KR20100011395A - Method for manufacturing hydroxy apatite - Google Patents

Abstract

PURPOSE: A method for manufacturing hydroxy apatite is provided to control the size and a particle shape of the hydroxy apatite which is adjustable to various uses according to the pH and uses of urea and gelatin, and to manufacture a massive quantity of the hydroxy apatite. CONSTITUTION: A method for manufacturing hydroxy apatite includes the following steps: supplying mixed liquid including calcium salt, phosphate, urea and gelatin(S1); adjusting the pH of the liquid to 3 ~ 13(S2); producing hydroxyl apatite precipitate by heating the liquid(S3); and drying the precipitate(S4). A making method of the hydroxy apatite includes a step for generating an intermediate material and a step for converting the intermediate material to the hydroxy apatite. The intermediate material is OCP(Octacalcium phosphate) or ACP(amorphous calcium phosphate).

Description

Method for manufacturing hydroxide apatite {Method for manufacturing hydroxy apatite}

The present invention relates to a method for preparing hydroxide apatite, and more particularly, to a method for preparing hydroxide apatite having various particle shapes and sizes.

Hydroxyapatite [Ca ₁₀ (PO ₄ ). (OH) ₂ ] is in the limelight as an artificial bone implant material because of its similarity to the substances that make up the bones of the human body. Hydroxyapatite is a reinforcing material for ceramics, fillers for bone defects, exchangers for heavy metal ions, fillers for column chromatography, biopolymers such as proteins and nucleic acids, adsorbents for amino acids, antibacterial and deodorizing materials, and a wide variety of fields. Is being applied to.

Such hydroxide apatite is required to have a suitable particle shape and size for each application in order to provide the characteristics suitable for the application.

For example, the addition of structural apatite reinforcements such as whiskers or fibers to the bone cement composition is very important to obtain high strength self-curing bone cement. For this purpose, much research has been conducted on hydroxide apatite whiskers (US Pat. No. 5,227,147, J. Am. Ceram. Soc., 84, 2, p 295, 2001).

Granular, spherical hydroxide apatite particles can be used as bone fillers because they have a large surface area and can increase bioabsorption, and in particular, they have been suggested as a preferred model as a surface coating material for drug carriers or metal implants (Korean Patent Application No. 2003) -0014133, Korean Patent Registration No. 10-0787526, US Patent No. 6,558,703).

The plate-shaped hydroxide apatite particles can be used as bone filler or reinforcing material such as plastic or rubber, and an adsorbent suitable for chromatography, and examples of the method for producing such plate-shaped hydroxide apatite are disclosed in Japanese Patent Application Laid-Open No. 2002-274821 and the United States. Patent No. 5,427,754.

Therefore, techniques for controlling the particle shape and size of hydroxide apatite for various applications are of great technical importance in industry. However, most of the prior art is limited to the method of preparing the hydroxide apatite particles of a specific particle shape, and the comprehensive technique for manufacturing the particle shape in various ways is limited.

Conventional methods for producing whiskers or acicular hydroxide apatite have been proposed by hydrothermal synthesis and solid phase reaction. The hydrothermal synthesis method is to react calcium salts and phosphates in a hydrothermal solvent under high temperature and high pressure conditions, and the solid phase reaction is to prepare calcium salts and phosphates by reacting them at a high temperature of 1000 ° C or higher.

Korean Patent Application No. 2001-0076509 discloses whisker type hydroxide apatite particles after synthesizing hydroxide apatite powder, mixing organic materials such as citric acid, lactic acid, EDTA and hydroxide apatite powder, and hydrothermal treatment in a pressure vessel. It is shown that it can be synthesized. However, this method is not preferable in terms of simplification of the process because the hydroapatite needs to be prepared in advance. U.S. Patent No. 6,228,339 discloses a needle-like apatite powder by first mixing a raw material such as calcium oxide in acicular beta-calcium phosphate (β-Ca (PO ₃ ) ₂ ) powder and then heat-treating it at a temperature ranging from 800 ° C to 1200 ° C. The method of preparation is shown. This solid phase reaction method is not industrially advantageous because complex subsequent processes such as mixing, calcining, and grinding after the reaction must be involved.

Korean Patent Registration No. 10-0787526 mentioned above discloses that spherical apatite particles can be prepared using a synthetic process irradiated with microwaves. According to the pH, it was suggested that 70-90 nm sized apatite hydroxide, alpha-tricalcium phosphate, beta-tricalcium phosphate spherical particles, and the like could be prepared. Spray drying methods are also known, as disclosed in US Pat. No. 4,836,994, US Pat. No. 5,858,318, and US Pat. No. 5,205,928. The methods require a separate additional heat treatment process in addition to the manufacturing process.

The hydrothermal synthesis method is mainly used as a manufacturing method of plate-shaped apatite. U.S. Patent No. 5,427,754 discloses a method of hydrothermally synthesizing a plated apatite powder under a pressure of 1 to 200 Kgf / cm ² and Japanese Patent Application Laid-open No. Hei 10-45405 discloses an amine such as fatty acid amine in a mixed aqueous solution of phosphate and calcium salt. A method of producing plate-shaped apatite by adding a hydrothermal compound is proposed.

As described above, the conventional technology is very finely divided into processes for producing apatite particles of each shape such as whiskers, spheres, and plates, and is an example of a technique that can change the shape of particles according to process variables in a single process. It is not presented.

Recently, a technique of controlling the shape of apatite particles by supplying various gases has been proposed (Korean Patent Registration No. 10-0593262). While this method has the advantage of being able to control the shape of the apatite particles very easily, there is a limitation in that it is not possible to produce whisker or spherical apatite.

The present invention has been made to solve the conventional problems, the problem to be solved by the present invention is to provide a hydroxide apatite production method having a variety of particle shapes and sizes.

Hydroxyapatite production method according to the present invention for solving the above technical problem, providing a mixed aqueous solution containing calcium salt, phosphate, urea and gelatin; Adjusting the pH of the aqueous solution to 3 to 13; Adding heat to the aqueous solution to produce hydroxide apatite precipitates; And drying the precipitate.

According to the present invention, after adding urea and gel latin to an aqueous solution in which calcium salt and phosphate are dissolved, the pH can be adjusted to change the intermediate product, thereby controlling the shape and size of the finally obtained hydroxide apatite. By simply adjusting the pH as urea and gelatin are added, it is possible to prepare hydroxide apatite having various shapes and sizes such as whiskers, needles, lobes (plates) and spheres.

The present invention is distinguished from the ways in which the process itself had to be different according to the apatite shape. The present invention can obtain various shapes of apatite hydroxide by adjusting the pH in one process, and control of the shape is possible as a whole.

In addition, the method according to the present invention is a very simple process (precipitation method of reacting water-soluble calcium salt and phosphate in an aqueous solution) without using an industrially disadvantaged method because the apparatus is expensive and the energy consumption is large, such as solid phase reaction method and hydrothermal synthesis method. It is very suitable for mass production.

According to the method of the present invention, it is possible to simply provide apatite hydroxide having physical properties that meet the specifications required in a particular application through pH adjustment. Accordingly, the present invention provides a whisker type apatite particles, bone fillers and spherical apatite particles for use as rubber and paper fillers, spherical apatite particles as surface coatings for drug carriers or metal implants, which are required as a high strength apatite composite for human implants. Can provide.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, embodiments of the present invention may be modified in many different forms, and the scope of the present invention should not be construed as being limited to the embodiments described below. The embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art.

1 is a flow chart of a method for preparing hydroxide apatite (hereinafter also referred to as HAp) according to the present invention.

Referring to Figure 1, in the first step (S1) of the present invention provides a mixed aqueous solution containing calcium salt, phosphate, urea and gelatin. The mixed aqueous solution can be provided by adding urea and gelatin to a solution in which calcium salt and phosphate are mixed.

At this time, the concentration of the calcium salt in the aqueous solution is 10 ^-3 ~ 1 M, preferably 0.01 ~ 0.5M to dissolve and the phosphate is dissolved so that the Ca / P molar ratio to calcium salt and phosphate is 1 ~ 10. For example, the stoichiometric molar ratio of Ca / P in the preparation of hydroxide apatite is about 1.67, but aqueous solutions having a value greater than or less than the molar ratio may be used in the present invention. If the molar ratio of Ca / P is less than 1, secondary phases such as calcium phosphate remain in the dried powder. If the molar ratio is greater than 10, calcium salts are present in the precipitate, which makes it difficult to produce pure apatite.

The calcium salt may include one or more salts selected from the group consisting of calcium nitrate (Ca (NO ₃ ) ₂ ), calcium chloride (CaCl ₂ ) and calcium acetate (Ca (CH ₃ CO ₂ ) ₂ ). Phosphates include phosphoric acid (H ₃ PO ₄ ), monobasic sodium phosphate (NaH ₂ PO ₄ ), dibasic sodium phosphate (Na ₂ HPO ₄ ), monobasic potassium phosphate (KH ₂ PO ₄ ), dibasic potassium phosphate ( K ₂ HPO ₄ ), a first ammonium phosphate ((NH ₄ ) H ₂ PO ₄ ) and a second ammonium phosphate ((NH ₄ ) ₂ HPO ₄ ).

Further, the concentration of gelatin (Sigma) is set to 10 ^-3 to 1 M in an aqueous solution, and preferably dissolved at 0.01 to 0.5 M. Further, urea is dissolved in the aqueous solution at 2 × 10 ⁻³ to 2 M, preferably at 0.02 to 1.0 M.

Gelatin has a major effect in the step (S3) described later. Step S3 is a step of producing hydroxide apatite, which may include a step of first producing an intermediate reactant having a phase different from that of the hydroxide apatite and then phase transitioning from the intermediate reactant to the hydroxide apatite.

Gelatin contained in the mixed aqueous solution in the step (S1) serves to precipitate the size of the calcium phosphate compound as an intermediate reactant as a precursor before the hydroxide apatite is produced. If the amount of gelatin is greater than 1M, the content is too high, the yield of calcium phosphate compound production is low, and less than 10 ^-3 M, it is difficult to obtain a calcium phosphate compound of uniform size.

Urea also acts in the step (S3) described later. The urea is hydrolyzed in water when the reaction temperature is 70 ℃ or more, as well as to increase the pH as well as to continuously provide OH ^- groups to promote the phase transition from the intermediate reactant to the hydroxide apatite as shown in the following reaction formula 1.

_{(NH 2) 2 CO + 3H} 2 O → 2NH 4 + + 2OH - + CO 2

Next, in the second step (S2) in the present invention, the pH of the aqueous solution is adjusted to 3 to 13 using various organic and inorganic acids and bases. Inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, perchloric acid and the like, bases such as aqueous sodium hydroxide solution, and organic acids such as citric acid may be used. As will be described later, the type of intermediate reactant and the form of the intermediate reactant are different depending on the pH, and thus the shape and particle size of the finally produced hydroxide apatite are determined.

Heat is added to the aqueous solution in the third step (S3) in the present invention, for example, to react at 30 ~ 200 ℃, preferably 70 ~ 95 ℃ to produce a precipitate. If the reaction temperature is lower than 30 ℃, the phase transition from the intermediate reactant to the hydroxide apatite is long, there is a problem in mass production. If the reaction temperature is higher than 200 ℃, the time to phase transition to the hydroxide apatite is short, but also because the pressure vessel is required Not desirable for mass production In particular, the reaction temperature of about 70 ~ 95 ℃ is preferable because it does not require a pressure vessel and can proceed with the apatite hydroxide phase transition reaction in a simple vessel.

The reaction time is suitable for 2 hours to 96 hours, preferably 2 hours to 24 hours. If the reaction time is too short, it is difficult to obtain pure hydroxide apatite and if it is too long, it is disadvantageous for the efficiency of the process. If necessary, the aqueous solution may be stirred, but may be selectively stirred only in some sections of the reaction (initial reaction).

According to the pH adjusted in the step (S2), in this step (S3), calcium phosphate compounds, such as DCPA (Dicalcium phosphate anhydrate), OCP (Octacalcium phosphate), ACP (amorphous calcium phosphate), are first produced as an intermediate reactant, and then hydroxide. Phase change to apatite Of course, it is sometimes produced as a hydroxide apatite from the beginning.

Table 1 below shows the initial product (intermediate reactant) and the final product according to the reaction time by adjusting the pH of the calcium salt concentration of 0.02 M and the Ca / P ratio of 1, 0.02 M gelatin, and 0.04 M urea The product (HAp) and its shape are summarized.

pH condition 4.7 7.5 10 13 0hr  No precipitation HAp (leaf) ACP (old) ACP 2hr OCP (whisker form) HAp HAp HAp 12hr  OCP, HAp HAp HAp HAp 24hr HAp (whisker type) HAp (leaf) HAp HAp (old)

In the final step S4, the precipitate produced in the step S3 is filtered and dried to obtain apatite hydroxide in powder form. In this step (S4) it can be dried at a conventional drying method, that is, the temperature and atmospheric pressure of 25 ~ 200 ℃, preferably lyophilization is used. General drying may cause agglomeration between particles due to the surface tension of water and may damage the particle structure due to rapid evaporation of water molecules trapped in the precipitate. The freeze drying method is preferable in that fine powder can be obtained because the aggregation of particles can be suppressed.

As described above, according to the present invention, the hydroxide apatite may be manufactured to have one of whiskers, needles, lobes, and spheres according to pH control, and the control of the shape is comprehensive compared to the existing methods. In other words, rather than using a separate process depending on the shape, the pH is controlled in one process to change the kind of intermediate reactants and to obtain various types of apatite hydroxide from its phase transition. As summarized in Table 1 above, the whisker form is obtained in the low pH range, and the higher the pH, the more foliar, acicular, and spherical. This technique for obtaining whiskers, lobes, needles and spherical hydroxide apatites in one process is not known prior to the present invention. As described above, according to the present invention, various types of apatite hydroxide can be prepared by a relatively simple precipitation process, thereby simplifying the manufacturing process, enabling cost reduction, and being more advantageous for mass production.

Hereinafter, various aspects of the present invention described above will be described in more detail through specific experimental examples. The following experimental examples do not limit the scope of the present invention, but are merely exemplary for implementing the present invention.

Experimental Example 1 is an experimental example showing the apatite generation mechanism of the present invention described above.

Experimental Example 1 Preparation of Whisker Hydroxyapatite Hydroxide at pH 4.7

Ca (NO ₃ ) ₂ (10 mmol, powder) and NaH ₂ PO ₄ (10 mmol, powder) were dissolved in 500 ml of distilled water, and gelatin (10 mmol) and urea (20 mmol) were dissolved to prepare a mixed aqueous solution. Thereafter, the pH of the aqueous solution was adjusted to 4.7 using nitric acid (HNO ₃ ), and then placed in a Corning bottle to react at a constant pressure and temperature. X-ray diffraction analysis was performed on the intermediate reactants and the final result and photographed by scanning electron microscope (SEM) to observe the shape and size.

FIG. 2A is an X-ray diffraction pattern of a calcium phosphate compound, which is an intermediate reactant produced according to reaction time, and an apatite finally produced. In the graph, the x-axis is the 2θ value and the y-axis is the intensity of the diffraction peak. Referring to FIG. 2A, it can be seen that the initial phase of the reaction is OCP is generated and the process of phase change into hydroxide apatite as time passes.

FIG. 2B is a SEM photograph of the intermediate reactant OCP, and FIG. 2C is a SEM photograph of the finally obtained whisker-shaped apatite of about 50-100 μm in length.

Through the present experimental example, the hydroxide apatite whisker synthesized in the aqueous solution can be confirmed that the phase change is precipitated to the hydroxide apatite after the first OCP in the form of whiskers, according to the present experimental example, is required as a high-strength apatite complex for human implants Whisker type apatite particles may be provided.

<Experimental Example 2: Preparation of leaf hydroxide apatite at pH 7.5>

After preparing a mixed aqueous solution under the same conditions as in Experimental Example 1 described above, the pH was adjusted to 7.5 using ammonia, and placed in a Corning bottle to react at a constant pressure and temperature.

Figure 3a is an X-ray diffraction pattern of the product produced according to the reaction time. 3b and 3c show SEM photographs of the initial reaction precipitate and the finally obtained apatite hydroxide.

As can be seen from Figures 3a to 3c, in the pH 7.5 conditions, the leaf-shaped apatite is produced from the beginning of the reaction and the leaf-shaped apatite is maintained even after a certain reaction time.

According to this experimental example, plate-shaped apatite particles for use as bone filler and rubber and paper filler can be obtained.

< Experimental Example 3: Preparation of spherical ACP and acicular hydroxide apatite at pH 10>

After preparing a mixed aqueous solution under the same conditions as in Experimental Example 1 described above, the pH was adjusted to 10 using ammonia, and placed in a Corning bottle to react at a constant pressure and temperature.

4A is an X-ray diffraction pattern of a calcium phosphate compound, which is an intermediate reactant produced according to reaction time, and a finally produced hydroxide hydroxide. 4b and 4c show SEM photographs of the reaction initial precipitate and the finally obtained apatite hydroxide.

4A to 4C, it can be seen that spherical ACP is produced at the beginning of the reaction, and acicular apatite having a length of 100 to 200 nm is produced after a certain reaction time.

Experimental Example 4 Preparation of Acicular ACP and Spherical Hydroxyapatite at pH 13

After preparing a mixed aqueous solution under the same conditions as in Experimental Example 1, the pH was adjusted to 13 using sodium hydroxide (NaOH) and placed in a Corning bottle to react at a constant pressure and temperature.

FIG. 5A is an X-ray diffraction pattern of the calcium phosphate compound, which is an intermediate reactant produced according to the reaction time, and the finally produced hydroxide apatite. 5B and 5C show SEM photographs of the initial precipitate and the finally obtained hydroxyapatite, and a uniform particle size of spherical hydroxide apatite having a length of 20 to 30 nm after a constant reaction time is formed after acicular ACP is formed at the beginning of the reaction. It can be seen that the distribution can be obtained.

According to this experimental example, it is possible to provide spherical apatite particles as the surface coating material of the drug carrier or the metal implant. In particular, since the size of the spherical particles is obtained at the nanometer level, they are well suited for use in the medical field requiring particle sizes in the nanometer level to several micrometers.

Experimental Example 5 Preparation of Whisker Hydroxyapatite by Adding 10 mmol of Urea

Except for the amount of urea it was carried out under the same conditions as in Experiment 1 described above. That is, Ca (NO ₃ ) ₂ (10 mmol, powder) and NaH ₂ PO ₄ (10 mmol, powder) were dissolved in 500 ml of distilled water, and gelatin (10 mmol) and urea (10 mmol) were dissolved to prepare a mixed aqueous solution. Then, the pH of the aqueous solution was adjusted to 4.7 using HNO ₃ . It was then placed in a Corning bottle to react at a constant pressure and temperature and reacted in a 90 ° C. oven.

6 is a SEM photograph of the hydroxide apatite finally obtained in this manner. As in Experimental Example 1, a whisker hydroxide apatite having a length of about 50 to 100 µm was obtained.

Comparative Example 1: No Urea Added

Ca (NO ₃ ) ₂ (10 mmol, powder) and NaH ₂ PO ₄ (10 mmol, powder) were dissolved in 500 ml distilled water, and only gelatin (10 mmol) was dissolved without adding urea. The pH of the aqueous solution was adjusted to 4.7 using HNO ₃ and then placed in a Corning bottle to react at a constant pressure and temperature.

7 is a SEM photograph of the finally obtained hydroxide apatite. When the urea was not added in this way, the yield was significantly lower than that of the present invention in which the precipitated powder was added to the urea in a very small amount.

Comparative Example 2: No Gelatin Added

A mixed aqueous solution was prepared by dissolving Ca (NO ₃ ) ₂ (10 mmol, powder) and NaH ₂ PO ₄ (10 mmol, powder) in 500 ml distilled water and dissolving only urea (20 mmol) without adding gelatin. The pH of the aqueous solution was adjusted to 4.7 using HNO ₃ and then placed in a Corning bottle to react at a constant pressure and temperature.

8 is a SEM image of the finally obtained hydroxide apatite, it can be seen that the uniformity of the size is very poor compared to the present invention, which is generally amorphous and added gelatin.

Comparative Example 3 When Urea and Gelatin were Not Added

After dissolving Ca (NO ₃ ) ₂ (10 mmol, powder) and NaH ₂ PO ₄ (10 mmol, powder) in 500 ml distilled water and adjusting the pH of the aqueous solution to 4.7 using HNO ₃ without adding urea and gelatin Into a Corning bottle to react at a constant pressure and temperature it was reacted in a 90 ℃ oven.

9 is a SEM image of the finally obtained hydroxide apatite, it can be seen that very uniform amorphous particles are produced and the uniformity of the size is very poor compared to the present invention to add both urea and gelatin.

From the above comparative examples, it can be seen that the use of urea and gelatin, as in the present invention, in order to obtain a hydroxide apatite of the desired shape, such as whiskers, lobes, needles, spheres according to the pH control.

In the above, the present invention has been described in detail with reference to preferred embodiments and experimental examples, but the present invention is not limited to the above examples, and various modifications made by those skilled in the art within the technical spirit of the present invention. This is possible. Examples of the invention have been considered by way of example and not limitation, all of which are intended to include the scope of the invention as indicated by the appended claims, their equivalents, and all modifications within the means rather than by the detailed description therein. will be.

1 is a flowchart of a method for preparing hydroxide apatite according to the present invention.

FIG. 2A is an X-ray diffraction pattern of a product generated according to reaction time in Experimental Example 1, FIG. 2B is a scanning electron microscope (SEM) photograph of an intermediate reactant OCP, and FIG. 2C is a finally obtained whisker type hydroxide apatite SEM. It is a photograph.

3A is an X-ray diffraction pattern of a product produced according to reaction time in Experimental Example 2, FIG. 3B is a SEM image of hydroxide apatite on the initial leaf of the reaction, and FIG. 3C is a SEM image of hydroxide apatite finally obtained.

FIG. 4A is an X-ray diffraction pattern of a product produced according to reaction time in Experimental Example 3, FIG. 4B is an ACP SEM photograph of an initial reaction sphere, and FIG. 4C is a finally obtained needle hydroxide apatite SEM photograph.

FIG. 5A is an X-ray diffraction pattern of a product produced according to reaction time in Experimental Example 4, FIG. 5B is an ACP SEM photograph of an initial acicular needle, and FIG. 5C is a finally obtained spherical hydroxide apatite SEM photograph.

6 is a SEM image of a whisker type hydroxide apatite finally obtained according to Experimental Example 5. FIG.

7 is a SEM photograph of hydroxide apatite finally obtained without adding urea as in Comparative Example 1. FIG.

8 is a SEM photograph of hydroxylated apatite finally obtained without adding gelatin as in Comparative Example 2.

9 is a SEM photograph of hydroxide apatite finally obtained without adding both urea and gelatin as in Comparative Example 3.

Claims (7)

Providing a mixed aqueous solution comprising calcium salt, phosphate, urea and gelatin; Adjusting the pH of the aqueous solution to 3 to 13; Adding heat to the aqueous solution to heat the aqueous solution to produce hydroxide apatite precipitates; And Method for producing apatite hydroxide comprising the step of drying the precipitate. The method of claim 1, wherein the step of producing the hydroxide apatite, Producing an intermediate reactant having a phase different from that of the hydroxide apatite; And Phase transition from the intermediate reactant to hydroxide apatite, The intermediate reactant is a method for producing apatite hydroxide, characterized in that any one of OCP (Octacalcium phosphate) or ACP (amorphous calcium phosphate). The method of claim 1, wherein the hydroxide apatite has a shape of any one of whiskers, needles, lobes and spheres according to the pH control. The method of claim 1, wherein the concentration of calcium salt in the aqueous solution is 10 ^-3 ~ 1 M, phosphate is dissolved so that the Ca / P molar ratio of calcium salt and phosphate is 1 ~ 10, characterized in that the hydroxide apatite production method. The method of claim 1, wherein the calcium salt comprises at least one salt selected from the group consisting of calcium nitrate (Ca (NO ₃ ) ₂ ), calcium chloride (CaCl ₂ ) and calcium acetate (Ca (CH ₃ CO ₂ ) ₂ ). A method for producing hydroxide apatite, characterized in that. The method of claim 1, wherein the phosphate is phosphoric acid (H ₃ PO ₄ ), monobasic sodium phosphate (NaH ₂ PO ₄ ), dibasic sodium phosphate (Na ₂ HPO ₄ ), monobasic potassium phosphate (KH ₂ PO ₄ ), At least one salt selected from the group consisting of dipotassium phosphate (K ₂ HPO ₄ ), monoammonium phosphate ((NH ₄ ) H ₂ PO ₄ ), and diammonium phosphate ((NH ₄ ) ₂ HPO ₄ ) A method for producing hydroxide apatite, characterized in that. The method of claim 1, wherein the concentration of gelatin in the aqueous solution is 10 ^-3 to 1 M, and the concentration of urea is 2 × 10 ^-3 to 2 M.

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