Method for producing carbonate apatite granules, medical materials, and dental materials

Abstract

Provided is a method for producing carbonate apatite granules, comprising: a granulation step for granulating a calcium carbonate powder to obtain calcium carbonate granules; and a phosphorylation step for phosphorylating the calcium carbonate granules to obtain carbonate apatite granules.

Description

Method for producing carbonate apatite granules, medical material, and dental material

[0001] This disclosure relates to a method for producing carbonate apatite granules, medical materials, and dental materials.

[0002] Carbonate apatite is a promising biomaterial for use as a bone graft. Powdered carbonate apatite may cause tissue damage, such as inflammation, when implanted in the body; therefore, in clinical practice, granular or block-shaped carbonate apatite molded bodies with larger particle sizes are used instead of powder.

[0003] One known method for producing such a carbonate apatite molded body involves a method in which either a block of a calcium compound or a solution containing a phosphate salt contains carbonate groups, and the block and the solution are brought into contact (see, for example, Patent Document 1). Another known method is for producing a calcium carbonate block as a precursor for a carbonate apatite molded body (see, for example, Patent Document 2).

[0004] Patent No. 4854300 Patent No. 6259926

[0005] Conventional methods for producing carbonate apatite molded bodies require at least two steps to obtain a calcium hydroxide molded body and a calcium carbonate block by contacting the calcium hydroxide molded body with carbon dioxide, in order to produce a calcium carbonate block as a precursor for the carbonate apatite molded body. These steps are labor-intensive and take several days, so there is a need to improve the efficiency of the manufacturing method.

[0006] The object of this disclosure is to provide a method for producing highly productive carbonate apatite granules.

[0007] A method for producing carbonate apatite granules according to one aspect of the present disclosure includes a granulation step of granulating calcium carbonate powder to obtain calcium carbonate granules, and a phosphorylation step of phosphorylating the calcium carbonate granules to obtain carbonate apatite granules.

[0008] According to one aspect of this disclosure, a method for producing highly productive carbonate apatite granules can be provided.

[0009] Hereinafter, embodiments for implementing the present disclosure will be described.

[0010] <Method for producing calcium carbonate granules> The method for producing calcium carbonate granules according to the embodiment includes a granulation step and a phosphorylation step. In this specification, calcium carbonate is Ca １０ (PO ４ ) ６ (OH) ２ represents apatite in which part or all of the phosphate groups or part or all of the hydroxyl groups of hydroxyapatite represented by are substituted with carbonate groups. Granules refer to granular substances having a larger particle size than the powder obtained by binding raw material powders.

[0011] The granulation step is a step of granulating calcium carbonate powder to obtain calcium carbonate granules. Calcium carbonate is a calcium carbonate represented by the composition formula CaCO ３ . Powder refers to a powder obtained by pulverizing a solid. Granulation refers to processing from a powder state to a granular state.

[0012] The granulation in the granulation step is at least one selected from compression granulation, extrusion granulation, and agitation granulation. In the granulation step of the present disclosure, any one of compression granulation, extrusion granulation, and agitation granulation may be performed, or any two or more of compression granulation, extrusion granulation, and agitation granulation may be combined.

[0013] Compression granulation refers to producing granules by crushing (or pulverizing) and sizing (or sieving) a plate-shaped material formed by supplying a raw material powder between rolls. When compression granulation is applied, since it is usually performed dry, there is an advantage that granules can be produced without performing a step of dispersing a liquid in the powder in advance and a step of drying after granulation.

[0014] In compression granulation, the forming pressure of the roll is not particularly limited, but it is preferably 0.01 t / cm ２ or more and 5 t / cm ２ or less, more preferably 0.02 t / cm ２ or more and 3 t / cm ２ or less, and even more preferably 0.03 t / cm ２ or more and 1.5 t / cm ２ or less. When the forming pressure of compression granulation is 0.01 t / cm２ 5 t / cm ２ The strength of the resulting calcium carbonate granules can be increased by the following conditions. Note that "t" represents tons (1000 kg).

[0015] Extrusion granulation refers to the process of producing granules by adding liquid to a raw material powder, mixing or kneading the mixture, and then extruding it through a die or screen with numerous holes using the pressure of rotating blades. Extrusion granulation offers the advantage of easily controlling particle size, thus enabling the production of granules of the desired size.

[0016] In extrusion granulation, the rotation speed of the blades is not particularly limited, but is preferably 10 rpm to 1000 rpm, more preferably 20 rpm to 500 rpm, and even more preferably 40 rpm to 200 rpm. When the rotation speed of extrusion granulation is 10 rpm to 1000 rpm, the strength of the resulting calcium carbonate granules can be increased.

[0017] Stir-fed granulation refers to the process of producing granules by placing raw material powder in a container and adding liquid while stirring with a rotating blade. When using stir-fed granulation, the mixing of liquid with powder and pressurization occur simultaneously, which has the advantage of enabling granule production in a small space and in a short time.

[0018] In stirring granulation, the rotation speed of the rotor blades is not particularly limited, but is preferably 50 rpm to 10,000 rpm, more preferably 500 rpm to 7,000 rpm, and even more preferably 1,000 rpm to 5,000 rpm. When the rotation speed of stirring granulation is 50 rpm to 10,000 rpm, the strength of the resulting calcium carbonate granules can be increased.

[0019] In stirring granulation, the stirring time is not particularly limited, but is preferably 0.1 minutes or more and 60 minutes or less, more preferably 1 minute or more and 30 minutes or less, and even more preferably 3 minutes or more and 10 minutes or less. If the stirring time in stirring granulation is 0.5 minutes or more and 60 minutes or less, the strength of the resulting calcium carbonate granules can be increased.

[0020] In addition, in agitated granulation, multiple rotation speeds and stirring times may be combined. For example, stirring may be performed at 500 rpm to 3000 rpm for 0.1 minutes to 1 minute, followed by stirring at 1000 rpm to 5000 rpm for 3 minutes to 10 minutes. This results in calcium carbonate granules with less variation in particle size.

[0021] The phosphorylation process involves phosphorylating calcium carbonate granules to obtain carbonate apatite granules. One method of phosphorylation is to immerse calcium carbonate granules in an aqueous solution containing phosphate (hereinafter referred to as a phosphate aqueous solution) to react the calcium carbonate with the phosphate. The phosphate aqueous solution contains phosphate ions (PO₄). ４ ３－ It is an aqueous solution containing sodium hydrogen phosphate (Na), for example. ２ HPO ４ An aqueous solution of ) is preferred.

[0022] The concentration of the phosphate aqueous solution is, for example, 0.1 mol / L or more and 5 mol / L or less, preferably 0.3 mol / L or more and 4 mol / L or less, and more preferably 0.5 mol / L or more and 3 mol / L or less.

[0023] The temperature of the phosphate aqueous solution (reaction temperature) is not particularly limited, but is preferably 30°C or higher, more preferably 40°C or higher, and even more preferably 50°C or higher. There is no upper limit to the temperature, but the upper limit of the feasible temperature is 200°C or lower, preferably 150°C or lower, and more preferably 100°C or lower.

[0024] Furthermore, when immersing the calcium carbonate granules in the phosphate aqueous solution, the ratio of calcium carbonate granules to the phosphate aqueous solution may be adjusted. The ratio of calcium carbonate granules to the phosphate aqueous solution is preferably 1:2 or higher, more preferably 1:3 or higher, and even more preferably 1:5 or higher.

[0025] In this manufacturing method, calcium carbonate granules are obtained by granulating calcium carbonate powder in this manner, and then phosphorylating these granules to obtain carbonate apatite granules. This eliminates the need for the conventional step of obtaining a molded calcium hydroxide body, thus providing a highly productive method for producing carbonate apatite granules. Furthermore, in this manufacturing method, since the granules are not produced by pulverization, a high yield and carbonate apatite granules with substantially uniform particle size and properties can be obtained.

[0026] In the manufacturing method of this embodiment, it is not necessary to add water to the calcium carbonate granules in the step of obtaining the calcium carbonate granules. When water is not added to the calcium carbonate granules, compression granulation is mainly applied as the granulation method. By not adding water to the calcium carbonate granules, the number of steps in the manufacturing method of carbonate apatite granules can be reduced. In addition, by not adding water to the calcium carbonate granules, calcium carbonate granules that do not become too strong can be obtained.

[0027] In the manufacturing method of this embodiment, water may be added to the calcium carbonate granules in the step of obtaining the calcium carbonate granules. When water is added to the calcium carbonate granules, the granulation method mainly applied is extrusion granulation or stir granulation, but compression granulation may also be applied. By adding water to the calcium carbonate granules, the strength of the resulting calcium carbonate granules can be increased.

[0028] The amount of water added is not particularly limited, but it is preferably 5% to 70% by mass relative to 100% by mass of the calcium carbonate powder before granulation, more preferably 15% to 65% by mass, and even more preferably 30% to 60% by mass. When the amount of water added is 5% to 70% by mass, granulation is easy and calcium carbonate granules are readily obtained.

[0029] Furthermore, when water is added during compression granulation, the amount of water added is preferably 20% by mass or less, and more preferably 10% by mass or less. In compression granulation, if too much water is added, the water tends to separate from the calcium carbonate powder under pressure, making granulation difficult.

[0030] Also, when adding water in extrusion granulation or stirring granulation, the amount of water added is preferably 5% by mass or more and 60% by mass or less, more preferably 20% by mass or more and 50% by mass or less. In extrusion granulation and stirring granulation, if the amount of water added is too small, it becomes difficult to knead the calcium carbonate powder, and if the amount of water added is too large, the calcium carbonate powder tends to become paste-like, both of which make granulation difficult.

[0031] When adding water in the step of obtaining calcium carbonate granules, the obtained calcium carbonate granules may be dried. The drying method is, for example, drying by a jacket dryer (hereinafter referred to as jacket drying). When adding water in the step of obtaining calcium carbonate granules and drying the calcium carbonate granules, the strength of the obtained calcium carbonate granules can be increased.

[0032] The drying temperature of the calcium carbonate granules is, for example, 50°C or higher and 200°C or lower, preferably 60°C or higher and 100°C or lower, more preferably 70°C or higher and 90°C or lower. By adjusting the drying temperature of the calcium carbonate granules to 50°C or higher and 200°C or lower, it is easy to obtain calcium carbonate granules with high strength.

[0033] Also, the drying of the calcium carbonate granules may be carried out under reduced pressure. When drying the calcium carbonate granules under reduced pressure, for example, the gauge pressure can be set to -200 kPaG or higher and -50 kPaG or lower, preferably -150 kPaG or higher and -70 kPaG or lower, more preferably -100 kPaG or higher and -90 kPaG or lower. By adjusting the gauge pressure when drying the calcium carbonate granules under reduced pressure to -200 kPaG or higher and -50 kPaG or lower, it is easy to obtain calcium carbonate granules with high strength.

[0034] The particle size of the calcium apatite particles obtained by the production method of the present embodiment is not particularly limited, but for example, it is 0.1 mm or more and 5 mm or less, preferably 0.2 mm or more and 4 mm or less, and more preferably 0.3 mm or more and 3 mm or less. Here, the particle size means the particle size (D50) at an integrated value of 50% in the volume-based particle size distribution measured by the laser diffraction / scattering method. When the particle size of the calcium apatite particles is within the range of 0.1 mm or more and 5 mm or less, it can be applied to medical or dental uses.

[0035] In the production method of the present embodiment, the crushing strength of the calcium carbonate particles in the step of obtaining the calcium carbonate particles is preferably 0.2 N or more, more preferably 0.2 N or more and 8 N or less, and still more preferably 0.3 N or more and 6 N or less. Here, the crushing strength indicates the strength of the calcium carbonate particles obtained by granulating the calcium carbonate powder. When the crushing strength of the calcium carbonate particles is 0.2 N or more, the reaction between calcium carbonate and phosphate can proceed in the step of phosphorylating the calcium carbonate particles. Further, calcium apatite particles applicable to medical or dental uses can be obtained.

[0036] <Medical material> The medical material of the present embodiment contains calcium apatite particles produced by the production method of the present embodiment. Specifically, the medical material of the present embodiment contains calcium apatite particles produced by a method of phosphorylating calcium carbonate particles obtained by granulating calcium carbonate powder. In this specification, the medical material indicates a material used in the medical field.

[0037] In the medical material of the present embodiment, by containing such calcium apatite particles, the same effects as the production method of the calcium apatite particles of the present embodiment can be obtained. Specifically, since the medical material of the present embodiment uses calcium apatite particles with high productivity, it can be said that the medical material also has high productivity. Further, since the medical material of the present embodiment uses calcium apatite particles with a high yield and substantially uniform particle size and properties, stable supply and quality improvement of the medical material containing calcium apatite particles are possible.

[0038] Furthermore, the uses of medical materials are not particularly limited and include, for example, artificial bone, bone graft materials, and coating materials for artificial joints.

[0039] <Dental Materials> The dental materials of this embodiment contain carbonate apatite granules produced by the manufacturing method of this embodiment. Specifically, the dental materials of this embodiment contain carbonate apatite granules produced by phosphorylating calcium carbonate granules obtained by granulating calcium carbonate powder. In this specification, dental materials refer to materials used in the dental field.

[0040] In the dental material of this embodiment, the inclusion of such carbonate apatite granules provides the same effects as the method for producing carbonate apatite granules in this embodiment. Specifically, since the dental material of this embodiment uses carbonate apatite granules with high productivity, it can be said to have high productivity from the viewpoint of dental materials. Furthermore, since the dental material of this embodiment uses carbonate apatite granules with high yield and substantially uniform particle size and properties, it is possible to ensure a stable supply and improve the quality of dental materials containing carbonate apatite granules.

[0041] Furthermore, the uses of dental materials are not particularly limited and include, for example, dental bone graft materials, artificial teeth, implants, and toothpaste.

[0042] The present disclosure will be further explained below with reference to examples. Various tests and evaluations will be carried out according to the methods described below. In the following, "%" refers to mass unless otherwise specified.

[0043] <Granulation Method> As shown in Tables 1-4, calcium carbonate granules were prepared using one of the following methods: compression granulation, extrusion granulation, agitation granulation, or grinding.

[0044] <Crushing Strength Test> The crushing strength of the prepared calcium carbonate granules was confirmed by a crushing strength test. The crushing strength was measured using a crushing strength measuring instrument (San Kagaku Co., Ltd., Rheometer CR-500DX) under the following measurement conditions. Calcium carbonate granules with a particle size of 0.6 mm to 1.0 mm were used.

[0045] [Measurement conditions] • Measurement speed: 1 mm / min • Measurement interval: 100 x 5 m / s • Set value: 5 N / mm • Direction of movement: Compression

[0046] In the crush strength test, an appropriate amount of calcium carbonate granules was placed on a glass plate using a spatula. One calcium carbonate granule was then placed in the center of the crush strength measuring instrument (the part with a hole in the base) using the spatula. The tip of the pressing rod was lowered to just above the top of the calcium carbonate granule sample. Measurement was started, and the measured value was checked as the load was applied. Measurement was stopped when the increase in the measured value stopped at a certain point and the value began to decrease. The red line was aligned with the first peak of the spectrum on the crush strength measuring instrument, the maximum load was determined, and the average of 10 measurements was recorded as the average crush strength before the reaction.

[0047] <Reaction Conditions> Based on Tables 1-5, 1 g of the prepared calcium carbonate granules was immersed in 20 g of sodium hydrogen phosphate solution (phosphate aqueous solution) of a predetermined concentration and left to stand at 80°C for a predetermined period. Reaction condition (1) was defined as a sodium hydrogen phosphate solution concentration of 1 M and a standing time of 7 days, and reaction condition (2) was defined as a sodium hydrogen phosphate solution concentration of 2 M and a standing time of 21 days.

[0048] <Maintaining Granule Shape in Reaction Solution> The prepared calcium carbonate granules were visually inspected according to the following criteria to determine whether their shape was maintained when immersed in the reaction solution (phosphate solution).

[0049] [Evaluation Criteria] Good: Granule shape was maintained. Poor: Granule shape was broken.

[0050] <Reaction Progress Rate> The reaction progress rate from calcium carbon to calcium carbon apatite was calculated based on the peak intensity ratio of the carbon apatite peak and the calcium carbon peak using X-ray diffraction (XRD) measurement. A reaction progress rate of 100% is considered to occur when the carbonate apatite peak is observed but the calcium carbonate peak is not. The reaction progress rate was evaluated according to the following criteria. A rating of "Excellent" or "Good" indicates a good reaction progress rate, while a rating of "Poor" indicates a poor reaction progress rate.

[0051] [Evaluation Criteria] Excellent: 100% response rate Good: 50% or more but less than 100% response rate Poor: Less than 50% response rate

[0052] Examples and comparative examples will be described below.

[0053] [Example 1] Calcium carbonate powder is molded at a pressure of 0.14 t / cm. ２ Calcium carbonate granules were prepared by compression granulation under pressure, and carbonate apatite granules were further prepared and evaluated under reaction condition (1). Tables 1 and 5 show the conditions and evaluation results for Example 1.

[0054] [Example 2] Compression granulation molding pressure set to 0.2 t / cm ２ Except for the changes made, carbonate apatite granules were prepared and evaluated in the same manner as in Example 1. Tables 1 and 5 show the conditions and evaluation results for Example 2.

[0055] [Example 3] Compression granulation molding pressure set to 0.3 t / cm ２ Except for the changes made, carbonate apatite granules were prepared and evaluated in the same manner as in Example 1. Tables 1 and 5 show the conditions and evaluation results for Example 3.

[0056] [Example 4] Compression granulation molding pressure set to 0.5 t / cm ２ Except for the changes made, carbonate apatite granules were prepared and evaluated in the same manner as in Example 1. Tables 1 and 5 show the conditions and evaluation results for Example 4.

[0057] [Example 5] Compression granulation molding pressure set to 1.0 t / cm ２ Except for the changes made, carbonate apatite granules were prepared and evaluated in the same manner as in Example 1. Tables 1 and 5 show the conditions and evaluation results for Example 5.

[0058] [Example 6] Calcium carbonate powder was mixed with 5% water, and the molding pressure for compression granulation was 0.03 t / cm². ２ Except for the changes made, carbonate apatite granules were prepared and evaluated in the same manner as in Example 1. Tables 1 and 5 show the conditions and evaluation results for Example 6.

[0059] [Example 7] Compression granulation molding pressure set to 0.14 t / cm ２Except for adopting reaction condition (2), carbonate apatite granules were prepared and evaluated in the same manner as in Example 6. Tables 1 and 5 show the conditions and evaluation results for Example 7.

[0060] [Example 8] Compression granulation molding pressure set to 0.2 t / cm ２ Except for the changes made, carbonate apatite granules were prepared and evaluated in the same manner as in Example 7. Tables 1 and 5 show the conditions and evaluation results for Example 8.

[0061] [Example 9] Compression granulation molding pressure set to 0.5 t / cm ２ Except for the above, carbonate apatite granules were prepared and evaluated in the same manner as in Example 7. Tables 1 and 5 show the conditions and evaluation results for Example 9.

[0062] [Example 10] Carbonate apatite granules were prepared and evaluated in the same manner as in Example 9, except that compression granulation was repeated twice. Tables 1 and 5 show the conditions and evaluation results for Example 10.

[0063] [Example 11] Carbonate apatite granules were prepared and evaluated in the same manner as in Example 9, except that the amount of water was 10%. Tables 1 and 5 show the conditions and evaluation results for Example 11.

[0064] [Example 12] Calcium carbonate granules were prepared by extrusion granulation, in which calcium carbonate powder mixed with 35% water was extruded at a rotation speed of 50 rpm. Carbonate apatite granules were then prepared and evaluated under reaction conditions (1). Tables 2 and 5 show the conditions and evaluation results for Example 12.

[0065] [Example 13] Carbonate apatite granules were prepared and evaluated in the same manner as in Example 12, except that the rotation speed of the extrusion granulation was set to 100 rpm. Tables 2 and 5 show the conditions and evaluation results for Example 13.

[0066] [Example 14] Carbonate apatite granules were prepared and evaluated in the same manner as in Example 12, except that the amount of water was 40%. Tables 2 and 5 show the conditions and evaluation results for Example 14.

[0067] [Example 15] Carbonate apatite granules were prepared and evaluated in the same manner as in Example 12, except that the amount of water was 50% and reaction conditions (2) were adopted. Tables 2 and 5 show the conditions and evaluation results for Example 15.

[0068] [Example 16] Carbonate apatite granules were prepared and evaluated in the same manner as in Example 15, except that the amount of water was 40% and the rotation speed of the extrusion granulation was 150 rpm. Tables 2 and 5 show the conditions and evaluation results for Example 16.

[0069] [Example 17] Carbonate apatite granules were prepared and evaluated in the same manner as in Example 16, except that the amount of water was 50%. Tables 2 and 5 show the conditions and evaluation results for Example 17.

[0070] [Example 18] Calcium carbonate granules were prepared by stirring granulation, in which calcium carbonate powder mixed with 30% water was stirred at a rotation speed of 2400 rpm for 4 minutes. Carbonate apatite granules were then prepared and evaluated under reaction conditions (1). Table 3 shows the conditions and evaluation results for Example 18.

[0071] [Example 19] Carbonate apatite granules were prepared and evaluated in the same manner as in Example 18, except that the rotation speed of the stirring granulation was set to 4800 rpm. Tables 3 and 5 show the conditions and evaluation results for Example 19.

[0072] [Example 20] Carbonate apatite granules were prepared and evaluated in the same manner as in Example 18, except that the amount of water was 35%, and the mixture was stirred at 2400 rpm for 0.5 minutes, followed by stirring at 4800 rpm for 3 minutes during the stirring granulation process. Tables 3 and 5 show the conditions and evaluation results for Example 20.

[0073] [Example 21] Carbonate apatite granules were prepared and evaluated in the same manner as in Example 20, except that the stirring time was 7 minutes at a rotation speed of 4800 rpm during the stirring granulation process, and reaction conditions (2) were adopted. Tables 3 and 5 show the conditions and evaluation results for Example 21.

[0074] [Example 22] Carbonate apatite granules were prepared and evaluated in the same manner as in Example 21, except that the calcium carbonate granules after stirring granulation were jacket-dried at 80°C. Tables 3 and 5 show the conditions and evaluation results for Example 22.

[0075] [Example 23] Carbonate apatite granules were prepared and evaluated in the same manner as in Example 22, except that jacket drying was performed under reduced pressure of -95 kPaG. Table 3 shows the conditions and evaluation results for Table 5, Example 23.

[0076] [Comparative Example 1] A calcium carbonate molded body was prepared by contacting a calcium hydroxide molded body with carbon dioxide. The calcium carbonate molded body was then pulverized to produce calcium carbonate granules. Carbonate apatite granules were then prepared under reaction condition (1) and evaluated. Table 4 shows the conditions and evaluation results for Comparative Example 1.

[0077]

[0078]

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[0080]

[0081]

[0082] Tables 1 to 3 and Table 5 show that in Examples 1 to 23, calcium carbonate granules obtained by granulating calcium carbonate powder were phosphorylated to produce calcium carbonate granules.

[0083] On the other hand, as shown in Tables 4 and 5, in Comparative Example 1, carbonate apatite granules were obtained, but a step of preparing calcium carbonate from calcium hydroxide was required.

[0084] From the above, it was found that by granulating calcium carbonate powder to obtain calcium carbonate granules and then phosphorylating those granules to obtain carbonate apatite granules, the conventional process of obtaining a molded calcium hydroxide body becomes unnecessary, thus providing a highly productive method for producing carbonate apatite granules.

[0085] The embodiments disclosed above include, for example, the following aspects:

[0086] <1> A method for producing carbonate apatite granules, comprising: a granulation step of granulating calcium carbonate powder to obtain calcium carbonate granules; and a phosphorylation step of phosphorylating the calcium carbonate granules to obtain carbonate apatite granules.

[0087] <2> The method for producing carbonate apatite granules according to <1> above, wherein the granulation is at least one selected from compression granulation, extrusion granulation, and stirring granulation.

[0088] <3> A method for producing carbonate apatite granules according to <1> or <2> above, wherein water is not added to the calcium carbonate granules.

[0089] <4> A method for producing carbonate apatite granules according to <1> or <2> above, wherein water is added to the calcium carbonate granules.

[0090] <5> A method for producing carbonate apatite granules according to any one of <1> to <4> above, wherein the crushing strength of the calcium carbonate granules is 0.2 N or more.

[0091] <6> The manufacturing method according to any one of <1> to <5> above, wherein the particle size of the carbonate apatite granules is 0.1 mm or more and 5 mm or less.

[0092] <7> A medical material containing carbonate apatite granules manufactured by the manufacturing method described in any one of <1> to <5> above.

[0093] <8> A dental material containing carbonate apatite granules manufactured by the manufacturing method described in any one of <1> to <5> above.

[0094] Although embodiments of this disclosure have been described above, this disclosure is not limited to any particular embodiment, and various modifications and changes are possible within the scope of the invention as described in the claims.

[0095] This application claims priority based on Japanese Patent Application No. 2024-161216, filed on 18 September 2024, the entire contents of which are incorporated herein by reference.

Claims

1. A method for producing carbonate apatite granules, comprising: a granulation step of granulating calcium carbonate powder to obtain calcium carbonate granules; and a phosphorylation step of phosphorylating the calcium carbonate granules to obtain carbonate apatite granules.

2. The method for producing carbonate apatite granules according to claim 1, wherein the granulation is at least one selected from compression granulation, extrusion granulation, and stir granulation.

3. A method for producing carbonate apatite granules according to claim 1, wherein water is not added to the calcium carbonate granules.

4. The method for producing carbonate apatite granules according to claim 1, wherein water is added to the calcium carbonate granules.

5. The method for producing carbonate apatite granules according to claim 1, wherein the crushing strength of the calcium carbonate granules is 0.2 N or more.

6. The manufacturing method according to any one of claims 1 to 5, wherein the particle size of the carbonate apatite granules is 0.1 mm or more and 5 mm or less.

7. A medical material containing carbonate apatite granules manufactured by the manufacturing method described in any one of claims 1 to 5.

8. A dental material containing carbonate apatite granules produced by the manufacturing method described in any one of claims 1 to 5.

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