,
A powder comprising an organic compound having a phosphoric acid group or a carboxyl group, a mixing amount of the organic compound with respect to the calcium phosphate powder is 50% by mass or less, the organic compound is etidronic acid, and the powder material for additive manufacturing The powder material for additive manufacturing according to any one of claims 1 to 4, wherein a hydroxyapatite (HAp) transition rate of a cured product obtained by curing the material is 1% or less.   The powder material for additive manufacturing according to any one of claims 1 to 5, wherein the powder made of the organic compound is a water-soluble powder, and the water-soluble powder is not in a salt state.   The calcium phosphate is at least one selected from β-tricalcium phosphate (β-TCP), α-tricalcium phosphate (α-TCP), and octacalcium phosphate (OCP). The powder material for additive manufacturing according to any one of the above.   The powder material for additive manufacturing according to any one of claims 1 to 7, wherein the average circularity is 0.70 or more and 0.80 or less.   9. The additive manufacturing powder material according to claim 1, wherein a particle size distribution Dv / Dn, which is a ratio of the volume average particle diameter Dv to the number average particle diameter Dn, is 1.10 or more and 1.80 or less. A manufacturing method of a layered object that repeats at least a layered powder material layer forming step of forming a layered powder material layer using a layered powder material on a support,
The layered modeling powder material contains calcium phosphate powder, and the hydroxyapatite (HAp) transition rate of a cured product obtained by curing the layered modeling powder material is 1% or less,
The calcium phosphate powder surface are applied organic compound having a phosphoric acid group or carboxyl group, the application amount is Der below 10,000ppm of the organic compound is, lamination molding of the organic compound is characterized in that the etidronate Manufacturing method.   The manufacturing method of the layered product according to claim 10, further comprising a layer curing step of applying a curing liquid to the layered modeling powder material layer by an inkjet method and curing a predetermined region of the layered modeling powder material layer.   The method for producing a layered object according to claim 11, further comprising a sintering step of sintering a layered cured product formed by sequentially repeating the layer forming step and the layer curing step.   The manufacturing method of the laminate-molded article according to claim 10, further comprising a sintering step in which either the laser irradiation or the electron beam irradiation is performed on the additive-molding powder material layer to sinter the additive-molding powder material layer. A powdered material for layered molding having a hydroxyapatite (HAp) transition rate of 1% or less of a cured product obtained by curing a powdered material for layered modeling containing calcium phosphate powder, and a curing solution,
A layered modeling set characterized in that an organic compound having a phosphate group or a carboxyl group is provided on the surface of the calcium phosphate powder, the applied amount of the organic compound is 10,000 ppm or less, and the organic compound is etidronic acid. .