Medical-grade calcium carbonate composition, related medical compositions, and methods for producing the same.

Abstract

This invention provides a medical calcium carbonate composition, a medical calcium phosphate composition related to the medical calcium carbonate composition, and a method for producing the same, which highly satisfy the requirements for medical materials implanted in the body: 1) tissue affinity, 2) bioavailability, 3) reactivity, and 4) mechanical strength. [Solution] By controlling the polymorphism and structure of calcium carbonate, medical compositions such as calcium carbonate and related medical compositions that highly satisfy the above elements can be manufactured.

Description

[Technical Field]

[0001] The present invention relates to medical compositions and methods for producing the same. Specifically, it relates to medical calcium carbonate compositions for implantation in vivo, cell culture scaffolds for use outside the body, and related medical calcium sulfate curable compositions, medical calcium phosphate compositions, medical calcium hydroxide compositions, bone defect reconstruction treatment kits, and methods for producing the same. More specifically, this invention relates to a medical calcium carbonate composition that highly satisfies 1) tissue affinity, 2) bioavailability, 3) reactivity, and 4) mechanical strength, as well as related medical compositions and methods for producing them. [Background technology]

[0002] The skeletal composition of invertebrates is calcium carbonate, while the skeletal composition of vertebrates is carbonate apatite, a type of calcium phosphate in which a phosphate component is added to calcium carbonate. Calcium carbonate is being studied as a bone graft material, and calcium phosphate and calcium sulfate, which contain carbonate apatite, are being used clinically as bone graft materials. (tissue affinity) Medical compositions, such as bone graft materials, differ from industrial compositions in their required properties, with in vivo reactions being paramount. Implanting powders into the body can trigger inflammatory responses. Therefore, medical compositions implanted in the body are required to have a certain volume or more from the perspective of tissue compatibility. Antibacterial properties may also be required from the perspective of infection prevention. As medical compositions, being substantially pure is also an essential requirement. (Bioabsorption) As bone graft materials, medical-grade calcium carbonate compounds and related medical compositions are sometimes expected to be absorbed in the body and replaced by the desired tissue. Tissue replacement requires both material absorption and tissue regeneration. Calcium carbonate and some calcium phosphates are absorbed by osteoclasts, but for absorption to occur, they must not contain materials that are not absorbed in the body. (Reactive) Medical calcium carbonate compositions are sometimes required to exhibit excellent tissue reactivity, such as tissue replacement, within the body, or to exhibit chemical reactivity. For the former, the penetration and dissolution of tissues, cells, and tissue fluid are key factors, and pore control, polymorphism, and crystallite size are important. For the latter, the penetration and dissolution of aqueous solutions are key factors, and pore control, polymorphism, and crystallite size are important. Regarding the latter, medical-grade calcium carbonate compositions are not only expected to be used as bone graft materials, but are also useful as precursors in the production of medical-grade calcium phosphate compositions, such as medical-grade carbonate apatite compositions. For example, when a calcium carbonate block is immersed in an aqueous phosphate solution, the composition changes to carbonate apatite while maintaining its macroscopic shape through a dissolution and extraction reaction, and carbonate apatite blocks can be produced (Patent Document 1). However, since the dissolution and extraction reaction proceeds from the surface of the calcium carbonate block, if the calcium carbonate block is large or has low reactivity, the composition may not be completely converted to carbonate apatite, and a core may remain. Therefore, there is a need for highly reactive medical-grade calcium carbonate compositions and manufacturing methods that accelerate the addition of phosphate components. The reactivity of calcium carbonate compositions is greatly influenced not only by their composition and polymorphism, but also by their structure. Interconnected porous structures, in particular, are desirable because they allow cells and tissues to migrate into them. While macropores of a certain size or larger are necessary for cell and tissue migration, smaller micropores are also important when tissue replacement is desired. (mechanical strength) Generally, a high number of macropores and micropores is desirable, but as porosity increases, mechanical strength decreases. Therefore, a balance between porosity and mechanical strength is important. Furthermore, medical-grade calcium phosphate compositions manufactured from medical-grade calcium carbonate compositions, as well as medical-grade calcium hydroxide compositions, medical-grade calcium sulfate compositions, and bone defect reconstruction treatment kits necessary for the manufacture of medical-grade calcium carbonate compositions, are also important as related medical compositions.

[0003] (Reactivity of calcium carbonate: polymorphism, stomata, and density) The reactivity of calcium carbonate is influenced by various factors such as polymorphism, stomata, and density. Vaterite is metastable at room temperature and pressure, does not exist in nature, but is the most reactive form of calcium carbonate. Its density is 2.64 g / cm³. 3 Calcite is a stable phase at room temperature and pressure and is less reactive than vaterite. Its density is 2.71 g / cm³. 3 Aragonite is a stable phase at high temperature and pressure, and a metastable phase at room temperature and pressure. Its density is 2.96 g / cm³. 3 When high-density calcium carbonate is used as a raw material for manufacturing medical materials, the resulting medical materials have a high density, which can lead to low reactivity. Therefore, calcium carbonate with a relatively low density is sometimes preferred. Furthermore, porosity has the greatest impact on the reactivity of calcium carbonate, and generally, higher porosity results in higher reactivity. Therefore, when using calcium carbonate as a raw material to manufacture other materials, using calcium carbonate with a lower density can sometimes result in the production of highly reactive materials. For these reasons, the present invention is limited to calcium carbonate composed of vaterite and calcite.

[0004] (Background of the vaterite composition) Vaterite is a metastable phase and is highly reactive not only compared to the stable phase calcite, but also compared to the metastable phase aragonite, making it extremely preferable as a medical calcium carbonate composition. To date, compositions containing 20% ​​or more by mass of vaterite and with a volume of 10 -12 m 3 No medical-grade vaterite composition met the above criteria. Vaterite powder can be produced by methods such as adding divalent cations other than calcium to slow down the transition to calcite when producing calcium carbonate by aqueous reaction of a water-soluble calcium salt and a carbonate (Patent Documents 2 and 3), controlling the Ca concentration, temperature, and pH of the slurry when carbonated calcium chloride or calcium nitrate (Patent Documents 4 and 5), passing an O / W emulsion consisting of a continuous aqueous phase in which calcium ions are dissolved and an organic phase through a porous membrane and then reacting it with an aqueous solution containing carbonate ions (Patent Document 6), introducing carbon dioxide into an alcohol-water mixed suspension solution of calcium hydroxide (Patent Document 7), adding alkylamine salt type surfactants (Non-Patent Document 1), and adding organic substances such as ethylene glycol (Non-Patent Document 2). However, the powder cannot be used because it induces inflammatory reactions in living organisms. The present inventors have discovered a method for producing calcite granules containing 17% by mass of vaterite by immersing anhydrous calcium sulfate granules in 50 mL of a 2-molar concentration sodium carbonate aqueous solution at 4°C for 14 days. However, this production method does not sufficiently suppress calcite formation, resulting in a vaterite content of 17% by mass (Patent Document 8). Furthermore, as described in Patent Document 8, it is considered essential to keep the electrolyte temperature below 10°C when producing inorganic compounds containing calcium carbonate and vaterite, which presented problems in terms of product and manufacturing. (Patent Document 8) In other words, no medical calcium carbonate composition containing 20% ​​or more by mass of vaterite that satisfies all the above-mentioned conditions for a medical calcium carbonate composition, nor a method for producing the same, is known. Furthermore, no method for producing vaterite at temperatures above 10°C was known. That is, no medical material of a certain size or larger that highly suppresses calcite formation and contains 20% or more by mass of vaterite was known. Naturally, no sintered bodies containing vaterite were known.

[0005] (Background of the calcite composition) Calcite, which is a stable phase within calcium carbonate, is relatively easy to manufacture in the form of granules or blocks, and methods such as exposing compacted calcium hydroxide powder to carbon dioxide have been reported (Patent Document 9). On the other hand, the reactivity of the stable phase, calcite, is lower than that of the metastable phases, vaterite and aragonite. When calcium phosphate is produced by adding phosphate to calcite, the calcium phosphate formation reaction proceeds from the surface of the calcite composition. As a result, a calcium carbonate core may remain, making it virtually impossible to produce a calcium phosphate composition, or a reaction temperature higher than 100°C may be required, or the production process may take a long time. To increase the apparent reactivity of medical-grade calcium carbonate compositions, creating interconnected porous materials is effective. For example, when producing a medical-grade calcium phosphate composition from a certain volume or more of medical-grade calcite, a dense material may leave a core or require a long manufacturing time. However, with the same volume of interconnected porous material, the reaction proceeds from the porous surface, resulting in no core remaining and enabling the production of the medical-grade calcium phosphate composition in a shorter time. Interconnected porous materials allow cells and tissues to penetrate into their interior. For example, in the case of interconnected porous carbonate apatite, bone replacement is dramatically enhanced. Various studies have been conducted on porous calcium carbonate for medical use, which serves as a precursor to porous carbonate apatite for medical use. For example, a method has been proposed to produce porous calcium carbonate by mixing calcium hydroxide with a pore-forming substance such as sodium chloride, compacting the mixture, carbonating it, and then removing the pore-forming substance (Patent Document 9). Although the reactivity is improved by forming a porous body, further improvement in reactivity was desired because it is a porous calcite material. In addition, limiting the pore size is extremely important from the viewpoint of mechanical strength and reactivity, but at the time, a specific pore size was not known. Until now, calcium carbonate has been considered difficult to sinter because it decomposes. However, a method has been proposed to easily produce a sintered calcium carbonate body by adding a foaming agent to a dispersion containing calcium carbonate and a gelling agent, stirring, and sintering the foam (Patent Document 10). In this manufacturing method, interconnected pores are formed, but they are large pores ranging from several hundred microns to more than 1 mm, and the walls are thick, resulting in poor reactivity. Furthermore, because foaming is used to form the pores, reproducibility is poor. Moreover, as described in Reference Example 1 of Patent Document 10, if potassium carbonate and lithium carbonate, which are sintering aids, are not added, a porous calcium carbonate sintered body cannot be obtained in the first place. Also, bone graft materials with added potassium or lithium are undesirable. Although porous calcium carbonate sintered bodies can be produced by adding sintering aids or using high-purity calcium carbonate, they have low mechanical strength and poor clinical practicality. Furthermore, a degreasing method for producing porous ceramic bodies has been proposed (Patent Document 11) characterized by raising the temperature to above the decomposition start temperature of the thermally meltable resin beads at a heating rate of 30°C / hour or more when producing porous ceramic bodies using thermally meltable resin beads as a pore-forming material. While this method is useful for thermally stable ceramics such as alumina, its usefulness is limited for ceramics that decompose at high temperatures such as calcium carbonate, and more advanced degreasing methods are required for medical compositions where high reactivity is expected. Although the method of mixing a pore-forming material with raw ceramics allows for precise adjustment of pore size, a relatively large amount of pore-forming material is required to form a connected porous body, and as the porosity increases, the mechanical strength of the produced porous ceramic body decreases significantly, thus requiring the introduction of an appropriate pore-forming material. The present inventors have proposed a method for producing interconnected porous calcium carbonate structures, which involves extruding calcium hydroxide containing a polymer material through a mold for forming a honeycomb structure, degreasing the polymer material, and then performing a carbonation treatment, or simultaneously degreasing and carbonating the polymer material, to produce a calcium carbonate honeycomb structure (Patent Document 12). They also disclose that a carbonate apatite honeycomb structure can be produced by adding a phosphate component to the calcium carbonate honeycomb structure of the present invention. The calcium carbonate honeycomb structure and the carbonate apatite honeycomb structure exhibit osteoconductivity and excellent properties such as the conduction of bone being highly oriented in the direction of the through-holes. While diligently conducting research and development on the carbonate apatite honeycomb structure, it was discovered that the degreasing of the calcium carbonate honeycomb structure was insufficient, and it was found that there is a possibility of producing a more functional medical calcium carbonate composition by improving the level of degreasing. In other words, in the production of the calcium carbonate honeycomb structure of the present invention, polymer materials such as wax-based organic binders were used, and therefore degreasing was performed. However, at the time, it was believed that the required degree of degreasing differed depending on the desired degree of whiteness, and the required level of degreasing for medical-grade calcium carbonate compositions had not been clarified, nor had a method been devised to quantify the degree of degreasing. Moreover, it was unimaginable that acid-dissolved residues due to the degree of degreasing would have a significant impact on the reactivity and usefulness of the calcium carbonate honeycomb structure. Therefore, the calcium carbonate honeycomb structure disclosed in Example 1 of Patent Document 12 (Comparative Example 6 of this specification) contained 1.2% by mass of acid-dissolved residue. Furthermore, the carbonate apatite honeycomb structure produced by adding a phosphate component to the calcium carbonate honeycomb structure (Example 11 of Patent Document 12) also contained 1.2% by mass of acid-dissolved residue. At the time, it was not predicted that these acid-dissolved residues, even if they caused discoloration, would necessarily affect long-term tissue affinity. In fact, even carbonate apatite honeycomb structures containing 1.2% by mass of acid-dissolved residue were confirmed to have a certain degree of osteoconductivity and excellent tissue affinity. While diligently investigating further functional improvements to the carbonate apatite honeycomb structure, it was discovered that even small amounts of acid-dissolved residue can affect osteoconductivity and bioabsorption. Therefore, we have been diligently researching medical-grade calcium carbonate honeycomb structures with acid-dissolved residue of 1% by mass or less, and ideally 0% by mass. Furthermore, in medical-grade calcium carbonate honeycomb structures, not only macropores that form interconnected structures but also micropores are important. This is because, in addition to macropores that are useful for the penetration of tissues and cells, micropores are useful for promoting the absorption of the porous material of medical-grade calcium carbonate by cells and bodily fluids, or for their reaction with aqueous solutions. However, until now, methods for identifying micropores useful in medical-grade calcium carbonate compositions and the effective range of micropores have not been found.

[0006] [Prior art documents] [Patent Documents]

[0007] [Patent Document 1] Republished Patent No. W02004 / 112856 [Patent Document 2] Japanese Patent Application Publication No. 57-92520 [Patent Document 3] Japanese Patent Application Publication No. 60-90822 [Patent Document 4] Japanese Patent Application Publication No. 54-150397 [Patent Document 5] Japanese Patent Publication No. 2011-126741 [Patent Document 6] Japanese Patent Publication No. 2011-157245 [Patent Document 7] Japanese Patent Application Publication No. 11-314915 [Patent Document 8] International Publication No. 2016 / 035751 [Patent Document 9] Japanese Patent Publication No. 2016-552061 [Patent Document 10] Japanese Patent Publication No. 2018-140890 [Patent Document 11] Japanese Patent Application Publication No. 7-223871 [Patent Document 12] International Publication No. 2018 / 074429

[0008] [Non-Patent Document 1] Journal of the Japan Adhesion Society, Vol. 22, No. 11, 1986, pp. 573-579 [Non-Patent Document 2] Materials, Vol. 30, No. 336, 1986, pp. 6-10

[0009] [Overview of the project] [Problems that the invention aims to solve]

[0010] The object of the present invention is to provide a medical calcium carbonate composition that highly satisfies 1) tissue affinity, 2) bioavailability, 3) reactivity, and 4) mechanical strength, as well as a medical calcium sulfate curable composition, a medical calcium phosphate composition, a medical calcium hydroxide composition, a bone defect reconstruction treatment kit, and methods for producing the same, all related to the said composition. [Means for solving the problem]

[0011] As a result of diligent research, the inventors have found that they can provide a medical-grade calcium carbonate composition that highly satisfies 1) tissue affinity, 2) bioavailability, 3) reactivity, and 4) mechanical strength, as well as a medical-grade calcium sulfate hemihydrate composition, a medical-grade calcium phosphate composition, a medical-grade calcium hydroxide composition, a kit for bone defect reconstruction treatment, and methods for producing the same, thereby completing the present invention.

[0012] In other words, the present invention is as follows: [1] A medical calcium carbonate composition characterized by satisfying all of the following conditions (A) to (C) and at least one condition selected from the group (D) to (K). (A) The volume is 10 -12 m 3 or more. (B) The acid-soluble residue is 1% by mass or less. (C) As a medical composition mainly composed of vaterite or calcite, it is substantially pure calcium carbonate. (D) Contains 20% by mass or more of vaterite. (E) It is a honeycomb structure having a plurality of through-holes extending in one direction, and in the measurement of pore size distribution by mercury intrusion porosimetry, the pore volume with a pore diameter of 10 μm or less with respect to the mass of the honeycomb structure is larger than 0.02 cm 3 / g. (F) A particle-bound porous body having a plurality of through-holes extending in a plurality of directions formed by binding a plurality of granules having a maximum diameter length of 50 μm or more and 500 μm or less, and the pore volume of the particle-bound porous body with a pore diameter of 10 μm or less by mercury intrusion porosimetry measurement is 0.05 cm 3 / g or more. (G) A pore-accumulated porous body in which a plurality of pores having a maximum diameter length of 50 μm or more and 400 μm or less are accumulated in the whole medical composition, and does not contain pores having a maximum diameter length of 800 μm or more, and the pore volume of the pore-accumulated porous body with a pore diameter of 10 μm or less by mercury intrusion porosimetry measurement is 0.05 cm 3 / g or more. (H) In the measurement by mercury intrusion porosimetry, the ratio of the pore volume with a pore diameter of 1 μm or more and 6 μm or less to the pore volume with a pore diameter of 6 μm or less is 10% or more. (I) The maximum compressive strength obtained in any direction is not less than the reference compressive strength [S] calculated by the following formula (however, except for a honeycomb structure having a plurality of through-holes extending in one direction, and in the measurement by mercury intrusion porosimetry, the pore volume with a pore diameter of less than 10 μm with respect to the mass of the honeycomb structure is 0.02 cm 3 / g or less). S = S0 × C × exp(-b × P) (Here, S0 and b are constants, where S0 is 500 and b is 0.068; C is a constant due to the polymorphism of calcium carbonate, 0.01 if it contains 20% or more by mass of vaterite, and 1 if it does not contain 20% or more by mass of vaterite; and P is the percentage of the porosity of the composition.) (J) Honeycomb structure granules having a minor axis of 1 mm or more and less than 5 mm, wherein in the projection diagram of the composition, if a circle with a radius of 0.2 mm is drawn from any point on the projection diagram's surrounding line, there is no point in the triangle formed by the three points where the circle intersects the projection diagram's surrounding line, where the angle with any point on the projection diagram's surrounding line is 90° or less. (K) Multiple composition particles are connected by fibers. [2] A medical calcium carbonate composition according to [1] that satisfies the conditions of (D) above, and is characterized in that it is a sintered body. [3] A medical calcium carbonate composition according to [1] or [2], characterized in that calcium carbonate powders satisfying any of the following conditions (AJ1) to (AJ4) are combined to form a calcium carbonate composition. (AJ1) The average particle size is between 2 μm and 8 μm. (AJ2) Sphericity is 0.9 or higher. (AJ3) Mg content is 5 × 10 -4 Mass% or more 3×10 -3 It is less than or equal to a percent of mass. (AJ4) Sr content is 3 × 10 -3 Mass% or more 1.5×10 -2 It is less than or equal to a percent of mass. [4] A medical calcium carbonate composition according to [1] or [3] that satisfies the conditions of (E) above, A medical calcium carbonate composition characterized by a curved honeycomb structure in which the diameter of a circle passing through three points—both ends of any one through-hole and the center of the through-hole—is between 1 cm and 50 cm. [5] A method for producing a medical calcium carbonate composition according to [1] or [3] that satisfies the conditions of (D) above, Volume is 10 -12m 3 A method for producing a medical calcium carbonate composition, characterized in that, in the step of exposing the raw material calcium composition described above to carbon dioxide or carbonate ions, at least one condition selected from the group (D1) to (D8) below is satisfied, and (D9) to (D12) are selected steps. (D1) Includes a step of suppressing calcite formation or the growth of calcite crystals and relatively promoting vaterite formation. (D2) The process includes exposing the raw material calcium composition to carbon dioxide or carbonate ions and at least one selected from the group consisting of organic solvents, water-soluble organic substances, ammonia, and ammonium salts. (D3) The process includes a step of exposing a raw material calcium composition containing at least one selected from the group consisting of organic solvents, water-soluble organic substances, ammonia, and ammonium salts to carbon dioxide or carbonate ions and at least one selected from the group consisting of organic solvents, water-soluble organic substances, ammonia, and ammonium salts. (D4) The process includes a step of exposing the raw material calcium composition to carbon dioxide or carbonate ions and at least one selected from methanol, ethanol, glycerin, ethylene glycol, and ammonium carbonate. (D5) The process includes a step of exposing a raw material calcium composition containing at least one selected from methanol, ethanol, glycerin, ethylene glycol, and ammonium carbonate to carbon dioxide or carbonate ions and at least one selected from methanol, ethanol, glycerin, ethylene glycol, and ammonium carbonate. (D6) Includes a step to suppress the transition from vaterite to calcite. (D7) Includes a step of removing water from the raw calcium composition. (D8) The process includes a step of flowing carbon dioxide containing an organic solvent or carbonate ions around the raw material calcium composition. (D9) The process includes a step of partially carbonating the raw calcium composition by exposing it to carbon dioxide or carbonate ions in the gas phase, and then exposing the raw calcium composition to carbon dioxide or carbonate ions in the liquid phase. The process includes exposing the raw material calcium composition placed in (D10) type to carbon dioxide or carbonate ions. (D11) The process includes a step of exposing a raw material calcium composition containing a pore-forming material to carbon dioxide or carbonate ions. (D12) This step includes exposing the raw calcium composition connected by fibers to carbon dioxide or carbonate ions. [6] A method for producing a medical-grade calcium carbonate composition according to [1] or [2] that satisfies the conditions of (D) above, characterized by compacting a calcium carbonate powder containing 20% ​​by mass or more of vaterite and then firing it, thereby producing a medical-grade vaterite sintered body. [7] A method for producing a medical calcium carbonate composition according to [1], [3] or [4] that satisfies the conditions of (E) above, A method for producing a medical calcium carbonate composition, characterized in that (E1) and one selected from the group (E5) to (E9) are required steps, and (E2) to (E4) and (E10) are optional steps. (E1) Extrusion process A polymer material-containing raw material calcium composition is extruded through a mold for forming a honeycomb structure, resulting in a volume of 3 × 10⁻⁶. -11 m 3 The above describes the process for manufacturing a raw material honeycomb structure having multiple through holes extending in one direction. (E2) Molding process after the extrusion process A process of softening a honeycomb structure composed of a polymer material-containing raw material calcium composition by heat treatment, and then applying pressure to mold it into a desired shape. (E3) Outer side wall removal process A step to remove the outer peripheral side wall after the extrusion process or the molding process following the extrusion process, and before the degreasing and carbonation process. (E4) Molding process after the removal of the outer peripheral wall After the outer periphery side wall removal process, the honeycomb structure, composed of a polymer material-containing raw material calcium composition, is softened by heat treatment and then molded into the desired shape by applying pressure. (E5) Degreasing calcium carbonate sintering process Degreasing and sintering process: Degreasing calcium carbonate containing polymer material by heating and degreasing so that the acid-dissolved residue is 1% by mass or less, and then sintering the calcium carbonate. (E6) Degreasing and carbonation process A process of degreasing a porous calcium hydroxide material containing polymer material by heating it at an oxygen concentration of less than 30% so that the acid-dissolved residue is 1% by mass or less, and simultaneously carbonating it. (E7) Degreasing and carbonation process via calcium oxide A process in which a porous calcium hydroxide material containing a polymer material or a porous calcium carbonate material containing a polymer material is degreased by heating so that the acid-dissolved residue is 1% by mass or less, and then the porous calcium oxide material is exposed to carbon dioxide to become a porous calcium carbonate material. (E8) Degreasing and carbonation process via calcium carbonate and calcium oxide Carbonation degreasing calcium oxide-via-carbonation process: A polymer material-containing calcium hydroxide is heat-treated in the presence of carbon dioxide to form a polymer material-containing porous calcium carbonate, then degreased by heating so that the acid-dissolved residue is 1% by mass or less to form a porous calcium oxide, and finally exposed to carbon dioxide to form a porous calcium carbonate. (E9) Calcium sulfate degreasing and carbonation process Degreasing and carbonation process: A polymer material containing calcium sulfate is degreased by heating until the acid-dissolved residue is 1% by mass or less, and then carbon dioxide or carbonate ions are added to the resulting porous calcium sulfate to produce calcium carbonate. (E10) Shape finishing process performed after the degreasing and carbonation process [8] A method for producing a medical calcium carbonate composition according to [7], characterized by satisfying at least one condition selected from the following groups (E11) to (E14). (E11) In the "(E1) extrusion process" described above, the thickness of the outer peripheral side wall of the honeycomb structure is greater than the thickness of the partition wall, and the cross-sectional area of ​​the surface perpendicular to the through hole is 1 cm². 2 Extrude as described above. (E12) In at least one of the steps of "(E1) Extrusion step", "(E2) Molding step after the extrusion step", "(E4) Molding step after the outer peripheral side wall removal step", and "(E10) Shape finishing step performed after the degreasing carbonation step", pressure is applied to a honeycomb structure composed of a thermally softened polymer material-containing raw material calcium composition to curve it so that the diameter of the circle passing through both ends of the through hole and the center of the through hole is 1 cm or more and 50 cm or less. (E13) The "(E3) outer peripheral side wall removal process" is performed by grinding, and the "(E10) shape finishing process performed after the degreasing and carbonation process" is performed by polishing. (E14) The raw material calcium composition for the "(E1) extrusion process" is anhydrous calcium sulfate. [9] A method for producing the medical calcium carbonate composition described in [1] that satisfies the conditions of (F) above, using calcium oxide granules as a raw material, A method for producing a medical calcium carbonate composition, comprising the steps (F1) and (F2) below, and at least one of the steps (F3) and (F4). (F1) Introduction and closing process The process involves placing calcium oxide granules into a reaction vessel and closing the opening of the reaction vessel to prevent them from being discharged. (F2) Porous body formation process A process in which calcium oxide granules inside a reaction vessel are treated with water or acetic acid to form calcium hydroxide or calcium acetate, and the granules are expanded to produce a porous material. (F3) Carbonation process A carbonation step to produce a calcium carbonate porous body by applying carbon dioxide to a calcium hydroxide porous body simultaneously with or after the porous body formation step, or a carbonation step to produce a calcium carbonate porous body by heat-treating calcium acetate after the porous body formation step. (F4) Calcium oxide carbonation process Carbonation process from a calcium oxide porous material: A porous material selected from the group of calcium hydroxide porous material, calcium carbonate porous material, and calcium acetate porous material is heat-treated to produce a calcium oxide porous material, and the calcium oxide porous material is exposed to carbon dioxide to produce a calcium carbonate porous material.

[10] A method for producing the medical calcium carbonate composition described in [1] that satisfies the conditions of (F) above, using calcium sulfate granules as a raw material, A method for producing a medical calcium carbonate composition, characterized by including the following steps (F5) and (F6), or including the following steps (F5), (F7) and (F9), with step (F8) being an optional step. (F5) Introduction process Steps to add calcium sulfate granules to the reaction vessel. (F6) Porous body formation carbonation process A process in which calcium sulfate granules and carbonate ions inside a reaction vessel react to convert the composition to calcium carbonate and harden the granules together to form a porous material. (F7) Porous body formation process A process for producing a porous calcium sulfate dihydrate by adding water to calcium sulfate hemihydrate granules or calcium sulfate anhydrous granules. (F8) Heat treatment process A process for producing porous calcium sulfate anhydrous material by heat treatment of porous calcium sulfate dihydrate. (F9) Carbonation process A process of exposing porous calcium sulfate dihydrate or porous anhydrous calcium sulfate to water containing carbonate ions to convert its composition to calcium carbonate.

[11] A method for producing the medical calcium carbonate composition described in [1] that satisfies the conditions of (F) above, A method for producing a medical calcium carbonate composition, characterized in that (F10) and (F11) below, and one selected from the group (F12) to (F16) are required steps, and (F17) is an optional step. (F10) Introduction process Volume is 10 -12 m3 The process of adding the above polymer material-containing raw material calcium composition granules to a reaction vessel. (F11) Porous body formation process In one of the following steps, the granules inside the reaction vessel are heated and fused together: the surfaces of the granules are dissolved to bond them together; or the surfaces of the granules are fused together with a plasticizer, and the volume is 3 × 10 -11 m 3 The above is a process for manufacturing a granule-bound porous body having multiple through holes extending in multiple directions, formed by the bonding of multiple granules with a maximum diameter and length of 50 μm or more and 500 μm or less. (F12) Degreasing calcium carbonate sintering process Degreasing and sintering process: Degreasing calcium carbonate containing polymer material by heating and degreasing so that the acid-dissolved residue is 1% by mass or less, and then sintering the calcium carbonate. (F13) Degreasing and carbonation process A process of degreasing a porous calcium hydroxide material containing polymer material by heating it at an oxygen concentration of less than 30% so that the acid-dissolved residue is 1% by mass or less, and simultaneously carbonating it. (F14) Degreasing and carbonation process via calcium oxide A process in which a porous calcium hydroxide material containing a polymer material or a porous calcium carbonate material containing a polymer material is degreased by heating so that the acid-dissolved residue is 1% by mass or less, and then the porous calcium oxide material is exposed to carbon dioxide to become a porous calcium carbonate material. (F15) Degreasing and carbonation process via calcium carbonate and calcium oxide Carbonation degreasing calcium oxide-via-carbonation process: A polymer material-containing calcium hydroxide is heat-treated in the presence of carbon dioxide to form a polymer material-containing porous calcium carbonate, then degreased by heating so that the acid-dissolved residue is 1% by mass or less to form a porous calcium oxide, and finally exposed to carbon dioxide to form a porous calcium carbonate. (F16) Calcium sulfate degreasing and carbonation process Degreasing and carbonation process: A polymer material containing calcium sulfate is degreased by heating until the acid-dissolved residue is 1% by mass or less, and then carbon dioxide or carbonate ions are added to the resulting porous calcium sulfate to produce calcium carbonate. (F17) Shape finishing process performed after the degreasing and carbonation process

[12] A method for producing the medical calcium carbonate composition described in [1] that satisfies the conditions of (G) above, A method for producing a medical calcium carbonate composition, characterized in that (G1) below and at least one selected from the groups (D1) to (D10) and (E5) to (E9) are required steps, and (G2), (G3), and (E10) below are optional steps. (G1) Mixing process A process of mixing raw calcium composition powder or raw calcium composition paste with a pore-forming material. (G2) Powder compaction process A process of compacting a mixture of raw calcium composition powder or raw calcium composition paste and a pore-forming material. (G3) Pore former removal process A process to remove pore-forming material by dissolving it in a solvent. (D1) Includes a step of suppressing calcite formation or the growth of calcite crystals and relatively promoting vaterite formation. (D2) The process includes exposing the raw material calcium composition to carbon dioxide or carbonate ions and at least one selected from the group consisting of organic solvents, water-soluble organic substances, ammonia, and ammonium salts. (D3) The process includes a step of exposing a raw material calcium composition containing at least one selected from the group consisting of organic solvents, water-soluble organic substances, ammonia, and ammonium salts to carbon dioxide or carbonate ions and at least one selected from the group consisting of organic solvents, water-soluble organic substances, ammonia, and ammonium salts. (D4) The process includes exposing the raw material calcium composition to carbon dioxide or carbonate ions and at least one selected from methanol, ethanol, and ammonium carbonate. (D5) The process includes exposing a raw material calcium composition containing at least one selected from methanol, ethanol, and ammonium carbonate to carbon dioxide or carbonate ions and at least one selected from methanol, ethanol, and ammonium carbonate. (D6) Includes a step to suppress the transition from vaterite to calcite. (D7) Includes a step of removing water from the raw calcium composition. (D8) The process includes a step of flowing carbon dioxide containing an organic solvent or carbonate ions around the raw material calcium composition. (D9) The process includes a step of partially carbonating the raw calcium composition by exposing it to carbon dioxide or carbonate ions in the gas phase, and then exposing the raw calcium composition to carbon dioxide or carbonate ions in the liquid phase. The process includes exposing the raw material calcium composition placed in (D10) type to carbon dioxide or carbonate ions. (E5) Degreasing calcium carbonate sintering process Degreasing and sintering process: Degreasing calcium carbonate containing polymer material by heating and degreasing so that the acid-dissolved residue is 1% by mass or less, and then sintering the calcium carbonate. (E6) Degreasing and carbonation process A process of degreasing a porous calcium hydroxide material containing polymer material by heating it at an oxygen concentration of less than 30% so that the acid-dissolved residue is 1% by mass or less, and simultaneously carbonating it. (E7) Degreasing and carbonation process via calcium oxide A process in which a porous calcium hydroxide material containing a polymer material or a porous calcium carbonate material containing a polymer material is degreased by heating so that the acid-dissolved residue is 1% by mass or less, and then the porous calcium oxide material is exposed to carbon dioxide to become a porous calcium carbonate material. (E8) Degreasing and carbonation process via calcium carbonate and calcium oxide Carbonation degreasing calcium oxide-via-carbonation process: A polymer material-containing calcium hydroxide is heat-treated in the presence of carbon dioxide to form a polymer material-containing porous calcium carbonate, then degreased by heating so that the acid-dissolved residue is 1% by mass or less to form a porous calcium oxide, and finally exposed to carbon dioxide to form a porous calcium carbonate. (E9) Calcium sulfate degreasing and carbonation process Degreasing and carbonation process: A polymer material containing calcium sulfate is degreased by heating until the acid-dissolved residue is 1% by mass or less, and then carbon dioxide or carbonate ions are added to the resulting porous calcium sulfate to produce calcium carbonate. (E10) Shape finishing process performed after the degreasing and carbonation process

[13] A method for producing a medical calcium carbonate composition according to any one of the following [7], [8],

[11] ,

[12] , characterized in that the heat degreasing is performed at 200°C or higher, and the mass loss of the polymer material in the polymer material-containing calcium composition during the heat degreasing is less than 1% by mass per minute.

[14] A method for producing a medical calcium carbonate composition according to any one of [5] to

[13] , characterized by comprising at least one step selected from the groups (L) to (Q) below. (L) Process of degreasing with an oxygen partial pressure of 30 kPa or higher. (M) A process of degreasing or carbonation using a partial pressure of carbon dioxide of 30 kPa or higher. (N) A process of degreasing or carbonation using a gas containing oxygen or carbon dioxide at a pressure of 150 kPa or higher. (O) A step of increasing the carbon dioxide concentration in the reaction vessel by replacing some or all of the air in the reaction vessel with carbon dioxide and then introducing carbon dioxide into the reaction vessel. (P) Carbonation process in which carbon dioxide is supplied to maintain a constant pressure in a closed reaction vessel. (Q) Carbonation process in which carbon dioxide in the reaction vessel is stirred or circulated.

[15] A method for producing a medical calcium carbonate composition according to any one of the following [5] to [9],

[11] to

[14] , characterized in that the composition of the raw material calcium composition is one selected from the group consisting of calcium oxide, calcium hydroxide, and calcium carbonate.

[16] A method for producing a medical calcium carbonate composition according to any one of [5] to

[15] , characterized in that it satisfies at least one of the following conditions (R1) to (R4). (R1) Use calcium carbonate powder with an average particle size of 2 μm or more and 8 μm or less. (R2) Use calcium carbonate powder with a sphericity of 0.9 or higher. (R3) Mg content is 5 × 10 -4 Mass% or more 3×10 -3 Use calcium carbonate powder at a mass percentage of % or less. (R4)Sr content is 3 × 10 -3 Mass% or more 1.5×10 -2 Use calcium carbonate powder at a mass percentage of % or less.

[17] A medical-grade calcium sulfate curable composition characterized by satisfying all of the following conditions (T1) to (T5). (T1) Acid dissolved residue is 1% by mass or less. (T2) Volume is 5 × 10 -13 m 3 That's all. (T3) As a medical composition, it is substantially pure calcium sulfate. (T4) The calcium sulfate hemihydrate content is 50% by mass or more. (T5) When the compositions are brought into contact with each other and immersed in water, they harden and form a porous body with a compressive strength of 0.3 MPa or more. [8] A method for producing a medical calcium sulfate hemihydrate granule, as described in

[17] , comprising (U2) and (U3) as essential steps and (U1) and (U4) as optional steps. (U1) Polymer material degreasing process A process of degreasing calcium sulfate granules or blocks containing polymer materials by heat treatment to reduce acid-dissolved residue to 1% by mass or less. (U2) Calcium sulfate dihydrate manufacturing process A process to produce calcium sulfate dihydrate granules or blocks by adding water to granules or blocks of anhydrous or hemihydrate calcium sulfate formed in a polymer material degreasing process, or by adding water to calcium sulfate hemihydrate powder and curing it. (U3) Calcium sulfate hemihydrate manufacturing process A process for producing calcium sulfate hemihydrate granules or blocks by dehydrating calcium sulfate dihydrate granules or blocks in the gas phase. (U4) Granule size adjustment process Volume is 5 × 10 -13 m 3 The process of adjusting the size so that the granules are as described above.

[19] A medical calcium phosphate composition characterized by satisfying all of the following conditions (V1) to (V3) and at least one condition selected from the group (V4) to (V10), with (V11) or (V12) as the selection condition. (V1) Volume is 10 -12 m 3 That's all. (V2) Acid dissolved residue is 1% by mass or less. (V3) As a medical composition, it is substantially pure calcium phosphate, and its composition is selected from the group consisting of carbonate apatite, apatite containing HPO4 groups, tricalcium phosphate, witrochite, and calcium hydrogen phosphate. (V4) A honeycomb structure having multiple through-holes extending in one direction (provided that the composition is tricalcium phosphate and the pore volume of the honeycomb structure, with a pore diameter of 10 μm or less relative to the mass of the honeycomb structure, is 0.01 cm³ as measured by mercury intrusion method) 3 Excluding honeycomb structures that do not satisfy any of the following conditions: the density is 1 / g or more, the diameter of the circle passing through three points—both ends of any one through-hole and the center of the through-hole—is between 1 cm and 50 cm, and the arithmetic mean roughness (Ra) of the partition surface in the direction of the through-hole in the honeycomb structure is 0.7 μm or more. (V5) A granular porous body having multiple through holes extending in multiple directions, formed by the bonding of multiple granules with a maximum diameter and length of 50 μm or more and 500 μm or less, wherein the pore volume of the granular porous body with a diameter of 10 μm or less is 0.05 cm³ as measured by mercury intrusion method. 3 It is 1 / g or more. (V6) A porous material having multiple pores with a maximum diameter and length of 50 μm or more and 400 μm or less accumulated throughout the medical composition, and not containing pores with a maximum diameter and length of 800 μm or more, wherein the pore volume of the granular porous material with a diameter of 10 μm or less, as measured by mercury intrusion method, is 0.05 cm³. 3 It must be at least / g (excluding those with a composition of tricalcium phosphate). (V7) In mercury intrusion measurement, the pore volume of pores with a diameter of 1 μm to 6 μm is 5% or more of the pore volume of pores with a diameter of 6 μm or less. (V8) The maximum compressive strength obtained in any direction is equal to or greater than the reference compressive strength [S] calculated by the following formula (provided that the honeycomb structure has multiple through holes extending in one direction, and the pore volume of the honeycomb structure with a pore diameter of 10 μm or less relative to the mass is 0.02 cm³ as measured by mercury intrusion method) 3 (Excluding those that are less than / g.) S = S0 × C × exp(-b × P) (Here, S0 and b are constants, where S0 is 500 and b is 0.068; C is a constant depending on the composition, 1 for carbonate apatite or apatite containing HPO4 groups or tricalcium phosphate, 0.5 for vitrocite, and 0.1 for calcium hydrogen phosphate; and P is the percentage of the porosity of the composition.) (V9) Honeycomb structure granules having a minor axis of 1 mm or more and less than 5 mm, wherein in the projection diagram of the composition, if a circle with radius 0.2 mm is drawn from any point on the projection diagram's surrounding line, there is no point in the triangle formed by the three points where the circle intersects the projection diagram's surrounding line, where the angle with any point on the projection diagram's surrounding line is 90° or less. (V10) Multiple composition particles are connected by fibers. (V11) The composition is apatite having a carbonate group content of 10% by mass or more. (V12) The composition is an apatite with a carbonate group content of less than 10% by mass.

[20] A medical calcium phosphate composition characterized by satisfying either (AG1) or (AG2) below, and selecting from (AG3) to (AG10) below. (AG1) The composition is one selected from the group consisting of carbonate apatite, apatite containing HPO4 groups, vitrocite, and calcium hydrogen phosphate, and the volume is 10 -12 m 3 The above-mentioned granules or blocks contain 0.01% to 3% by mass of silver or a silver compound. (AG2) The composition is one selected from the group consisting of hydroxyapatite sintered body, tricalcium phosphate sintered body, carbonate apatite, apatite containing HPO4 groups, vitrocite, and calcium hydrogen phosphate, and the volume is 10 -12 m 3 The granules or blocks described above contain silver phosphate crystals bound to the surface of calcium phosphate, and the silver phosphate content is 0.01% by mass or more and 3% by mass or less. (AG3) The silver compound is silver phosphate. (AG4) The calcium phosphate composition contains silver or a silver compound in both the surface and interior, and the ratio of the silver concentration in the surface to the silver concentration at a distance of at least 50 μm from the surface toward the center is 1.2 or higher. (AG5) A honeycomb structure having multiple through holes extending in one direction. (AG6) This is a granular porous body formed by the bonding of multiple granules with a maximum diameter and length of 50 μm or more and 500 μm or less, and having multiple through-holes extending in multiple directions. (AG7) The entire medical composition is a porous material with multiple pores having a maximum diameter and length of 50 μm or more and 400 μm or less, and does not contain any pores with a maximum diameter and length of 800 μm or more. (AG8) Mercury intrusion method measurement shows that the pore volume of pores with a diameter of 1 μm to 6 μm is 5% or more of the pore volume of pores with a diameter of 6 μm or less. (AG9) The maximum compressive strength obtained in any direction is equal to or greater than the reference compressive strength [S] calculated by the following formula. S = S0 × C × exp(-b × P) (Here, S0 and b are constants, where S0 is 500 and b is 0.068; C is a constant depending on the composition, 1 for carbonate apatite or apatite containing HPO4 groups, 0.5 for vitrokite, 0.1 for calcium hydrogen phosphate, and 2 for hydroxyapatite sintered bodies and tricalcium phosphate sintered bodies; and P is the percentage of the porosity of the composition.) (AG10) Honeycomb structure granules having a minor axis of 1 mm or more and less than 5 mm, wherein in the projection diagram of the composition, if a circle with radius 0.2 mm is drawn from any point on the projection diagram's surrounding line, there is no point in the triangle formed by the three points where the circle intersects the projection diagram's surrounding line, where the angle with any point on the projection diagram's surrounding line is 90° or less. [twenty one] A medical calcium phosphate composition according to

[19] or

[20] , characterized by satisfying at least one of the following conditions (W1) to (W7). (W1) A honeycomb structure having multiple through holes extending in one direction, wherein the pore volume of the honeycomb structure, with a pore diameter of 10 μm or less relative to the mass of the honeycomb structure, is 0.01 cm³ as measured by mercury intrusion method. 3 It is 1 / g or more. (W2) A honeycomb structure having multiple through holes extending in one direction, wherein the diameter of the circle passing through the two ends of any one through hole and the center of the through hole is between 1 cm and 50 cm. (W3) A honeycomb structure in which the arithmetic mean roughness (Ra) of the partition surface in the direction of the through-hole is 0.7 μm or more. (W4) This is an aggregate of calcium phosphate with an average particle size of 2 μm or more and 8 μm or less. (W5) These are aggregates of calcium phosphate with a sphericity of 0.9 or higher. (W6) Mg content is 5 × 10 -4 Mass% or more 3×10 -3 It is less than or equal to a percent of mass. (W7)Sr content is 3 × 10 -3 Mass% or more 1.5×10 -2 It is less than or equal to a percent of mass. [twenty two] A method for producing a medical calcium phosphate composition, characterized by satisfying the following conditions (AH1) or (AH2), and selecting (AH3) to (AH9). (AH1) Contains 0.01% to 3% by mass of silver or a silver compound, and its composition is one selected from the group consisting of calcium carbonate, calcium hydroxide, calcium oxide, calcium sulfate, and calcium hydrogen phosphate, and its volume is 10 -12 m 3 Using the above granular or block-type raw material calcium composition, Furthermore, if the raw material calcium composition is other than calcium carbonate, the process includes a step of imparting carbonate groups to the composition. The method also includes a step of exposing the material to an aqueous phosphate solution or a mixed aqueous solution of phosphate and magnesium salt to convert its composition to one selected from the group consisting of apatite carbonate, apatite containing HPO4 groups, vitrocite, and calcium hydrogen phosphate, which contains silver or a silver compound. (AH2) One selected from the group consisting of apatite, tricalcium phosphate, vitrocite, octacalcium phosphate, and calcium hydrogen phosphate, and having a volume of 10 -12 m 3 The process includes a step of exposing the raw material calcium composition, which is in the form of granules or blocks, to an aqueous solution containing silver ions to form silver phosphate in the raw material calcium composition. The process includes exposing a raw material calcium compound having (AH3) calcium phosphate to a first aqueous solution containing silver ions to form silver phosphate in the raw material calcium composition, and then exposing it to a second aqueous solution with a higher silver ion concentration than the first aqueous solution. (AH4) The raw material calcium composition is a honeycomb structure having multiple through-holes extending in one direction. The (AH5) raw material calcium composition is a granular porous body formed by the bonding of multiple granules with a maximum diameter and length of 50 μm or more and 500 μm or less, and having multiple through-pores extending in multiple directions. (AH6) The raw material calcium composition is a porous material in which multiple pores with a maximum diameter and length of 50 μm or more and 400 μm or less are accumulated throughout the medical composition, and no pores with a maximum diameter and length of 800 μm or more are included. (AH7) A raw calcium composition is used in which, in mercury intrusion measurement, the pore volume of pores with a diameter of 1 μm to 6 μm is 5% or more relative to the pore volume of pores with a diameter of 6 μm or less. (AH8) A raw calcium composition is used in which the maximum compressive strength obtained in any direction is equal to or greater than the reference compressive strength [S] calculated by the following formula. S = S0 × C × exp(-b × P) (Here, S0 and b are constants, where S0 is 500 and b is 0.068; C is a constant depending on the composition, 1 for carbonate apatite or apatite containing HPO4 groups, 0.5 for vitrokite, 0.1 for calcium hydrogen phosphate, and 2 for all others; and P is the percentage of the porosity of the composition.) (AH9) As the raw material calcium composition, honeycomb structure granules are used, in which the minor axis is 1 mm or more and less than 5 mm, and in the projection diagram of the composition, if a circle with a radius of 0.2 mm is drawn from any point on the projection diagram's surrounding line, there is no point in the triangle formed by the three points where the circle intersects the projection diagram's surrounding line that has an angle of 90° or less with any point on the projection diagram's surrounding line as its vertex. [twenty three] A method for producing a medical calcium phosphate composition as described in any of

[19] to

[21] , A method for producing a medical calcium phosphate composition, characterized by satisfying any one of the following conditions (AI1) to (AI4). (AI1) Use calcium carbonate powder with an average particle size of 2 μm or more and 8 μm or less. (AI2) Use calcium carbonate powder with a sphericity of 0.9 or higher. (AI3)Mg content is 5 × 10 -4 Mass% or more 3×10 -3 Use calcium carbonate powder at a mass percentage of % or less. (AI4)Sr content is 3 × 10 -3 Mass% or more 1.5×10 -2 Use calcium carbonate powder at a mass percentage of % or less. [twenty four] A method for producing a medical calcium phosphate composition according to any of

[19] to

[21] by adding a phosphate component to a medical calcium carbonate composition according to any of [1] to [4] or a medical calcium carbonate composition produced by the manufacturing method according to any of [5] to

[16] , A method for producing a medical calcium phosphate composition, characterized by immersing the aforementioned medical calcium carbonate composition in at least one aqueous solution selected from the group (X1) to (X5) to impart a phosphate component to the medical calcium carbonate composition. (X1) Aqueous solution containing a phosphate component with a pH of 8.5 or higher (X2) Aqueous solution containing a phosphate component with a pH of less than 8.5 (X3) An aqueous solution containing both a phosphate component and a carbonate component at a concentration of 0.5 molars or less, with a pH of 8.5 or higher. (X4) An aqueous solution containing both a phosphate component and a carbonate component at a concentration of 0.5 molars or less, with a pH of less than 8.5. (X5) Aqueous solution containing both phosphate and magnesium components [twenty five] A method for producing a medical calcium phosphate composition according to any of

[19] to

[21] by adding a phosphate component to a medical calcium carbonate composition according to any of [1] to [4] or a medical calcium carbonate composition produced by the manufacturing method according to any of [5] to

[16] , A method for producing a medical calcium phosphate composition, characterized by having a step that satisfies at least one condition selected from the group (Y1) to (Y6) for the medical calcium carbonate composition. (Y1) A step of replacing some or all of the gas in the pores of a medical calcium carbonate composition immersed in an aqueous solution containing a phosphate component with the aqueous solution containing a phosphate component. (Y2) A step of vibrating a medical-grade calcium carbonate composition immersed in an aqueous solution containing a phosphate component, thereby replacing some or all of the gas in the pores of the medical-grade calcium carbonate composition with the aqueous solution containing a phosphate component. (Y3) A step of flowing an aqueous solution containing phosphate components around the medical calcium carbonate composition to replace some or all of the gas in the internal pores of the medical calcium carbonate composition with the aqueous solution containing phosphate components. (Y4) A process of replacing some or all of the gas in the pores of the medical calcium carbonate composition with the aqueous solution containing the phosphoric acid component by degassing a container in a reduced pressure. (Y5) A step of replacing some or all of the gas in the pores of a medical calcium carbonate composition with a gas that has a higher solubility in an aqueous solution containing a phosphoric acid component than air. (Y6) A step of replacing some or all of the gas in the pores of a medical calcium carbonate composition with a solvent that has a smaller contact angle than water and a lower boiling point than water.

[26] A method for producing a medical calcium phosphate composition, characterized by performing the following steps (Z1) to (Z4), or (Z1), (Z3), (Z4), or (Z1), (Z3) in that order consecutively, and performing all of them in the same container. (Z1) Process for producing a medical-grade calcium carbonate composition by adding a carbonate component to a raw calcium composition. (Z2) Washing process for medical calcium carbonate composition (Z3) Step of adding a phosphate component to a medical calcium carbonate composition. (Z4) Washing process for medical calcium phosphate composition

[27] A medical calcium hydroxide composition characterized by satisfying all of the following conditions (AB1) to (AB3) and at least one condition selected from the group (AB4) to (AB8). (AB1) Volume is 10 -12 m 3 That's all. (AB2) Acid dissolved residue is 1% by mass or less. (AB3) As a medical composition, it is substantially pure calcium hydroxide. (AB4) Honeycomb structure with multiple through holes extending in one direction (AB5) A granular porous body formed by the bonding of multiple granules with a maximum diameter and length of 50 μm or more and 500 μm or less, having multiple through-holes extending in multiple directions. (AB6) The medical composition as a whole has multiple pores with a maximum diameter and length of 50 μm or more and 400 μm or less, and does not contain any pores with a maximum diameter and length of 800 μm or more. (AB7) Honeycomb structure granules having a minor axis of 1 mm or more and less than 5 mm, wherein in the projection diagram of the composition, if a circle with radius 0.2 mm is drawn from any point on the projection diagram's surrounding line, there is no point in the triangle formed by the three points where the circle intersects the projection diagram's surrounding line, where the angle with any point on the projection diagram's surrounding line is 90° or less. (AB8) Multiple composition particles are connected by fibers.

[28] A method for producing the medical calcium hydroxide composition described in

[27] that satisfies the conditions of (AB4) above, A method for producing a medical calcium hydroxide composition, characterized in that the raw material calcium composition is calcium hydroxide, (AD1) and one selected from the group (AD2) to (AD5) below are essential steps, and (AD6) to (AD8) are optional steps. (AD1) Extrusion process A polymer material-containing raw material calcium composition is extruded through a mold for forming a honeycomb structure, resulting in a volume of 3 × 10⁻⁶. -11 m 3 The above describes the process for manufacturing a raw material honeycomb structure having multiple through holes extending in one direction. (AD2) Degreasing process A process of degreasing a porous calcium hydroxide material containing polymer materials so that the acid-dissolved residue is 1% by mass or less. (AD3) Hydration process via calcium oxide A process in which a porous calcium hydroxide material containing polymer material is degreased to a state where the acid-dissolved residue is 1% by mass or less, and then the porous calcium oxide material is hydrated to form a porous calcium hydroxide material. (AD4) Hydration process via calcium carbonate and calcium oxide A carbonated, degreased calcium oxide-via-hydration process involves heat-treating polymer material-containing calcium hydroxide in the presence of carbon dioxide to form a polymer material-containing porous calcium carbonate, then degreasing it so that the acid-dissolved residue is 1% by mass or less to form a porous calcium oxide, and finally hydrating the porous calcium oxide to form a porous calcium hydroxide. (AD5) Manufacturing process from porous calcium carbonate A process in which a porous calcium carbonate body containing polymer material is degreased to a state where the acid-dissolved residue is 1% by mass or less, and then converted into a porous calcium oxide body, and subsequently hydrated to form a porous calcium hydroxide body. (AD6) Molding process after the extrusion process A process of softening a honeycomb structure composed of a polymer material-containing raw material calcium composition by heat treatment, and then applying pressure to mold it into a desired shape. (AD7) Outer side wall removal process A step to remove the outer peripheral side wall after the extrusion process or the molding process following the extrusion process, and before the degreasing and carbonation process. (AD8) Molding process after the removal of the outer peripheral side wall After the outer periphery side wall removal process, the honeycomb structure, composed of a polymer material-containing raw material calcium composition, is softened by heat treatment and then molded into the desired shape by applying pressure.

[29] A method for producing the medical calcium hydroxide composition described in

[27] that satisfies the conditions of (AB5) above, A method for producing a medical calcium hydroxide composition, characterized in that the following (AE1) and (AE2) and at least one selected from the group (AD2) to (AD5) are essential steps. (AE1) Introduction process Volume is 10 -12 m 3 The process of adding the above polymer material-containing calcium hydroxide granules to the reaction vessel. (AE2) Granule binding process The process involves one of the following steps: a step in which the granules inside the reaction vessel are thermally softened and fused together by heat treatment; a step in which the surfaces of the granules are dissolved to bond them together; and a step in which the surfaces of the granules are fused together with a plasticizer, with a volume of 3 × 10 -11 m 3 The above is a process for manufacturing a granule-bound porous body having multiple through holes extending in multiple directions, formed by the bonding of multiple granules with a maximum diameter and length of 50 μm or more and 500 μm or less. (AD2) Degreasing process A process of degreasing a porous calcium hydroxide material containing polymer materials so that the acid-dissolved residue is 1% by mass or less. (AD3) Hydration process via calcium oxide A process in which a porous calcium hydroxide material containing polymer material is degreased to a state where the acid-dissolved residue is 1% by mass or less, and then the porous calcium oxide material is hydrated to form a porous calcium hydroxide material. (AD4) Hydration process via calcium carbonate and calcium oxide A carbonated, degreased calcium oxide-via-hydration process involves heat-treating polymer material-containing calcium hydroxide in the presence of carbon dioxide to form a polymer material-containing porous calcium carbonate, then degreasing it so that the acid-dissolved residue is 1% by mass or less to form a porous calcium oxide, and finally hydrating the porous calcium oxide to form a porous calcium hydroxide. (AD5) Manufacturing process from porous calcium carbonate A process in which a porous calcium carbonate body containing polymer material is degreased to a state where the acid-dissolved residue is 1% by mass or less, and then converted into a porous calcium oxide body, and subsequently hydrated to form a porous calcium hydroxide body.

[30] A method for producing the medical calcium hydroxide composition described in

[27] , using a porous calcium hydroxide or porous calcium carbonate as a raw material, A method for producing a medical calcium hydroxide composition, characterized by first converting a porous calcium hydroxide or porous calcium carbonate into a porous calcium oxide, and then hydrating the porous calcium oxide to obtain a porous calcium hydroxide.

[31] A method for producing a medical calcium composition according to any one of [9] to

[11] ,

[14] , and

[29] , characterized in that the introduction closing step or introduction step satisfies at least one of the following conditions (AF1) to (AF3). (AF1) The sphericity of the granules is 0.9 or higher. (AF2) The granules are hollow. (AF3) Add granules to the reaction vessel with a bulk volume of 105% or more of the volume of the reaction vessel.

[32] A bone defect reconstruction treatment kit comprising a solid portion containing vaterite and α-tricalcium phosphate, and a solution portion containing phosphate, wherein when the solid portion and the solution portion are kneaded together, carbonate apatite is formed and hardens.

[33] The bone defect reconstruction treatment kit according to

[32] , characterized in that the vatelite content in the solid portion is 10% by mass or more and 60% by mass or less.

[34] A bone defect reconstruction treatment kit according to either

[32] or

[33] , characterized in that the solution portion contains at least one of an acid having multiple carboxyl groups, a bisulfite, a cellulose derivative, a dextran sulfate, a chondroitin sulfate, an alginate, and a glucomannan.

[35] The solid part has a volume of 10 -12 m 3 A bone defect reconstruction treatment kit according to

[32] -

[34] , characterized by containing the above-mentioned vatelite.

[36] The bone defect reconstruction treatment kit according to

[32] -

[34] , characterized in that the average particle size of the vatelite is 6 μm or less. [Brief explanation of the drawing]

[0013] [Figure 1] This is a schematic diagram of a honeycomb structure with outer side walls. [Figure 2] This shows the pore distribution measurement results by mercury intrusion method for a medical calcite composition manufactured at a final temperature of 480°C in Example 7. [Figure 3] This is the powder X-ray diffraction (XRD) pattern of the medical vatelite composition according to Example 1. [Figure 4] This is the XRD pattern of the medical carbonate apatite composition according to Example 1. [Figure 5] This is an electron microscope image (SEM image) of the honeycomb structure according to Example 7. [Figure 6] This is the particle size distribution analysis result for Example 8. [Figure 7] This is a histopathological image obtained from a histopathological examination using a medical carbonate apatite honeycomb structure according to Example 9. [Figure 8] This is an electron microscope image (SEM image) of the medical carbonate apatite honeycomb structure according to Example 12. [Figure 9] This is a histopathological image of the medical carbonate apatite honeycomb structure according to Example 14, obtained from a histopathological examination four weeks after implantation. [Figure 10] This is a histopathological image of the medical carbonate apatite honeycomb structure according to Example 14, obtained from a histopathological examination 12 weeks after implantation. [Figure 11] These are the histopathological images of the medical carbonate apatite composition of Example 15 and the hydroxyapatite composition of Comparative Example 10 at 4 and 12 weeks after implantation. [Figure 12] This is an electron microscope image (SEM image) of a medical vaterite porous material according to Example 16. [Figure 13] This is a histopathological image obtained from a histopathological examination of a medical carbonate apatite porous body four weeks after implantation, according to Example 16. [Figure 14] This is an electron microscope image (SEM image) of a porous medical calcite material according to Example 17. [Figure 15] This is an electron microscope image (SEM image) of the medical carbonate apatite honeycomb structure according to Example 22. [Figure 16] This is a histopathological image of the medical carbonate apatite honeycomb structure according to Example 22, obtained from a histopathological examination four weeks after implantation. [Figure 17]This is an electron microscope image (SEM image) of the medical carbonate apatite honeycomb structure according to Example 24. [Modes for carrying out the invention]

[0014] (Definition of terms) The terms used in this invention are defined as follows: In this invention, "medical-grade calcium carbonate composition" refers to a calcium carbonate composition used as a medical composition (medical material) or a calcium carbonate composition used as a raw material for a medical composition. Bone grafts and drug delivery carriers implanted in living tissue are naturally medical materials, but cell culture scaffolds used outside of living tissue are also included as medical materials. If the composition is porous, it may be referred to as medical-grade porous calcium carbonate, and if the porous structure is a honeycomb structure, it may be referred to as medical-grade calcium carbonate honeycomb structure, and so on. The "medical-grade calcium carbonate composition" as used in this invention may also be used in the manufacture of other medical compositions, and therefore may contain pore-forming agents such as sodium chloride. Furthermore, in order to improve the handling properties of medical-grade calcium carbonate and other medical compositions, the composition particles may be bonded together with fibers. Materials containing these pore-forming agents and fibers are also defined as "medical-grade calcium carbonate composition." In this invention, "volume" refers to bulk volume, also known as total volume. It is the volume including stomata, and is also called bulk volume or total volume. In this invention, "vaterite," "aragonite," and "calcite" refer to polymorphs of calcium carbonate crystals. In this invention, "medical vatelite composition" refers to a medical calcium carbonate composition containing 20% ​​by mass or more of vatelite. Here, the mass of pore-forming material and fibers is excluded from the calculation of the vatelite content. The content of vaterite and calcite in the medical calcium carbonate composition is calculated from the peak area ratio of each in powder X-ray diffraction (XRD) analysis using the method described later. In this invention, "medical calcium phosphate composition" refers to a calcium phosphate composition used in medicine, such as an artificial bone graft material. In this invention, "calcium phosphate" refers to a compound containing phosphoric acid and calcium as its composition, and examples include condensed calcium phosphate compounds such as orthophosphate, metaphosphate, amorphous calcium phosphate, and calcium pyrophosphate. Orthophosphate is a salt of orthophosphate and calcium. Examples include tetracalcium phosphate, apatite including hydroxyapatite and carbonate apatite, α-tricalcium phosphate, β-tricalcium phosphate, and calcium hydrogen phosphate. Although β-tricalcium phosphate may contain witrokhite, in this invention, those without HPO4 are classified as tricalcium phosphate, and those containing HPO4 are classified as witrokhite. α-tricalcium phosphate is sometimes abbreviated as αTCP, and β-tricalcium phosphate as βTCP. In this invention, "medical apatite composition" refers to a type of medical calcium phosphate composition, which is an apatite composition used as a medical material, such as an artificial filler. Furthermore, the term "medical carbonate apatite composition" as used in this invention refers to a carbonate apatite composition used for medical purposes. The carbonate group content of carbonate apatite is not particularly limited, but is preferably 0.5% by mass or more, more preferably 3% by mass or more, and even more preferably 6% by mass or more. In this invention, carbonate apatite is defined as apatite containing carbonate groups. Generally, it is apatite in which some or all of the phosphate groups or hydroxyl groups of calcium phosphate apatite are replaced with carbonate groups. In addition, in conjunction with carbonate group substitution, Na, K, etc., are often included in the crystalline structure to balance the charge of the apatite. In this invention, carbonate apatite in which some of the carbonate apatite is replaced with other elements or voids is also defined as carbonate apatite. As the carbonate group content increases, the material becomes more susceptible to absorption by osteoclasts, leading to a faster rate of bone replacement. However, in some cases, medical materials that promote slow bone replacement or materials that do not promote bone replacement are desired. When a medical material that promotes slow bone replacement is desired, carbonate apatite with a low carbonate group content is desirable. When a medical material that does not promote bone replacement is desired, apatite with a carbonate group content of less than 0.2% by mass is desirable. In this invention, the term "honeycomb structure" refers to a porous body having a plurality of through-holes with polygonal or circular cross-sectional shapes extending in one direction, as described in Japanese Patent Publication No. 2004-298407 and Japanese Patent Publication No. 2005-152006. These through-holes are arranged substantially without gaps, separated by partitions, although some of the through-holes may be missing. In this invention, "one direction" is not limited to a linear direction, but means substantially the same direction. The through-holes in the curved honeycomb structure described later are not one-dimensional, but have a shape with multiple through-holes extending substantially in the same direction, and are therefore a honeycomb structure. Here, an example of the honeycomb structure of the present invention will be described using Figure 1. As shown in Figure 1, the honeycomb structure 14 is a structure that has a plurality of through holes 11 extending in one direction and partition walls 12 that separate the through holes. The honeycomb structure has an outer peripheral side wall 13 that surrounds the honeycomb structure part consisting of through holes, and there are also cases where part or all of the outer peripheral side wall has been removed, but both are honeycomb structures.

[0015] The mercury intrusion method measurement referred to in this invention is a type of pore distribution measurement method that utilizes the high surface tension of mercury to apply pressure to infiltrate mercury into the pores of a powder, and determines the pore distribution from the pressure and the amount of mercury infiltrated. In this invention, the advancing and receding contact angles between mercury and the material are assumed to be 130°, and the surface tension of mercury is assumed to be 485 mN / m for pore calculation. To visualize the pore distribution, the common logarithm of the differential pore volume is plotted against the pore diameter at the measurement point. The pore volume is calculated from the difference in the cumulative data of mercury injected between pores of different diameters. Pore ​​diameter is sometimes referred to as pore size, but it is basically a value calculated from the results of mercury intrusion analysis, assuming that mercury has been injected into a cylindrical pore, regardless of the shape of the pore. In this invention, "average particle size" refers to the particle size at 50% of the cumulative value in the particle size distribution determined by laser diffraction and scattering. The powder is dispersed in 100 mL of distilled water, and after dispersion using an ultrasonic cleaner at a frequency of 45 kHz and 100 W for 30 seconds, the measurement is taken within 1 minute. In this invention, "surface roughness (arithmetic mean roughness Ra)" refers to the surface roughness (arithmetic mean roughness Ra) measured with a 3D laser microscope. In this invention, "sphericity" refers to Wadell's practical sphericity. Wadell's practical sphericity is calculated by dividing the diameter of a circle equal to the projected area of ​​the material by the diameter of the smallest circle that circumscribes the projected image of the material. In this invention, "compressive strength" is defined as the value obtained by dividing the maximum load by the original cross-sectional area of ​​the columnar test specimen subjected to the compression test, with a crosshead speed of 10 mm per minute. In this invention, if the sample is not columnar and the sample volume is 1 × 10⁻⁶ -8 m 3 In the above cases, the sample is processed into a columnar shape and a compression test is performed. If the sample is not columnar and the sample volume is 1 × 10⁻⁶ -8 m 3 If the value is less than the original cross-sectional area of ​​the test specimen, the projected image area of ​​the sample shall be used as the original cross-sectional area of ​​the test specimen. Furthermore, the medical calcium carbonate composition of the present invention may be anisotropic. Materials with anisotropy have different compressive strengths depending on the direction. In the present invention, the maximum compressive strength obtained in any direction is defined as the compressive strength of the composition. Furthermore, considering that medical calcium carbonate compositions and the like are ceramic materials, the indirect tensile strength may be measured, and the value obtained by multiplying the indirect tensile strength by five may be used as the compressive strength. If the compressive strength and the value obtained by multiplying the indirect tensile strength by five are different, the higher value shall be used as the compressive strength value in this invention. The gas pressure used in this invention is an absolute pressure, with the pressure near sea level being 101.3 kPa, and not a relative pressure based on atmospheric pressure. Therefore, if the pressure exceeds 101.3 kPa, it is pressurized relative to atmospheric pressure, and if it is less than 101.3 kPa, it is depressurized relative to atmospheric pressure. In this invention, "accumulation" is defined as the gathering of multiple elements. In the case of stomata, accumulation means that multiple stomata are gathered together, and the stomata may or may not be connected to each other. Therefore, the stomata do not need to be in contact with each other. In this invention, "short diameter" is a term relating to the form of the composition and is defined as the size related to whether or not it can pass through a sieve. Specifically, a short diameter of 1 mm or more and less than 5 mm is defined as a composition that can pass through a sieve with a mesh size of 5 mm but cannot pass through a sieve with a double-sided mesh size of 1 mm. In this invention, a "closed reaction vessel" is defined as a reaction vessel that is not open. For example, when producing calcium carbonate by carbonating calcium hydroxide compacts with carbon dioxide in a reaction vessel, it is necessary to expose the calcium hydroxide compacts to carbon dioxide. If carbon dioxide is released into the atmosphere from the reaction vessel, it is carbonation in an open reaction vessel; if carbon dioxide is not released into the atmosphere from the reaction vessel, it is carbonation in a closed reaction vessel. From this perspective, carbon dioxide is defined as being released into the atmosphere even if it is emitted from an outlet, etc., if it is not released into the atmosphere. For example, if carbon dioxide emitted from an outlet is circulated back into the reaction vessel by a pump, etc., it is defined as being being released into a closed reaction vessel. Furthermore, if the reaction vessel is connected to a carbon dioxide cylinder, etc., it is also defined as being being released into a closed reaction vessel. In this invention, aqueous methanol, aqueous ethanol, and the like are simply expressed as the volume percentage of the solvent other than water. For example, methanol containing 10 volume percent water is called 90% methanol. "Granules" generally refer to particles with a larger particle size than powder, especially those formed by solidifying powder into larger particles. In this invention, "granules" also refer to particles with a larger particle size than powder, but unless otherwise specified regarding volume or shortest diameter, they refer to particles with a shortest diameter of 50 μm or more and 500 μm or less, or 1 × 10⁻⁶ -13 cm 3 The above 1 x 10 -7 cm 3 It must fall under one of the following categories:

[0016] [Medical Calcium Carbonate Composition: Essential Conditions] First, [1] will be described. <(A) The volume is 10 -12 m 3 or more.> Regarding In the medical calcium carbonate composition of the present invention, it is an essential condition that the volume is 10 -12 m 3 or more. A medical composition is required to have excellent tissue affinity in vivo, but both calcium carbonate powder and calcium phosphate powder cause an inflammatory reaction. On the other hand, a medical calcium carbonate composition with a volume of 10 -12 m 3 or more, or a medical calcium phosphate composition produced from the medical calcium carbonate composition with a volume of 10 -12 m 3 or more has excellent tissue affinity. When the medical calcium carbonate composition is used as a bone filling material or a raw material for a bone filling material, when the volume is 10 -11 m 3 or more, preferably 3 × 10 -11 m 3 or more, it is more preferable because it is easier to form communication pores suitable for cell invasion when filled in a bone defect part. When the volume is 10 -10 m 3 or more, it is further preferable because pores effective for tissue invasion are formed when filled in a bone defect part. When the volume is 10 -9 m 3 or more, it exhibits the characteristic of being easy to fill in a relatively large bone defect part, which is particularly preferable clinically. There is no particular limitation on the upper limit of the volume of the medical calcium carbonate composition, but when the volume is large, it takes time to manufacture, and also because the demand is small, it is preferably 10 -3 m 3 or less.

[0017] <(B) The acid-soluble residue is 1% by mass or less.> Regarding (B) is related to substantially pure calcium carbonate as a medical composition. In particular, it is an essential condition that the acid-soluble residue is 1% by mass or less, which is a very important factor regarding the usefulness of the medical calcium carbonate composition. This is because the medical calcium carbonate composition of the present invention or calcium apatite produced from the medical calcium carbonate composition as a raw material is expected to have excellent tissue affinity and in vivo absorbability. In vivo, calcium carbonate, calcium apatite, etc. are absorbed by the weak acid environment formed by osteoclasts, etc. The presence of the acid-soluble residue is synonymous with not being absorbed by osteoclasts, etc., and thus is inappropriate as a medical composition. The acid-soluble residue becomes a problem when producing a medical calcium carbonate composition from a raw material containing a polymer material. The polymer material is not dissolved in acid, and the presence of the acid-soluble residue is synonymous with the polymer material or its decomposition product remaining. The acid-soluble residue is defined as the residue when calcium carbonate, etc. is dissolved in 1 mol / L hydrochloric acid in a volume equal to 20 molar equivalents of the calcium carbonate, etc., and is expressed as the % of the dry mass with respect to the mass of the calcium carbonate, etc. It is an essential condition that the acid-soluble residue is 1% by mass or less, preferably 0.5% by mass or less, more preferably 0.3% by mass or less where the influence is reduced, even more preferably 0.1% by mass or less where the influence is almost negligible, and ideally substantially 0% by mass. Note that the medical calcium carbonate composition may contain a pore-forming material or may connect between a plurality of composition particles with fibers. Regarding the pore-forming material and the fibers connecting between the plurality of composition particles, they are not subject to the acid-soluble residue. That is, it is an essential condition of the present invention that the acid-soluble residue of the calcium carbonate composition other than the pore-forming material and the fibers connecting between the plurality of composition particles is 1% by mass or less.

[0018] Regarding <(C) which mainly consists of willemite or calcite and is substantially pure calcium carbonate as a medical composition.> The medical calcium carbonate composition of the present invention is a medical material used for medical purposes, and any composition containing impurities other than pore-forming materials and fibers connecting multiple composition particles cannot be used as a medical material. Therefore, natural materials are not included in the present invention. Furthermore, calcium carbonate compositions produced from coal ash containing calcium oxide discharged from boilers or slag generated in steel manufacturing processes also contain impurities and are therefore not included in the present invention. In research on natural minerals, organic gels, silicon-containing gels, metaphosphate gels, etc., are sometimes used, but calcium carbonate compositions to which these have been added also have tissue compatibility issues and are therefore not included in the present invention. In the medical calcium carbonate composition of the present invention, it is essential that the composition is substantially pure as a medical calcium carbonate composition, consisting mainly of vaterite or calcite; that is, it is substantially pure calcium carbonate, and its polymorphs are mainly vaterite or calcite. It is also required that it substantially contains no impurities other than sodium, strontium, and magnesium. Here, in (C) of the present invention, the amount of impurities other than sodium, strontium, and magnesium is preferably 1% by mass or less, more preferably 0.5% by mass or less, and even more preferably 0.1% by mass or less. Ideally, it should contain no impurities at all. Furthermore, in medical calcium carbonate compositions, sodium, strontium, and magnesium, unlike other impurities, are less likely to cause tissue damage. Although the mechanism is not clear, it is inferred that the calcium carbonate selected by invertebrates that originated in seawater containing sodium, strontium, and magnesium contained sodium, strontium, and magnesium, and thus evolved into organisms that can tolerate sodium, strontium, and magnesium. However, magnesium, strontium, and sodium are also impurities, and in the "substantially pure calcium carbonate as a medical composition" of the present invention, their content is preferably 2% by mass or less, more preferably 1.0% by mass or less, and even more preferably 0.2% by mass or less. As mentioned above, this medical-grade calcium carbonate composition may contain pore-forming materials and fibers connecting multiple composition particles, and these fibers are not considered impurities. In other words, it is an essential condition of this invention that the calcium carbonate composition, excluding the pore-forming materials and fibers connecting multiple composition particles, is substantially pure calcium carbonate. As mentioned above, in addition to vaterite and calcite, aragonite also exists as a polymorph of calcium carbonate. Since aragonite is essentially calcium carbonate, its presence does not hinder the effects of the present invention. However, from the viewpoint of the reactivity of the medical composition produced using the medical calcium carbonate composition of the present invention as a raw material, the aragonite content is preferably 20% by mass or less, more preferably 10% by mass or less, and even more preferably 5% by mass or less. In other words, "mainly consisting of vaterite or calcite" in the present invention means that the proportion of vaterite or calcite is preferably more than 80% by mass, more preferably more than 90% by mass, even more preferably more than 95% by mass, and particularly preferably 100% by mass. Furthermore, since calcium hydroxide and calcium oxide react with carbon dioxide in the air over time to form calcium carbonate, it is not necessary to strictly exclude them. Therefore, in the "substantially pure calcium carbonate composition as a medical calcium carbonate composition" as defined in this invention, calcium hydroxide and calcium oxide are not considered impurities. However, it is preferable that calcium hydroxide and calcium oxide are not included. Accordingly, the content of calcium hydroxide and calcium oxide is preferably 3% by mass or less, more preferably 2% by mass or less, and even more preferably 1% by mass or less. It is ideal that they are not included at all.

[0019] Regarding <(D) Contains 20% or more by mass of vaterite.> Calcium carbonate compositions containing vaterite, a metastable phase within calcium carbonate, are preferred due to their high reactivity. While a vaterite content of less than 20% by mass is also effective in improving reactivity, its effect is limited; therefore, in this invention, the content is limited to 20% by mass or more. While a vaterite content of 20% by mass or more is an essential condition, a content of 30% by mass or more is preferable because the amount of active ingredient approaches a sufficient amount, a content of 50% by mass or more is more preferable because the amount of active ingredient is sufficient, a content of 80% by mass or more is even more preferable because the composition exhibits almost the same properties as vaterite, and a content of 90% by mass or more is particularly preferable. As mentioned above, the mass of the porosity-forming material and the fibers connecting the multiple composition particles are excluded from the calculation of the vaterite content because they do not participate in the reactivity.

[0020] (E) A honeycomb structure having multiple through holes extending in one direction, and in pore distribution measurement by mercury intrusion method, the pore volume of the honeycomb structure with a pore diameter of 10 μm or less relative to the mass of the honeycomb structure is 0.02 cm³. 3 Greater than / g. > As shown in Figure 1, the honeycomb structure is formed from a solid part consisting of partition walls and outer peripheral side walls, and a space part consisting of through-holes. Therefore, when pore distribution is measured using the mercury intrusion method, a pore distribution due to through-holes is always observed. Figure 2 shows an example of the mercury intrusion method pore distribution measurement results for the medical calcium carbonate honeycomb structure of the present invention. In addition to the peak around 70 μm in pore diameter due to macropores in the honeycomb structure, it can be seen that there are pores with a diameter of 1 μm or less due to micropores in the honeycomb partition walls. There are no medical-grade calcium carbonate honeycomb structures with through-pores smaller than 10 μm. Therefore, pores with a diameter of 10 μm or less are pores located in the septa. Since tissues and cells cannot penetrate pores with a diameter of 10 μm or less, these pores have not been studied until now. However, since tissue fluid and aqueous solutions can penetrate them, it has been found that pores with a diameter of 10 μm or less play an important role in in vivo reactions and in the production of medical-grade calcium phosphate honeycomb structures by adding phosphates to the medical-grade calcium carbonate honeycomb structure. When the pore diameter with respect to the mass of the honeycomb structure increases, the reactivity increases, but the mechanical strength decreases. Therefore, it is necessary to balance the two. From the perspective of reactivity, the pore volume with a pore diameter of 10 μm or less with respect to the mass of the honeycomb structure must be greater than 0.02 cm 3 / g, preferably 0.03 cm 3 / g or more, more preferably 0.10 cm 3 / g or more, and even more preferably 0.15 cm 3 / g or more. Also, from the perspective of compressive strength, it is preferably 0.15 cm 3 / g or less, more preferably 0.10 cm 3 / g or less, and even more preferably 0.03 cm 3 / g or less.

[0021] <(F) A granular bonded porous body having a plurality of through-holes extending in a plurality of directions formed by bonding a plurality of granules having a maximum diameter length of 50 μm or more and 500 μm or less, wherein the pore volume of the granular bonded porous body with a pore diameter of 10 μm or less by mercury intrusion porosimetry is 0.05 cm 3 / g or more.> Regarding In some cases, a porous body having three-dimensional through-holes may be desired. In the case of a medical bone filler, the pore size is particularly important. Since adipose tissue other than bone tissue penetrates into pores with a large size, control of the pore size is important. A granular bonded porous body having a plurality of through-holes extending in a plurality of directions formed by bonding a plurality of granules having a maximum diameter length of 50 μm or more and 500 μm or less has high permeability, such as the through-holes formed by a hexagonal close-packed structure, and has the characteristic that osteoblasts, osteoclasts, and bone tissue can easily migrate and conduct inside. Also, in the tissue replacement of the granular bonded porous body, the pores in the granular part play an important role. The pore volume of the granular part must be 0.05 cm as the pore volume with a pore diameter of 10 μm or less of the granular bonded porous body by mercury intrusion porosimetry 3 / g or more, and preferably 0.1 cm 3 / g or more, and more preferably 0.2 cm 3It is more preferable that it be 0.3 cm or more. 3 It is even more preferable that the amount be 1 / g or more.

[0022] (G) A porous material having multiple pores with a maximum diameter and length of 50 μm or more and 400 μm or less accumulated throughout the medical composition, and not containing any pores with a maximum diameter and length of 800 μm or more, wherein the pore volume of the porous material with a diameter of 10 μm or less, as measured by mercury intrusion method, is 0.05 cm³. 3 It is / g or more. The aforementioned granular porous material is extremely useful as a bone graft material from the viewpoint of permeability, but it generally has the disadvantages of low mechanical strength and difficulty in manufacturing. On the other hand, a porous material with specific pores formed using a pore-forming material, for example, has inferior permeability, but can be manufactured relatively easily by using a polymer pore-forming material, and has the advantage of relatively good mechanical strength, making it useful as medical calcium carbonate. Specifically, in a porous material with a pore-forming material, pores are accumulated through pore walls made of calcium carbonate or through-holes formed in a part of the pore wall. When the through-holes penetrate throughout, it becomes a porous material with three-dimensional through-holes, which is particularly useful. Furthermore, the pore size must be between 50 μm and 400 μm. This pore size is useful from the standpoint of cell and tissue invasion. Preferably, the pore size is between 70 μm and 350 μm, more preferably between 90 μm and 300 μm, and even more preferably between 100 μm and 300 μm. On the other hand, it is also a necessary condition that the material does not contain pores with a maximum diameter and length of 800 μm or more. As mentioned above, adipose tissue, not bone tissue, migrates to large pores. Furthermore, compositions with large pores have lower mechanical strength. While it is a necessary condition that the material does not contain pores with a maximum diameter of 800 μm or more, it is preferable that the pores to be excluded have a maximum diameter of 700 μm or more, and more preferably 600 μm or more. Furthermore, considering the balance between cell and tissue penetration, absorption, and mechanical strength, the porosity is preferably 40% to 80% by volume, more preferably 45% to 78% by volume, and even more preferably 50% to 77% by volume. Furthermore, in the tissue replacement of this porous material, not only the pores themselves, but also the calcium carbonate pores surrounding the pores play an important role. The volume of these pores is 0.05 cm³, measured by the mercury intrusion method as the volume of pores smaller than 10 μm in this porous material. 3 It must be at least / g, and the pore volume must be 0.1cm³. 3 It is preferable that it be 0.2 cm or more. 3 It is more preferable that it be 0.3 cm or more. 3 It is even more preferable that the amount be 1 / g or more. Porous materials with a high concentration of pores are classified into those containing pore-forming materials and those without. In the case of porous materials containing pore-forming materials, they are used as raw materials for the manufacture of medical compositions and are removed during the manufacturing process; therefore, the pore-forming material portion is essentially pores. For this reason, in calculating the porosity of such porous materials, the pore-forming material is calculated as pores.

[0023] Regarding <(H) In mercury intrusion measurement, the ratio of pore volume between 1 μm and 6 μm in diameter to pore volume between 6 μm and 6 μm in diameter is 10% or more.> As mentioned above, micropores, as well as macropores, are important for the reactivity of porous calcium carbonate materials. While the absolute amount of micropores is important, the distribution of specific micropores can be useful. Specifically, in mercury intrusion measurements, it is preferable that the ratio of the volume of pores with a diameter of 1 μm to 6 μm to the volume of pores with a diameter of 6 μm or less is 10% or more. More preferably, the ratio of the volume of pores with a diameter of 1 μm to 6 μm to the volume of pores with a diameter of 6 μm or less is 15% or more, and even more preferably 20% or more.

[0024] (I) The maximum compressive strength obtained in any direction is equal to or greater than the reference compressive strength [S] calculated by the following formula (provided that the honeycomb structure has multiple through holes extending in one direction, and the pore volume of the honeycomb structure with a pore diameter of 10 μm or less relative to the mass is 0.02 cm³ as measured by mercury intrusion method) 3 (Excluding those that are less than / g.) S = S0 × C × exp(-b × P) (Here, S0 and b are constants, S0 is 500 and b is 0.068, C is a constant due to the polymorphism of calcium carbonate, 0.01 if it contains 20% or more by mass of vaterite, and 1 if it does not contain 20% or more by mass of vaterite, and P is the percentage of the porosity of the composition.) As described above, the medical calcium carbonate composition of the present invention is preferably porous, and its usefulness increases with higher porosity. On the other hand, as porosity increases, the mechanical strength of the medical calcium carbonate decreases. An empirical formula (Duckworth formula) S = S0exp(-bP) is known to exist between mechanical strength [S] and porosity percentage [P], and is cited in academic journals such as the Journal of Biomedical Research (vol. 29, pp. 1537-1543) and the Journal of the American Ceramics Society (vol. 36, number 2, p. 68). Here, S0 is the mechanical strength of the dense material, and b is an empirical constant. As mentioned above, reactivity is also affected by composition; therefore, even compositions with low porosity can have high reactivity depending on their composition. This compositional factor is represented as C, and the requirement for compressive strength is adjusted accordingly. If the composition contains 20% or more by mass of highly reactive vaterite, the value is set to 0.01; if it does not contain 20% or more by mass of vaterite, the value is set to 1. P is the percentage of porosity of the composition. Furthermore, in this invention, we refer to the values ​​reported as coefficients for hydroxyapatite, a similar ceramic, in Volume 29, pp. 1537-1543 of the Journal of Biomedical Research. Specifically, S0 is set to 500 and b to 0.068. Since a higher compressive strength is preferable, S0 is preferably set to 700, more preferably to 900, and even more preferably to 1000. Furthermore, in the case of a honeycomb structure with multiple through-holes extending in one direction, mercury intrusion measurement indicates that the pore volume of the honeycomb structure with a pore diameter of 10 μm or less relative to its mass is 0.02 cm³. 3 Substances below / g are excluded from this invention due to their low reactivity.

[0025] <(J) Honeycomb structure granules having a minor axis of 1 mm or more and less than 5 mm, and in the projection diagram of the composition, if a circle with a radius of 0.2 mm is drawn from any point on the projection diagram's surrounding line, there is no point in the triangle formed by the three points where the circle intersects the projection diagram's surrounding line that has an angle of 90° or less with any point on the projection diagram's surrounding line as its vertex.> This relates to the external shape of honeycomb structure granules, specifically to compositions with rounded corners that do not damage surrounding tissues. Compositions with a short diameter of less than 5 mm may be used as granules to fill bone defects. In the medical calcium carbonate compositions of the present invention, the honeycomb structure exhibits high anisotropy. Therefore, when crushed, it forms a spindle shape. When the short diameter is less than 1 mm, the granules are highly fluid, making it difficult for sharp angles to be perpendicular to surrounding tissues such as the periosteum covering the defect. However, as the short diameter increases, the fluidity of the granules becomes limited, making it easier to damage surrounding tissues. Furthermore, when the short diameter is 5 mm or more, it is easier to prevent the formation of sharp angles. Therefore, it is desirable to round the corners of honeycomb structure granules with a short diameter of 1 mm or more and less than 5 mm. Specifically, the granules should have a minor axis of 1 mm or more and less than 5 mm, and in the projection diagram of the composition, if a circle with radius 0.2 mm is drawn from any point on the projection diagram's perimeter, there should be no point in the triangle formed by the three points where the circle intersects the projection diagram's perimeter, where the angle with any point on the projection diagram's perimeter is 90° or less. The minor axis is defined by whether or not it passes through a sieve. That is, a composition with a minor axis of 1 mm or more and less than 5 mm is a composition that passes through a sieve with a mesh size of 5 mm but does not pass through a sieve with a mesh size of 1 mm. The minor axis is preferably 1 mm or more and less than 5 mm, more preferably 1.2 mm or more and less than 4 mm, and even more preferably 1.4 mm or more and less than 3 mm. From the perspective of rounded corners, it is preferable that "there is no point in the triangle formed by the three points where the angle with any point on the surrounding line of the projection is 60° or less", but more preferably 80° or less, and even more preferably 100° or less. In these honeycomb-structured granules, not only the external shape of the granules that does not damage the surrounding tissue, but also the pores of the granules play an important role in tissue reaction. The volume of these pores is 0.02 cm³, measured by mercury intrusion method for pores smaller than 10 μm in the honeycomb-structured granules. 3 It is preferable that it be 0.05 cm or more, and 0.05 cm 3 It is more preferable that it be 0.1 cm or more. 3 It is even more preferable that the amount be 1 / g or more.

[0026] Regarding <(K) A plurality of compositions are connected by fibers.> Medical calcium carbonate compositions or medical calcium phosphate compositions produced from medical calcium carbonate compositions as raw materials may be implanted in the living body as bone fillers, etc. However, when the composition is in the form of particles such as granules, the operation of implanting the particles into the bone defect part is complicated. A composition in which a plurality of composition particles are connected by fibers like beads is rich in operability. From the viewpoints of tissue affinity and connection strength, it is more preferable that the fiber passes through the inside of the composition particles and connects a plurality of composition particles. The size of the particles is not particularly limited as long as they can be connected by fibers. For example, granules having a minor axis of 1 mm or more and less than 5 mm are preferable. The type of fiber is not limited, but in the case of a medical composition produced by a manufacturing method using a firing operation, it needs to be carbon fiber in order to have tissue affinity and not be burned. Also, when no firing operation is performed, it is preferable that the fiber is a bioabsorbable fiber. For example, polyglycolic acid, polylactic acid, polycaprolactone, etc., and copolymers thereof are exemplified. In this composition as well, pores play an important role in tissue reaction. The volume of the pores is preferably larger than 0.02 cm 3 / g as the pore volume of the composition with a pore size of 10 μm or less measured by mercury intrusion porosimetry, more preferably 0.05 cm 3 / g or more, and even more preferably 0.1 cm 3 / g or more.

[0027] In the present invention, it is an essential condition to satisfy at least one selected from the group (D) to (K), but it is preferable to satisfy a plurality of them.

[0028] (Shape of medical calcium carbonate composition) The shape of the medical calcium carbonate composition of the present invention is not particularly limited. It may be any shape such as a dense body, a porous body, a block body, granules, a plate shape, etc., but a specific porous body described later is particularly preferable.

[0029] [I Medical-grade calcium carbonate composition: Vaterite sintered body] Next, I will explain [2]. Vaterite is a highly reactive polymorph of calcium carbonate, but it is a metastable phase and a low-temperature stable phase. Therefore, it was not expected that vaterite could be sintered, and no vaterite sintered bodies have been found to date. However, as described later, it has been found that medical-grade vaterite sintered bodies can be produced by compacting calcium carbonate powder containing 20% ​​or more by mass of vaterite and then firing it. The medical calcium carbonate composition of the present invention and the medical compositions manufactured using this composition as a raw material are used in humid environments such as inside the body. A sintered body is an object in which powder is solidified. When water is applied to a vaterite compact and rubbed, the powder is released, and when immersed in water, the powder is released from the compact and crumbles, and the shape cannot be maintained. Therefore, in the present invention, the presence or absence of sintering in a medical vaterite sintered body is determined by the shape retention of the sintered body in water. A glass container is filled with calcium carbonate saturated water in an amount 10 times that of the composition, and the composition is immersed in it. The glass container is placed in an ultrasonic cleaner with a 28kHz output of 75W, and ultrasonic waves are irradiated for 1 minute. If the dry weight of the composition is 95% or more of the dry weight before ultrasonic irradiation, the composition is determined to be able to maintain its shape in water and is defined as a sintered body. If part of the composition is damaged by ultrasonic irradiation, the dry weight of the composition with the largest volume is used.

[0030] [I Medical-grade calcium carbonate compositions: specific microstructure and composition] Next, I will explain [3]. The medical calcium carbonate composition described in [1] or [2] is characterized in that calcium carbonate powders satisfying any of the conditions selected from the group (AJ1) to (AJ4) are bonded together to form a calcium carbonate composition, and is preferred in terms of the balance between compressive strength and reactivity. The larger the average particle size, the more interconnected pores are formed and the higher the reactivity, but the lower the compressive strength. Furthermore, in order to form interconnected pores while maintaining compressive strength, particles with high sphericity are preferable to approach close-packing. From these viewpoints, the average particle size is preferably 2 μm to 8 μm, more preferably 3 μm to 7 μm, and even more preferably 4 μm to 6 μm. The sphericity is preferably 0.9 or higher, more preferably 0.95 or higher, and even more preferably 0.97 or higher. The average particle size and sphericity are measured and calculated by separating the particles at the grain boundaries of the calcium carbonate composition. Furthermore, if the calcium carbonate composition is sintered too much, it cannot maintain its interconnected pores. For this reason, it is preferable that the calcium carbonate particles contain trace elements that can control their sinterability. These elements must not affect biocompatibility. From these viewpoints, Mg and Sr were selected, and the Mg content was 5 × 10⁻⁶. -4 Mass% or more 3×10 -3 Preferably less than 1% by mass, and 1 × 10 -3 Mass% or more 2.5×10 -3 More preferably less than or equal to mass%, such as 1.5 × 10 -3 Mass% or more 2.5×10 -3 A mass percentage or less is even more preferable. The Sr content is 3 × 10 -3 Mass% or more 1.5×10 -2 Preferably less than % by mass, 4 × 10 -3 Mass% or more 1.3×10 -2 More preferably less than or equal to % by mass, 5 × 10 -3 Mass% or more 1×10 -2 A mass percentage or less is even more preferable. It is preferable to satisfy any of the conditions (AJ1) to (AJ4), more preferably to satisfy multiple conditions, and even more preferably to satisfy all of them.

[0031] [I: Medical-grade calcium carbonate composition: curved honeycomb structure] Next, I will explain [4]. A medical calcium carbonate composition that satisfies the conditions of (E) above, The statement, "The diameter of the circle passing through the two ends of any one through-hole and the center of the through-hole is between 1 cm and 50 cm," is a specific condition relating to the morphology of a medical carbonate apatite honeycomb structure. Bones are not always straight; some are curved or prism-shaped. In bone reconstruction surgery for such bones, curved-prism-shaped medical calcium carbonate honeycomb structures are useful. This is because bone conduction occurs within the perforations of the medical calcium carbonate honeycomb structure. Even if a curved-prism honeycomb structure is manufactured by processing a straight-prism honeycomb structure, bone conduction will not occur within the perforations unless the perforations are in contact with bone. Furthermore, when creating bone perpendicular to the bone surface, it is preferable that the through-holes in the honeycomb structure do not open to the connective tissue surrounding the bone, but only to the bone surface. This is because connective tissue cannot penetrate the honeycomb structure of this structure, and only bone tissue conducts through it. This honeycomb structure can be manufactured by curving the honeycomb structure and, if necessary, cutting it so that through-holes open on only one side. To reduce the angle of the rising portion of the curved honeycomb structure from the bone surface, it is useful to further curve the honeycomb structure in a direction that is not parallel to the plane formed by the circle passing through the two ends of the through-hole and the center of the through-hole. In a honeycomb structure, it is preferable that the diameter of the circle passing through the two ends of one through-hole and the center of the through-hole is between 1 cm and 50 cm. It is more preferable that the diameter of the circle is between 2 cm and 20 cm, and even more preferable that the diameter of the circle is between 3 cm and 10 cm.

[0032] [II. Method for producing medical-grade calcium carbonate] Next, the manufacturing process of the medical calcium carbonate composition of the present invention will be described. Furthermore, the raw calcium composition may contain pore-forming material and fibers connecting multiple composition particles. However, the pore-forming material and the fibers connecting multiple composition particles are excluded from calculations such as the vaterite content. The pore-forming material is the material that is removed to form pores. The pore-forming material does not need to be removed during the manufacturing stage of the medical calcium carbonate composition; it may be a material that is removed during the manufacturing stage of other medical compositions using the medical calcium carbonate composition as a raw material. Examples include salts such as sodium chloride, potassium chloride, and disodium hydrogen phosphate, and acrylic polymer beads, but water-soluble inorganic materials are preferred from the viewpoint of ease of removal. For example, when sodium chloride is used as a pore-forming material and calcium hydroxide is used as the raw material calcium composition, the two are mixed and then compacted, and carbon dioxide is added to convert the calcium hydroxide compact into vaterite. When carbon dioxide is added to calcium hydroxide, sodium chloride does not react and is not removed. Although sodium chloride, which is the pore-forming material, is present in the medical vaterite block, for example, in the process of immersing the block in an aqueous solution of disodium hydrogen phosphate to produce a medical carbonate apatite block, the vaterite is converted into carbonate apatite and the pore-forming material dissolves at the same time. As a result, a porous medical carbonate apatite body is produced. As described above, fibers are used to connect composition particles in order to improve the handling properties of the composition. Since fibers are used to improve the handling properties of medical-grade calcium carbonate granules, or medical-grade calcium phosphate granules manufactured using the composition as a raw material, it is preferable that the fibers be present inside the particles of such granules.

[0033] [II Method for producing medical-grade calcium carbonate: (D) Vaterite composition] First, let's explain [5]. For the production of vaterite compositions, which are metastable phases, a method is useful that suppresses the formation of calcite, the stable phase, thereby relatively forming a vaterite composition, and inhibiting the transition from the metastable vaterite phase to the stable calcite phase. Organic substances suppress the formation of calcite, the stable phase, and relatively promote vaterite formation. (Inorganic substances such as ammonia and ammonia salts are also useful in suppressing the transition to calcite, but for simplicity, we will explain using organic substances.) Water functions to promote both the carbonation of the raw calcium composition and the transfer from vaterite to calcite. In the absence of water, the raw calcium composition will not be ionized. Furthermore, the solubility of carbon dioxide in organic solvents is limited, and carbon dioxide will not dissolve in water to form carbonate ions. In the presence of water, calcium ions formed from the raw calcium react with carbonate ions formed from carbon dioxide, thus promoting the formation of calcium carbonate. When carbon dioxide is added to a raw calcium composition, water is formed within the raw calcium composition. For example, in the process of producing vaterite by exposing a compacted calcium hydroxide powder to carbon dioxide, the same number of moles of water as vaterite are formed within the compacted calcium hydroxide powder. Water is necessary for vaterite formation, but excess water is undesirable for vaterite production because it promotes the phase transition from the metastable phase of vaterite to the stable phase of calcite. In the production of vaterite powder using calcium hydroxide powder as a raw material, water is easily diffused into the surroundings and is not a problem, but the subject of the present invention is "(A) Volume 10 -12 m 3 The above is a medical-grade calcium carbonate composition, and diffusion from within the composition to outside is not easy. Therefore, a process to discharge water formed within the raw calcium composition to the outside of the raw calcium composition is important. A medical calcium carbonate composition that satisfies all of the above conditions (A) to (C) and condition (D) has a volume of 10 -12 m 3 The raw material calcium composition described above (which may include pore-forming material and fibers connecting multiple composition particles) is produced by exposing it to carbon dioxide or carbonate ions under specific conditions. In other words, the step of "(D1) suppressing calcite formation or the growth of calcite crystals and relatively promoting the formation of calcium carbonate other than calcite" is useful as a method for producing a medical calcium carbonate composition that satisfies condition (D). Since at least one selected from the group consisting of organic solvents, water-soluble organic substances, ammonia, and ammonium salts inhibits calcite formation or the growth of calcite crystals, the step of "(D2) exposing the raw material calcium composition to carbon dioxide or carbonate ions and at least one selected from the group consisting of organic solvents, water-soluble organic substances, ammonia, and ammonium salts" is preferred.

[0034] Since the reaction for forming a medical-grade calcium carbonate composition that satisfies condition (D) from the raw calcium composition must proceed within the raw calcium composition itself, it is preferable to add the substance that inhibits calcite formation or the growth of calcite crystals to the raw calcium composition. In other words, the step of "(D3) Exposing a raw material calcium composition containing at least one selected from the group consisting of organic solvents, water-soluble organic substances, ammonia, and ammonium salts to carbon dioxide or carbonate ions and at least one selected from the group consisting of organic solvents, water-soluble organic substances, ammonia, and ammonium salts" may be preferred as a method for producing a medical calcium carbonate composition that satisfies condition (D). Since the raw material calcium composition containing organic solvents can be handled as a paste, it may also be useful from the viewpoint of ease of handling.

[0035] Methanol, ethanol, and ammonium carbonate are evaporative substances and are easily removed from the manufactured medical vaterite composition. Glycerin and ethylene glycols are highly water-soluble substances and are also easily removed from the manufactured medical vaterite composition. Here, ethylene glycols refer to ethylene glycol and polyethylene glycol. These are preferred substances from the viewpoint of balancing the simplicity of the manufacturing process with the effect of suppressing vaterite. Specifically, the step of "(D4) Exposing the raw material calcium composition to carbon dioxide or carbonate ions and at least one selected from the group of methanol, ethanol, glycerin, ethylene glycols, and ammonium carbonate" is more preferred as a method for producing a medical calcium carbonate composition that satisfies the conditions of (D), and the step of "(D5) Exposing the raw material calcium composition containing at least one selected from the group of methanol, ethanol, glycerin, ethylene glycols, and ammonium carbonate to carbon dioxide or carbonate ions and at least one selected from the group of methanol, ethanol, and ammonium carbonate" is even more preferred.

[0036] As described above, the metastable phase, vaterite, transitions to the stable phase, calcite. Therefore, "(D6) the step of suppressing the transition from vaterite to calcite" is useful for a medical calcium carbonate composition that satisfies condition (D). As described above, the transition from vaterite to calcite is promoted by water. When a medical vaterite composition is produced by the reaction of a raw calcium composition with carbon dioxide, equimolar water is produced as a by-product inside the raw calcium composition, so "(D7) the step of removing water from the raw calcium composition" is useful for a medical calcium carbonate composition that satisfies condition (D). To remove water produced as a by-product within the raw calcium composition, it is necessary to diffuse the water by evaporation or other means and discharge it from the inside of the raw calcium composition to the outside. While it is possible to perform a vacuum operation to remove water during the carbonation of the raw calcium composition, the step of "(D8) flowing carbon dioxide or carbonate ions containing an organic solvent around the raw calcium composition" is useful because it facilitates the evaporation of water inside the raw calcium composition and can be performed continuously. Examples of methods for flowing carbon dioxide or carbonate ions containing an organic solvent around the raw calcium composition include blowing the carbon dioxide or carbonate ions containing an organic solvent onto the raw calcium composition with a fan or by circulating the carbon dioxide or carbonate ions containing an organic solvent around the raw calcium composition.

[0037] Medical vaterite compositions are manufactured by adding carbon dioxide to a raw calcium composition under specific conditions, with calcium hydroxide being preferred as the raw calcium composition. This is because it does not produce any by-products other than water. Generally, compressed calcium hydroxide is used, but when compressed calcium hydroxide is immersed in a liquid phase such as an organic solvent, it crumbles and cannot maintain its shape. Therefore, it is necessary to add carbon dioxide in the gas phase. On the other hand, a uniform reaction is less likely to occur in the gas phase compared to the liquid phase. For this reason, in the process of manufacturing a medical vaterite composition under at least one condition selected from the group (D1) to (D8), the step of "(D9) partially carbonating the raw calcium composition by exposing it to carbon dioxide or carbonate ions in the gas phase, and then exposing the raw calcium composition to carbon dioxide or carbonate ions in the liquid phase" is useful. When calcium hydroxide powder is immersed in a liquid phase such as 90% ethanol, it collapses, but when calcium hydroxide paste is placed in a mold and immersed in the liquid phase, it does not collapse. Therefore, in the process of manufacturing a medical vaterite composition under at least one condition selected from the group (D1) to (D8), the step of "(D10) exposing the raw material calcium composition in a mold to carbon dioxide or carbonate ions" is useful. The shape of the mold is not particularly limited, but since it is necessary to react with carbon dioxide or carbonate ions, it is necessary that at least a part of it is open and can react with external carbon dioxide or carbonate ions. Since the reaction proceeds from the entire surface, a mold made of a breathable material is preferred. The raw material calcium composition in the mold does not need to be immersed in the liquid phase and is also useful when reacting in the gas phase, from the viewpoint of manufacturing a medical vaterite composition in a desired form.

[0038] When a raw calcium composition, such as calcium hydroxide powder or calcium hydroxide paste, is exposed to carbon dioxide or carbonate ions, a medical vaterite composition is produced. However, even if the raw calcium composition contains pore-forming materials such as sodium chloride, sodium dihydrogen phosphate, or polymer beads, or fibers, these materials do not react. Pore-forming materials are useful for producing porous materials, and fibers are useful for producing compositions with excellent handling properties. For example, in a process for producing a medical vaterite composition under at least one condition selected from the group (D1) to (D8), if "(D11) the raw calcium composition containing pore-forming materials is exposed to carbon dioxide or carbonate ions," a medical calcium carbonate composition containing pore-forming materials and satisfying condition (D) can be produced. By removing the pore-forming materials, medical calcium carbonate porous materials and medical calcium phosphate porous materials can be produced. The pore-forming materials can be mixed with the raw calcium carbonate. Furthermore, in the process of manufacturing a medical vaterite composition under at least one condition selected from the group (D1) to (D8), and by "(D12) exposing the fiber-connected raw calcium composition to carbon dioxide or carbonate ions," a medical calcium carbonate composition that satisfies condition (D), such as fiber-connected granules, can be manufactured. As described above, fiber-connected medical calcium carbonate compositions and medical calcium phosphate compositions offer excellent handling properties.

[0039] (Preferred raw material calcium composition) In the manufacturing process of a medical calcium carbonate composition that satisfies condition (D), the raw material calcium composition is not particularly limited as long as it is a calcium-containing composition, but calcium hydroxide and calcium oxide are particularly preferred. This is because, as mentioned above, when calcium carbonate is formed in the process of exposing both to carbonic acid or carbonate ions, no compositions other than water are produced as by-products.

[0040] (organic solvent) In this invention, the term "organic solvent" refers to a solvent for organic substances and includes aqueous organic solvents. Examples of organic solvents include alcohols, ketones, and hexane. From the viewpoint of calcite formation inhibitory ability, cost, water content, and ease of removal, alcohols or ketones are preferred, lower alcohols or lower alkyl ketones are more preferred, and aliphatic alcohols having 1 to 4 carbon atoms or di-lower alkyl ketones having a total of 3 to 6 carbon atoms are even more preferred. Examples of lower alcohols include methanol, ethanol, and propanol. Methanol, ethanol, and propanol are preferred, and methanol and ethanol are more preferred. Examples of lower alkyl ketones include acetone, methyl ethyl ketone, diethyl ketone, and methyl isobutyl ketone, with acetone and methyl ethyl ketone being particularly suitable.

[0041] (Water-soluble organic matter) In this invention, water-soluble organic substances refer to organic substances that dissolve in water, and include salts of organic substances. Examples include nonionic surfactants, lignin sulfonates, sugars such as sucrose, alkylamine salt-type surfactants, glycerin, ethylene glycol, polyethylene glycol, propylene glycol, and polypropylene glycol. Water-soluble organic substances must be completely removed after the manufacture of medical-grade calcium carbonate compositions. While they are often less useful than evaporating organic solvents, ammonia, and ammonium chloride, glycerin, ethylene glycol, and polyethylene glycol may be useful in extrusion molding and removal from the product due to their high viscosity and solubility in water.

[0042] (Ammonia, ammonium salts) In this invention, ammonia refers to NH3, and includes aqueous ammonia (NH4OH). Furthermore, in this invention, ammonium salts refer to salts of ammonia, and examples include ammonium carbonate, ammonium chloride, and ammonium nitrate. Among these, ammonium carbonate is particularly useful because it is also used in the carbonation process.

[0043] [II Method for producing medical calcium carbonate composition: (D) Vaterite sintered body] Next, we will explain [6]. As mentioned above, vaterite is a metastable phase and was known to be a low-temperature stable phase, so it was not thought that it could be sintered. However, it has been found that a medical vaterite sintered body containing 20% ​​or more by mass of vaterite can be produced by the process of "compacting calcium carbonate powder containing 20% ​​or more by mass of vaterite and firing it." The compaction and firing conditions are not particularly limited and are acceptable as long as the conditions allow the powder to solidify and a sintered body to be produced, but the compaction pressure is preferably 100 MPa or higher, more preferably 130 MPa or higher, and even more preferably 160 MPa or higher. The firing temperature is preferably 200°C or higher, more preferably 220°C or higher, and even more preferably 240°C or higher. When a calcium carbonate compact containing 20% ​​or more by mass of vaterite is fired, it sintersects, but above a certain temperature the vaterite decomposes into calcite. This temperature is also dependent on the environment and is not particularly limited, but in the case of atmospheric firing, the firing temperature is preferably 600°C or lower, more preferably 550°C or lower, and even more preferably 500°C or lower. As mentioned above, the phase transition from the metastable phase vaterite to the stable phase calcite is accelerated by moisture. Therefore, firing conditions that do not contain moisture are preferable, and a carbon dioxide atmosphere is even more preferable from the viewpoint of suppressing decomposition. Consequently, a carbon dioxide atmosphere that does not contain moisture is even more preferable.

[0044] [II Method for producing medical-grade calcium carbonate composition: (E) Carbonate apatite honeycomb structure] Next, we will explain [7]. Medical-grade calcium carbonate honeycomb structures are manufactured using the "(E1) extrusion process" and one "degreasing carbonation process" selected from the group (E5) to (E9) as essential processes, with additional processes selected from the group (E2) to (E4) and (E10) as needed. <(E1) Extrusion Process> In the extrusion process, the polymer material-containing raw material calcium composition is extruded through a mold for forming a honeycomb structure, with a volume of 3 × 10 -11 m 3 The above is achieved, and a raw material honeycomb structure having multiple through holes extending in one direction is manufactured. Known polymer materials are used as the polymer material. Note that polymer materials are sometimes called polymer binders or organic binders in the sense that they bind powders together, but in this invention, they have the same meaning. As the polymer material, a polymer material that is an organic binder of wax-acrylic resin (also simply called wax-based) is preferred. This is because, unlike other molding methods, the molding of honeycomb structures requires fluidity during extrusion and curability after extrusion. <(E2) Molding process after the extrusion process> In some cases, it may be useful to perform the molding process after the essential process (E1). In this process, a honeycomb structure composed of a polymer material-containing calcium composition is softened by heat treatment and then molded into the desired shape by applying pressure. The softening temperature is adjusted depending on the type of polymer material, but is generally between 50°C and 200°C. By molding into the desired shape, the "(E3) outer peripheral side wall removal process" becomes easier. Note that "after the extrusion process" refers to the time after the polymer material-containing raw material calcium composition has passed through the mold for forming the honeycomb structure. Even when molding is performed immediately after the polymer material-containing raw material calcium composition has passed through the mold for forming the honeycomb structure while the polymer material-containing raw material calcium composition is being extruded, this is also defined as "after the extrusion process." Furthermore, when manufacturing a honeycomb structure in which the diameter of the circle passing through the two ends of the through-hole and the center of the through-hole is between 1 cm and 50 cm, it is preferable to form the structure into this shape at this stage. In the "(E3) outer periphery side wall removal process," the outer periphery side wall is removed after (E1) or (E2) and before one of the "degreasing carbonation processes" selected from the group (E5) to (E9). In the "(E4) Molding process after the removal of the outer peripheral sidewall," a honeycomb structure composed of a polymer material-containing raw material calcium composition is softened by heat treatment and then molded into the desired shape by applying pressure. The softening temperature is adjusted depending on the type of polymer material, but is generally between 50°C and 200°C.

[0045] Following the mandatory step (E1) and the optional steps (E2) to (E4), a "degreasing and carbonation step" is performed. Here, the "degreasing and carbonation step" refers to the step of degreasing and forming or retaining calcium carbonate. If the raw material calcium composition is calcium carbonate, it is not necessary to add carbon dioxide, but in this invention, even when calcium carbonate is used as the raw material, it is defined as a degreasing and carbonation step. Furthermore, if a sintering step is performed simultaneously, it is also included in the "degreasing and carbonation step." Degreasing is a process of removing polymer materials, and is generally carried out by heat treatment. When preparing alumina or cordierite honeycomb structures, degreasing is relatively easy because these ceramics do not decompose under heat. However, in the production of the highly reactive medical calcium carbonate composition of the present invention, degreasing is extremely difficult. This is because calcium carbonate or the raw materials for calcium carbonate production decompose under heat at high temperatures, or become less reactive calcium carbonate. Therefore, it is necessary to perform degreasing under specific conditions to reduce the amount of polymer materials or acid-dissolved residues, which are their thermal decomposition products, to 1% by mass or less. Reducing the acid-dissolved residue to 1% by mass or less after the degreasing process is an essential condition, preferably 0.5% by mass or less, more preferably 0.3% by mass or less, even more preferably 0.1% by mass or less, and ideally substantially 0% by mass. Various conditions such as composition, porosity, particle size, atmosphere, temperature, degreasing time, and heating rate affect degreasing. The indicator of degreasing is the acid-dissolved residue of the calcium carbonate composition after degreasing; it cannot be evaluated by color tone or other factors. As mentioned above, there are cases where carbonation needs to be performed simultaneously with or after degreasing. The degreasing and carbonation process is a process that includes at least one step selected from the groups (E5) to (E9) below. Furthermore, in pore distribution measurement by mercury intrusion, the pore volume of the honeycomb structure with a pore diameter of 10 μm or less relative to its mass is 0.02 cm³. 3 Degreasing and carbonation are performed so that the volume is greater than / g. Since the pore volume decreases at higher degreasing temperatures, the pore volume is 0.02 cm³. 3 If the value is less than / g, the pore volume can be increased by lowering the degreasing temperature. Regarding the <(E5) Degreasing Calcium Carbonate Sintering Process> As described in Patent Document 11, regarding the manufacture of calcium carbonate honeycomb structures, calcium carbonate is unsuitable as a raw material because it has poor sinterability and decomposes at high temperatures, and a method using calcium hydroxide was considered useful. In other words, in the manufacture of honeycomb structures which require a relatively large amount of polymer material, when manufacturing a medical-grade calcium carbonate honeycomb structure from a calcium composition honeycomb structure containing polymer material, it is not possible to apply pressure between the powders, so a higher temperature is required compared to the sintering of ceramic compacts. However, calcium carbonate decomposes at high temperatures. Furthermore, because calcium carbonate has poor sinterability, it was considered impossible to sinter a polymer material-containing calcium carbonate honeycomb structure manufactured using polymer material-containing calcium carbonate powder. However, surprisingly, under certain conditions, it was found that calcium carbonate containing polymer materials could be degreased by heating to reduce the acid-dissolved residue to 1% by mass or less, and that the calcium carbonate could be sintered to produce a porous medical-grade calcium carbonate with high mechanical strength. The essential condition for producing a medical-grade calcium carbonate honeycomb structure with superior mechanical strength from a polymer-containing calcium carbonate honeycomb structure is to degrease it by heating under the specific conditions described below, so that the acid-dissolved residue is 1% by mass or less. However, the detailed reasons for this are not yet fully understood. Calcium carbonate is not easily decomposed by heat up to approximately 500°C. Therefore, there is no need to control the atmosphere up to approximately 500°C, and it can be heated in the air. In the air, it begins to decompose at temperatures above approximately 500°C, eventually becoming calcium oxide, but it remains stable up to 920°C in a carbon dioxide atmosphere. Therefore, when degreasing by heating at temperatures above approximately 500°C, it is necessary to increase the partial pressure of carbon dioxide to ensure that calcium carbonate does not decompose. The sintering temperature of calcium carbonate varies depending on the powder size, as will be discussed later. Also, when manufacturing highly reactive calcium carbonate honeycomb, pore distribution measurement by mercury intrusion method should show that the pore volume of a honeycomb structure with a pore diameter of 10 μm or less relative to its mass is 0.02 cm³. 3 It is necessary to degrease and carbonate the material so that the carbon dioxide concentration is greater than / g. Generally, due to cost considerations, heat degreasing in air is preferable, but from the viewpoint of suppressing the decomposition of calcium carbonate, it is preferable to heat degreasing at a carbon dioxide concentration higher than the carbon dioxide concentration in the air. As described above, in this invention, the presence or absence of sintering is determined by whether or not the material can maintain its shape without collapsing under the condition of being immersed in water and irradiated with ultrasonic waves. Regarding the <(E6) Degreasing and Carbonation Process> In the process of degreasing a porous calcium hydroxide material containing polymer material by heating at an oxygen concentration of less than 30% so that the acid-dissolved residue is 1% by mass or less, and simultaneously carbonizing it, the calcium hydroxide containing polymer material is degreased by heating and simultaneously carbonized. Here, "simultaneously" means simultaneously within a single process, and in practice, degreasing by heating is performed first. When carbonizing simultaneously with degreasing the polymer material, the control of the heating degreasing temperature, heating degreasing atmosphere, and heating degreasing time are important. This is because, under conditions of low carbon dioxide partial pressure, calcium hydroxide is thermally decomposed into calcium oxide from about 345°C. It is not necessary to increase the carbon dioxide partial pressure up to this temperature, but since it is complicated to fluctuate the carbon dioxide partial pressure during the process, it is preferable to increase the carbon dioxide partial pressure from the beginning. As described in Patent Document 12, it was previously thought that degreasing required incineration of polymer materials. However, after thorough investigation, it was found that incineration is only one method of degreasing, and that degreasing can be achieved through methods such as open polymerization or evaporation without incineration. Furthermore, it was found that incineration of polymer materials can lead to incomplete combustion, potentially leaving behind carbon, which is an acid-dissolved residue. Therefore, surprisingly, it has been found that in some cases it is preferable to degrease polymer materials under conditions where they are not incinerated. In order to degrease polymer materials by methods other than incineration, such as open polymerization or evaporation, the oxygen concentration must be less than 30% by volume. Preferably, the oxygen concentration is less than 15%, more preferably less than 10%, and even more preferably a situation where oxygen is absent, i.e., substantially 0% oxygen concentration. Furthermore, the degreasing behavior of calcium hydroxide containing polymer materials and calcium carbonate containing polymer materials differs. When calcium carbonate containing polymer materials is degreased by heat, acid-dissolved residues are less likely to remain even in the presence of oxygen. On the other hand, when calcium hydroxide containing polymer materials is degreased, acid-dissolved residues are more likely to remain in the presence of oxygen. The reason for this is not fully understood, but it is thought to be due to the reactivity between calcium hydroxide and polymer materials. In other words, since calcium carbonate has limited reactivity with polymer materials, polymer materials are easily degreased by open polymerization or evaporation. On the other hand, since calcium hydroxide has relatively high reactivity with polymer materials, it is thought that calcium hydroxide interacts with or reacts with polymer materials. Polymer materials that have interacted with or reacted with calcium hydroxide are thought to be easily degreased by open polymerization or evaporation. To prevent the thermal decomposition of calcium hydroxide and to perform degreasing and carbonation, it is preferable to perform degreasing and carbonation at a temperature of 600°C to 800°C with a carbon dioxide content of 50% or more by volume and an oxygen content of less than 30% by volume. One of the essential conditions of this invention is the complete degreasing of the polymer material. If degreasing is not achieved even when degreasing carbonation is performed at a temperature between 600°C and 800°C with carbon dioxide at a concentration of 50% or more by volume and oxygen at a concentration of less than 30% by volume, the manufacturing method is not included in this invention. Furthermore, in the case of a honeycomb structure, if the pore volume of the honeycomb structure with a pore diameter of 10 μm or less relative to its mass is 0.02 cm³, then the pore volume must be 0.02 cm³. 3 It is essential to degrease and carbonate the material so that the amount is greater than / g. The heat treatment temperature, heat treatment atmosphere, and heat treatment time should be considered as appropriate, and the heat treatment should be performed under conditions that allow the polymer material to be completely degreased. <(E7) Regarding the degreasing and carbonation process via calcium oxide> In the aforementioned "(E6) Degreasing and Carbonation Process," a porous calcite material can be produced relatively easily from a porous calcium hydroxide material containing polymer materials. However, because the calcite is formed at a temperature between 600°C and 800°C, the resulting porous calcite often exhibits poor reactivity. The reason for this is not fully understood, but it is generally thought to be because a heat treatment at a temperature between 600°C and 800°C is required, resulting in the formation of less reactive calcite. From this perspective, it is advisable to perform the degreasing process at a high temperature, then lower the temperature to allow the formation of calcite or vaterite. When a porous calcium hydroxide material containing polymer materials is degreased by heat without forming calcite, the calcium hydroxide decomposes thermally to form calcium oxide. This high-temperature treatment has the advantage of completely degreasing the material. However, if the heat treatment temperature is too high, the porous calcium oxide material becomes denser and its crystallinity increases, making it impossible to produce calcium carbonate with low crystallinity. Therefore, the heat treatment temperature for producing calcium oxide is preferably 700°C to 1000°C, more preferably 750°C to 950°C, and even more preferably 800°C to 900°C. When porous calcium carbonate containing polymer materials is degreased by heat, the calcium carbonate decomposes into calcium oxide. Since calcium carbonate is less reactive than calcium hydroxide, degreasing can be performed at lower temperatures. The heat treatment temperature for producing calcium oxide from porous calcium carbonate containing polymer materials is preferably 500°C to 1000°C, more preferably 530°C to 800°C, and even more preferably 550°C to 650°C. After degreasing, carbon dioxide is added to the porous calcium oxide material after lowering the temperature to produce either a porous calcite material or a porous vaterite material. Lower temperatures at which carbon dioxide is added to the porous calcium oxide material result in the production of a more reactive porous calcite material, but the addition of carbon dioxide takes longer. Considering the balance between these two factors, the temperature at which carbon dioxide is added to the porous calcium oxide material is preferably 300°C to 500°C, more preferably 310°C to 400°C, and even more preferably 320°C to 380°C. When producing a porous vaterite material from a porous calcium oxide material, carbon dioxide is added to the porous calcium oxide material using methods such as (D1) to (D12) described above. <(E8) Regarding the degreasing and carbonation process via calcium carbonate and calcium oxide> In the aforementioned "(E7) Degreasing and Carbonation Process via Calcium Oxide," relatively reactive calcite porous materials or extremely reactive vaterite porous materials can be produced. However, compared to directly forming calcium oxide porous materials from polymer material-containing calcium hydroxide porous materials, if polymer material-containing calcium hydroxide is heat-treated in the presence of carbon dioxide to form polymer material-containing calcium carbonate porous materials, then degreased by heating to form calcium oxide porous materials, and then carbon dioxide is added to the calcium oxide porous materials after the temperature is lowered to produce calcite porous materials or vaterite porous materials, then calcium carbonate porous materials with greater mechanical strength can be produced, and the formation of cracked calcium carbonate porous materials is less likely. The reason for this is not fully understood, but it is thought that the time during which the calcium hydroxide porous material, which has inferior mechanical strength, is heated by the addition of carbon dioxide is reduced. Similar to the "(E7) Degreasing and Carbonation Process via Calcium Oxide," the temperature at which carbon dioxide is applied to the porous calcium oxide material is preferably 300°C to 500°C, more preferably 310°C to 400°C, and even more preferably 320°C to 380°C. <(E9) Regarding the calcium sulfate degreasing and carbonation process> Compared to the cases using calcium carbonate or calcium hydroxide, using calcium sulfate allows for the production of calcite porous materials with more micropores. Although the reason for this is not fully understood, it is presumed that one reason is the coarse crystal structure of calcium sulfate. In the degreasing and carbonation process, in which polymer material-containing calcium sulfate is degreased by heating to reduce acid-dissolved residue to 1% by mass or less, and then carbon dioxide or carbonate ions are added to the resulting porous calcium sulfate, calcium sulfate is used as the raw material calcium composition. First, the polymer material-containing porous calcium sulfate is degreased by heat treatment at 700°C or higher to reduce acid-dissolved residue to 1% by mass or less. Next, carbonate ions are added to the resulting porous calcium sulfate to produce porous calcium carbonate for medical use. Calcium sulfate is relatively stable even at high temperatures. Degreasing at 700°C or higher is essential, but the final heat treatment temperature is preferably 750°C to 1100°C, more preferably 800°C to 1000°C, and even more preferably 850°C to 950°C. <(E10) Shape finishing process performed after the degreasing and carbonation process> After any one of the degreasing and carbonization steps described in (E5) to (E9), the "(E10) Shape finishing step performed after the degreasing and carbonization step" is carried out. In the shape finishing step, the shape is finished, such as removing the outer side walls.

[0046] [II Method for producing medical calcium carbonate compositions: (E) Specific calcium carbonate honeycomb structures] Next, we will explain [8]. A method for producing a medical calcium carbonate composition that satisfies the above (E), characterized in that it satisfies at least one condition selected from the group (E11) to (E14) below, is useful. (E11) is a result of the "(E1) extrusion process" in which the thickness of the outer peripheral side wall of the honeycomb structure is greater than the thickness of the partition wall, and the cross-sectional area of ​​the surface perpendicular to the through hole is 1 cm². 2 The process is as described above: extrusion. This is because the cross-sectional area of ​​the surface perpendicular to the through hole is 1 cm². 2 Therefore, to maintain the shape during extrusion, it is easier to extrude the material so that the thickness of the outer sidewall is greater than the wall thickness of the honeycomb structure. On the other hand, the thickness of the outer perimeter side wall is greater than the wall thickness of the honeycomb structure, and the cross-sectional area of ​​the surface perpendicular to the through hole is 1 cm². 2 In the degreasing and carbonization process of the polymer material-containing raw material calcium composition honeycomb structure described above, cracks are likely to form between the outer peripheral side walls and the partition walls, and inside the honeycomb structure, due to the difference in shrinkage between the outer peripheral side walls and the partition walls. Therefore, it is preferable to perform the "(E3) outer peripheral side wall removal process" before one of the degreasing and carbonization processes selected from the group (E5) to (E9) above. The cross-sectional area of ​​the surface perpendicular to the through hole is 1 cm² 2If it is less than 1 cm², the problem of maintaining the shape during extrusion is limited. If the thickness of the outer peripheral sidewall is the same as or less than the thickness of the partition wall of the honeycomb structure, the shrinkage rate is the same or less, so the need for the "(E3) outer peripheral sidewall removal process" is limited. Also, if the cross-sectional area of ​​the surface perpendicular to the through hole is 1 cm² 2 If the values ​​are less than the specified limit, even if the shrinkage rates differ, the difference in shrinkage amount is limited, making crack formation less likely. Therefore, the necessity of the "(E3) outer perimeter sidewall removal process" is limited. (E12) is a manufacturing method in which pressure is applied to a honeycomb structure composed of a thermally softened polymer material-containing raw material calcium composition in at least one step selected from the group "(E1) extrusion step", "(E2) molding step after the extrusion step", "(E4) molding step after the outer peripheral side wall removal step", and "(E10) shape finishing step performed after the degreasing carbonation step", so that the diameter of the circle passing through both ends of the through hole and the center of the through hole is 1 cm or more and 50 cm or less. The softening temperature is adjusted depending on the type of polymer material, but it is generally between 50°C and 200°C. (E13) is a manufacturing method in which the "(E3) outer peripheral side wall removal process" is performed by grinding and the "(E10) shape finishing process performed after the degreasing and carbonation process" is performed by polishing, and is useful as a method for manufacturing medical calcium carbonate honeycomb with excellent external shape. This phenomenon is thought to be specific to the removal of the outer peripheral sidewalls of a raw material honeycomb structure made from a polymer material-containing raw material calcium composition. When attempting to remove the outer peripheral sidewalls of the raw material honeycomb structure by polishing with a diamond point or the like, the outer peripheral sidewalls are removed, but new outer peripheral sidewalls are formed. This is thought to be due to the softening of the outer peripheral sidewalls by the heat generated during the polishing process. On the other hand, the heat generated during the grinding process is limited compared to the polishing process. Therefore, it is preferable to perform the outer peripheral sidewall removal process by grinding with a plane or the like. When the raw material honeycomb structure is degreased and carbonated to produce a calcium carbonate honeycomb structure, chipping occurs when the outer periphery sidewalls are removed by grinding. Therefore, it is preferable to perform the outer periphery sidewall removal finishing process by polishing using a diamond point or the like, rather than grinding. (E14) is a manufacturing method in which the raw material calcium composition for the "(E1) extrusion process" is anhydrous calcium sulfate. To date, calcium sulfate honeycomb structures have not been manufactured. In the extrusion process for forming the raw material honeycomb structure, a mixture of the raw material calcium composition and polymer material is heated. Calcium sulfate exists in anhydrous, hemihydrate, and dihydrate forms, but if hydrated calcium sulfate is used as the raw material calcium composition, the water evaporates, causing the raw material honeycomb structure, which consists of polymer material-containing calcium sulfate, to swell and the honeycomb structure to become distorted. Therefore, it is essential to use anhydrous calcium sulfate as the calcium sulfate.

[0047] [II Method for producing medical-grade calcium carbonate composition: (F) Expansion of calcium oxide granules] Next, [9], that is, the manufacturing process of a medical calcium carbonate composition that satisfies (F) above, using calcium oxide granules as a raw material, will be described. To bind granules together while leaving voids, it is necessary to impart some kind of binding ability to the granules. Methods for imparting binding ability to granules can be divided into those that use polymer materials and those that do not. First, we will explain the manufacturing method that does not use polymer materials. When polymer materials are not used, it is necessary to utilize the binding of the raw material calcium composition, and the expansion due to the hydration of calcium oxide and the hardening reaction of calcium sulfate are useful. First, we will explain the manufacturing method that uses calcium oxide granules as the raw material. When calcium oxide is exposed to water or acetic acid, it expands to form calcium hydroxide or calcium acetate. This reaction is used to bind the granules together and carbonate them. This manufacturing method requires that it contains (F1) and (F2) below, and at least one of (F3) and (F4). Regarding the <(F1) Introduction and Closure Process> In this process, calcium oxide granules are placed in a reaction vessel, and the opening of the reaction vessel is closed to prevent the granules from being discharged. This process is performed to uniformly bind the granules together in the reaction vessel and to apply compressive stress between the granules. If the closing process is not performed, the granules will not bind together uniformly, which is undesirable for a porous material used in medicine. Closing the opening of the reaction vessel is essential to form a uniform porous structure, and an introduction process that does not close the opening is not included in this invention. The criterion for determining whether or not the opening has been closed is whether or not the granules are discharged from the reaction vessel, and an opening that prevents the granules from being discharged from the reaction vessel is defined as substantially closed. Furthermore, even in the case of a mesh-like reaction vessel, if the opening is closed in a way that prevents the granules from being discharged from the reaction vessel, it is defined as having performed the introduction and closing process. Regarding the (F2) porous material formation process: This step, following the introduction and closure process, involves adding water or acetic acid to the calcium oxide granules inside the reaction vessel. The calcium oxide granules react with water or acetic acid to form calcium hydroxide or calcium acetate, and expand. Because the opening of the reaction vessel is closed during the introduction and closure process, the degree of contact between the granules increases, forming a porous calcium hydroxide or calcium acetate body with a uniform pore structure. Furthermore, due to the expansion of the calcium oxide granules, the pore volume of the granule-bound porous body with a diameter of 10 μm or less, as measured by the mercury intrusion method, is 0.05 cm³. 3 The result will be / g or more. Regarding the <(F3) Carbonation Process> When a porous calcium hydroxide material is produced, carbon dioxide is then added to the porous calcium hydroxide material either simultaneously with or after the porous calcium hydroxide material formation process. The porous calcium hydroxide material is carbonated and becomes a porous calcium carbonate material. On the other hand, when producing a porous calcium acetate material, the formation of the porous calcium acetate material is heat-treated. The calcium acetate is thermally decomposed to form a porous calcium carbonate material. The heat treatment is carried out at a temperature of 400°C or higher, which is the decomposition temperature of calcium acetate. Regarding the <(F4) Calcium Oxide Carbonation Process> Medical-grade porous calcium carbonate can also be produced using a manufacturing process that includes all of the above (F1) to (F3). However, the compressive strength of such porous material may be low. To increase the compressive strength, it is useful to heat-treat a porous calcium hydroxide, porous calcium carbonate, or porous calcium acetate to produce a porous calcium oxide, and then expose the calcium oxide to carbon dioxide to produce a porous calcium carbonate.

[0048] [II Method for producing medical-grade calcium carbonate composition: (F) Hardening reaction of calcium sulfate granules] Next, we will explain

[10] . A medical-grade calcium carbonate composition satisfying (F) can also be produced by hardening calcium sulfate granules of appropriate size together. In other words, porous materials can be produced by a hardening reaction between calcium sulfate granules and water containing carbonate ions, or by a hardening reaction between calcium sulfate hemihydrate granules or calcium sulfate anhydrous granules and water. In the former case, a porous calcium carbonate material is produced directly. In the latter case, a porous calcium sulfate dihydrate material is produced, and the composition of the porous material is changed from calcium sulfate dihydrate to calcium carbonate by a carbonation step. In other words, the former is a manufacturing method that includes the steps (F5) and (F6) below, and the latter is a manufacturing method that includes the steps (F5), (F7) and (F9) below, with step (F8) being an optional step. These methods provide a method for producing a medical calcium carbonate composition that satisfies (F) above. Regarding the <(F5) Introduction Process> In this step, calcium sulfate granules are placed in the reaction vessel. Regarding <(F6) Porous Body Formation Carbonation Process> This process involves reacting calcium sulfate granules with carbonate ions in a reaction vessel. For example, calcium sulfate granules placed in a reaction vessel can be immersed in an aqueous sodium carbonate solution. In this process, the calcium sulfate granules are converted to calcium carbonate while maintaining their macroscopic form. Simultaneously, the granules harden together through bridging of the formed calcium carbonate crystals, creating a granule-bound porous body. Regarding <(F7) Porous Body Formation Process> If the composition of calcium sulfate granules is calcium sulfate hemihydrate or calcium sulfate anhydrous, adding water to the granules in the reaction vessel will convert the composition of the granules to calcium carbonate while maintaining their macroscopic form. Simultaneously, the granules harden together through bridging of the formed calcium carbonate crystals, creating a granule-bound porous body. Regarding the <(F8) Heat Treatment Process> This process involves heat-treating the porous calcium sulfate dihydrate produced in the "(F7) Porous Body Formation Process" as needed to dehydrate it and produce anhydrous porous calcium sulfate. The heat treatment process allows for the production of medical-grade porous calcium carbonate with high compressive strength. Regarding the <(F9) Carbonation Process> In this process, porous calcium sulfate dihydrate or porous anhydrous calcium sulfate is exposed to water containing carbonate ions. The porous calcium sulfate dihydrate or porous anhydrous calcium sulfate maintains its macromorphology while its composition is converted to calcium carbonate, thereby producing porous calcium carbonate for medical use. By step (F5) or (F9), the pore volume of the granular porous material with a diameter of 10 μm or less, as measured by mercury intrusion, is 0.05 cm³. 3 The result will be / g or more.

[0049] [II Method for producing medical calcium carbonate composition: (F) Step using polymer] Next,

[11] , that is, a method for producing a medical calcium carbonate composition that satisfies (F) using polymer materials, will be described. When a polymer-containing raw material calcium composition, which is a mixture of a raw material calcium composition and a polymer material, is used, the polymer material can bind the mixture granules together. On the other hand, because a polymer material is used, as mentioned above, in order to manufacture the medical calcium carbonate composition of the present invention, it is necessary to remove the polymer material by degreasing. As with the case of the medical calcium carbonate honeycomb structure, it is also necessary to perform degreasing under specific conditions and reduce the polymer material or its thermal decomposition product, the acid-dissolved residue, to 1% by mass or less. A method for producing a medical calcium carbonate composition that satisfies (F) can be provided by making (F10) and (F11) below, and one selected from the group (E5) to (E9) above, an essential step, and (E10) an optional step. Regarding the <(F10) Introduction Process> Volume is 10 -12 m 3 This step involves placing the above-mentioned polymer material-containing calcium composition granules into a reaction vessel. Regarding the <(F11) Porous Body Formation Process> In this process, the granules inside the reaction vessel are subjected to one of the following steps: a step of thermally softening and fusing the surfaces of the granules by heat treatment; a step of bonding the surfaces of the granules by dissolving the surfaces of the granules; or a step of fusing the surfaces of the granules with a plasticizer, resulting in a volume of 3 × 10 -11 m 3 The above is true, and the granular porous body is formed by the bonding of multiple granules with a maximum diameter and length of 50 μm or more and 500 μm or less, and has multiple through holes extending in multiple directions, wherein the pore volume of the granular porous body with a diameter of 10 μm or less is 0.05 cm³ as measured by mercury intrusion method. 3 A porous material with granules bound together is manufactured, having a content of 1 / g or more. In the process of thermally softening and fusing surfaces together through heat treatment, the granules are heated. In the case of thermoplastic polymers, the granules soften, and the softened granules are fused together by their own weight or by compressive stress from the reaction vessel. In the step of dissolving the surface of the granules to bond the surfaces of the granules together, the surface of the granules is dissolved with a solvent such as acetone or dimethyl sulfoxide, and the granules are bonded together. In the process of fusing the surfaces of the granules with a plasticizer, examples include adding a plasticizer inside the granules of the polymer material-containing raw material calcium composition and fusing the granules by bringing them into contact with each other, or applying a plasticizer to the surface of the granules to soften the granule surface and fuse the granules together.

[0050] [II Method for producing medical-grade calcium carbonate composition: (G) Porous material] Next,

[12] , that is, a method for producing a medical calcium carbonate composition that satisfies (G) above, will be described. The manufacturing method is a method in which (G1) below and one selected from the groups (D1) to (D10) and (E5) to (E9) are mandatory steps, and (G2) and (G3) below and (E10) above are optional steps. Regarding the <(G1) Mixing Process> The "(G1) Mixing Step" is a step in which the raw material calcium composition powder or raw material calcium composition paste is mixed with the pore-forming material. When the raw material calcium has limited solubility in water, such as calcium hydroxide, calcium carbonate, or calcium sulfate, calcium carbonate paste is preferable as it ensures fluidity. On the other hand, in the case of water-soluble calcium compounds such as calcium acetate, it is preferable to mix them in powder form. There are no particular restrictions on the raw material calcium composition, but calcium oxide, calcium hydroxide, and calcium carbonate are preferred, and calcium hydroxide and calcium carbonate are particularly preferred. As mentioned above, there are no particular restrictions on the pore-forming material, but examples include sodium chloride, sodium dihydrogen phosphate, and polymer beads. Since the pore size is controlled by the pore-forming material, it is a necessary condition that the material does not contain any pore-forming material with a maximum diameter and length of 800 μm or more. Furthermore, pore-forming materials with a maximum diameter and length of 50 μm or more and 400 μm or less are preferred. Regarding the <(G2) Flour Compaction Process> The "(G2) Compaction Process" is a process of compacting a mixture of raw calcium composition powder or raw calcium composition paste and pore-forming material. Known compaction methods, such as uniaxial pressurization including manual pressure or hydrostatic pressurization, can be used without limitation. If raw calcium composition paste is used, drying is performed after this process as needed. In the process of mixing the raw calcium composition paste and pore-forming material, a certain pressure is applied, and the compaction process may become unnecessary, therefore this process is optional. Regarding the <(G3) Hole-forming material removal process> "(G3) Pore-forming material removal process" is a process in which pore-forming materials are removed by dissolving them in a solvent. When manufacturing porous materials such as medical-grade calcium phosphate using medical-grade calcium carbonate composition as a raw material, the pore-forming material is removed by processes such as immersing the medical-grade calcium carbonate composition in disodium hydrogen phosphate. Therefore, it is not always necessary to remove the pore-forming material during the manufacturing stage of the medical-grade calcium carbonate composition. Accordingly, (G3) is an optional process. In this manufacturing method, polymer materials may be used as pore-forming materials. In such cases, the "(E10) shaping process performed after the degreasing and carbonation process" in the carbonate apatite honeycomb structure using polymer materials may be useful. Therefore, (E10) is also an optional process. Furthermore, in order to satisfy condition (G), the pore volume of the porous material with a pore size of 10 μm or less, as measured by the mercury intrusion method, must be 0.05 cm³. 3 It must be at least / g. The pore volume is adjusted by the mixing ratio of the raw calcium composition powder and the solvent in the mixing step (G1) and the compaction pressure in the compaction step (G2).

[0051] [II. Method for producing medical-grade calcium carbonate composition: Degreasing conditions] Next, we will explain

[13] . In the method for producing medical-grade calcium carbonate compositions using polymer materials, it is necessary to remove the used polymer materials. This process is called degreasing, and specifically, the polymer materials are removed by depolymerization, evaporation, etc. In the present invention, when producing medical-grade calcium carbonate honeycomb structures, the distance between calcium composition powders in the polymer material-containing calcium composition increases due to the degreasing of the polymer materials. Therefore, it is preferable to adjust the degreasing rate of the polymer materials to prevent the distance between calcium composition powders from increasing. Note that when the degreasing temperature is below 200°C, a relatively large amount of polymer material remains, and because of its high fluidity, the distance between calcium composition powders does not increase significantly. Therefore, it is preferable that the mass loss of the polymer material in the polymer material-containing calcium composition is less than 1% by mass per minute during the degreasing process at 200°C or higher. However, the temperature at which the mass loss of the polymer material-containing calcium composition is less than 1% by mass per minute is preferably 150°C or higher, more preferably 100°C or higher, and even more preferably 50°C or higher. The decrease in the polymer material is more preferably less than 0.9% by mass per minute, and even more preferably less than 0.8% by mass per minute. Furthermore, the rate of decrease in polymer materials is not constant with increasing temperature, but occurs rapidly at specific temperatures. For example, the depolymerization of acrylic resin occurs rapidly at 250°C. Therefore, the degreasing conditions can be optimized by thermomass measurement. Basically, the heating rate should be adjusted according to the differential value of the mass decrease in thermomass measurement, but it may also be acceptable to hold the material for a certain period of time at a temperature approximately 20°C lower than the temperature at which the rapid mass decrease begins.

[0052] [II. Method for producing medical calcium carbonate composition: Specific manufacturing method] Next, we will explain

[14] . In the manufacturing process of medical-grade calcium carbonate compositions, it is sometimes preferable to control carbon dioxide and oxygen levels. The step of "degreasing with an oxygen partial pressure of 30 kPa or higher" is sometimes preferable in the degreasing process. Polymer materials are degreased by depolymerization, evaporation, thermal decomposition, and incineration through heat treatment, but a higher oxygen partial pressure may make degreasing easier and reduce acid-dissolved residue, which is sometimes preferable. The oxygen partial pressure in air is approximately 20 kPa, but it is preferably 30 kPa or higher, more preferably 60 kPa or higher, and even more preferably 90 kPa or higher. The step of degreasing or carbonation at a carbon dioxide partial pressure of 30 kPa or higher is sometimes preferable in the degreasing or carbonation process. This is because carbon dioxide is necessary for the carbonation of the raw material calcium composition, and degreasing does not require the incineration of polymer materials, but rather involves only the depolymerization, evaporation, and thermal decomposition of the polymer materials, and in some cases, the acid decomposition residue can be reduced to 1% by mass or less through degreasing. In addition, when the carbon dioxide partial pressure is 0 kPa, calcium carbonate is thermally decomposed into calcium oxide from around 340°C. Therefore, a process of degreasing or degreasing and carbonation at a carbon dioxide partial pressure above a certain level is sometimes preferable. The amount of carbon dioxide in the atmosphere is limited, and in order to efficiently perform carbonation, a carbon dioxide partial pressure of 30 kPa or higher is preferable in the carbonation process, more preferably 60 kPa or higher, and even more preferably 90 kPa or higher. In addition, it is sometimes preferable to degrease in an environment equivalent to a pure carbon dioxide environment, i.e., at a carbon dioxide partial pressure of 101.3 kPa. The "step of degreasing or carbonation using a gas containing (N) oxygen or carbon dioxide at a pressure of 150 kPa or higher" may be preferred in the degreasing and carbonation steps. In the manufacturing process of medical-grade calcium carbonate compositions, degreasing or carbonation may be performed. For example, if the raw calcium composition is exposed to carbon dioxide, such as by flowing carbon dioxide through it, the raw calcium composition will be carbonated and medical-grade calcium carbonate composition will be produced. However, when carbon dioxide is flowed through it, most of the carbon dioxide is not used in the manufacturing process and is discarded. Furthermore, when carbonizing porous or compacted raw calcium composition materials, there is a problem in that carbon dioxide is not easily introduced into the interior of the porous material or compacted material. In such cases, it is preferable to use a substantially closed system and pressurize the inside of the closed system. Theoretically, pressurizing allows oxygen or carbon dioxide to penetrate into the interior of the porous material or compacted powder, exposing the raw calcium composition to oxygen or carbon dioxide. However, from the viewpoint of efficiency, a process of degreasing or carbonation using a gas containing oxygen or carbon dioxide at 150 kPa or higher is preferred. The gas pressure is preferably 150 kPa or higher, more preferably 200 kPa or higher, and even more preferably 300 kPa or higher. Theoretically, there is no upper limit to the gas pressure, but since a pressurized closed-system reactor is required, the gas pressure is preferably 2 MPa or less, more preferably 1 MPa or less, and even more preferably 500 kPa or less. In order to maintain the pressurized state, the reaction apparatus needs to be a substantially closed system. However, it is also possible to make it an open system while maintaining pressurization temporarily or continuously for purposes such as discharging the degreased polymer material components from the reaction apparatus. The step of "(O) replacing some or all of the air in the reaction vessel with carbon dioxide, and then introducing carbon dioxide into the reaction vessel to increase the carbon dioxide concentration in the reaction vessel" can be useful in the carbonation process. This is because it increases the partial pressure of carbon dioxide and accelerates the carbonation rate. A simple and effective method is to replace the air inside a reaction vessel with carbon dioxide by introducing carbon dioxide from one end of the vessel and exhausting air from the other. Furthermore, by reducing the amount of gas contained in the raw calcium composition through a depressurization process and then introducing carbon dioxide into the reaction vessel, the degree of air-to-carbon dioxide replacement is increased. In other words, to produce medical calcium carbonate compositions such as medical calcium carbonate blocks that do not contain the raw calcium composition from raw calcium compositions such as calcium hydroxide compacts, it is necessary to introduce carbon dioxide into the interior of the compacts, etc. Diffusion alone is time-consuming and may not be able to carbonize the interior. By reducing the amount of air inside the calcium hydroxide compact through a depressurization process and then introducing a gas with a higher carbon dioxide concentration than air into the reaction vessel, carbon dioxide can be introduced into the interior of the calcium hydroxide compact. To reduce the pressure in the reaction vessel, it is sufficient to reduce the pressure below atmospheric pressure (101.3 kPa), but it is preferable to reduce it to 90 kPa or less, more preferably to 60 kPa or less, and even more preferably to 30 kPa or less. The depressurization process reduces the amount of air and other contaminants inside the calcium hydroxide compact, and then it is necessary to introduce a gas with a higher carbon dioxide concentration than air into the reaction vessel. In principle, any gas with a higher carbon dioxide concentration than air is sufficient, but the carbon dioxide concentration of the gas to be introduced is preferably 10% by volume or more, preferably 50% by volume or more, more preferably 90% by volume or more, and ideally substantially pure carbon dioxide. The pressure of the reaction vessel when introducing carbon dioxide into the reaction vessel is not particularly limited. However, from the viewpoint of increasing the reaction rate of the raw material calcium composition, it is preferable to introduce carbon dioxide so that the pressure of the reaction vessel is 101.3 kPa or higher, more preferably 150 kPa or higher, and even more preferably 200 kPa or higher. The "(P) Carbonation step of supplying carbon dioxide so that the pressure in a closed reaction vessel becomes constant" is useful in the process of adding carbon dioxide to a medical calcium composition in a closed reaction vessel. In this invention, a "closed reaction vessel" refers to a reaction vessel that is not open, as described above. Generally, carbonation using a closed reaction vessel is costly, but the medical calcium carbonate composition of this invention is a medical material, and in some cases, manufacturing in a closed system is preferable from the viewpoint of preventing contamination by foreign matter. Except when manufacturing a medical-grade calcium carbonate composition from raw calcium carbonate, carbon dioxide or carbonate ions are required to impart carbonate groups to the raw calcium composition. For example, to produce 1 mole of calcium carbonate by imparting carbon dioxide to 1 mole of calcium hydroxide, 1 mole of carbon dioxide is required, and 1 mole of carbon dioxide is approximately 22.4 L at standard conditions. Therefore, producing 1 mole of medical-grade calcium carbonate composition requires a relatively large reaction vessel capable of holding at least 22.4 L of carbon dioxide under standard conditions. On the other hand, production can be carried out using a relatively small reaction vessel by supplying carbon dioxide in a closed system so that the pressure inside the reaction vessel remains constant. There are no particular restrictions on the pressure value, but it is preferable that the pressure inside the reaction vessel be greater than atmospheric pressure, as it is convenient to supply carbon dioxide from a carbon dioxide cylinder to the reaction vessel using a pressure reducing valve so that the pressure inside the reaction vessel remains constant. Furthermore, the purpose is to supply carbon dioxide into the reaction vessel, and increasing the pressure inside the reaction vessel unnecessarily would only make the reaction vessel more expensive and complicate the operation. For this reason, the pressure of carbon dioxide inside the reaction vessel is preferably 0.5 MPa or less in addition to atmospheric pressure, more preferably 0.3 MPa or less, and even more preferably 0.2 MPa or less. This process is useful not only for carbonation in the gas phase but also for carbonation in the liquid phase as described in (D9) above. Furthermore, since no gases other than carbon dioxide are consumed in the closed system, the carbon dioxide concentration in the reaction vessel will be low if only this process is performed. For this reason, a process that includes both this process and the "O" process is desirable. The "(Q) Carbonation step of stirring or circulating carbon dioxide in the reaction vessel" may be useful in the process of adding carbon dioxide to a medical calcium composition in a reaction vessel, and may be particularly useful when using a closed-system reaction vessel. This step is also useful in "(D8)", which is one method for producing a medical calcium carbonate composition characterized by "(D)", but is not limited to the method for producing a medical calcium carbonate composition characterized by "(D)", and may be useful as a method for producing a medical calcium carbonate composition of the present invention.

[0053] [II. Method for producing medical-grade calcium carbonate composition: Specific raw material calcium composition] Next,

[15] will be explained. Compositions containing calcium are widely used as raw material calcium compositions, but it is preferable that the composition of the raw material calcium composition is one selected from the group of calcium oxide, calcium hydroxide, and calcium carbonate. This is because, in processes such as adding carbonate components to the raw material calcium composition to produce medical calcium carbonate compositions, no compositions other than water are produced as by-products.

[0054] [II. Method for producing medical-grade calcium carbonate composition: Specific raw material calcium composition] Next,

[16] will be explained.

[16] relates in particular to the method for producing the calcium carbonate composition of [3], (R1) Use calcium carbonate powder with an average particle size of 2 μm or more and 8 μm or less. (R2) Use calcium carbonate powder with a sphericity of 0.9 or higher. (R3) Mg content is 5 × 10 -4 Mass% or more 3×10 -3 Use calcium carbonate powder at a mass percentage of % or less. (R4)Sr content is 3 × 10 -3 Mass% or more 1.5×10 -2 Use calcium carbonate powder at a mass percentage of % or less. A manufacturing method that satisfies at least one of the following conditions. These are all conditions for enhancing the reactivity of medical calcium carbonate compositions produced by controlling micropores, and by using specific raw calcium powders, desirable micropores are formed. (R1) relates to the specific average particle size of the calcium carbonate powder, which is the raw material calcium composition. The average particle size is preferably 2 μm or more and 8 μm or less, more preferably 3 μm or more and 7 μm or less, and even more preferably 4 μm or more and 6 μm or less. The sphericity of (R2) is preferably 0.9 or higher, and more preferably 0.95 or higher. The Mg content of (R3) is 5 × 10 -4 Mass% or more 3×10 -3 Preferably less than 1% by mass, and 1 × 10 -3 Mass% or more 2.5×10-3 More preferably less than or equal to mass%, such as 1.5 × 10 -3 Mass% or more 2.5×10 -3 A mass percentage or less is even more preferable. The Sr content of (R4) is 3 × 10 -3 Mass% or more 1.5×10 -2 Preferably less than % by mass, 4 × 10 -3 Mass% or more 1.3×10 -2 More preferably less than or equal to % by mass, 5 × 10 -3 Mass% or more 1×10 -2 A mass percentage or less is even more preferable. It is preferable that any of the conditions (R1) to (R4) be met, but it is more preferable that multiple conditions be met, and even more preferable that all conditions be met.

[0055] [III. Medical-grade calcium sulfate curable composition] Next,

[17] , a medical calcium sulfate curable composition that can also be used as a raw material for medical calcium carbonate compositions, will be described. A medical-grade calcium sulfate curable composition that satisfies all of the following conditions (T1) to (T5) exhibits curability and is therefore a useful medical material. (T1) Acid dissolved residue is 1% by mass or less. (T2) Volume is 5 × 10 -13 m 3 That's all. (T3) As a medical composition, it is substantially pure calcium sulfate. (T4) The calcium sulfate hemihydrate content is 50% by mass or more. (T5) When multiple compositions that have come into contact are immersed in water, they harden and form a porous body with a compressive strength of 0.3 MPa or more. While it was previously known that calcium sulfate hemihydrate powder hardens, this new formulation has an acid-dissolved residue of 1% by mass or less and is substantially pure calcium sulfate as a medical composition, with a volume of 5 × 10⁻⁶. -13 m 3 It was previously unknown that the above-mentioned calcium sulfate granules would harden and form a porous material with a compressive strength of 0.3 MPa or higher. When the granules contain 50% by mass or more of calcium sulfate hemihydrate, when mixed with water, some or all of them become calcium sulfate dihydrate, and the granules bind together through bridging of the precipitated calcium sulfate dihydrate crystals to form a porous body. Volume is 5 × 10 -13 m 3 Even at levels below a certain point, it has usefulness such as being able to harden and form a porous material, but its usefulness is limited, so the volume is 5 × 10 -13 m 3 The above is necessary. From the viewpoint of forming a porous structure useful for tissue penetration and compressive strength, the volume should be 5 × 10 -13 m 3 The above 1 x 10 -9 m 3 The following is preferable: 4 × 10 -12 m 3 The above 5 x 10 -10 m 3 It is more preferable that the volume is 1.4 × 10 -11 m 3 The above 1.1 × 10 -10 m 3 The following is even more preferable: From the viewpoint of curability, it is essential that the calcium sulfate hemihydrate content be 50% by mass or more. Since curability increases as the calcium sulfate hemihydrate content increases, it is preferable that the calcium sulfate hemihydrate content be 70% by mass or more, more preferably 80% by mass or more, and even more preferably 90% by mass or more. While the formation of a porous calcium sulfate body itself has utility, its utility is limited if the mechanical strength of the porous body is low. In this invention, it is an essential condition that when multiple contacted compositions are immersed in water, they harden and form a porous body with a compressive strength of 0.3 MPa or more. The compressive strength of the hardened body is preferably 0.5 MPa or more, and more preferably 1.0 MPa or more. Since the compressive strength differs depending on the degree of contact, if different compressive strengths are obtained, the higher compressive strength is used as the compressive strength of the composition.

[0056] [IV. Method for producing medical-grade calcium sulfate composition] Next,

[18] will be explained. The method for producing the "III Medical calcium sulfate curable composition" described above, which includes (U2) and (U3) as essential steps and (U1) and (U4) as optional steps, is useful. The "(U1) Polymer Material Degreasing Process" is a process in which calcium sulfate granules or blocks containing polymer materials are degreased by heat treatment to reduce the acid-dissolved residue to 1% by mass or less. This process is used when polymer material-containing calcium sulfate blocks or granules are used as raw materials. The process involves degreasing the raw material by heat treatment to reduce the acid-dissolved residue to 1% by mass or less. It is essential that the acid-dissolved residue be 1% by mass or less, preferably 0.5% by mass or less, more preferably 0.3% by mass or less, even more preferably 0.1% by mass or less, and ideally 0% by mass. The heat treatment is generally performed at 700°C or higher. Since calcium sulfate becomes anhydrous at 700°C or higher, this process produces anhydrous calcium sulfate blocks or anhydrous calcium sulfate granules. The "(U2) Calcium Sulfate Dihydrate Manufacturing Process" is a process in which water is added to granules or blocks of anhydrous or hemihydrate calcium sulfate formed in the polymer material degreasing process, or water is added to calcium sulfate hemihydrate powder, and the mixture is hardened to produce calcium sulfate dihydrate granules or blocks. When using calcium sulfate containing polymer materials, anhydrous calcium sulfate granules or blocks are produced by the polymer material degreasing process, and then water is added to produce calcium sulfate dihydrate granules or blocks. If it is not necessary to use calcium sulfate containing polymer materials, calcium sulfate hemihydrate powder and water are mixed and hardened to produce calcium sulfate dihydrate granules or blocks. The "(U3) Calcium Sulfate Hemihydrate Manufacturing Process" is a process for producing calcium sulfate hemihydrate granules or blocks by dehydrating calcium sulfate dihydrate granules or blocks. This process involves dehydrating calcium sulfate dihydrate granules or blocks in the gas phase to produce calcium sulfate hemihydrate granules or blocks such that the calcium sulfate hemihydrate content is 50% by mass or more. Generally, dehydration in the gas phase, such as in the atmosphere, is performed by known heat treatments, and the calcium sulfate hemihydrate content can be easily controlled by optimizing the heat treatment time and heat treatment temperature. The "(U4) Granule size adjustment process" is performed when the volume is 5 × 10 -13 m 3 This is the process of adjusting the size so that the granules are as described above. This process involves a volume of 5 × 10 -13 m 3 This is a step to adjust the size so that the granules are as described above. This step can be performed at any point in the entire process. For example, calcium sulfate powder can be mixed with a polymer material such as polyvinyl alcohol and spray-dried to produce a volume of 5 × 10⁻⁶. -13 m 3 The goal is to create spherical granules as described above. Alternatively, the calcium sulfate block can be crushed and sieved. As mentioned above, the volume is 5 × 10 -13 m 3 The above adjustments are necessary. From the viewpoint of forming porous bodies useful for tissue penetration and compressive strength, the volume should be 5 × 10 -13 m 3 The above 1 x 10 -9 m 3 It is preferable to adjust as follows: 4 × 10 -12 m 3 The above 5 x 10 -10 m 3 It is more preferable to adjust it as follows: 1.4 × 10 -11 m 3 The above 1.1 × 10 -10 m 3 The following adjustments are even more preferable.

[0057] [V Medical-grade calcium phosphate composition] Next,

[19] , namely, a medical calcium phosphate composition produced from a medical calcium carbonate composition, will be described. A medical calcium phosphate composition that satisfies all of the following conditions (V1) to (V3) and at least one condition selected from the group (V4) to (V10), and is characterized by selecting (V11) or (V12), is highly useful. Furthermore, the requirements for (V1), (V2), (V5), (V6), (V9), and (V10) are the same as those for (A), (B), (F), (G), (J), and (K) mentioned above. The condition "(V3) As a medical composition, it is substantially pure calcium phosphate, and its composition is one selected from the group consisting of apatite carbonate, apatite containing HPO4 groups, tricalcium phosphate, witrokhite, and calcium hydrogen phosphate" is common to all medical calcium compositions of the present invention, but among them, those whose composition is one selected from the group consisting of apatite carbonate, apatite containing HPO4 groups, tricalcium phosphate, witrokhite, and calcium hydrogen phosphate are particularly preferred due to their excellent reactivity. These calcium phosphates, excluding tricalcium phosphate, cannot be produced by sintering in principle, but can be produced by a dissolution-type compositional transformation reaction using calcium carbonate or the like as a precursor in an aqueous solution. As for apatite carbonate, it is as described in Patent Document 1. Apatite containing HPO4 groups, witrokhite, and calcium hydrogen phosphate, which have high reactivity, can also be produced in an aqueous solution, but since the HPO4 groups become pyrophosphate when heated, they cannot be produced by sintering. Furthermore, "(V4) A honeycomb structure having multiple through-holes extending in one direction (provided that the composition is tricalcium phosphate, and the pore volume of the honeycomb structure with a pore diameter of 10 μm or less relative to its mass is 0.01 cm³ as measured by mercury intrusion method) 3(E) A honeycomb structure that does not satisfy any of the following conditions: the density is 1 / g or more, the diameter of the circle passing through three points at both ends of any one through-hole and the center of said through-hole is 1 cm or more and 50 cm or less, and the arithmetic mean roughness (Ra) of the partition surface in the direction of the through-hole in the honeycomb structure is 0.7 μm or more. 3 The condition is similar to "greater than / g", but there is no condition regarding pore volume when the composition is other than tricalcium phosphate. However, from the viewpoint of bone replacement and tissue affinity of medical calcium phosphate compositions, in pore distribution measurement by mercury intrusion, the pore volume of a honeycomb structure with a pore diameter of 10 μm or less relative to the mass is 0.02 cm³. 3 It is preferable that the volume be greater than / g, and the volume is 0.04 cm³. 3 It is more preferable that it be 0.08 cm or more, and 0.08 cm 3 It is even more preferable that the amount be 1 / g or more. "(V7) In mercury intrusion measurement, the volume of pores with a diameter of 1 μm to 6 μm is 5% or more of the volume of pores with a diameter of 6 μm or less." is a condition similar to "(H)" above. When medical calcium phosphate composition is manufactured using medical calcium carbonate composition as a raw material, phosphate components are added, which reduces the number of pores with small pore volumes. For this reason, the volume of pores with a diameter of 1 μm to 6 μm is set to 5% or more of the volume of pores with a diameter of 6 μm or less, but it is more preferable that this pore volume be 7% or more, and even more preferable that it be 10% or more. "(V8) The maximum compressive strength obtained in either direction is equal to or greater than the reference compressive strength [S] calculated by the following formula (provided that the honeycomb structure has multiple through holes extending in one direction, and the pore volume of the honeycomb structure with a pore diameter of 10 μm or less relative to the mass is 0.02 cm³ as measured by mercury intrusion method) 3 (Excluding those that are less than / g.) S = S0 × C × exp(-b × P) "(Here, S0 and b are constants, S0 is 500 and b is 0.068, C is a constant depending on the composition, 1 for carbonate apatite or apatite containing HPO4 groups or tricalcium phosphate, 0.5 for vitrocite, and 0.1 for calcium hydrogen phosphate, and P is the percentage of porosity of the composition.)" is similar to the conditions in (I) above, but the constant C is a constant depending on the composition, not a polymorph of calcium carbonate. The selection condition is "(V11) The composition shall be apatite with a carbonate group content of 10% by mass or more." Furthermore, since the carbonate content is 10% by mass or more, it is carbonate apatite. Carbonate apatite is highly useful because it is a component of vertebrate bones. "(V12) The composition shall be apatite having a carbonate group content of less than 10% by mass." is also a selection condition. Since the apatite has a carbonate group content of less than 10% by mass, it will be carbonate apatite and hydroxyapatite with a low carbonate group content. In some cases, slow bone replacement may be desired. In such cases, a medical calcium phosphate composition having apatite with a carbonate group content of less than 10% by mass is preferred. Since the bone replacement rate is controlled by the amount of carbonate groups in the apatite structure, a carbonate group content of 6% by mass or less is more preferable, and 3% by mass or less may be even more preferable. In addition, hydroxyapatite that does not contain carbonate groups may be preferred.

[0058] [V Medical Calcium Phosphate Composition: Specific Trace Components] Next,

[20] will be explained. Calcium phosphate compositions, particularly apatite, have high adsorption capacity. In addition, calcium phosphate produced in aqueous solution has a high specific surface area. If these calcium phosphate compositions become infected, tissue affinity cannot be expected. Therefore, calcium phosphate compositions containing trace components to prevent infection may be preferable. Silver or silver compounds are useful as trace components. A medical calcium phosphate composition that satisfies either (AG1) or (AG2) is a useful medical calcium phosphate composition from the viewpoint of infection prevention. A medical calcium phosphate composition that satisfies either (AG1) or (AG2) and also satisfies one of the following selection conditions (AG3) to (AG10) may be a more preferable medical calcium phosphate composition. The requirements for the volume of (AG1) and (AG2) are the same as those for (A). In (AG1), it is essential that the calcium phosphate compound contains 0.01% to 3% by mass of silver or a silver compound, and in (AG2), it is essential that the calcium phosphate compound contains 0.01% to 3% by mass of silver phosphate. Although silver may be incorporated into the calcium phosphate crystal structure, silver mainly exerts its antibacterial properties as silver ions, so silver or a silver compound not contained in the calcium phosphate crystal structure is effective in preventing postoperative infections. Furthermore, the content of silver or a silver compound is extremely important; if the content is too low, the antibacterial effect will not be exhibited, and if the content is too high, it will adversely affect tissue affinity. For this reason, the amount of silver or a silver compound contained in the medical calcium phosphate composition must be 0.01% to 3% by mass. The content is preferably 0.02% to 2% by mass, more preferably 0.03% to 1% by mass, and even more preferably 0.05% to 1% by mass. It is also preferable that these contents are ensured excluding the silver contained in the calcium phosphate crystal structure. The condition for (AG1), "one selected from the group consisting of carbonate apatite, apatite containing HPO4 groups, vitrocite, and calcium hydrogen phosphate," cannot be produced by sintering and is a condition for calcium phosphate produced in aqueous solution. To date, no calcium phosphate composition containing silver or a silver compound in a calcium phosphate compound that cannot be produced by sintering is known. (AG2) includes hydroxyapatite sintered bodies and tricalcium phosphate sintered bodies that can be produced by sintering as calcium phosphate compositions, but it is an essential condition that silver phosphate crystals are bonded to the surface of the calcium phosphate composition. When silver phosphate crystals are bonded to the surface of the calcium phosphate composition, silver phosphate dissolves from the surface of the composition, resulting in a high antibacterial effect. Furthermore, since the dissolution of silver phosphate occurs from the surface that is not bonded to the calcium phosphate composition, the calcium phosphate composition exhibits relatively long-term antibacterial function. The area ratio in which silver phosphate crystals are bonded to the surface of the calcium phosphate composition is preferably 20% or more of the surface area of ​​the silver phosphate crystals, more preferably 30% or more, and even more preferably 40% or more. Also, the area of ​​silver phosphate bonded to calcium phosphate is 2 × 10⁻⁶. -12 m 2 It is preferable that the above is true, 6 × 10 -12 m 2 More preferably, the above is true, 1 × 10 -11 m 2 It is even more preferable that the above conditions are met. (AG3) to (AG10) are selection criteria and do not necessarily need to be satisfied. (AG3) is a selection criterion related to (AG1). Silver phosphate, which has low solubility, may be preferred over other silver compounds because it can be expected to have a long-term antibacterial effect. The phrase, "(AG4) calcium phosphate composition contains silver or a silver compound in both its surface and interior, and the ratio of the silver concentration in the surface to the silver concentration at a distance of at least 50 μm from the surface toward the center is 1.2 or greater," is a selection criterion for a specific calcium phosphate composition having different silver concentrations within the composition. Postoperative infections include early infections that occur shortly after surgery and late infections that occur, for example, two months or more after surgery, and it is desirable to prevent both. In the early postoperative period, infection prevention takes priority over tissue affinity, so a relatively high silver concentration is preferable. Therefore, when tissue reconstruction is performed using a calcium phosphate composition, it is desirable that a relatively high amount of silver ions are released around the composition. This can be achieved by increasing the concentration of silver or silver phosphate in the surface layer of the composition. In the case of bioabsorbable calcium phosphate such as carbonate apatite or tricalcium phosphate, when the surface layer is absorbed, the silver or silver compounds in the surface layer also disappear. After a certain period has passed postoperatively, the risk of infection decreases, so tissue affinity becomes a higher priority, but prevention of delayed infection is also necessary. Therefore, it is preferable that silver or silver compounds are contained in both the surface layer and the interior of the calcium phosphate composition, and it is preferable that the ratio of the silver concentration in the surface layer to the silver concentration at a site at least 50 μm away from the surface of the composition in the direction toward the center is 1.2 or higher. It is more preferable that the ratio is 2 or higher, and even more preferable that it is 3 or higher. In this composition, the surface and interior are essentially the surface absorbed by osteoclasts and the interior excluding the surface. In the case of a porous material having interconnected pores of 30 μm or more that osteoclasts can penetrate, the interior is defined not as the apparent surface, but as the area excluding the surface where there are no interconnected pores of 30 μm or more. The ratio of the concentration of silver or silver compounds in the surface and interior is quantified by performing surface analysis and interior analysis using an energy-dispersive X-ray analyzer or an X-ray photoelectron spectroscopy analyzer. The surface is defined as the area less than 50 μm from the surface, and the interior is defined as the area at least 50 μm from the surface. If it is difficult to measure the silver concentration in the surface and interior using the above measurement method, the calcium phosphate composition is subjected to a dissolution rate test as defined in JIS-T0330-3 9.3 using an aqueous solution with a pH of 5.5, and the ratio of the silver concentration in the surface, calculated from the amount of silver component dissolved until the same weight loss as when the surface 50 μm is dissolved, is calculated from the silver concentration in the surface and the silver concentration in the sample. (AG5) to (AG10) are selection criteria for specific porous calcium phosphate materials. Compared to dense materials, porous materials are more likely to become infection sites, and since these porous materials are useful as medical calcium phosphate compositions, infection prevention is desirable for medical calcium phosphate compositions.

[0059] [V Medical Calcium Phosphate Composition: Specific Honeycomb Structure and Specific Microstructure and Composition] Next,

[21] , that is, compositions that are particularly useful among medical calcium phosphate compositions, will be described. Similar to medical-grade calcium carbonate compositions, medical-grade calcium phosphate compositions require high reactivity and properties tailored to specific cases. Therefore, it is preferable that at least one of the following conditions (W1) to (W7) is satisfied. "(W1) A honeycomb structure having multiple through holes extending in one direction, wherein the pore volume of the honeycomb structure, with a pore diameter of 10 μm or less relative to the mass of the honeycomb structure, is 0.01 cm³ as measured by mercury intrusion method." 3 The statement " / g or more" refers to the micropores of the trabecular bone. Composition is one factor involved in bone conduction and bone replacement, and macropores and micropores also have a significant impact on the usefulness of medical compositions. The presence of specific micropores in amounts above a certain level affects useful properties such as promoting absorption by osteoclasts. The pore volume of a honeycomb structure with a pore diameter of 10 μm or less relative to its mass is 0.01 cm³. 3 It is preferable that it be 0.03 cm or more, and 0.03 cm 3 It is more preferable that it be 0.05 cm or more. 3 It is even more preferable that the amount be 1 / g or more. "(W2) A honeycomb structure having multiple through-holes extending in one direction, wherein the diameter of the circle passing through the two ends of one of the through-holes and the center of the through-hole is 1 cm or more and 50 cm or less." is a honeycomb structure useful in specific cases. As mentioned above, bones are not just straight columns, but also curved columns. In bone reconstruction surgery for such bones, a curved column-shaped medical calcium phosphate honeycomb structure is useful. Furthermore, when creating bone perpendicular to the bone surface, a honeycomb structure in which the through-holes do not open to the connective tissue surrounding the bone, but only to the bone surface, is desirable. In a honeycomb structure, it is preferable that the diameter of the circle passing through the two ends of one through-hole and the center of the through-hole is between 1 cm and 50 cm. It is more preferable that the diameter of the circle is between 2 cm and 20 cm, and even more preferable that the diameter of the circle is between 3 cm and 10 cm. "(W3) In the honeycomb structure, the arithmetic mean roughness (Ra) of the septum surface in the direction of the through-holes is 0.7 μm or more." This indicates a honeycomb structure effective for cell adhesion, etc. Here, the arithmetic mean roughness (Ra) of the septum surface in the direction of the through-holes refers to the arithmetic mean roughness of the honeycomb surface that does not depend on the septums. In medical carbonate apatite honeycomb structures, a larger arithmetic mean roughness (Ra) improves cell adhesion, and as a result, osteoconductivity also improves. An arithmetic mean roughness (Ra) of 1.0 μm or more is more preferable, and 1.5 μm or more is even more preferable. (W4) to (W7) correspond to (AJ1) to (AJ4) in [3], and are medical calcium phosphate compositions with excellent tissue affinity and bone replacement properties. The average particle size of (W4) is preferably 2 μm or more and 8 μm or less, more preferably 3 μm or more and 7 μm or less, and even more preferably 4 μm or more and 6 μm or less. The sphericity of (W5) is preferably 0.9 or higher, and more preferably 0.95 or higher. The Mg content of (W6) is 5 × 10 -4 Mass% or more 3×10 -3 Preferably less than 1% by mass, and 1 × 10 -3 Mass% or more 2.5×10 -3 More preferably less than or equal to mass%, such as 1.5 × 10 -3 Mass% or more 2.5×10 -3 A mass percentage or less is even more preferable. The Sr content of (W7) is 3 × 10 -3 Mass% or more 1.5×10 -2 Preferably less than % by mass, 4 × 10 -3 Mass% or more 1.3×10 -2 More preferably less than or equal to % by mass, 5 × 10 -3 Mass% or more 1×10 -2 A mass percentage or less is even more preferable. The average particle size and sphericity are measured and calculated by separating the particles at the grain boundaries of the calcium phosphate composition. It is preferable that any of the conditions (W1) to (W7) be met, more preferably that multiple conditions be met, and even more preferably that all conditions be met.

[0060] [VI. Method for producing medical calcium phosphate composition: specific trace components] Next, a method for producing a medical-grade calcium phosphate composition will be described. First, let's explain

[22] . Calcium phosphate compositions such as

[20] and

[21] , which contain silver or silver phosphate, can be produced under the conditions of (AH1) or (AH2). If necessary, more preferable compositions can be produced under specific conditions, with (AH3) to (AH9) as the selection criteria. The common feature of (AH1) and (AH2) is that the volume is 10 -12 m 3 The condition that the composition is in the form of granules or blocks is necessary for producing a calcium phosphate composition with excellent tissue affinity. (AH1) relates to a method for producing a calcium phosphate composition that cannot be manufactured by sintering, and is characterized by containing 0.01% to 3% by mass of silver or a silver compound, and having a composition selected from the group of calcium carbonate, calcium hydroxide, calcium oxide, calcium sulfate, and calcium hydrogen phosphate, and having a volume of 10 -12 m 3 The process involves using the above-mentioned granular or block-type raw material calcium compositions. If the raw material calcium composition is other than calcium carbonate, a step is taken to impart carbonate groups to the composition, thereby converting the calcium composition to calcium carbonate. For example, in the case of calcium hydroxide, the calcium hydroxide is exposed to carbon dioxide. Furthermore, the process includes "exposure to an aqueous phosphate solution or a mixed aqueous solution of phosphate and magnesium salt to convert the composition to one selected from the group consisting of apatite carbonate, apatite containing HPO4 groups, vitrokite, and calcium hydrogen phosphate, which contains silver or a silver compound." Exposure to the aqueous phosphate solution or the mixed aqueous solution of phosphate and magnesium salt may be achieved by simply immersing the raw calcium composition in the solution, or by spraying the solution onto the raw calcium composition. The exposure process can produce a calcium phosphate composition. The carbonation process and the process of exposure to the aqueous phosphate solution or the mixed aqueous solution of phosphate and magnesium salt may be performed simultaneously. (AH2) is a calcium phosphate composition, which includes a step of exposing a raw material calcium composition selected from the group consisting of apatite, tricalcium phosphate, witrokhite, octacalcium phosphate, and calcium hydrogen phosphate to an aqueous solution containing silver ions to form silver phosphate on the raw material calcium composition. For example, when tricalcium phosphate is immersed in an aqueous solution of silver nitrate, the tricalcium phosphate partially dissolves, and phosphate ions and calcium ions are released. Since the solubility of silver phosphate, which is formed from silver ions and phosphate ions, is lower than that of tricalcium phosphate, silver phosphate precipitates on the surface of the tricalcium phosphate composition. If the tricalcium phosphate is a porous material and the aqueous solution of silver nitrate penetrates the porous material, silver phosphate precipitates on the surface of the tricalcium phosphate that comes into contact with the aqueous solution of silver nitrate. The type and concentration of the aqueous solution containing silver ions and the immersion time are not particularly limited, but silver nitrate or silver carbonate are preferred in terms of solubility. While satisfying (AG1) or (AG2) is a necessary condition, a more preferable medical calcium phosphate composition may be produced by further satisfying (AG3) to (AG10). (AH3) is a manufacturing method relating to (AG4) of

[20] . Although it is possible to manufacture calcium phosphate compositions with different silver concentrations in the interior and surface by adjusting the silver ion concentration of the aqueous solution and the immersion time, using aqueous solutions with different silver ion concentrations results in a shorter manufacturing time. In many cases, the raw material calcium phosphate composition is immersed in a first aqueous solution to precipitate a relatively low concentration of silver phosphate in the interior, and then immersed in a second aqueous solution to precipitate a relatively high concentration of silver phosphate on the surface. Therefore, the silver ion concentration of the second aqueous solution needs to be higher than that of the first aqueous solution. (AH4) to (AH9) are conditions relating to the raw material calcium composition required when producing (AG5) to (AG10) of

[20] .

[0061] [VI. Method for producing medical-grade calcium phosphate composition: Specific raw materials] Next,

[23] will be explained.

[23] relates to a medical calcium phosphate composition described in any of

[19] to

[21] , and in particular to (W4) to (W7) of

[21] . A medical calcium phosphate composition that satisfies the conditions of (W4) to (W7) is achieved by using calcium carbonate powder that satisfies the conditions of (AI1) to (AI4) as a calcium raw material. The average particle size of (AI1) is preferably 2 μm or more and 8 μm or less, more preferably 3 μm or more and 7 μm or less, and even more preferably 4 μm or more and 6 μm or less. The sphericity of (AI2) is preferably 0.9 or higher, and more preferably 0.95 or higher. The Mg content of (AI3) is 5 × 10 -4 Mass% or more 3×10 -3 Preferably less than 1% by mass, and 1 × 10 -3 Mass% or more 2.5×10 -3 More preferably less than or equal to mass%, such as 1.5 × 10 -3 Mass% or more 2.5×10 -3 A mass percentage or less is even more preferable. The Sr content of (AI4) is 3 × 10 -3 Mass% or more 1.5×10 -2 Preferably less than % by mass, 4 × 10 -3 Mass% or more 1.3×10 -2 More preferably less than or equal to % by mass, 5 × 10 -3 Mass% or more 1×10 -2 A mass percentage or less is even more preferable. It is preferable to satisfy any of the conditions (AI1) to (AI4), more preferably to satisfy multiple conditions, and even more preferably to satisfy all of them.

[0062] Next,

[24] will be described. A method for producing a medical calcium phosphate composition is useful, which involves adding a phosphate component to the medical calcium carbonate composition of the present invention or a medical calcium carbonate composition produced by the method for producing a medical calcium carbonate composition of the present invention under specific conditions. A preferred method for imparting the composition is to immerse the medical-grade calcium carbonate composition in an aqueous solution containing a phosphate component, such as an aqueous phosphate solution. The type of calcium phosphate formed by adding a phosphate component to a calcium carbonate composition can be controlled by the pH of the solution and the coexisting ions, allowing for the production of medical-grade calcium phosphate compositions containing carbonate apatite, hydroxyapatite, tricalcium phosphate, vitrokite, octacalcium phosphate, calcium hydrogen phosphate, and calcium dihydrogen phosphate. In producing these medical-grade calcium phosphate compositions, medical-grade calcium carbonate, which contains carbonate groups in its composition, is particularly useful. The amount of carbonate groups in a medical-grade carbonate apatite composition can be controlled by pH. Previously, Na2HPO4 with a pH of 8.9 or Na3PO4 with a pH of 13.1 at a 1 molar concentration were used. However, it has been found that the amount of carbonate groups in a medical-grade carbonate apatite composition can be controlled by setting the pH below 8.9. While setting the pH below 8.9 allows for the production of a medical-grade carbonate apatite composition with a lower carbonate group content than previously manufactured carbonate apatites, the effect is limited at a pH of 8.8. Therefore, in this invention, aqueous solutions containing phosphate components with a pH of 8.5 or higher are distinguished from aqueous solutions containing phosphate components with a pH below 8.5. Even more surprisingly, it was found that lowering the pH of the phosphate aqueous solution accelerated the dissolution reaction from calcium carbonate to calcium phosphate, thus shortening the time required to produce calcium phosphate. It is presumed that this is because the dissolution reaction from calcium carbonate to calcium phosphate is faster at lower pH levels, but the details have not been elucidated. Furthermore, by lowering the pH to 5.5 or below, it is possible to convert the composition of calcium carbonate to calcium hydrogen phosphate, and by creating an aqueous solution containing both phosphate and magnesium components, tricalcium phosphate such as vitrocite can be produced. Lowering the pH of phosphate shortens the production time of calcium phosphate, but when producing carbonate apatite, the amount of carbonate groups also decreases. To shorten the production time of carbonate apatite without reducing the amount of carbonate groups, it is necessary to include carbonate components in the phosphate with a low pH. However, it was found that carbonate apatite cannot be produced if the concentration of the carbonate component is higher than 1.0 molar. Furthermore, it was found that even with a carbonate component concentration of 0.6 molar, the production of carbonate apatite takes a long time. The details of this have not been elucidated, but it is thought that the presence of carbonate ions in the aqueous solution reduces the difference in the degree of supersaturation between calcium carbonate and carbonate apatite, making it difficult for carbonate apatite to form. In other words, for this purpose, an aqueous solution with a pH of less than 8.5 containing both a phosphoric acid component and a carbonate component at a concentration of 0.5 molars or less is useful. Furthermore, it was found that when the phosphate component was added to a medical-grade calcium carbonate composition using an aqueous solution containing both the phosphate component and the carbonate component at a concentration of 0.5 molars or less, the arithmetic mean roughness (Ra) increased. Although the mechanism is not yet clear, it is thought that the presence of carbonate groups in the solution reduces the difference in supersaturation between calcium carbonate and carbonate apatite, resulting in limited nucleation. As a result, the growth of the formed carbonate apatite is promoted, and the arithmetic mean roughness (Ra) of the honeycomb structure surface increases. From these combinations, aqueous solutions that impart a phosphate component to a medical calcium carbonate composition are: (X1) Aqueous solution containing a phosphate component with a pH of 8.5 or higher (X2) Aqueous solution containing a phosphate component with a pH of less than 8.5 (X3) An aqueous solution containing both a phosphate component and a carbonate component at a concentration of 0.5 molars or less, with a pH of 8.5 or higher. (X4) An aqueous solution containing both a phosphate component and a carbonate component at a concentration of 0.5 molars or less, with a pH of less than 8.5. (X5) Aqueous solution containing both phosphate and magnesium components At least one aqueous solution selected from the group is useful.

[0063] [VI. Method for producing a medical-grade calcium phosphate composition: Method for replacing gases within the composition] Next,

[25] will be explained. As mentioned above, a medical-grade calcium phosphate composition is produced by exposing a medical-grade calcium carbonate composition to an aqueous phosphate solution or the like, but as mentioned above, the method for producing a medical-grade calcium phosphate composition from a medical-grade calcium carbonate composition uses a dissolution-type reaction. Therefore, the medical-grade calcium carbonate composition needs to be dissolved from the surface. Basically, it is sufficient to immerse the medical-grade calcium carbonate composition in an aqueous phosphate solution or the like, but a medical-grade calcium carbonate composition basically has internal pores, which are macropores or micropores. Therefore, the dissolution reaction may be inhibited by gases such as air in the internal pores. In that case, the calcium phosphate composition will have unreacted calcium carbonate remaining, which may be undesirable as a medical-grade calcium phosphate composition. To prevent inhibition of the reaction, the gas in the internal pores of the medical-grade calcium carbonate composition can be replaced with an aqueous solution containing a phosphate component. In other words, the process involves "replacing some or all of the gas in the pores of a medical calcium carbonate composition immersed in an aqueous solution containing (Y1) phosphoric acid with the aqueous solution containing phosphoric acid." There are several useful steps to replace some or all of the gas in the pores of a medical-grade calcium carbonate composition immersed in an aqueous solution containing phosphate with the aqueous solution containing phosphate. However, since medical-grade calcium carbonate is basically a material that wets well with aqueous solutions containing phosphate, the step of "(Y2) applying vibration to a medical-grade calcium carbonate composition immersed in an aqueous solution containing phosphate to replace some or all of the gas in the pores of the medical-grade calcium carbonate composition with the aqueous solution containing phosphate" is also effective. An ultrasonic transducer is effective for applying vibration, for example. As a process similar to the vibration process, (Y3) a process in which an aqueous solution containing phosphate components is flowed around the medical calcium carbonate composition, and some or all of the gas in the pores of the medical calcium carbonate composition is replaced with the aqueous solution containing phosphate components, is also useful. By flowing the aqueous solution containing phosphate components around the medical calcium carbonate composition, it is possible to promote wetting of the surface of the pores inside the medical calcium phosphate composition with the aqueous solution containing phosphate components. The step of "(Y4) Replacing some or all of the gas in the pores of the medical calcium carbonate composition with the aqueous solution containing the phosphoric acid component by degassing a container containing an aqueous solution containing the phosphoric acid component under reduced pressure" relates to so-called degassing under reduced pressure. By reducing the pressure, the gas in the internal pores of the medical calcium carbonate composition is reduced, and by releasing the pressure, the surrounding aqueous solution containing the phosphoric acid component is introduced into the internal pores of the medical calcium carbonate composition. Repeating the process of reducing and releasing the pressure is preferable from the viewpoint of improving the degree of replacement. The step of "(Y5) replacing some or all of the gas in the internal pores of the medical calcium carbonate composition with a gas that has a higher solubility in an aqueous solution containing phosphate than air" is also useful. For example, carbon dioxide has a higher solubility in an aqueous solution containing phosphate than air. When a medical calcium carbonate composition in which the internal pores have been replaced with carbon dioxide is immersed in an aqueous solution containing phosphate, the carbon dioxide dissolves in the aqueous solution containing phosphate, and thus the air in the internal pores of the medical calcium carbonate composition is replaced with the aqueous solution containing phosphate. The step of "(Y6) Replacing some or all of the gas in the internal pores of the medical calcium carbonate composition with a solvent that has a smaller contact angle than water and is compatible with water" is also effective. For example, ethanol has a smaller contact angle than water. Therefore, ethanol easily penetrates the internal pores of the medical calcium carbonate composition. When a medical calcium carbonate composition with some or all of its internal pores filled with ethanol is immersed in an aqueous solution containing a phosphoric acid component, the ethanol becomes compatible with the aqueous solution, and the ethanol in the internal pores is replaced by the aqueous solution containing the phosphoric acid component by diffusion. A solvent that has a smaller contact angle than water and is compatible with water reduces the contact angle of the aqueous solution containing the phosphoric acid component to the medical calcium carbonate composition, similar to a surfactant. Therefore, it is not necessarily required to replace all of the gas in the internal pores of the medical calcium carbonate composition; replacing only a small portion is sufficient.

[0064] [VI. Method for producing medical-grade calcium phosphate composition: Reaction vessel] Next,

[26] will be explained. The medical calcium phosphate composition is produced by adding a phosphate component to the medical calcium carbonate composition of the present invention, which is produced by adding a carbonate component to the raw calcium composition. Generally, medical materials need to be kept free from foreign matter contamination, and from the viewpoint of a simple manufacturing process, it is preferable to carry out the manufacturing process without removing the materials and using the same reaction vessel. The "reaction vessel" is not particularly limited, and a general-purpose container can be used, but a container with an inlet and an outlet is preferred. This is because it is necessary to add the carbonate component and the phosphate component in the reaction vessel. An inlet is necessary to introduce carbon dioxide or the like into the reaction vessel in order to add the carbonate component. An outlet is also necessary to expel the air inside the reaction vessel to the outside. Furthermore, it is possible to apply pressure to the reaction vessel from the inlet and push out the solvent and other substances inside the reaction vessel from the outlet. From the viewpoint of ensuring a uniform reaction, a reaction vessel capable of accommodating a column-shaped container used in chromatography or a mesh container for holding a raw material calcium composition or a medical-grade calcium carbonate composition is preferred as the container. In the case of a column-shaped container, a uniform reaction of the composition inside the container is ensured by flowing a gas or solution through the column-shaped container. In the case of a reaction vessel capable of accommodating a mesh container, a uniform reaction of the composition inside the mesh container is ensured by flowing a gas or liquid through the mesh. This process prevents contamination and allows for the production of a medical-grade calcium phosphate composition with simple operations. Therefore, "a process for producing a medical-grade calcium phosphate composition characterized by performing the following steps (Z1) to (Z4), or (Z1), (Z3), (Z4), or (Z1), (Z3) in this order consecutively in the same reaction vessel without removing any materials" is a useful method for producing a medical-grade calcium phosphate composition. The step of "(Z1) imparting a carbonate component to a raw calcium composition to produce a medical-grade calcium carbonate composition" is an essential step, and involves exposing the raw calcium composition to carbon dioxide or carbonate ions to impart a carbonate component. Alternatively, as described in (D9) above, there may be a step of partially carbonating the raw calcium composition by exposing it to carbon dioxide or carbonate ions in the gas phase, and then exposing the raw calcium composition to carbon dioxide or carbonate ions in the liquid phase. In such cases, it is essential, in principle, to perform the step after (D9) and (Z2) or (Z3) consecutively. It is preferable to perform all of the steps in (D9) above. "(Z2) Washing step for medical calcium carbonate composition" is an optional step. For example, it is a useful step when a raw calcium composition containing a pore-forming agent is carbonated to produce a medical calcium carbonate composition, and then the pore-forming agent is washed off. This process involves adding a carbonate component to a raw calcium composition to produce a medical-grade calcium carbonate composition. It is not necessary to perform partial carbonation and subsequent carbonation without removing the material and using the same reaction vessel; the process focuses on the carbonation following partial carbonation. However, it is preferable to perform partial carbonation and subsequent carbonation without removing the material and using the same reaction vessel. The step of "(Z3) imparting a phosphate component to the medical-grade calcium carbonate composition" is an essential step. For example, by immersing the medical-grade calcium carbonate composition in an aqueous phosphate solution, a phosphate component is imparted to the medical-grade calcium carbonate composition, and a medical-grade calcium phosphate composition can be produced. "(Z4) Washing step for medical calcium carbonate composition" is an optional step. Although a medical calcium phosphate composition is manufactured by (Z3) above, this composition contains phosphates and other substances, and this step removes substances other than the composition. A washing step is necessary in the manufacture of medical calcium phosphate composition, but since washing and size adjustment are performed simultaneously, other containers such as sieves may be used, making it an optional step.

[0065] [VII Medical-grade calcium hydroxide composition] Next,

[27] , namely, medical calcium hydroxide composition, will be described. A medical calcium hydroxide composition is useful because it satisfies all of (AB1) to (AB3) and at least one condition selected from the group (AB4) to (AB8). Note that (AB1), (AB2), (AB4), (AB5), (AB6), (AB7), and (AB8) are the same as (A), (B), (V4), (F), (G), (J), and (K) mentioned above, respectively. The statement "(AB3) As a medical composition, it is substantially pure calcium hydroxide" is common to all medical calcium compositions of the present invention, but the requirement of (AB3) is that the composition is calcium hydroxide.

[0066] [XIII Method for producing medical-grade calcium hydroxide composition: Honeycomb structure] Next, we will describe the process for producing a medical calcium hydroxide composition that satisfies the conditions of (AB4) described above. Medical-grade calcium hydroxide honeycomb structures are manufactured using (AD1) and one selected from the group (AD2) to (AD5) as essential processes, and (AD6) to (AD8) as optional processes. Note that (AD1), (AD6), (AD7), and (AD8) are the same as (E1), (E2), (E3), and (E4), respectively. The "(AD2) Degreasing process" is a process for degreasing a porous calcium hydroxide body containing polymer material so that the acid-dissolved residue is 1% by mass or less. It is necessary to degrease the body under conditions that prevent the calcium hydroxide from decomposing into calcium oxide or from carbonating into carbonate apatite. For example, polymer material that has been converted into monomers can be removed by depolymerization or other means under reduced pressure at a temperature at which calcium hydroxide does not decompose. The "(AD3) Calcium Oxide Hydration Process" is a process in which a porous calcium hydroxide body containing polymer material is degreased so that the acid-dissolved residue is 1% by mass or less, and then the porous calcium oxide body is hydrated to form a porous calcium hydroxide body. The "(AD4) Calcium Carbonate-Calcium Oxide Hydration Process" is a process in which calcium hydroxide containing a polymer material is heat-treated in the presence of carbon dioxide to form a porous calcium carbonate containing a polymer material, then degreased so that the acid-dissolved residue is 1% by mass or less to form a porous calcium oxide, and then the porous calcium oxide is hydrated to form a porous calcium hydroxide. The "(AD5) Manufacturing process from porous calcium carbonate" is a process in which porous calcium carbonate containing polymer material is degreased so that the acid-dissolved residue is 1% by mass or less, and converted into porous calcium oxide, and then the porous calcium oxide is hydrated to convert into porous calcium hydroxide.

[0067] [XIII Method for producing a medical-grade calcium hydroxide composition: Granule-bound porous material] Next,

[29] , that is, the process for producing a medical calcium hydroxide composition that satisfies the conditions of (AB5) described above, will be explained. A porous material bound to granules of medical-grade calcium hydroxide that satisfies the conditions of (AB5) above is manufactured using the following essential steps: (AE1) and (AE2), and at least one selected from the group (AD2) to (AD5). "(AE1) Introduction process" has a volume of 10 -12 m 3 This step involves placing the calcium hydroxide granules containing the polymer material into a reaction vessel. The "(AE2) Granule bonding process" is a process in which the granules inside the reaction vessel are thermally softened and fused together by heat treatment, the surfaces of the granules are bonded together by dissolving the surfaces of the granules, or the surfaces of the granules are fused together by a plasticizer, with a volume of 3 × 10 -11 m 3 The above describes the process for producing a granule-bound porous body having multiple through-holes extending in multiple directions, formed by the bonding of multiple granules with a maximum diameter and length of 50 μm or more and 500 μm or less. During heat treatment, the polymer material softens and the granules bond together. To dissolve the surface of the granules, the granules should be exposed to a solvent that dissolves the polymer contained in them. For example, if the polymer material is acrylic resin, it can be brought into contact with acetone or the like. Plasticizers soften polymer materials. Any known plasticizer can be used without limitation.

[0068] [XIII Method for producing medical-grade calcium hydroxide composition: Manufacturing method using porous calcium oxide] Next, we will describe the process for manufacturing a porous calcium hydroxide for medical use, namely,

[30] , which uses a porous calcium hydroxide or a porous calcium carbonate as a raw material. Medical-grade porous calcium hydroxide can be produced by thermally decomposing a porous calcium hydroxide or porous calcium carbonate to produce a porous calcium oxide, and then hydrating the porous calcium oxide.

[0069] [IX Method for producing medical calcium composition: introduction closure step or introduction step] Next,

[31] will be described. In the introduction closure step or introduction step for manufacturing a granule-bound porous body by bonding multiple granules, the shape of the granules is not particularly limited, and spherical, uneven, or crushed granules can be used. Furthermore, dense, porous, or hollow bodies can also be used without restriction. However, from the viewpoint of improving the permeability and compressive strength of the porous medical calcium carbonate manufactured, it may be preferable to use granules that satisfy either "(AF1) the sphericity of the granules is 0.9 or higher" or "(AF2) the granules are hollow" in the introduction sealing process or introduction process. The statement "(AF1) The sphericity of the granules is 0.9 or higher" is due to the fact that using spherical or nearly spherical granules improves the continuity of the pores formed between the granules, and because spherical granules come into contact with each other easily, a porous material with high compressive strength can be produced. The degree of sphericity is preferably 0.9 or higher, more preferably 0.92 or higher, and even more preferably 0.95 or higher. Furthermore, in the case of granules that satisfy the condition "(AF2) The granules are hollow," the hollow granules combine to form a granule-bound porous body, resulting in a double pore shape. Such porous bodies with specific shapes can be particularly superior from the standpoint of cell and tissue migration, conduction, and bone replacement. Furthermore, when adding granules to the reaction vessel, it may also be preferable to "(AF3) add granules to the reaction vessel in a bulk volume of 105% or more of the volume of the reaction vessel." In the production of a granule-bound porous body having multiple through-holes extending in multiple directions, formed by the bonding of multiple granules, an introduction-closing step or introduction step is performed in which the granules are placed in a reaction vessel and the opening of the reaction vessel is closed to prevent them from being discharged. Following the introduction-closing step or introduction step, the granules are expanded or their composition is changed to bond them together. For porous body formation, it is necessary for the granules to be in contact or bonded to each other by some method, and increasing the contact area between the granules is effective in improving the compressive strength of the porous body. Furthermore, applying compressive stress between the granules is effective in increasing the contact area. As a method of applying compressive stress between the granules, it is effective to place the granules in the introduction-closing step or introduction step in a bulk volume greater than the volume of the reaction vessel, and, if necessary, close the opening of the reaction vessel to prevent them from being discharged. In principle, compressive stress is applied between the granules by placing granules with a bulk volume exceeding 100% of the reaction vessel's volume into the reaction vessel. However, from the viewpoint of increasing the compressive stress applied between the granules, the bulk volume of the granules placed into the reaction vessel is preferably 105% or more of the reaction vessel's volume, more preferably 110% or more, and even more preferably 120% or more.

[0070] [X Bone Defect Regeneration Treatment Kit] Next, we will describe

[32] , that is, "a kit for bone defect reconstruction treatment comprising a solid part containing vaterite and α-type tricalcium phosphate and a solution part containing a phosphate, wherein when the solid part and the solution part are kneaded together, carbonate apatite is formed and hardens." Medical vaterite compositions and medical carbonate apatite block compositions are useful for bone defect reconstruction, but in block form, shaping them to match the bone defect can be cumbersome, and in granular form, they may migrate from the bone defect. Therefore, bone defect reconstruction treatment kits that harden to form carbonate apatite are useful. On the other hand, when α-type tricalcium phosphate (αTCP) is mixed with a solution such as water, it dissolves, and calcium ions and phosphate ions are formed in the solution. This solution becomes supersaturated with respect to calcium-deficient hydroxyapatite, causing calcium-deficient hydroxyapatite crystals to precipitate from the solution. The entanglement of these crystals forms a hardened calcium-deficient hydroxyapatite. However, calcium-deficient hydroxyapatite is not part of the bone composition and, for example, exhibits inferior osteoclastic resorption compared to carbonate apatite, which is part of the bone composition. If the calcium ions and phosphate ions formed in the solution when αTCP dissolves coexist with carbonate ions, carbonate apatite crystals are formed instead of calcium-deficient hydroxyapatite crystals, and the entanglement of carbonate apatite crystals forms a hardened carbonate apatite. Calcium carbonate is useful as a carbonate ion source, but among calcium carbonates, calcite, which is the stable phase, has a low dissolution rate and cannot supply sufficient carbonate ions to the solution. Therefore, when a mixture of calcite and αTCP is kneaded in solution, although some carbonate apatite crystals precipitate, the precipitation of calcium-deficient hydroxyapatite crystals is predominant. On the other hand, vaterite, being a metastable phase, has a higher dissolution rate compared to calcite, allowing it to supply a larger amount of carbonate ions to the solution. Therefore, when a mixture of vaterite and αTCP is kneaded in solution, the precipitation of calcium-deficient hydroxyapatite crystals is minimal, while the precipitation of carbonate apatite crystals is dominant. For this reason, the solid portion must contain both vaterite and αTCP. Furthermore, it is essential that the solution used to knead the solid portion contains phosphate. This is because calcium ions, carbonate ions, and phosphate ions dissolve from vaterite and αTCP into the phosphate ion-containing solution, causing the solution to become supersaturated with respect to carbonate apatite. This allows carbonate apatite to form in a relatively short time, thus ensuring an appropriate curing time. The phosphate is not particularly limited as long as it is a phosphate that can dissolve and supply phosphate ions to the solution, but NaH2PO4, Na2HPO4, Na3PO4, KH2PO4, K2HPO4, K3PO4, (NH4)H2PO4, (NH4)2HPO4, (NH4)3PO4 and mixed salts thereof are more preferred from the viewpoint of solubility and other factors. Furthermore, the phosphate concentration in the solution is preferably 0.1 molar or higher, more preferably 0.2 molar or higher, and even more preferably 0.4 molar or higher. This is because a higher phosphate concentration results in a higher degree of supersaturation of the solution with respect to carbonate apatite. Furthermore, while the pH of the solution is not particularly limited, it is preferable that the pH of the solution be between 6.0 and 9.0 from the viewpoint of tissue affinity.

[0071] [X Bone Defect Regeneration Treatment Kit: Vatelite Content] Next,

[33] will be explained. An essential requirement for the solid portion of the above-mentioned defect reconstruction treatment kit is that it contains vaterite and α-type tricalcium phosphate. As a result, when mixed with the above-mentioned solution portion, it hardens and forms carbonate apatite. From the viewpoint of the amount of carbonate apatite formed, the amount of carbonate groups in the carbonate apatite structure, and the mechanical strength of the hardened body, the vaterite content in the solid portion is preferably 10% by mass or more and 60% by mass or less, more preferably 15% by mass or more and 50% by mass or less, and even more preferably 20% by mass or more and 40% by mass or less.

[0072] [X Bone Defect Regeneration Treatment Kit: Solution Section] Next,

[34] will be explained. The solution portion must contain a phosphate, but it is preferable that it contains at least one of the following: an acid having multiple carboxyl groups, a bisulfite, a cellulose derivative, a dextran sulfate, a chondroitin sulfate, an alginate, and a glucomannan. Since a phosphate is essential in the solution portion, an acid having multiple carboxyl groups and a salt of an acid having multiple carboxyl groups are substantially the same. Acids containing multiple carboxyl groups include dicarboxylic acids and tricarboxylic acids. Examples of dicarboxylic acids include oxalic acid, malonic acid, succinic acid, malic acid, itaconic acid, phthalic acid, glutaric acid, and maleic acid, while an example of a tricarboxylic acid is aconitic acid. Adding an acid containing multiple carboxyl groups to the solution shortens the hardening time. This is thought to be because the acid containing multiple carboxyl groups chelates with αTCP or vatelite, and when the solid part is mixed with the solution part, hardening proceeds due to the chelation reaction. Examples of bisulfites include sodium bisulfite and potassium bisulfite. Although the mechanism of action of bisulfites is not fully understood, the presence of bisulfites in the solution shortens the curing time. Cellulose derivatives, dextran sulfate, chondroitin sulfate, alginate, and glucomannan, when added to the solution, increase viscosity. This improves the handling properties when mixing the solid and solution portions. Cellulose derivatives are cellulose that has been chemically modified to impart solubility to a solvent. Examples include carboxymethylcellulose, methylcellulose, hydroxypropylcellulose, hypromellose, and their salts. Adding a cellulose derivative to a solution increases the viscosity of the solution, which in turn improves the handling when mixing it with the solid. The concentration of the added cellulose derivative varies depending on the degree of polymerization, but is generally preferably 2% by mass or less. Pastes prepared by kneading the solid portion with a solution containing these additives may have their tendency to disintegrate upon contact with bodily fluids suppressed. This is thought to be because the disintegration is caused by the penetration of moisture into the paste before it hardens. In other words, it is thought that disintegration due to water can be suppressed by increasing the viscosity of the paste to suppress the penetration of moisture into the paste, or by accelerating its hardening.

[0073] [X Bone defect regeneration treatment kit: Volume of Vatelite] Next,

[35] will be explained. The volume of vaterite contained in the solid part is not particularly limited, but the volume is 10 -12 m 3The above-mentioned kit for bone defect reconstruction treatment, which includes vatelite in the solid part, is preferable because the mechanical strength of the hardened body may be high. The mechanism of increased mechanical strength has not been elucidated, but the volume is 10 -12 m 3 It is presumed that the vaterite described above plays the same role as a filler in composite materials. Also, the volume is 10 -12 m 3 The vaterite described above is not completely consumed in the reaction with αTCP. That is, calcite coated with carbonate apatite is formed within the hardened body. The calcium carbonate coating on the carbonate apatite surface is useful because it can increase osteoconductivity by releasing calcium ions. -12 m 3 The vaterite described above is preferably present in an amount of 10% by mass or more, and more preferably 20% by mass or more, in the vaterite contained in the solid portion.

[0074] [X Bone defect regeneration treatment kit: Volume of Vatelite] Next,

[36] will be explained. On the other hand, if it is desired to increase the purity or content of carbonate apatite formed by imparting porosity to the hardened body, it is preferable that the average particle size of the vaterite contained in the solid part be 6 μm or less. It is more preferable that the particle size be 4 μm or less, and even more preferable that be 2 μm or less. This is because a smaller particle size results in a larger specific surface area, which increases the dissolution rate of carbonate ions and calcium ions in the solution, thereby promoting carbonate apatite formation. On the other hand, if the particle size is too small, the consistency may be poor when the kit for bone defect reconstruction treatment is mixed. For this reason, it is preferable that the particle size be 0.5 μm or more, or 1 μm or more.

[0075] The present invention will be described in more detail below using examples, but the scope of the present invention is not limited to these examples. The general conditions are as follows. Any differences from these conditions are noted in the individual examples or comparative examples.

[0076] <Raw materials> In this example and comparative example, unless otherwise specified, the calcium hydroxide used was ultra-high purity (CSH) from Ube Material Co., Ltd., the calcium carbonate used was Karumaru from Sakai Chemical Industry Co., Ltd. with an average particle size of 5 μm, the α-type tricalcium phosphate used was α-TCP-B from Taihei Chemical Industry Co., Ltd., and the superhard gypsum used was a custom-made product from GC Corporation's New Fuji Rock White, with components other than calcium sulfate removed. Calcined gypsum is calcium sulfate hemihydrate. All of these satisfy (B). All other materials were also prepared using special grade reagents. Therefore, all materials produced in this example and comparative example are artificial materials. Calcium hydroxide spheres were produced by spray-drying calcium hydroxide, to which 0.5% by mass of Kuraray PVA-205C (manufactured by Kuraray Co., Ltd.) was added as a binder. The spheres were then sieved to identify those that passed through a 200 μm sieve but not a 100 μm sieve. In spray drying, spheres are formed by surface tension. Additionally, hollow spheres were produced, possibly due to drying from the outside. The produced calcium hydroxide spheres were heated in an electric furnace at a rate of 5°C per minute up to 1000°C, heated at 1000°C for 6 hours, and then furnace-cooled. In the production of the honeycomb structure, the raw calcium composition was mixed with a wax-based binder manufactured by Nagamine Seisakusho Co., Ltd. in a mass ratio of 75:25. Then, a mold for forming the honeycomb structure was attached to a Laboplast Mill manufactured by Toyo Seiki Seisakusho Co., Ltd., and extrusion molding was performed. Basically, a honeycomb structure of a binder-containing raw calcium composition containing a polymer material manufactured by extrusion molding was produced, and a cylindrical binder-containing raw calcium composition with an outer side wall was manufactured. Degreasing, and carbonation and removal of the outer side wall, etc., were performed as needed. <Reaction vessel> Unless otherwise specified, a segmented reaction vessel with a diameter of 6 mm and a height of 3 mm was used. The bottom of the reaction vessel was closed with a glass plate, and the top was open. The raw materials were introduced into the reaction vessel from the open top, and by closing it with the glass plate, the raw materials were prevented from being discharged from the reaction vessel, but water and water vapor could penetrate into the inside of the reaction vessel through the gap. Hereafter, for simplicity, this reaction vessel will be referred to as a segmented reaction vessel with a diameter of 6 mm and a height of 3 mm. Note that the volumes of the calcium composition, calcium phosphate composition, and raw material calcium composition in the examples are all 3 × 10⁻⁶. -11 m 3 For the reasons stated above, the volume may be omitted in the examples and comparative examples. 90% methanol is a mixture of methanol and water in 90% and 10% by volume ratios, 90% ethanol is a mixture of ethanol and water in 90% and 10% by volume ratios, and 90% acetone is a mixture of acetone and water in 90% and 10% by volume ratios. "Carbonation with 90% methanol at 4°C" means introducing 100 mL per minute of carbon dioxide at 4°C containing 90% methanol into a 500 mL container at 4°C containing the raw calcium composition. If the container volume was different, the amount to be introduced was determined by proportional calculation. This causes 90% methanol at 4°C to flow around the raw calcium compound. Excess carbon dioxide is discharged through the container's outlet, the reaction is allowed to proceed for 7 days, and then the mixture is dried. <Powder X-ray diffraction analysis: XRD analysis> In this invention, compositional analysis was performed using a BRUKER D8 ADVANCE powder X-ray diffractometer. The output was 40kV, 40mA, and the X-ray source was CuKα (λ=0.15418nm). The pattern obtained by XRD analysis is called the XRD pattern. The vaterite and calcite content in medical-grade calcium carbonate compositions is calculated from the XRD pattern peak area ratio. For vaterite peaks, the peak areas of the 110, 112, and 114 faces of vaterite shown in Figure 3 are used, and for calcite peaks, the peak area of ​​the 104 face of calcite shown in Figure 3 is used. If substances other than vaterite and calcite are present in the medical calcium carbonate composition, the vaterite and calcite content shall be calculated using the internal standard substance method. <Average particle size> The powder was dispersed in 100 mL of distilled water, and after dispersion using an ultrasonic cleaner at a frequency of 45 kHz and 100 W for 30 seconds, the particle size distribution was determined within 1 minute using a laser diffraction particle size distribution analyzer (Shimadzu Corporation, SALD-300V). The particle size at which the cumulative value of the particle size distribution reached 50% was defined as the average particle size. <Arithmetic mean roughness (Ra)> The arithmetic mean roughness (Ra) of the material surface was measured using a Keyence VK-9710 color 3D laser microscope. <Pore distribution measurement using mercury intrusion method> The pore distribution was measured using a Shimadzu Autopore 9420. The contact angles between mercury and the material used in the calculations are as described above. <Acid-dissolved residue> The acid-dissolved residue is defined as the residue obtained when calcium carbonate or the like is dissolved in 1 molar hydrochloric acid in a volume equivalent to 20 molar equivalents of the calcium carbonate or the like, and the dry mass is expressed as a percentage of the mass of the calcium carbonate or the like. For example, in the case of a sample composed of 0.2 g of calcium carbonate, it was dissolved in 40 mL of 1 molar hydrochloric acid aqueous solution, and the mixture was filtered and washed with water. The unfiltered acid-dissolved residue was dried and its mass was measured, and the ratio of this mass to the sample mass was expressed as a percentage. The acid-dissolved residue is a meaningful value only when the raw calcium composition contains polymer materials; therefore, it may be omitted when using a raw calcium composition that does not contain polymer materials. <Compressive strength> Compressive strength was measured as an indicator of mechanical strength. The compressive strength of the calcium hydroxide block product was measured using a Shimadzu universal testing machine (AGS-J type). The sample was fractured at a crosshead speed of 10 mm per minute, and the compressive strength was measured from the maximum force at which fracture occurred. <Volume> The bulk volume of the manufactured cylindrical composition was calculated by measuring its diameter and height. The same procedure was followed for other forms. Except for Comparative Example 3, the volume of all materials manufactured in the Examples and Comparative Examples was 10 -12 m 3 For the reasons stated above, descriptions of the examples and comparative examples may be omitted. <Antibacterial and cytotoxicity tests> Antimicrobial activity was tested in accordance with JIS Z2801. Staphylococcus epidermidis (NBRC12993) was used as the test strain. The bacterial count was measured using 1 / 500 ordinary broth medium, resulting in 4.35 × 10⁶ bacteria. 4 The bacterial suspension, adjusted to CFU / mL, was inoculated onto the sample surface. One side of the sample was then covered with a polyethylene film, and the sample was incubated at 37°C and 90% relative humidity for 24 hours. After incubation, the bacterial suspension was collected, diluted as needed, and the number of bacteria was counted using the agar plate method. Cytotoxicity testing was performed in accordance with ISO 10993-5:2009. Specifically, 1 × 10⁶ MC3T3-E1 cells were placed on the sample surface. 4 Individual seeds were seeded and cultured in an incubator at 37°C with a carbon dioxide concentration of 5 vol% using a mixture of Eagle's Minimum Essential Medium α modified, 10% fetal bovine serum, and 1% antibiotic as the culture medium. After 24 hours of incubation, the cells were fixed with 2% glutaraldehyde, stained with Hoechst stain, and the number of cells was counted. A cell viability of 70% or less was considered cytotoxic, and a cell viability of 70% or more was considered non-cytotoxic. <Evaluation of physical properties of kits for bone defect reconstruction treatment> The hardening properties of the bone defect reconstruction kit were measured under conditions of 37°C and 100% relative humidity. Hardening time was measured using the Vicker needle method, and indirect tensile strength was measured 24 hours after hardening. The composition of the hardened material was analyzed by XRD and FT-IR analysis.

[0077] (Example 1) Wako Pure Chemical Industries' reagent-grade calcium hydroxide powder was placed in a mold and subjected to uniaxial pressure at a pressure of 20 MPa to produce a calcium hydroxide powder compact with a diameter of 6 mm and a height of 9 mm. Next, 100 mL of 90% methanol was placed in a 500 mL reaction vessel, and the calcium hydroxide compact was placed on a mesh that was set up so that the sample and solvent did not come into contact, and the temperature was maintained at 4°C. 100 mL of carbon dioxide per minute was introduced into the 90% methanol portion of the reaction vessel through a bubbler and discharged through a discharge valve at the top of the reaction vessel. As a result, the calcium hydroxide compact was exposed to carbon dioxide containing 90% methanol, and the carbon dioxide containing 90% methanol flowed around the calcium hydroxide compact. Furthermore, methanol inhibits calcite formation or the growth of calcite crystals, while relatively promoting the formation of calcium carbonate other than calcite. Calcium hydroxide hardens, and its volume is 2.5 × 10⁻⁶. -4 m 3 The blocks were manufactured. Furthermore, since carbon dioxide containing 90% methanol flowed around the calcium hydroxide compact during production, the water produced as a by-product of the reaction between calcium hydroxide and carbon dioxide was removed by evaporation from inside the calcium hydroxide compact. XRD analysis (Figure 3) revealed unreacted calcium hydroxide when the exposure period was 2 days. However, when the exposure period was 7 days, the composition was confirmed to be pure calcium carbonate with a vaterite content of 97% by mass and a calcite content of 3% by mass. There was 0% by mass of acid-soluble residue. These results confirm that the medical vatelite composition of the present invention could be manufactured. Furthermore, the porosity of the medical vaterite composition is 45%, and since it contains 20% or more by mass of vaterite, the polymorphic constant is 0.01. The standard compressive strength was calculated to be 0.23 MPa, but the compressive strength of the composition was 24 MPa, which was confirmed to be above the standard compressive strength. Next, the medical vatelite composition was immersed in a 1 molar concentration Na2HPO4 aqueous solution with a pH of 8.9 at 80°C for 3 days to impart phosphate to the medical vatelite composition. The volume of the manufactured composition is 2.5 × 10⁻⁶ -4 m 3 XRD analysis (Figure 4) and infrared spectroscopy revealed peaks of carbonate groups, confirming that the composition is pure carbonate apatite. Elemental analysis showed that the amount of carbonate groups was 10.8% by mass. Furthermore, there was 0% by mass of acid-soluble residue. The porosity was 42%, and the standard compressive strength was calculated to be 29 MPa. However, the compressive strength of the composition was 32 MPa, confirming that it was above the standard compressive strength. These findings confirm that a medical carbonate apatite composition can be produced by adding phosphate to a medical vaterite composition.

[0078] (Comparative Example 1) Carbon dioxide was exposed to the calcium hydroxide compact in the same manner as in Example 1, except that water was used instead of 90% methanol. When calcium hydroxide compacted powder is exposed to carbon dioxide for 7 days, the calcium hydroxide hardens, and its volume increases to 2.5 × 10⁻⁶. -4 m 3 A block was produced. XRD analysis revealed that the block's composition consisted of 98% calcite by mass and 2% unreacted calcium hydroxide by mass. Acid-dissolved residue was 0% by mass. In mercury intrusion testing, the ratio of pore volume between 1 μm and 6 μm in diameter to pore volume between 6 μm and 6 μm in diameter was 0%. Furthermore, the porosity was 44%, and the standard compressive strength was calculated to be 25 MPa, but the compressive strength of the composition was 22 MPa, which was below the standard compressive strength. Also, since it did not meet any of the criteria (D) to (K) of [1], the manufactured calcite composition is not a material included in the present invention. From a comparison between Example 1 and this comparative example, it was found that calcium carbonate containing 20% ​​or more by mass of vaterite can be produced by a process that suppresses calcite formation or the growth of calcite crystals and relatively promotes the formation of calcium carbonate other than calcite, that methanol, an organic solvent, is useful in this process, and that vaterite formation proceeds faster than calcite formation. Next, the calcite block was immersed in a 2-molar concentration disodium hydrogen phosphate solution at 80°C for 3 days to impart phosphate to the medical vatelite composition. The volume of the manufactured composition is 2.5 × 10⁻⁶ -4 m 3The acid-dissolved residue was 0% by mass. However, XRD analysis confirmed that although apatite had formed, the raw material, calcite, remained. From a comparison between Example 1 and this comparative example, it was confirmed that the medical-grade vaterite composition is more reactive than the calcite composition and is useful for apatite production.

[0079] (Comparative Example 2) The same manufacturing method as in Example 11 of Patent Document 8 was carried out. Sieved 1-2 mm interconnected porous anhydrous granules were immersed in 50 mL of a 2 molar concentration sodium carbonate aqueous solution at 4°C for 14 days. Composition analysis by XRD revealed the same XRD pattern as in Figure 3b) of Patent Document 8, and the polymorphs of calcium carbonate were 83% by mass of calcite and 17% by mass of vaterite. The vaterite content was 20% by mass or less. Furthermore, since it did not fall under any of (D) to (K) of [1], the manufactured calcium carbonate composition is not a material included in the present invention. A comparison between Example 1 and this comparative example revealed the usefulness of steps that suppress calcite formation or the growth of calcite crystals, such as the step using methanol, and relatively promote the formation of calcium carbonate other than calcite.

[0080] (Comparative Example 3) The calcium hydroxide compact prepared in Example 1 was immersed in 50 mL of a 2 molar concentration sodium carbonate aqueous solution at 4°C. Immediately after immersion, the compact crumbled into powder. The powder had a volume of 10 -12 m 3 It was less than [amount missing]. Therefore, the calcite powder produced is not a material included in the present invention. From a comparison of Examples 1, Comparative Examples 1 and 2 with this comparative example, it was found that when carbonation is performed using a 2-molar concentration sodium carbonate aqueous solution at 4°C, not only is the amount of vaterite formed limited, but it is also necessary to use calcium sulfate blocks that do not disintegrate even when immersed in the aqueous solution, and vaterite blocks cannot be produced from calcium hydroxide powder. Therefore, it was found that the process of producing a medical vaterite composition by suppressing calcite formation or the growth of calcite crystals and relatively promoting the formation of calcium carbonate other than calcite in the present invention is superior.

[0081] (Example 2) <1. Manufacturing of the raw material calcium hydroxide composition> Calcium hydroxide powder was placed in a mold and subjected to uniaxial pressure at a pressure of 5 MPa to produce a compacted calcium hydroxide powder with a diameter of 6 mm and a height of 9 mm. Furthermore, a calcium hydroxide paste was prepared by kneading the calcium hydroxide powder and ethanol in a liquid-to-liquid ratio of 1.0, and then compacting the resulting paste at 5 MPa to produce a compacted calcium hydroxide paste. Furthermore, the calcium hydroxide paste raw material was filled into a silicone tube with an inner diameter of 5 mm and a length of 5 mm, which served as a mold, to produce a calcium paste composition in the mold. Furthermore, the calcium hydroxide paste was mixed with sodium chloride granules, a pore-forming material whose mesh size passed through a 100 μm sieve but not through a 50 μm sieve. This mixture was then uniaxially pressed at a pressure of 5 MPa to produce a calcium hydroxide paste powder containing sodium chloride granules that met the (AB6) criteria, with a diameter of 6 mmφ and a height of 9 mm. All of these samples satisfied all of the conditions (AB1) to (AB3). Furthermore, calcium hydroxide compacts were used to produce calcium hydroxide compacts granules. Specifically, the calcium hydroxide compacts were crushed by poking them with a scalpel, and calcium hydroxide compacts granules were produced that passed through a 2 mm sieve but not through a 1.18 mm sieve. The granules had a short diameter of 1 mm or more and less than 5 mm. Furthermore, calcium hydroxide powder was uniaxially pressed at a pressure of 5 MPa with fibers of a glycolic acid lactate copolymer sandwiched between them to produce a calcium hydroxide compact with a diameter of 2 mmφ and a height of 2 mm. Another calcium hydroxide compact was produced using the same process so that the end was 2 mm away from the calcium hydroxide compact. This process was repeated to produce a bead-like fiber-bound raw calcium hydroxide compact in which fibers passed through the center of a calcium hydroxide compact with a diameter of 2 mmφ and a height of 2 mm that satisfies (AB8), and the raw calcium hydroxide compacts were bound together by the fibers at a distance of 2 mm. Since all of the manufactured calcium hydroxide compositions satisfied (AB1) to (AB3), it was confirmed that medical-grade calcium hydroxide compositions could be manufactured using the raw material calcium hydroxide compositions that satisfied (AB6) and (AB8) above. <2. Placement of raw materials such as calcium composition into the reaction vessel> A stainless steel pressurized vessel (TA125N) manufactured by AS ONE Corporation was used as the reaction vessel. The reaction vessel has three screw holes (holes A, B, and C) and a top lid. Using a tube fitting manufactured by Pisco Corporation, a pipe was installed from hole A to reach the bottom of the reaction vessel, a pipe was installed from hole B to extend 5 cm downward from the lid of the reaction vessel, and a power cord for a fan was passed through hole C from the outside into the reaction vessel, and the inside of the tube fitting was sealed with epoxy resin. Holes A and B function as an inlet and outlet. 90% ethanol and a stirrer piece were placed in the reaction vessel. Next, a mesh container containing the raw material composition was placed so that it did not come into contact with the 90% ethanol. A fan was placed above the mesh container. When the fan was turned on, it would blow air towards the mesh container. <3. Carbon dioxide replacement process> With the lid of the reaction vessel closed, carbon dioxide was introduced into the reaction vessel from a carbon dioxide cylinder through hole A. The air inside the reaction vessel was discharged through hole B, replacing the air inside the reaction vessel with carbon dioxide. <4. Partial Carbonation Process> Next, hole B was closed, and the carbon dioxide pressure in the reaction vessel was increased to atmospheric pressure (100 kPa) using the carbon dioxide cylinder pressure reducing valve, and the fan was turned on. As a result, carbon dioxide containing 90% ethanol flowed around the raw material calcium composition. When hole A was sealed, the carbon dioxide in the reaction vessel was consumed and the pressure decreased as the carbonate component was added to the raw calcium composition. However, the pressure reducing valve of the carbon dioxide pump supplied carbon dioxide when the pressure fell below the set pressure, so the carbon dioxide pressure in the reaction vessel was kept constant at atmospheric pressure plus 100 kPa. XRD analysis of the composition after 24 hours revealed that all samples contained calcium hydroxide with vaterite and trace amounts of calcite. Excluding the pore-forming materials, sodium chloride and fibers, the composition of the calcium hydroxide compacts, calcium hydroxide compacts granules, and fiber-bound raw material calcium hydroxide compacts was 72% by mass of vaterite, 3% by mass of calcite, and 25% by mass of calcium hydroxide. For calcium hydroxide paste compacts, calcium paste compositions in molds, and raw material calcium hydroxide paste compacts containing sodium chloride granules, the composition was 62% by mass of vaterite, 4% by mass of calcite, and 34% by mass of calcium hydroxide. Although some unreacted calcium hydroxide remained, the raw calcium composition was partially carbonated and remained intact even when immersed in 90% ethanol. <5. Carbonation Process> I opened the lid of the reaction vessel and took out the fan. Next, 90% methanol was added so that the mesh container was completely submerged and so as not to come into contact with the pipe installed through hole B. After repeating the carbon dioxide replacement process, hole B was closed. Next, the pressure inside the reaction vessel was increased using the pressure reducing valve on the carbon dioxide cylinder so that the carbon dioxide pressure was 100 kPa in addition to atmospheric pressure, and the stirrer was rotated with hole A open. Six days after the start of the carbonation process, the connection to the carbon dioxide cylinder connected to hole A was disconnected, hole B was opened to return the pressurized state to atmospheric pressure, and then air was introduced into the reaction vessel through hole B to discharge the solvent from the reaction vessel through hole A. Next, hole A was closed, and the medical vatelite composition was dried by reducing the pressure inside the reaction vessel using a pump through screw hole B. After drying, the pump was stopped, and air was introduced into the reaction vessel through screw hole A to restore atmospheric pressure. Separately, compositional analysis by XRD revealed that, excluding the pore-forming materials sodium chloride and fibers, the composition of the calcium hydroxide compacts, calcium hydroxide compacts granules, and fiber-binding raw material calcium hydroxide compacts contained 95% by mass of vaterite and 5% by mass of calcite. In the case of calcium hydroxide paste compacts, calcium paste compositions in molds, and calcium hydroxide paste compacts containing sodium chloride granules, the vaterite content was 93% by mass and the calcite content was 7% by mass. In the calcium carbonate composition produced from a calcium hydroxide paste powder containing sodium chloride granules, an accumulation of multiple pores ranging from 50 μm to 100 μm was observed, but no pores with a maximum diameter and length exceeding 100 μm were found. Furthermore, the pore volume of pores smaller than 10 μm, measured by mercury intrusion, was 0.53 cm³. 3 It was / g. Calcium hydroxide was not detected in any of the samples. Furthermore, the acid-dissolved residue, excluding the fibers, was 0% by mass in all samples. Therefore, it was confirmed that medical vaterite blocks satisfying (D) were manufactured from the calcium hydroxide compact, calcium hydroxide paste compact, and raw calcium paste placed in a mold. Furthermore, it was confirmed that medical-grade vatelite granules satisfying conditions (D) and (G) were produced from the calcium hydroxide paste powder containing sodium chloride granules. Furthermore, it was confirmed that medical-grade vatelite granules satisfying (K) were produced from the bead-like fiber-binding raw material calcium hydroxide compact. <6. Phosphate component addition process> To ensure the mesh container was submerged, a 1 molar concentration Na2HPO4 aqueous solution with a pH of 8.9 at 80°C was introduced into the reaction vessel through hole A. Hole A was sealed, and the air inside the reaction vessel was depressurized through screw hole B using a diaphragm pump. Subsequently, air was introduced through hole B. This operation degassed the air from the internal pores of the medical-grade calcium carbonate composition, and filled the internal pores of the medical-grade calcium carbonate composition with the Na2HPO4 aqueous solution. Next, the stirrer piece was rotated to maintain the temperature of the reaction vessel at 80°C. <7. Washing and Drying Process> Seven days after the phosphoric acid component addition step, air was introduced through hole B and the Na2HPO4 aqueous solution was discharged through hole A. Next, the product was washed by introducing 80°C water into the reaction vessel through hole A and discharging the water through hole B. Next, air was introduced through hole B and water was discharged through hole A. Hole A was sealed, and while maintaining the reaction vessel temperature at 80°C, air was discharged through hole B using a pump, and the product was dried under reduced pressure. XRD analysis and infrared spectroscopy detected peaks of carbonate groups, confirming that both samples were composed of pure carbonate apatite. Elemental analysis revealed a carbonate group content of 10.8% by mass. Furthermore, there was 0% by mass of acid-soluble residue. The volume of each sample was 10%. -12 m 3 That was all. These analysis results confirmed that medical-grade carbonate apatite blocks satisfying all conditions (V1) to (V3) were produced from the raw calcium hydroxide compacted powder, the raw calcium hydroxide paste compacted powder, and the raw calcium paste placed in a mold. The carbonate apatite composition produced from a calcium carbonate composition manufactured from a calcium hydroxide paste compact containing sodium chloride granules retained its pore structure, and an accumulation of multiple pores ranging from 50 μm to 100 μm was observed, but no pores with a maximum diameter and length exceeding 100 μm were found. Furthermore, the pore volume of pores smaller than 10 μm, as measured by mercury intrusion, was 0.80 cm³. 3 It was / g. It was confirmed that a porous, porosity-accumulating medical carbonate apatite block was produced, in which sodium chloride granules, which act as a porosity-forming agent, dissolved and filled (V6). Furthermore, it was confirmed that a fiber-bound medical carbonate apatite block satisfying the bead-like (V10) was produced from the bead-like fiber-binding raw material calcium hydroxide compact.

[0082] (Example 3) Using the calcium hydroxide powder produced in <1. Manufacturing process of the raw material calcium composition> of Example 2, <2. Placement of the raw material calcium composition etc. into the reaction vessel> and <3. Carbon dioxide replacement process> of Example 2 were carried out, and then the reaction time in <4. Partial carbonation process> was extended to 7 days to perform carbonation. Seven days later, the composition of the manufactured product was analyzed by XRD, revealing that it consisted of 95% by mass of vaterite, 4% by mass of calcite, and 1% by mass of calcium hydroxide. A comparison of Example 2 and this example shows that while a medical vaterite composition can be produced from compressed calcium hydroxide powder by gas-phase carbonation alone, 1% by mass of unreacted calcium hydroxide remains. Therefore, it was found that a higher purity medical vaterite composition can be produced by performing partial carbonation in the gas phase followed by carbonation in the liquid phase, rather than producing the medical vaterite composition by gas-phase carbonation alone.

[0083] (Comparative Example 4) The same process as in Example 3 was performed without rotating the fan. Seven days later, the composition of the product was analyzed by XRD and found to be a mixture of 71% by mass of vaterite, 4% by mass of calcite, and 25% by mass of calcium hydroxide. In Example 3, where a fan was used to ensure that carbon dioxide containing 90% ethanol flowed around the raw material calcium composition, the mixture after one day consisted of 72% by mass of vaterite, 3% by mass of calcite, and 25% by mass of calcium hydroxide. This indicates that, in a closed reaction vessel, the carbonation of the raw material calcium compound is slow if carbon dioxide containing an organic solvent or carbonate ions is not circulated around the raw material calcium composition. Furthermore, it was found that because the water formed inside the compressed calcium hydroxide raw material is not removed, a phase transition from vaterite to calcite occurs, resulting in a decrease in vaterite content. In other words, in the production of medical vaterite compositions from raw calcium compounds using a closed-system reaction vessel, it has been found that it is useful to circulate a substance that inhibits calcite formation or the growth of calcite crystals, such as ethanol, and relatively promotes vaterite formation, along with carbon dioxide, around the raw calcium composition, while simultaneously removing the water produced as a by-product of the reaction between the raw calcium composition and carbon dioxide by evaporation or other means.

[0084] (Example 4) <1. Manufacturing of the raw material calcium hydroxide composition> Calcium hydroxide and ammonium nitrate granules, a pore-forming material that passed through a 100 μm sieve but not through a 50 μm sieve, were mixed to a 20% by mass ammonium nitrate content. The mixture was then uniaxially pressed at a pressure of 5 MPa to produce a calcium hydroxide powder containing ammonium nitrate granules that met the (AB7) standard with a diameter of 6 mmφ and a height of 9 mm. <2. Placement of raw materials such as calcium composition into the reaction vessel> The reaction vessel from Example 2 was used. However, instead of adding 90% ethanol and a stirrer piece to the reaction vessel, approximately 10 g of ammonium carbonate manufactured by Wako Pure Chemical Industries was added. Next, a mesh container containing the compressed powder was placed so that it did not come into contact with the ammonium carbonate. A fan was also placed on top of the mesh container. <3. Carbon dioxide replacement process> The same procedure as in Example 2 was followed. <4. Carbonation Process> Next, hole B was closed and the reaction vessel was heated to 70°C. It is known that ammonium carbonate decomposes into carbon dioxide and ammonia at 58°C. The carbon dioxide pressure in the reaction vessel was increased to atmospheric pressure (100 kPa) using a carbon dioxide cylinder pressure reducing valve, and a fan was turned on. As a result, carbon dioxide containing ammonia flowed around the raw material calcium composition. Seven days later, the composition of the manufactured product was analyzed separately by XRD, revealing that it consisted of 91% by mass of vaterite and 9% by mass of calcite. <5. Pore former removal process> The product was removed from the reaction vessel and immersed in 100 mL of ethanol at 25°C. Replacing the ethanol five times at one-hour intervals completely removed the ammonium nitrate, which is the pore-forming agent. XRD analysis of the product composition revealed 91% by mass of vaterite and 9% by mass of calcite. The pore volume of 10 μm or smaller, measured by mercury intrusion, was 0.49 cm³. 3 It was / g. This confirms that a medical-grade vaterite porous material satisfying (G) has been manufactured.

[0085] (Example 5) A vaterite-containing composition was prepared under the same conditions as in Example 1, except that 90% acetone was used instead of 90% methanol. The volume of the composition produced by carbonation over 7 days is 2.5 × 10⁻⁶ -4 m 3 Furthermore, XRD analysis revealed that the vaterite content was 38% by mass, the calcite content was 62% by mass, and the acid-soluble residue was 0% by mass, confirming that the composition was pure calcium carbonate. Furthermore, the porosity of the medical vatelite composition was 45%, and the standard compressive strength was calculated to be 0.23 MPa. However, the actual compressive strength of the composition was 14 MPa, which was confirmed to be above the standard compressive strength. These results indicate that acetone, an organic solvent, also has the effect of suppressing calcite formation or the growth of calcite crystals, while relatively promoting the formation of calcium carbonate other than calcite.

[0086] (Example 6) 50 g of calcium hydroxide powder was suspended in a mixed solvent of 450 mL of methanol and 50 mL of water, and the mixture was stirred while bubbling 1000 mL of carbon dioxide per minute at 4°C. After 2 hours, the carbon dioxide bubbling was stopped. After holding for 12 hours, the powder was removed from the suspension by decantation and centrifugation, and dried at 110°C for 2 hours. XRD analysis confirmed that 100% by mass of vatelite powder was produced. The average particle size was 1 μm. The vaterite powder was compacted at 300 MPa to produce vaterite powder compacts. These vaterite powder compacts were heated in an electric furnace at a rate of 1°C per minute to 200°C, 250°C, 300°C, 350°C, 400°C, and 450°C, fired at these temperatures for 6 hours, and then cooled to room temperature. XRD analysis revealed that the sintered bodies fired at 200°C, 250°C, 300°C, and 350°C consisted of 98% vaterite and 2% calcite. The sintered body fired at 400°C consisted of 78% vaterite and 22% calcite. The vaterite powder compacts crumbled and lost their shape when immersed in water, and became cloudy when rubbed with water. On the other hand, none of the sintered bodies crumbled when immersed in water, and did not become cloudy when rubbed with water. The heat-treated material was immersed in a glass container containing 10 times the amount of saturated calcium carbonate water, and ultrasonic testing was performed for 1 minute at 28kHz with an output of 75W. The dry weight of the composition after irradiation was compared to the dry weight before ultrasonic irradiation, and in all cases it was 100%. The compressive strength of the vaterite powder compact was 3.2 MPa, while the estimated compressive strengths of the sintered bodies fired at 200°C, 250°C, 300°C, 350°C, 400°C, and 450°C were 4.6 MPa, 6.9 MPa, 11.3 MPa, 11.7 MPa, 12.1 MPa, and 11.8 MPa, respectively. These results confirmed that a vaterite sintered body was being manufactured.

[0087] (Example 7) <Calcium composition containing polymer materials> Mg content 2 × 10 -5 Mass%, Sr content is 1.6×10 -4High-purity calcium carbonate powder manufactured by Shiraishi Laboratory, with a mass percentage, average particle size of 3 μm, and sphericity of 0.88, was mixed with a polymer material, a wax-based organic binder manufactured by Nagamine Seisakusho, in a mass ratio of 75:25. <(E1) Extrusion Process> A honeycomb structure forming mold was attached to a Laboplast Mill manufactured by Toyo Seiki Seisakusho Co., Ltd., and extrusion molding was performed to produce a columnar polymer material-containing raw material calcium composition honeycomb structure with an outer peripheral side wall as an intermediate. <(E2) Molding process after the extrusion process> To straighten the honeycomb structure of the polymer-containing calcium composition raw material, an aluminum angle with release paper placed on it was used as a mold. The honeycomb structure was then sandwiched between the aluminum angle and heat-treated at 80°C for 24 hours, followed by cooling to room temperature. This molding operation straightened the honeycomb structure of the polymer-containing calcium composition raw material. <(E3) Outer peripheral side wall removal process> The outer periphery of a columnar polymer-containing raw material calcium composition honeycomb structure was removed using an electric planer. Compared to a polymer-containing raw material calcium composition honeycomb structure that had not undergone the molding process, the outer periphery of the polymer-containing raw material calcium composition honeycomb structure that had been smoothed by the molding process was easier to remove with an electric planer. Furthermore, when attempting to remove the outer periphery by polishing with a rotary grinding wheel, it was observed that new outer periphery walls were formed, but no new outer periphery walls were formed when cutting with an electric planer. <(E4) Molding process after the removal of the outer peripheral wall> To completely remove the deformation caused in "(E3) Peripheral side wall removal process," the material was heat-treated at 80°C for 24 hours and then cooled to room temperature. This molding operation removed the deformation from the polymer material-containing raw material calcium composition honeycomb structure. <(E5) Degreasing calcium carbonate sintering process> The honeycomb structure was heated at a rate of 0.15°C per minute up to 250°C, held at 250°C for 1 hour, then heated at a rate of 0.15°C per minute up to 400°C to 510°C, held at that temperature (final temperature) for 24 hours, and then furnace-cooled. Analysis of the mass increase and decrease under these degreasing and carbonation conditions using a thermomass spectrometer confirmed that the weight loss of polymer material was less than 1.0% by mass per minute. Figure 2 shows an example of the mercury intrusion pore distribution analysis results for a honeycomb structure manufactured at a final temperature of 480°C. As can be seen, in addition to the peak around 70 μm in pore size caused by macropores in the honeycomb structure, there are also pores with a diameter of 1 μm or less caused by micropores in the honeycomb septa. XRD analysis confirmed that all samples, regardless of the final temperature, were composed of pure calcite. Table 1 summarizes the final temperature, the porosity of the manufactured calcite honeycomb structure, the reference compressive strength for that porosity, the compressive strength, and the pore volume of honeycomb structures with a diameter of 10 μm or less relative to the mass, as measured by mercury intrusion. Note that all acid-dissolved residues were 0% by mass. [Table 1] As shown in Table 1, in pore distribution measurements using the mercury intrusion method, the pore volume of honeycomb structures with a pore diameter of 10 μm or less relative to the mass was 0.02 cm³ in all cases. 3 The value was greater than / g. Therefore, the medical calcite honeycomb structure of the present invention could be manufactured. Furthermore, all of them showed compressive strengths greater than the standard compressive strength. Figure 5 shows an electron microscope image of the surface of the manufactured medical calcite honeycomb structure. Significant grain growth was not observed up to a final temperature of 480°C, but it was confirmed that grain growth was observed when the final temperature reached 510°C. <Phosphate component addition process> Next, the medical calcite honeycomb structure was immersed in a 1 molar concentration Na2HPO4 aqueous solution at 80°C with a pH of 8.9 for 7 or 28 days. Table 1 summarizes whether or not the composition was completely converted to apatite. If calcite remained after 28 days, it was indicated with an "x" in the table, indicating that the composition conversion to apatite had not occurred. Note that all acid-dissolved residues were 0% by mass. XRD and FT-IR analyses confirmed that in the case of medical-grade calcium carbonate honeycomb structures manufactured at a final temperature of 480°C or lower, immersion for 7 days resulted in the addition of phosphate components to the medical-grade calcite honeycomb structures, transforming their composition to pure carbonate apatite. This was confirmed by immersion for 28 days when the final temperature was 510°C. The carbonate group content was 10.8% by mass in both cases. These findings confirm that a medical-grade carbonated apatite honeycomb structure was manufactured. Furthermore, it was revealed that this medical-grade carbonated apatite honeycomb structure exhibits a compressive strength exceeding the standard compressive strength. Pore ​​volume of 10 μm or less, manufactured at 510°C, is 0.12 cm³. 3 When a medical calcite honeycomb structure containing 10 μm / g was immersed in the aqueous solution for 7 days, unreacted calcite was observed. Therefore, the pore volume of the honeycomb structure with a pore diameter of 10 μm or less relative to its mass was 0.02 cm³. 3 If the value is greater than / g, the composition will be converted to carbonate apatite after 28 days of immersion. However, since the composition conversion takes time, it was found that a larger pore volume is preferable.

[0088] (Comparative Example 5) A calcite honeycomb structure was manufactured using the same method as in Example 7, except that the final temperature was set to 550°C. All acid-dissolved residues were 0% by mass. Other results are summarized in Table 1, but the pore volume of the honeycomb struct...

Claims

1. A medical-grade calcium carbonate composition or a medical-grade calcium phosphate composition characterized by satisfying all of the following conditions (A) to (C) and (F). (A) Volume is 10 －１２ I understand ３ That's all. (B) When the composition is dissolved in 1 molar concentration hydrochloric acid in a volume equivalent to 20 molars, the acid-dissolved residue, which is a mass percentage of the mass of the calcium carbonate composition or calcium phosphate composition, is 1% by mass or less. (C) Primarily consisting of vaterite or calcite, and having a purity of 99% by mass or more as calcium carbonate, or having a composition of carbonate apatite, HPO ４ It is one of the group consisting of apatite, tricalcium phosphate, witrochite, and calcium hydrogen phosphate containing the group, and has a purity of 99% by mass or higher as calcium phosphate. (F) A granular porous body having multiple through holes extending in multiple directions, formed by the bonding of multiple granules with a maximum diameter and length of 50 μm or more and 500 μm or less, wherein the pore volume of the granular porous body with a diameter of 10 μm or less is 0.05 cm³ as measured by mercury intrusion method. ３ It is 1 / g or more.

2. The calcium carbonate composition is formed by the bonding of calcium carbonate powders that satisfy any of the following conditions (AJ1) to (AJ4). Alternatively, it is a medical calcium phosphate composition that satisfies any of the following conditions (W4), (W5), (W6), or (W7): A medical calcium carbonate composition or a medical calcium phosphate composition according to feature 1. (AJ1) The average particle size is between 2 μm and 8 μm. (AJ2) The degree of sphericity is 0.9 or higher. (AJ3) Mg content is 5 x 10 －４ Mass% or more 3×10 －３ It is less than or equal to a mass percent. (AJ4) Sr content is 3 × 10 －３ Mass% or more 1.5×10 －２ It is less than or equal to a mass percent. (W4) This is an aggregate of calcium phosphate with an average particle size of 2 μm or more and 8 μm or less. (W5) An aggregate of calcium phosphate with a sphericity of 0.9 or higher. (W6) The Mg content is 5×10 －４ mass% or more and 3×10 －３ mass% or less. (W7) Sr content is 3 × 10 －３ Mass% or more 1.5×10 －２ It is less than or equal to a mass percent.

3. A method for producing a medical calcium carbonate composition according to claim 1 that satisfies the above condition (F), using calcium oxide granules as a raw material, A method for producing a medical calcium carbonate composition, comprising the steps of (F1) and (F2) below, and at least one of the steps of (F3) and (F4). (F1) Introduction and closing process The process involves placing calcium oxide granules into a reaction vessel and closing the opening of the reaction vessel to prevent them from being discharged. (F2) Porous body formation step A process in which calcium oxide granules inside a reaction vessel are treated with water or acetic acid to form calcium hydroxide or calcium acetate, and the granules are expanded to produce a porous material. (F3) Carbonation process A carbonation step to produce a calcium carbonate porous body by applying carbon dioxide to a calcium hydroxide porous body simultaneously with or after the porous body formation step, or a carbonation step to produce a calcium carbonate porous body by heat-treating calcium acetate after the porous body formation step. (F4) Calcium oxide carbonation process Carbonation process from a calcium oxide porous material: A porous material selected from the group of calcium hydroxide porous material, calcium carbonate porous material, and calcium acetate porous material is heat-treated to produce a calcium oxide porous material, and the calcium oxide porous material is exposed to carbon dioxide to produce a calcium carbonate porous material.

4. A method for producing a medical calcium carbonate composition according to claim 1 that satisfies the above condition (F), using calcium sulfate granules as a raw material, A method for producing a medical calcium carbonate composition, characterized by including the steps (F5) and (F6) below, or including the steps (F5), (F7), and (F9) below, with step (F8) being an optional step. (F5) Introduction process Steps to add calcium sulfate granules to the reaction vessel. (F6) Porous body formation carbonation process A process in which calcium sulfate granules and carbonate ions inside a reaction vessel react to convert the composition to calcium carbonate and harden the granules together to form a porous material. (F7) Porous body formation step A process for producing a porous calcium sulfate dihydrate by adding water to calcium sulfate hemihydrate granules or calcium sulfate anhydrous granules. (F8) Heat treatment process A process for producing porous calcium sulfate anhydrous material by heat treatment of porous calcium sulfate dihydrate. (F9) Carbonation process A process of exposing porous calcium sulfate dihydrate or porous anhydrous calcium sulfate to water containing carbonate ions to convert its composition to calcium carbonate.

5. A method for producing the medical calcium carbonate composition according to claim 1 that satisfies the conditions of (F) above, A method for producing a medical calcium carbonate composition, characterized in that (F10) and (F11) below, and one selected from the group (F12) to (F16) are required steps, and (F17) is an optional step. (F10) Introduction process Volume is 10 －１２ I understand ３ The process of adding the above polymer material-containing raw material calcium composition granules to a reaction vessel. (F11) Porous body formation step In one of the following steps, the granules inside the reaction vessel are heated and fused together: the surfaces of the granules are dissolved to bond them together; or the surfaces of the granules are fused together with a plasticizer, and the volume is 3 × 10 －１１ I understand ３ The above is a process for manufacturing a granule-bound porous body having multiple through holes extending in multiple directions, formed by the bonding of multiple granules with a maximum diameter and length of 50 μm or more and 500 μm or less. (F12) Degreasing calcium carbonate sintering process Degreasing and sintering process: Heating and degreasing the polymer material containing calcium carbonate so that the acid-dissolved residue is 1% by mass or less, and then sintering the calcium carbonate. (F13) Degreasing and carbonation process A porous calcium hydroxide material containing polymer material is degreased by heating it at an oxygen concentration of less than 30% so that the acid-dissolved residue is 1% by mass or less, and simultaneously carbonated. (F14) Degreasing and carbonation process via calcium oxide A process in which a porous calcium hydroxide material containing a polymer material or a porous calcium carbonate material containing a polymer material is degreased by heating so that the acid-dissolved residue is 1% by mass or less, and then the porous calcium oxide material is exposed to carbon dioxide to become a porous calcium carbonate material. (F15) Degreasing and carbonation process via calcium carbonate and calcium oxide Carbonation degreasing calcium oxide-via-carbonation process: A polymer material-containing calcium hydroxide is heat-treated in the presence of carbon dioxide to form a polymer material-containing porous calcium carbonate; then, the acid-dissolved residue is heated and degreased to 1% by mass or less to form a porous calcium oxide; and finally, the porous calcium oxide is exposed to carbon dioxide to form a porous calcium carbonate. (F16) Calcium sulfate degreasing and carbonation process Degreasing and carbonation process: A polymer material containing calcium sulfate is degreased by heating so that the acid-dissolved residue is 1% by mass or less, and then carbon dioxide or carbonate ions are added to the porous calcium sulfate produced to produce calcium carbonate. (F17) Shape finishing process performed after the degreasing and carbonation process

6. A method for producing a medical calcium carbonate composition according to any one of 3 to 5, characterized by comprising at least one step selected from the group (L) to (Q) below. (L) A process of degreasing with an oxygen partial pressure of 30 kPa or higher. (M) A process of degreasing or carbonation at a partial pressure of carbon dioxide of 30 kPa or higher. (N) A process of degreasing or carbonation using a gas containing oxygen or carbon dioxide at a pressure of 150 kPa or higher. (O) A step of increasing the carbon dioxide concentration in the reaction vessel by replacing some or all of the air in the reaction vessel with carbon dioxide and then introducing carbon dioxide into the reaction vessel. (P) Carbonation process, in which carbon dioxide is supplied to maintain a constant pressure in a closed reaction vessel. (Q) Carbonation process in which carbon dioxide in the reaction vessel is stirred or circulated.

7. A medical-grade calcium sulfate curable composition characterized by satisfying all of the following conditions (T1) to (T5). (T1) The acid-dissolved residue is 1% by mass or less. (T2) Volume is 5 × 10 －１３ I understand ３ That's all. (T3) The purity of calcium sulfate is 99% by mass or higher. (T4) The calcium sulfate hemihydrate content is 50% by mass or more. (T5) When the compositions are brought into contact with each other and immersed in water, they harden and form a porous body with a compressive strength of 0.3 MPa or more.

8. A method for producing a medical calcium sulfate hemihydrate granule, as described in claim 7, comprising (U2) and (U3) as essential steps and (U1) and (U4) as optional steps. (U1) Polymer material degreasing process A process of degreasing calcium sulfate granules or blocks containing polymer material by heat treatment to reduce the acid-dissolved residue to 1% by mass or less. (U2) Calcium sulfate dihydrate manufacturing process A process to produce calcium sulfate dihydrate granules or blocks by adding water to granules or blocks of anhydrous or hemihydrate calcium sulfate formed in a polymer material degreasing process, or by adding water to calcium sulfate hemihydrate powder and curing it. (U3) Calcium sulfate hemihydrate manufacturing process A process for producing calcium sulfate hemihydrate granules or blocks by dehydrating calcium sulfate dihydrate granules or blocks in the gas phase. (U4) Granule size adjustment process Volume is 5 × 10 －１３ I understand ３ The process of adjusting the size so that the granules are as described above.

9. A medical calcium phosphate composition characterized by satisfying the following (AG6) and (AG1) or (AG2), and selecting the following (AG3) or (AG4). (AG1) Composition is carbonate apatite, HPO ４ It is one selected from the group consisting of apatite, vitrokite, and calcium hydrogen phosphate, and has a volume of 10 －１２ I understand ３ The above-mentioned granules or blocks contain 0.01% to 3% by mass of silver or a silver compound. (AG2) Composition is hydroxyapatite sintered body, tricalcium phosphate sintered body, carbonate apatite, HPO ４ It is one selected from the group consisting of apatite, vitrokite, and calcium hydrogen phosphate, and has a volume of 10 －１２ I understand ３ The granules or blocks described above contain silver phosphate crystals bonded to the surface of calcium phosphate, and the silver phosphate content is 0.01% by mass or more and 3% by mass or less. (AG3) The silver compound is silver phosphate. (AG4) The calcium phosphate composition contains silver or a silver compound in both the surface and interior, and the ratio of the silver concentration in the surface to the silver concentration at a location at least 50 μm away from the surface in the direction toward the center is 1.2 or more. (AG6) A granular porous body formed by the bonding of multiple granules with a maximum diameter and length of 50 μm or more and 500 μm or less, having multiple through-holes extending in multiple directions.

10. A method for producing a medical calcium phosphate composition according to claim 1, 2, or 9, The medical calcium carbonate composition is immersed in an aqueous solution of (X3) or (X5) to impart a phosphoric acid component to the medical calcium carbonate composition. Alternatively, a method for producing a medical calcium phosphate composition by adding a phosphate component to a medical calcium carbonate composition produced by the manufacturing method described in any one of claims 3 to 6, characterized in that it includes a step that satisfies at least one condition selected from the group (Y1) to (Y6), A method for producing a medical-grade calcium phosphate composition. (X3) Aqueous solution containing both a phosphoric acid component and a carbonate component at a concentration of 0.5 molars or less. (X5) Aqueous solution containing both phosphate and magnesium components (Y1) A step of replacing some or all of the gas in the pores of a medical calcium carbonate composition immersed in an aqueous solution containing a phosphoric acid component with the aqueous solution containing a phosphoric acid component. (Y2) A step of vibrating a medical calcium carbonate composition immersed in an aqueous solution containing a phosphate component, thereby replacing some or all of the gas in the pores of the medical calcium carbonate composition with the aqueous solution containing a phosphate component. (Y3) A step of flowing an aqueous solution containing a phosphate component around the medical calcium carbonate composition to replace some or all of the gas in the internal pores of the medical calcium carbonate composition with the aqueous solution containing a phosphate component. (Y4) A step of replacing some or all of the gas in the pores of the medical calcium carbonate composition with the aqueous solution containing the phosphoric acid component by degassing a container containing an aqueous solution containing a phosphoric acid component under reduced pressure. (Y5) A step of replacing some or all of the gas in the pores of a medical calcium carbonate composition with a gas that has a higher solubility in an aqueous solution containing a phosphoric acid component than air. (Y6) A step of replacing some or all of the gas in the pores of a medical calcium carbonate composition with a solvent that has a smaller contact angle than water and a lower boiling point than water.

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