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

Abstract

This invention provides a method for producing highly productive carbonate apatite granules. [Solution] A method for producing carbonate apatite granules 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.

Description

[Technical Field]

[0001] This invention relates to a method for producing carbonate apatite granules, a medical material, and a dental material. [Background technology]

[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 contacting a calcium compound block and a phosphate solution, in which one of the two components contains carbonate groups (see, for example, Patent Document 1). Another known method is for producing calcium carbonate blocks as precursors for carbonate apatite molded bodies (see, for example, Patent Document 2). [Prior art documents] [Patent Documents]

[0004] [Patent Document 1] Patent No. 4854300 [Patent Document 2] Patent No. 6259926 [Overview of the project] [Problems that the invention aims to solve]

[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 the present invention is to provide a method for producing highly productive carbonate apatite granules. [Means for solving the problem]

[0007] A method for producing carbonate apatite granules according to one aspect of the present invention 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. [Effects of the Invention]

[0008] According to one aspect of the present invention, a method for producing highly productive carbonate apatite granules can be provided. [Modes for carrying out the invention]

[0009] The following describes embodiments for carrying out the present invention.

[0010] <Method for producing carbonate apatite granules> The method for producing carbonate apatite granules according to this embodiment includes a granulation step and a phosphorylation step. In this specification, carbonate apatite is Ca 10 This refers to apatite in which some or all of the phosphate groups or some or all of the hydroxyl groups of hydroxyapatite represented by (PO4)6(OH)2 are replaced by carbonate groups. Granules refer to granular material with a larger particle size than the powder obtained by binding the raw material powders together.

[0011] The granulation process is the process of granulating calcium carbonate powder to obtain calcium carbonate granules. Calcium carbonate is a calcium carbonate salt represented by the chemical formula CaCO3. Powder refers to a finely ground solid. Granules refer to particles with a larger particle size than powder. Granulation refers to the process of processing a powder into a granular state.

[0012] Examples of granulation methods include compression granulation, extrusion granulation, or agitation granulation.

[0013] Compression granulation refers to manufacturing granules by feeding raw material powder between rolls to form it into a plate shape and then crushing (or pulverizing) and sizing (or screening) it. When applying compression granulation, since it is usually carried out dry, there is an advantage that granules can be produced without performing the steps of dispersing a liquid in the powder in advance and drying after granulation.

[0014] In compression granulation, the forming pressure of the rolls 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 / cm 2 or more and 5 t / cm 2 or less, the strength of the obtained calcium carbonate granules can be increased. Note that "t" represents ton (1000 kg).

[0015] Extrusion granulation refers to manufacturing granules by adding a liquid to raw material powder, mixing or kneading it, and extruding it through a die or screen with many holes opened by the pressure of a rotating blade to form granules. When applying extrusion granulation, since it is easy to control the particle size, there is an advantage that granules of a desired size can be obtained.

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

[0017] Agitation granulation refers to putting raw material powder into a container and adding a liquid while stirring with a rotating blade to produce granules. When agitation granulation is applied, since mixing and pressurization of the liquid with respect to the powder are performed simultaneously, there is an advantage that granules can be produced in a small space and in a short time.

[0018] In agitation granulation, the rotation speed of the rotating blade is not particularly limited, but it is preferably 50 rpm or more and 10,000 rpm or less, more preferably 500 rpm or more and 7,000 rpm or less, and even more preferably 1,000 rpm or more and 5,000 rpm or less. When the rotation speed of agitation granulation is 50 rpm or more and 10,000 rpm or less, the strength of the obtained calcium carbonate granules can be increased.

[0019] In agitation granulation, the agitation time is not particularly limited, but it is preferably 0.5 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. When the agitation time of agitation granulation is 0.5 minutes or more and 60 minutes or less, the strength of the obtained calcium carbonate granules can be increased.

[0020] In addition, in agitation granulation, a plurality of rotation speeds and agitation times may be combined. For example, after stirring at 500 rpm or more and 3,000 rpm or less for 0.1 minutes or more and 1 minute or less, it may be stirred at 1,000 rpm or more and 5,000 rpm or less for 3 minutes or more and 10 minutes or less. Thereby, calcium carbonate granules with less variation in particle size can be obtained.

[0021] The phosphorylation step is a step of phosphorylating calcium carbonate granules to obtain carbonated apatite granules. Examples of the phosphorylation method include a method of immersing calcium carbonate granules in an aqueous solution containing a phosphate (hereinafter referred to as a phosphate aqueous solution) and reacting calcium carbonate with the phosphate. The phosphate aqueous solution is an aqueous solution containing phosphate ions (PO4 3- ) and, for example, an aqueous solution of sodium hydrogen phosphate (Na2HPO4) is preferable.

[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] 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] Furthermore, when water is added in extrusion granulation and agitation granulation, the amount of water added is preferably 5% by mass or more and 60% by mass or less, and more preferably 20% by mass or more and 50% by mass or less. In extrusion granulation and agitation granulation, if the amount of water added is too little, the calcium carbonate powder becomes difficult to knead, and if the amount of water added is too much, the calcium carbonate powder tends to become paste-like, making granulation difficult in both cases.

[0031] Furthermore, if water is added during the process of obtaining calcium carbonate granules, the resulting calcium carbonate granules may be dried. Drying methods include, for example, drying using a jacketed dryer (hereinafter referred to as jacket drying). When water is added during the process of obtaining calcium carbonate granules, drying the granules can increase the strength of the resulting calcium carbonate granules.

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

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

[0034] The particle size of the carbonate apatite granules obtained by the manufacturing method of this embodiment is not particularly limited, but is, for example, 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, particle size refers to the particle size at 50% of the cumulative value (D50) in the volume-based particle size distribution measured by laser diffraction-scattering method. Since the particle size of the carbonate apatite granules is within the range of 0.1 mm or more and 5 mm or less, it can be applied to medical or dental applications.

[0035] In the manufacturing method of this embodiment, the crushing strength of the calcium carbonate granules in the step of obtaining calcium carbonate granules is preferably 0.2N or higher, more preferably 0.2N to 8N, and even more preferably 0.3N to 6N. Here, crushing strength refers to the strength of the calcium carbonate granules obtained by granulating calcium carbonate powder. A crushing strength of 0.2N or higher of the calcium carbonate granules allows the reaction between calcium carbonate and phosphate to proceed in the step of phosphorylating the calcium carbonate granules. Furthermore, carbonate apatite granules applicable to medical or dental use can be obtained.

[0036] <Medical materials> The medical material of this embodiment contains carbonate apatite granules produced by the manufacturing method of this embodiment. Specifically, the medical material of this embodiment contains carbonate apatite granules produced by phosphorylating calcium carbonate granules obtained by granulating calcium carbonate powder. In this specification, "medical material" refers to a material used in the medical field.

[0037] In the medical 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, because the medical material of this embodiment uses carbonate apatite granules with high productivity, it can be said to have high productivity as a medical material. Furthermore, because the medical 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 medical materials containing carbonate apatite granules.

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

[0039] <Dental materials> The dental material of this embodiment contains carbonate apatite granules produced by the manufacturing method of this embodiment. Specifically, the dental material of this embodiment contains carbonate apatite granules produced by phosphorylating calcium carbonate granules obtained by granulating calcium carbonate powder. In this specification, dental material refers to a material 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. [Examples]

[0042] The present invention will be further described 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] <Granule manufacturing 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. <Measurement conditions> ·Measurement speed: 1mm / min Measurement interval: 100 x 5 m / s • Setting value: 5N / mm Movement direction: Compression

[0045] In the crushing 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 crushing 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 crushing strength measuring instrument, the maximum load was determined, and the average of 10 measurements was recorded as the average crushing strength before the reaction.

[0046] <Reaction conditions> As shown in 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.

[0047] <Maintaining granular shape in the 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).

[0048] <Evaluation Criteria> Good: The granular shape was maintained. Unacceptable: The granular shape was broken.

[0049] <Reaction progress rate> The reaction 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) measurements. A reaction rate of 100% was considered to occur when the carbonate apatite peak was observed but the calcium carbonate peak was not. The reaction rate was evaluated according to the following criteria. A rating of "Excellent" or "Good" indicated a good reaction rate, while a rating of "Poor" indicated a poor reaction rate.

[0050] <Evaluation Criteria> Excellent: 100% response rate Good: Reaction rate between 50% and 100% Unacceptable: Reaction rate less than 50%

[0051] Examples and comparative examples will be described below.

[0052] [Example 1] Calcium carbonate powder is molded at a pressure of 0.14 t / cm². 2Calcium carbonate granules were prepared by compression granulation under pressure, and carbonate apatite granules were further prepared and evaluated under reaction condition (1). Table 1 shows the conditions and evaluation results for Example 1.

[0053] [Example 2] The molding pressure for compression granulation is 0.2 t / cm². 2 Except for the changes made, carbonate apatite granules were prepared and evaluated in the same manner as in Example 1. Table 1 shows the conditions and evaluation results for Example 2.

[0054] [Example 3] The molding pressure for compression granulation is 0.3 t / cm². 2 Except for the changes made, carbonate apatite granules were prepared and evaluated in the same manner as in Example 1. Table 1 shows the conditions and evaluation results for Example 3.

[0055] [Example 4] The molding pressure for compression granulation is 0.5 t / cm². 2 Except for the changes made, carbonate apatite granules were prepared and evaluated in the same manner as in Example 1. Table 1 shows the conditions and evaluation results for Example 4.

[0056] [Example 5] The molding pressure for compression granulation is 1.0 t / cm². 2 Except for the changes made, carbonate apatite granules were prepared and evaluated in the same manner as in Example 1. Table 1 shows the conditions and evaluation results for Example 5.

[0057] [Example 6] Calcium carbonate powder is mixed with 5% water, and the compression granulation is performed at a molding pressure of 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. Table 1 shows the conditions and evaluation results for Example 6.

[0058] [Example 7] The molding pressure for compression granulation is 0.14 t / cm². 2 Except for adopting reaction condition (2), carbonate apatite granules were prepared and evaluated in the same manner as in Example 6. Table 1 shows the conditions and evaluation results for Example 7.

[0059] [Example 8] The molding pressure for compression granulation is 0.2 t / cm². 2 Except for the changes made, carbonate apatite granules were prepared and evaluated in the same manner as in Example 7. Table 1 shows the conditions and evaluation results for Example 8.

[0060] [Example 9] The molding pressure for compression granulation is 0.5 t / cm². 2 Except for the changes made, carbonate apatite granules were prepared and evaluated in the same manner as in Example 7. Table 1 shows the conditions and evaluation results for Example 9.

[0061] [Example 10] Except for repeating compression granulation twice, carbonate apatite granules were prepared and evaluated in the same manner as in Example 9. Table 1 shows the conditions and evaluation results for Example 10.

[0062] [Example 11] Except for using 10% water, carbonate apatite granules were prepared and evaluated in the same manner as in Example 9. Table 1 shows the conditions and evaluation results for Example 11.

[0063] [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 condition (1). Table 2 shows the conditions and evaluation results for Example 12.

[0064] [Example 13] Except for setting the extrusion granulation rotation speed to 100 rpm, carbonate apatite granules were prepared and evaluated in the same manner as in Example 12. Table 2 shows the conditions and evaluation results for Example 13.

[0065] [Example 14] Except for using 40% water, carbonate apatite granules were prepared and evaluated in the same manner as in Example 12. Table 2 shows the conditions and evaluation results for Example 14.

[0066] [Example 15] Except for using 50% water and adopting reaction conditions (2), carbonate apatite granules were prepared and evaluated in the same manner as in Example 12. Table 2 shows the conditions and evaluation results for Example 15.

[0067] [Example 16] Except for using 40% water and 150 rpm for extrusion granulation, carbonate apatite granules were prepared and evaluated in the same manner as in Example 15. Table 2 shows the conditions and evaluation results for Example 16.

[0068] [Example 17] Except for using 50% water, carbonate apatite granules were prepared and evaluated in the same manner as in Example 16. Table 2 shows the conditions and evaluation results for Example 17.

[0069] [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 condition (1). Table 3 shows the conditions and evaluation results for Example 18.

[0070] [Example 19] Except for setting the rotation speed of the stirring granulation to 4800 rpm, carbonate apatite granules were prepared and evaluated in the same manner as in Example 18. Table 3 shows the conditions and evaluation results for Example 19.

[0071] [Example 20] Except for using 35% water and stirring at 2400 rpm for 0.5 minutes followed by stirring at 4800 rpm for 3 minutes during the stirring granulation process, carbonate apatite granules were prepared and evaluated in the same manner as in Example 18. Table 3 shows the conditions and evaluation results for Example 20.

[0072] [Example 21] Except for using reaction conditions (2) in the stirring granulation process, which involved stirring at a rotation speed of 4800 rpm for 7 minutes, carbonate apatite granules were prepared and evaluated in the same manner as in Example 20. Table 3 shows the conditions and evaluation results for Example 21.

[0073] [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. Table 3 shows the conditions and evaluation results for Example 22.

[0074] [Example 23] Except for jacket drying being performed under reduced pressure of -95 kPaG, carbonate apatite granules were prepared and evaluated in the same manner as in Example 22. Table 3 shows the conditions and evaluation results for Example 23.

[0075] [Comparative Example 1] A calcium carbonate molded body was prepared by contacting a calcium hydroxide molded body with carbon dioxide, and calcium carbonate granules were prepared by pulverizing the calcium carbonate molded body. Furthermore, carbonate apatite granules were prepared under reaction condition (1) and evaluated. Table 4 shows the conditions and evaluation results for Comparative Example 1.

[0076] [Table 1]

[0077] [Table 2]

[0078] [Table 3]

[0079] [Table 4]

[0080] [Table 5]

[0081] From Tables 1 to 3 and Table 5, in Examples 1 to 23, apatite carbonate granules were obtained by phosphorylating calcium carbonate granules obtained by granulating calcium carbonate powder.

[0082] On the other hand, as shown in Table 4, while comparative example 1 yielded carbonate apatite granules, it required a step to produce calcium carbonate from calcium hydroxide.

[0083] 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.

[0084] The embodiments disclosed above include, for example, the following aspects:

[0085] <1> A granulation process to obtain calcium carbonate granules by granulating calcium carbonate powder, The process includes a phosphorylation step of phosphorylating the calcium carbonate granules to obtain carbonate apatite granules. A method for producing carbonate apatite granules.

[0086] <2> The granulation method is selected from compression granulation, extrusion granulation, and agitation granulation. the above <1> A method for producing carbonate apatite granules as described above.

[0087] <3> No water is added to the calcium carbonate granules. the above <1> A method for producing carbonate apatite granules as described above.

[0088] <4> Add water to the calcium carbonate granules. the above <1> or <2> A method for producing carbonate apatite granules as described above.

[0089] <5> The crushing strength of the calcium carbonate granules is 0.2 N or more. the above <1> ~ <4> A method for producing carbonate apatite granules as described in any one of the following.

[0090] <6> The particle size of the carbonate apatite granules is 0.1 mm or more and 5 mm or less. the above <1> ~ <5> The manufacturing method described in any one of the following.

[0091] <7> the above <1> ~ <5> A medical material containing carbonate apatite granules manufactured by any one of the manufacturing methods described above.

[0092] <8> the above <1> ~ <5> A dental material containing carbonate apatite granules manufactured by any one of the manufacturing methods described above.

[0093] Although embodiments of the present invention have been described above, the present invention 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.

Claims

1. A granulation process to obtain calcium carbonate granules by granulating calcium carbonate powder, The process includes a phosphorylation step of phosphorylating the calcium carbonate granules to obtain carbonate apatite granules. A method for producing carbonate apatite granules.

2. The granulation method is selected from compression granulation, extrusion granulation, and agitation granulation. A method for producing carbonate apatite granules according to claim 1.

3. No water is added to the calcium carbonate granules. A method for producing carbonate apatite granules according to claim 1.

4. Add water to the calcium carbonate granules. A method for producing carbonate apatite granules according to claim 1.

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

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

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 manufactured by the manufacturing method described in any one of claims 1 to 5.

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