KR102236992B1 - Method For Preparing Whitlockite by Temporal Separation - Google Patents

Abstract

A method for preparing whitlockite according to one embodiment of the present application comprises: a first process of mixing a first solution including calcium ions and a second solution including a first amount of phosphate ions for a first time; a second process of forming a first mixed solution in which the product of the first process is reacted for a second time to form a first phosphate material - a terminal point of the second time is located at a later point in time than a terminal point of the first time; a third process of mixing a third solution including cations other than calcium ions and a fourth solution including a second amount of phosphate ions in the first mixed solution for a third time - an initial point of the third time is located later than a terminal point of the first time; a fourth process of forming a second mixed solution in which the product of the third process is reacted for a fourth time to form a second phosphate material - a terminal point of the fourth time is located at a later point in time than a terminal point of the third time; a fifth process of mixing a fifth solution including a third amount of phosphate ions in the second mixed solution for a fifth time - an initial point of the fifth time is located later than a terminal point of the third time; and a sixth process of aging the product of the fifth process for a sixth time - a terminal point of the sixth time is located at a later point in time than a terminal point of the fifth time.

Description

Method for producing whitlockite by temporal separation {Method For Preparing Whitlockite by Temporal Separation}

According to the present application, a method of preparing a calcium phosphate compound is disclosed. More specifically, a method of producing whitlockite is disclosed.

Currently, calcium phosphate compounds are widely used as biocompatible inorganic materials. The calcium phosphate compound is used as a raw material for products such as artificial bone inserted into the body for regeneration or treatment of human tissues, dental restorations, bone cement, oral compositions, and fillers.

))와 β-트리칼슘 포스페이트(tricalcium phosphate, TCP: (

))가 있다. As a representative calcium phosphate compound, hydroxy apatite (HAp (

)) and β-tricalcium phosphate (TCP: (

)).

The artificially synthesized HAp is excellent in biocompatibility and has almost the same chemical properties as bone, but has a disadvantage in that it cannot be replaced by natural bone because it is not degraded in vivo because it has too large crystallinity.

Since β-TCP is decomposed in vivo and induces natural bone growth, many studies on a single phase β-TCP or a mixture of β-TCP and HAp (biphasic calcium phosphate) have been conducted. However, there is a difficulty in synthesizing nano-sized β-TCP in large quantities with the prior art, and thus there is a limit to the application of β-TCP to various fields.

In order to solve this problem, whitlockite, which is a calcium phosphate compound similar to HAp and β-TCP, but a different calcium phosphate material having different chemical structures, components, and crystal structures, has been studied.

)는 어린 나이의 몸과 생체미네랄화의 초기 단계에 높은 비율로 존재한다. 이는 휘트록카이트가 경조직의 발달에 중요한 역할을 수행함을 의미한다는 것은 간접적으로 나타낸다. 특히, 휘트록카이트에 포함된 마그네슘이 인체 내에서 주변 골 조직의 골 형성을 촉진하는 역할을 수행한다고 알려져 있다. 이러한 휘트록카이트가 경조직으로의 발달에 있어 중요한 역할을 한다는 점에 기초하여, 기존의 하이드록시아파타이트와 베타-트리칼슘포스페이트(β-tricalciumphosphate, β-TCP)를 대체하는 생체 적합성 무기 재료로서 휘트록카이트에 대한 관심이 증가되고 있는 실정이다. 다만, 하이드록시아파타이트와 베타 트리칼슘포스페이트에 대하여는 활발히 연구되어 왔으나, 휘트록카이트에 대하여는 연구가 많이 이루어지지 않아, 휘트록카이트의 역할, 합성 메커니즘을 규명하기 위한 연구에 대한 필요성이 증대되고 있고 있다.Whitlockite (WH, one of the most abundant biomaterials in hard tissue)

) Is present in a high proportion in the body at a young age and in the early stages of biomineralization. This indirectly indicates that whitlockite plays an important role in the development of hard tissue. In particular, it is known that magnesium contained in whitlockite plays a role in promoting bone formation of surrounding bone tissues in the human body. Based on the fact that whitlockite plays an important role in the development of hard tissue, Whitlock is a biocompatible inorganic material that replaces existing hydroxyapatite and beta-tricalciumphosphate (β-TCP). Interest in kite is increasing. However, hydroxyapatite and beta tricalcium phosphate have been actively studied, but there are not many studies on whitlockite, so the need for research to clarify the role of whitlockite and its synthesis mechanism is increasing. .

However, compared to HAp and β-TCP, the production process of whitlockite is more difficult, so much research has not been conducted academically, and it is difficult to find an industrially applied example.

In order to solve such a problem that it is difficult to synthesize whitlockite, a method of manufacturing whitlockite has been proposed by a conventional patent (Korean Patent Publication No. 10-1423982 (Jul. 22, 2014)).

However, the conventional method for manufacturing whitlockite takes a long manufacturing time and requires a lot of manufacturing cost.In the intermediate process, the pH of the aqueous solution is precisely adjusted to form a target intermediate product and form high-purity whitlockite. There is a problem that the manufacturing method is complicated because it must be controlled.

In order to solve the above problems, the present application provides a process of reacting calcium ions and phosphate ions and a process of reacting phosphate ions other than calcium ions constituting whitlockite with phosphate ions. Provides a method of manufacturing lockite.

The present application provides a method of manufacturing whitlockite, which can easily control process conditions while reducing manufacturing time compared to a conventional method for manufacturing whitlockite.

According to an aspect provided by the present application, a method of manufacturing whitlockite by spatial separation is disclosed.

According to another aspect provided by the present application, a method of manufacturing whitlockite by temporal separation is disclosed.

Disclosed in the present application According to an embodiment of the method for manufacturing whitlockite disclosed in the present application, a first solution containing calcium ions and a second solution containing a first amount of phosphate ions are mixed for a first time. Process- A second process in which the result of the first process forms a first mixed solution reacted for a second time so that the first phosphate material is formed-The terminal point of the second time is later than the terminal point of the first time Located at the time point; A third process in which a third solution containing a cation other than calcium ions and a fourth solution containing a second amount of phosphate ions are mixed with the first mixed solution for a third time-the initial point of the third time is Located at a later point than the terminal point of the first time; A fourth process in which the result of the third process is reacted for a fourth time to form a second phosphate material to form a second mixed solution-the terminal point of the fourth time is at a later point than the terminal point of the third time Located; A fifth process in which a fifth solution containing a third amount of phosphate ions is mixed for a fifth time in the second mixed solution-the initial point of the fifth time is located at a later point than the terminal point of the third time ; And a sixth process of aging the result of the fifth process for a sixth time-the terminal point of the sixth time is located at a later point than the terminal point of the fifth time. It may include.

According to an embodiment of the method for manufacturing whitlockite disclosed in the present application, at least a part of the first time and at least a part of the second time overlap, and at least a part of the third time and at least a part of the fourth time Are overlapped, and at least a part of the fifth time and at least a part of the sixth time may overlap.

According to an embodiment of the method for manufacturing whitlockite disclosed in the present application, the ratio of the amount of phosphate ions contained in the fifth solution to the sum of the amount of phosphate ions contained in the second solution and the fourth solution is It may be in the range of 0.3 or more and 0.55 or less.

According to an embodiment of the method for producing whitlockite disclosed in the present application, the phosphate ion is selected from phosphoric acid, diammonium hydrogen phosphate, ammonium phosphate, and phosphate. It may be supplied by a phosphate ion supply material comprising one or more.

According to an embodiment of the method for producing whitlockite disclosed in the present application, the calcium ion is selected from among calcium hydroxide, calcium carbonate, calcium nitrate, and calcium acetate. It may be supplied by a calcium ion supply material including one or more selected.

According to an embodiment of the method for producing whitlockite disclosed in the present application, cations other than the calcium ion are magnesium ions, and the magnesium ions are magnesium hydroxide, magnesium carbonate, and magnesium nitrate. (Magnesium nitrate) and magnesium acetate (Magnesium acetate) may be supplied by a magnesium ion supply material containing at least one selected from.

According to an embodiment of the method for manufacturing whitlockite disclosed in the present application, it further comprises a seventh process of mixing an oxidizing agent for a seventh time, wherein the initial point of the seventh time is a point prior to the initial point of the first time Or overlap with at least a portion of the first time to the sixth time.

According to an embodiment of the method for manufacturing whitlockite disclosed in the present application, the oxidizing agent may be hydrogen peroxide.

According to an embodiment of the method for manufacturing whitlockite disclosed in the present application, cations other than calcium ions are magnesium ions, and the second solution with respect to the amount of calcium ions contained in the first solution of the first process The ratio of the amount of phosphate ions contained in is in the range of 0.6 or more and 1.4 or less, and the ratio of the amount of phosphate ions contained in the fourth solution to the amount of magnesium ions contained in the third solution in the third process This may be in the range of 0.6 or more and 5 or less.

According to an embodiment of the method for producing whitlockite disclosed in the present application, the first mixed solution contains a solid first phosphate material, and the second mixed solution is a solid first phosphate material and a solid second phosphate. All substances are included, and the second mixed solution may be formed by adding the third solution and the fourth solution to the first mixed solution after the first mixed solution is formed.

According to an embodiment of the method for preparing whitlockite disclosed in the present application, the first phosphate material is hydroxyapatite, brushite, and dicalcium phosphate dehydrate (DCPD) or their It may be a material comprising a combination.

), 디마그네슘 포스페이트(Dimagnesium phosphate,

), 뉴베리아이트(Newberyite), 트리마그네슘 포스페이트(Trimagnesium phosphate,

) 및이들의 조합을 포함하는 물질일 수 있다. According to an embodiment of the method for manufacturing whitlockite disclosed in the present application, the second phosphate material is monomagnesium phosphate (Monomagnesium phosphate,

), Dimagnesium phosphate (Dimagnesium phosphate,

), Newberyite, Trimagnesium phosphate,

) And a combination thereof.

According to an embodiment of the method for manufacturing whitlockite disclosed in the present application, at least one or more processes in the first to sixth processes may be performed at 50° C. or more and 95° C. or less.

According to the embodiment according to the present application, a method of manufacturing whitlockite can be provided that significantly shortens the manufacturing time.

According to the embodiment according to the present application, a method of manufacturing whitlockite, which can significantly reduce the cost of operating a process, can be provided.

According to the embodiment according to the present application, a manufacturing method capable of manufacturing whitlockite can be provided simply and intuitively.

According to the embodiment according to the present application, a manufacturing method capable of manufacturing high purity whitlockite may be provided.

1 is a flow chart schematically showing a method for manufacturing whitlockite in the related art.
FIG. 2 is a timeline schematically showing steps of a conventional method for manufacturing whitlockite on a time axis.
3 is a flowchart schematically showing an embodiment of a method for manufacturing whitlockite by spatial separation disclosed in the present application.
4 is a flow chart showing a subdivided step (S10) of forming a mixed solution containing the first phosphate material of FIG. 3.
5 is a flow chart showing a subdivided step (S20) of forming a mixed solution containing the second phosphate material of FIG. 3.
6 is a flow chart showing a subdivided process (S40) of aging a mixed solution including a first phosphate material and a second phosphate material of FIG. 3.
7 is a timeline schematically showing an embodiment of a method for manufacturing whitlockite by spatial separation disclosed in the present application on a time axis.
FIG. 8 is a timeline schematically showing time and time points at which each process of FIG. 7 proceeds.
9 is SEM data of a result formed according to an embodiment of a method for manufacturing whitlockite by spatial separation disclosed in the present application.
10 is a graph showing a result of XRD DATA of a result formed according to an embodiment of a method for manufacturing whitlockite by spatial separation disclosed in the present application.
11 is a flowchart schematically showing an embodiment of a method for manufacturing whitlockite by temporal separation disclosed in the present application.
12 is a flow chart showing a subdivided step (S100) of forming a mixed solution containing the first phosphate material of FIG. 11.
13 is a flow chart showing a subdivided process (S200) of forming a mixed solution containing a second phosphate material of FIG. 11.
14 is a flow chart showing a subdivided process (S300) of aging a mixed solution including a first phosphate material and a second phosphate material of FIG. 11.
15 is a timeline schematically showing an embodiment of a method for manufacturing whitlockite by temporal separation disclosed in the present application on a time axis.
16 is a timeline schematically showing time and time points at which each process of FIG. 15 proceeds.
17 is SEM data of a result formed according to an embodiment of a method for manufacturing whitlockite by temporal separation disclosed in the present application.
18 is a graph showing a result of XRD DATA of a result formed according to an embodiment of a method for manufacturing whitlockite by temporal separation disclosed in the present application.
19 is SEM data of the result formed according to the second experiment of the method for manufacturing whitlockite by temporal separation disclosed in the present application.
20 is an XRD DATA of a result formed according to a second experiment of a method for manufacturing whitlockite by temporal separation disclosed in the present application.
21 is a graph showing a result of XRD DATA of a result formed according to a second experiment of a method for manufacturing whitlockite by temporal separation disclosed in the present application.
22 is SEM DATA of a result formed according to a third experiment of a method for manufacturing whitlockite by temporal separation disclosed in the present application.
23 is a graph showing a result of XRD DATA of a result formed according to a third experiment of a method for manufacturing whitlockite by temporal separation disclosed in the present application.
24 is SEM data of the result formed according to the fourth experiment of the method for manufacturing whitlockite by temporal separation disclosed in the present application.
25 is an XRD DATA of a result formed according to a fourth experiment of a method for manufacturing whitlockite by temporal separation disclosed in the present application.
26 is a graph showing a result of XRD DATA of a result formed according to a fourth experiment of a method for manufacturing whitlockite by temporal separation disclosed in the present application.

The above objects, features, and advantages of the present invention will become more apparent through the following detailed description in conjunction with the accompanying drawings. However, in the present invention, various modifications may be made and various embodiments may be provided. Hereinafter, specific embodiments will be illustrated in the drawings and described in detail.

The same reference numerals throughout the specification refer to the same elements in principle. In addition, components having the same function within the scope of the same idea shown in the drawings of each embodiment will be described using the same reference numerals.

If it is determined that a detailed description of known functions or configurations related to the present invention may unnecessarily obscure the subject matter of the present invention, a detailed description thereof will be omitted. In addition, numbers (eg, first, second, etc.) used in the description of the present specification are merely identification symbols for distinguishing one component from other components.

1. Conventional method for producing whitlockite

Referring to Figures 1 and 2, the conventional method for manufacturing whitlockite (Korean Patent Publication No. 10-1423982 (Jul. 22, 2014)) adds a calcium ion supplying material and a cation supplying material to water to form an aqueous cation solution. Forming (S1), adding a phosphoric acid supply material to the cation aqueous solution (Dropwise method) and aging (S2), and drying the aged aqueous solution to form whitlockite powder (S3).

The conventional method for manufacturing whitlockite has a fatal disadvantage in that the manufacturing time is long.

The reason is first, in the step of forming an aqueous cation solution by adding a calcium ion supplying material and a cation supplying material to water (S1), a calcium ion supplying material and a cation supplying material other than calcium are added to the water'simultaneously'. It is in the ship. Although the first reaction conditions required for calcium ions to react with phosphate ions and the second reaction conditions required for cation other than calcium to react with phosphate ions are different, a calcium ion supplying material and a cation supplying material other than calcium are used. By adding'at the same time', the first reaction condition and the second reaction condition cannot be provided differently, thereby increasing the manufacturing time.

The second reason is that the phosphoric acid feed material is slowly added dropwise. Referring to FIG. 2, it can be seen that the phosphoric acid supply material is added (S21) in a dropwise manner before aging (S22). Therefore, it takes a long time to add all of the phosphate ions required to form whitlockite, which leads to a longer manufacturing time.

In addition, the conventional method for manufacturing whitlockite has a problem that the manufacturing method is complicated.

In the conventional method for producing whitlockite, the pH of the first phosphate and the second phosphate depends on the thermodynamic stability according to the pH to form whitlockite, so the pH must be precisely controlled to form the whitlockite. In order to precisely control the pH, the phosphoric acid feed material was added dropwise, and there was a problem that the manufacturing method was complicated because the addition rate and the amount of the phosphoric acid feed material according to the dropping method had to be accurately set.

In order to solve these problems, there is an increasing need for a method for manufacturing whitlockite, which is simpler and shorter in manufacturing time.

2. Method for manufacturing whitlockite by spatial separation (First Example)

Hereinafter, a method of manufacturing whitlockite according to an embodiment of the present application will be described with reference to FIGS. 3 to 8.

Referring to FIG. 3, the method of manufacturing whitlockite according to an embodiment of the present application is a process of making a mixed solution containing a first phosphate material (S10), a process of making a mixed solution containing a second phosphate material ( S20), the process of combining into one mixed solution to make a mixed solution containing both the first phosphate material and the second phosphate material (S30), aging the mixed solution containing both the first phosphate material and the second phosphate material It includes a step (S40). At this time, in the method of manufacturing whitlockite according to the present application, the process of making a mixed solution containing the first phosphate material (S10) and the process of making a mixed solution containing the second phosphate material (S20) are performed in separate containers. I can.

In other words, if the process of making the mixed solution containing the first phosphate material is performed in the first container, the process of making the mixed solution containing the second phosphate material is performed in a second container separate from the first container. I can.

According to the manufacturing method of whitlockite disclosed by the present application, preferably, mixing and reaction may be performed in the same container, but the mixing and reaction do not necessarily have to be performed in the same container.

In other words, according to the present application, if the mixed solution containing the first phosphate material is made in a first container, and the mixed solution containing the second phosphate material is made in a second container separate from the first container The purpose of the application can be achieved.

Through this spatial separation, preferably, the process of making a mixed solution containing the first phosphate material (S10) and the process of making a mixed solution containing the second phosphate material (S20) may be partially overlapped on the time axis. That is, the time during which the process of making the mixed solution containing the first phosphate material (S10) proceeds and the time during which the process of making the mixed solution containing the second phosphate material (S20) proceeds partially overlapped (partially overlapped) Can be. For example, the process of making the mixed solution containing the first phosphate material (S10) and the process of making the mixed solution containing the second phosphate material (S20) may be performed simultaneously. Through spatial separation, the two processes can be carried out at the same time, which can significantly shorten the total manufacturing time for making whitlockite.

Since the process of making a mixed solution containing the first phosphate material (S10) and the process of making the mixed solution containing the second phosphate material (S20) are performed in separate containers, the first phosphate material and the second phosphate material are In order to prepare a mixed solution including all of the included materials, a step (S30) of combining the first phosphate material and the second phosphate material included in each container into one mixed solution may be included. A mixed solution including both the first phosphate material and the second phosphate material may be formed through a process (S30) of combining the first phosphate material and the second phosphate material into one mixed solution.

After the mixed solution containing both the first phosphate material and the second phosphate material is formed, the aging process (S40) is performed.

In the process of aging the solution including the first phosphate material and the second phosphate material (S40), a solution containing phosphate ions may be additionally added.

As described above, in the conventional method for producing whitlockite, phosphate ions were added dropwise throughout the entire process to finely adjust the pH to gradually change the pH condition from the basic condition to the acidic condition. However, since phosphate ions are added dropwise, there is a fatal disadvantage that it takes a long time to manufacture. For example, a first pH condition required for preparing stabilized calcium phosphate by reacting calcium ions and phosphate ions with each other, and a second required for preparing stabilized magnesium phosphate by reacting magnesium ions and phosphate ions with each other. The pH conditions may be different, and according to the dropping method, an inevitable time is required to change from the first pH condition to the second pH condition. The inevitable time required to change the pH condition acts as one of the reasons for prolonging the manufacturing time of whitlockite.

In addition, there was a problem that the method for preparing whitlockite was complicated because the pH must be precisely controlled throughout the process of aging from the beginning of the reaction, and the addition rate and amount of the phosphate ion supplying material according to the dropping method must be accurately set. .

On the contrary, the method for manufacturing whitlockite disclosed by the present application has the following advantages compared to the conventional method for manufacturing whitlockite.

According to a preferred embodiment of the present invention, the method for preparing whitlockite includes a first reaction condition for reacting calcium ions with phosphate ions through spatial separation and a second reaction condition for cation other than calcium to react with phosphate ions. The reaction conditions can be provided differently, and the manufacturing time can be shortened because the method of adding the phosphate ion supply material to the required amount at a time (Pouring method) is adopted instead of dropwise. . The reaction conditions can be provided in consideration of the pH or the amount of phosphoric acid.

In addition, since a specific amount of phosphate ions can be added without complicated adjustment of the pH, whitlockite can be produced simply and intuitively.

Hereinafter, each process will be described in more detail with reference to FIGS. 3 to 8.

In the process (S10) of making a mixed solution containing a first phosphate material, a solution containing calcium ions and a solution containing phosphate ions are mixed and reacted to form a solid first phosphate material in a first container for a first time. Includes telling.

The first phosphate material is a phosphate material containing calcium ions. That is, it is a calcium phosphate substance. For example, it may be a material containing a calcium phosphate substance such as hydroxyapatite, dicalcium phosphate dehydrate (DCPD), brushite, monetite, or a combination thereof. have. However, it is not limited to the exemplified material, and a material in which calcium ions and phosphate ions are combined may be regarded as a calcium phosphate material. Preferably, the first phosphate material may be hydroxyapatite.

The first time refers to a time from a time point when a solution containing calcium ions and a solution containing phosphate ions are started to be mixed and a time when a reaction in which the first phosphate material is formed is completed. However, if the reaction in which the first phosphate material is formed is not completely completed before the process of combining into one mixed solution (S30) begins, the first time is to mix the solution containing calcium ions and the solution containing phosphate ions. It may be a time from the start of the following to the start of the process (S30) of combining into one mixed solution to be described later.

A solution containing calcium ions can be prepared by dissolving a substance that contains calcium atoms and is well ionized when dissolved in water. That is, the solution containing calcium ions may be prepared by dissolving a calcium ion providing material (or a calcium ion supplying material) in water. The calcium ion providing material may be calcium hydroxide, calcium carbonate, calcium nitrate, calcium acetate, or the like.

As described above, the process of forming a mixed solution containing the first phosphate material (S10) has been described as mixing a solution containing phosphate ions and a solution containing calcium ions with each other. If a solution that coexists within can be prepared, the calcium ion providing material is directly mixed with the phosphate ion supplying material (or phosphate ion providing material) to be described later, or the phosphate ion supplying material and the calcium ion providing material are all at once in water. It could also be done in a mixed way.

In this case, it is described that a solution containing phosphate ions and a solution containing calcium ions are mixed with each other, but phosphate ions and calcium ions are mixed with water by mixing the phosphate ion supplying material and the calcium ion supplying material together. In the case of preparing a solution that coexists within the solution, the first time is from the time when calcium ions and phosphate ions begin to coexist, and calcium ions and phosphoric acid coexist in the aqueous solution by mixing the calcium ion supply material and the phosphate ion supply material. It may mean until the time when the reaction of ions is completed.

3 and 4, in the present process (S10), a solution containing calcium ions and a solution containing phosphate ions are mixed and reacted for a first time. According to a preferred embodiment of the present application, in the process (S10), a solution containing calcium ions and a solution containing phosphate ions are mixed (S11) for a second time, and calcium ions are included for a third time. The solution and the solution containing phosphate ions are reacted to form a mixed solution containing the first phosphate material (S12).

7 and 8, the second time is, more specifically, the solution containing calcium ions and the phosphate ions from the point when the solution containing calcium ions and the solution containing phosphate ions begin to be mixed. It means the time until the mixing of the containing solution is completed.

The third time is the earlier of the time from the time when calcium ions and phosphate ions start to react to generate the first phosphate, the time when the reaction is completed, or the time when the process of combining into one mixed solution (S30) starts. It means the time until.

The first time is the sum of the second time and the third time, but refers to a time excluding the overlapping time.

At least a portion of the second time and at least a portion of the third time may overlap on the time axis. That is, at least a portion of the mixing process (S11) and at least a portion of the reaction (S12) may occur at the same time.

For example, as soon as a solution containing calcium ions and a solution containing phosphate ions are mixed, a reaction to form the first phosphate material may be performed. In this case, the first time may have the same value as the time of the third time.

According to an embodiment according to the present application, the time when the'mixing' process (S11) of the solution containing calcium ions and the solution containing phosphate ions is completed, that is, at the terminal point of the second time, calcium ions and phosphate ions are Can be included within. However, since the mixing process S11 and the reaction process S12 to be described later may partially occur at the same time, a calcium phosphate material, which is a first phosphate material, may be further included at the terminal point of the second time.

In the'reaction' process (S12) of a solution containing calcium ions and a solution containing phosphate ions, a calcium phosphate material, which is a solid first phosphate material formed by reacting calcium ions and phosphate ions, may be included in the mixed solution. Therefore, when the reaction process S12 is completed, that is, at the terminal point of the third time, a solid calcium phosphate material may be included in the mixed solution.

According to the exemplary embodiment of the present application, the process (S12) of reacting at least the solution containing calcium ions and the solution containing phosphate ions may be performed at 50°C or more and 100°C or less. The process of mixing a solution containing calcium ions and a solution containing phosphate ions (S11) may also be performed at 50°C or more and 100°C or less, but the reaction process for forming the first phosphate (S12) is 50°C or more and 100°C or less If it proceeds in, the object of the present application can be achieved.

Referring back to FIG. 3, the process of making a mixed solution containing a second phosphate material (S20) is performed in a second container to form a solid second phosphate material for a fourth time. A solution containing cations) and a solution containing phosphate ions are mixed and reacted.

The second cation is a cation other than a calcium ion, for example, at least one of Mg, Co, Sb, Fe, Mn, Y, Eu, Cd, Nd, Na, La, Sr, Pb, Ba, and K It may be in the form of ions. Preferably, the second cation may be a magnesium ion.

The fourth time refers to a time from the time when the solution containing the cation other than the calcium ion and the solution containing the phosphate ion is started to be mixed, and the time from the time when the reaction in which the second phosphate material is formed is completed. However, if the reaction in which the second phosphate material is formed is not completely completed before the process of combining into one mixed solution (S30) starts, the fourth time includes a solution containing a cation other than calcium ions and phosphate ions. It may be a time from a time point from the start of mixing the solution to the start of the process (S30) of combining into one mixed solution to be described later.

), 디마그네슘 포스페이트(Dimagnesium phosphate,

), 뉴베리아이트(Newberyite), 트리마그네슘 포스페이트(Trimagnesium phosphate,

) 또는 이들의 조합을 포함하는 물질일 수 있다. 다만, 예시된 물질로 제한되지 않으며, 마그네슘 이온과 인산 이온이 결합된 물질이라면 마그네슘 포스페이트 물질로 볼 수 있을 것이다. The second phosphate material is a phosphate material containing the second cation. That is, the second phosphate material may be regarded as a material in which the second cation and phosphate ion are combined. For example, if the second cation is a magnesium ion, the second phosphate material is a magnesium phosphate material, and monomagnesium phosphate (Monomagnesium phosphate,

), Dimagnesium phosphate (Dimagnesium phosphate,

), Newberyite, Trimagnesium phosphate,

) Or a combination thereof. However, it is not limited to the exemplified material, and a material in which magnesium ions and phosphate ions are combined may be regarded as a magnesium phosphate material.

)일 수 있다.In addition, if the second cation is a cobalt ion, the second phosphate material is cobalt (II) phosphate hydrate,

) Can be.

), 아이언(III) 포스페이트 테트라하이드레이트(Iron(III) phosphate tetrahydrate,

) 또는 이들의 조합을 포함하는 물질일 수 있다.In addition, if the second cation is an iron ion, the second phosphate material is iron (III) phosphate dihydrate,

), Iron (III) phosphate tetrahydrate,

) Or a combination thereof.

)일 수 있다.In addition, if the second cation is a sodium ion, the second phosphate material is sodium phosphate (Sodium phosphate,

) Can be.

)일 수 있다.In addition, if the second cation is a potassium ion, the second phosphate material is potassium phosphate tribasic (Potassium phosphate tribasic,

) Can be.

)일 수 있다.In addition, if the second cation is a strontium ion, the second phosphate material is strontium phosphate (Strontium phosphate,

) Can be.

)일 수 있다.In addition, if the second cation is a barium ion, the second phosphate material is barium phosphate (Barium phosphate,

) Can be.

However, the second phosphate material is not limited to the exemplified material, and any material that can exist in an aqueous solution by combining the above-described second cation and phosphate ions may be regarded as the second phosphate material.

The solution containing the second cation may be prepared by dissolving in water a material that contains the atomic form (X) of the second cation and is well ionized when dissolved in water. That is, the solution containing the second cation may be prepared by dissolving the second cation providing material (or the second cation supplying material) in water. The second cation-providing material may be X hydroxide, X carbonate, X nitrate, and X acetate.

For example, if the second cation is magnesium ions, the solution containing the second cation dissolves magnesium hydroxide or magnesium carbonate, magnesium nitrate, magnesium acetate, etc. containing the magnesium atom form as a magnesium ion supply material in water. It can be produced by

However, according to the above, the process of forming a mixed solution containing the second phosphate material (S20) is described as mixing a solution containing a phosphate ion and a solution containing a second cation. 2 If a solution in which cations coexist in the solution can be prepared, the second cation-providing material is directly mixed with the phosphate ion-providing material, or the phosphate ion-providing material and the second cation-providing material are mixed in water at once. It could also be done with.

For example, if the second cation is magnesium ions, a solution containing the second cation may be prepared by dissolving solid magnesium hydroxide in water, and this may be mixed with a solution containing phosphate ions. In addition, it may be performed by directly mixing a solid magnesium hydroxide material into a solution containing phosphate ions, or by mixing a phosphoric acid-providing material and magnesium hydroxide in water at once.

In this case, it is described that a solution containing a phosphate ion and a solution containing a second cation are mixed with each other, but the phosphate ion and the second cation are mixed in water by mixing the phosphate ion supplying material and the second cation supplying material together. In the case of preparing a solution in which cations coexist in the solution, the fourth time is from the time when the second cations and phosphate ions begin to coexist, and the second cation supply material and the phosphate ion supply material are mixed to coexist in the aqueous solution. It may mean until the reaction between the second cation and phosphate ion is completed.

3 and 5, in the process of forming a mixed solution containing a second phosphate material (S20), a solution containing a second cation, which is a cation other than calcium ions, and a solution containing phosphate ions are added to the fourth. Mix and react for hours. According to a preferred embodiment of the present application, in the process of forming a mixed solution containing a second phosphate material (S20), a solution containing a second cation and a solution containing phosphate ions are mixed for a fifth time (S21). And a step of forming a mixed solution containing a second phosphate material by reacting a solution containing a second cation and a solution containing phosphate ions for a sixth time period (S22).

7 and 8, the fifth time is, more specifically, the solution containing the second cation from the point when the solution containing the second cation and the solution containing the phosphate ion begin to be mixed. It means the time until the mixing of the solution containing the phosphate ions is completed.

The sixth time period is from the time when the reaction of the second cation and the phosphate ion to generate the second phosphate starts, the time when the reaction is completed, or the time when the process of combining into one mixed solution (S30) starts, whichever is earlier. It means the time to the point in time.

The fourth time is the sum of the fifth time and the sixth time, but refers to the time excluding the overlapping time.

At least a part of the fifth time and at least a part of the sixth time may overlap on a time axis. That is, at least part of the mixing process (S21) and at least part of the reaction process (S22) may occur at the same time.

For example, as soon as the solution containing magnesium ions and the solution containing phosphate ions are mixed, a reaction for forming the second phosphate material may proceed. In this case, the fourth time may be substantially the same as the value of the sixth time.

In addition, according to an embodiment according to the present application, when the'mixing' process (S21) of a solution containing a cation other than a calcium ion, which is a second cation, and a solution containing phosphate ions is completed, that is, the terminal at the fifth time At the point, the second cations and phosphate ions may be included in the aqueous solution. However, since the mixing process S21 and the reaction process S22 to be described later may partially occur at the same time, a second phosphate material, for example, a magnesium phosphate material may be further included at the terminal point of the fifth time.

However, the process of making the mixed solution containing the second phosphate material (S20) is performed in a separate container from the process of making the mixed solution containing the first phosphate material (S10), and mixing at the terminal point of the fifth time The solution may not contain a solid calcium phosphate material.

In the'reaction' process (S22) of a solution containing a second cation and a solution containing phosphate ions, a mixed solution containing a solid second phosphate material formed by reacting the second cation and phosphate ions may be formed. Therefore, at the time when the reaction process S22 is completed, that is, at the terminal point of the sixth time, the solid second phosphate material may be included in the mixed solution.

According to an exemplary embodiment of the present application, the process (S22) of reacting at least a solution containing a cation other than the calcium ion and a solution containing a phosphate ion may be performed at 50°C or more and 100°C or less. The process of mixing a solution containing a cation other than calcium ions and a solution containing phosphate ions (S21) may also be performed at 50°C or more and 100°C or less, but the reaction process of forming the second phosphate (S22) is 50°C. If it proceeds at more than 100 ℃ can achieve the object of the present application.

7 and 8, since the process of making a mixed solution containing the first phosphate material (S10) and the process of making a mixed solution containing the second phosphate material (S20) can be performed in separate containers, The process of making a mixed solution containing the first phosphate material (S10) and the process of making a mixed solution containing the second phosphate material (S20) may be performed simultaneously. That is, at least a part of the first time and at least a part of the fourth time may overlap on a time axis.

In addition, the initial point and the terminal point of the second time may be independently located independently of the initial point and the terminal point of the fourth and fifth time.

In addition, the initial point and the terminal point of the third time may be independently located irrespective of the initial point and the terminal point of the fourth and fifth time.

In other words, since they are spatially separated, the process of making a mixed solution containing the first phosphate material (S10) and the process of making a mixed solution containing the second phosphate material (S20) can be independently performed.

In the case of the conventional method for producing whitlockite, a solution containing phosphate ions is added dropwise to a solution containing both calcium ions and a second cation in one container to prepare the first phosphate material. Sequentially forms the material of the second phosphate. Thereafter, the pH is gradually lowered to form an acidic condition, and some atoms of the first phosphate material are replaced with some atoms of the second phosphate material or ions contained in the aqueous solution to change the crystal structure to form whitlockite. As such, the conventional method for manufacturing whitlockite has a problem in that the manufacturing time is long in that the second phosphate material is formed'after' the formation of the first phosphate material, and phosphate ions are added through a dropwise method. .

In the method for producing whitlockite according to the present application, a first phosphate material and a second phosphate material may be simultaneously formed through spatial separation, and reaction conditions such as phosphoric acid in each container to form a target intermediate product from the beginning. The amount and pH of can be appropriately provided, and in order to create a different reaction environment in each container, the amount and pH of the phosphate ions to be added can be provided differently. In other words, the first reaction conditions required to form the first phosphate material and the second reaction conditions required to form the second phosphate material may be different from each other.

At this time, according to the conventional method for producing whitlockite, the first reaction condition and the second reaction condition cannot be provided at the same time, and the first reaction condition is given to the reaction vessel at the first time point, and the reaction proceeds. Accordingly, at the second time point, the second reaction condition was designed to be given to the reaction vessel, so that the process time could not be shortened.

However, in the method for manufacturing whitlockite according to the present application, the first reaction condition can be directly applied to the first container while the second reaction condition can be directly applied to the second container. It is possible to allow the first phosphate material to be produced immediately, while at the same time allowing the second phosphate material to be produced in the second container. In other words, through spatial separation, the reaction conditions of each container can be set differently from the beginning so that the reaction proceeding in the first container and the second container proceed at the same time. Can be shortened considerably.

In addition, the fact that phosphate ions can be added by pouring instead of dropwise also contributes to significantly shortening the manufacturing time of whitlockite. The pouring method will be described in detail later. As the manufacturing time is shortened, there is also an effect that the operating cost of the process can be reduced.

Referring to FIG. 3 again, in order to prepare a mixed solution containing both the first phosphate material and the second phosphate material, the first phosphate material included in the first container and the second phosphate material included in the second container are combined. A process (S30) of combining into a mixed solution of may be included. When combined into one mixed solution, the mixed solution may be combined into one of the first container or the second container, or may be combined into a third container.

According to a preferred embodiment of the present application, by combining the mixed solution containing the first phosphate material and the mixed solution containing the second phosphate material into one mixed solution (S30), the first phosphate material and the second A mixed solution containing all of the phosphate substances is formed. For example, the result of this process (S30) may include both hydroxyapatite and dimagnesium phosphate.

Referring again to Figs. 7 and 8, the process of combining the mixed solution of the first container containing the first phosphate material and the mixed solution of the second container containing the second phosphate material into one mixed solution (S30). The starting initial point may be located at a later point than the terminal point of the second time or the terminal point of the fifth time.

That is, the present process (S30) may be started after the time when the mixing process (S11) of the process of making a mixed solution containing the first phosphate material is completed (terminal point of the second time).

Similarly, the present process (S30) may be started after the time when the mixing process (S21) of the process of making a mixed solution containing the second phosphate material is completed (terminal point of the fifth time).

In addition, the initial point of the process (S30) of combining the mixed solution of the first container containing the first phosphate material and the mixed solution of the second container containing the second phosphate material into one mixed solution (S30) is the terminal of the third time. It can be located at a later point rather than at a point. In other words, according to the manufacturing method of whitlockite disclosed by the present application, the step of combining into one mixed solution after the reaction step (S12) of the step of making a mixed solution containing the first phosphate material is completed ( S30) does not have to be started, but preferably this process (S30) may be started after the reaction process (S12) of the process of making a mixed solution containing the first phosphate material is completed.

Referring again to FIG. 3, after the mixed solution containing both the first phosphate material and the second phosphate material is formed, a process of mixing and aging the solution containing phosphate ions for a seventh time (S40) is performed. In this case, conditions for sufficient transformation may be provided so that whitlockite is formed from the mixed solution containing the first phosphate material and the second phosphate material.

See Figs. 3 and 6. According to a preferred embodiment of the present application, the process of aging the mixed solution containing both the first phosphate material and the second phosphate material (S40) is a mixture containing the first phosphate material and the second phosphate material for an eighth hour. Including a process of mixing a solution containing phosphate ions in the solution (S41) and a process of aging for the 9th hour to change the crystal structure of the first phosphate material in which some atoms are substituted with different atoms to form whitlockite (S42). can do.

Referring again to Figs. 7 and 8, the eighth time period is from the time when the mixing of the solution containing phosphate ions and the mixed solution containing the first phosphate material and the second phosphate material starts to the time when the mixing is completed. It's time.

The ninth time refers to a time from the start of aging of the mixed solution containing the first phosphate material and the second phosphate material to the completion of aging to form whitlockite.

The seventh time is the sum of the eighth time and the ninth time, but refers to the time excluding the overlapping time.

At least a part of the eighth time and at least a part of the ninth time may overlap on a time axis. That is, the mixing process (S41) and the aging process (S42) of the solution containing phosphate ions and the mixed solution containing the first phosphate material and the second phosphate material may occur at the same time.

For example, as soon as a solution containing phosphate ions is mixed with a mixed solution containing hydroxyapatite and dimagnesium phosphate, the mixed solution containing hydroxyapatite and magnesium phosphate may be aged. In this case, the seventh time may be a value substantially the same as the value of the ninth time.

According to an embodiment of the present application, the time point when the'mixing' process (S41) of the mixed solution containing the first phosphate material and the second phosphate material and the solution containing phosphate ions is completed, that is, the terminal point of the eighth time In, the first phosphate material, the second phosphate material, and phosphate ions may be included in the mixed solution. However, since the mixing process (S41) and the aging process (S42) to be described later may partially occur at the same time, whitlockite may be further included at the terminal point of the eighth time.

In the'aging' process (S42) of the mixed solution containing the first phosphate material, the second phosphate material, and phosphate ions, aging is performed for the ninth hour, and the crystal structure of the first phosphate material is changed to form whitlockite. I can. Therefore, at the terminal point of the ninth time, the mixed solution may contain solid whitlockite.

According to an embodiment of the present application, the'aging' process (S42) of the mixed solution containing the first phosphate material, the second phosphate material, and phosphate ions may be performed at 50°C or more and 100°C or less. The'mixing' process (S41) of the mixed solution containing the first phosphate material and the second phosphate material and the solution containing phosphate ions may also be performed at 50°C or more and 100°C or less, but the first phosphate material and the second phosphate material And if the'aging' process (S42) of the mixed solution containing phosphate ions is performed at 50°C or more and 100°C or less, the object of the present application may be achieved.

A process of forming a mixed solution containing a first phosphate material (S10), a process of forming a mixed solution containing a second phosphate material (S20), and aging a solution containing the first phosphate material and the second phosphate material In step S40, a solution containing phosphate ions is mixed.

를 의미한다고 볼 수 있으나, 이에 제한되지는 않으며, 수용액 상에서 인산(Phosphoric acid)가 존재할 수 있는 형태를 모두 포함할 수 있다. 예를 들어,

,

,

,

모두 상기 인산 이온으로 볼 수 있다.The phosphate ion may include all forms of phosphoric acid that may exist depending on the pH of the aqueous solution. Generally speaking of phosphate ion,

Although it may be regarded as meaning, it is not limited thereto, and all forms in which phosphoric acid may exist in an aqueous solution may be included. E.g,

,

,

,

All can be seen as the phosphate ions.

The phosphate ion may be supplied by a phosphate ion supply material including at least one selected from phosphoric acid, diammonium hydrogen phosphate, ammonium phosphate, and phosphate, It may preferably be supplied by phosphoric acid.

The solution containing phosphate ions may be prepared by dissolving a phosphate ion-providing material (eg, diammonium phosphate, ammonium phosphate, phosphate) present as a solid at room temperature in water or an aqueous solution. Alternatively, a phosphate ion-providing material such as phosphoric acid may contain phosphate ions in the phosphate ion-providing material itself because water is present as a solvent.

For example, when a solution containing calcium ions and a solution containing phosphate ions are mixed in the process (S10) of forming a mixed solution containing a first phosphate material, an aqueous solution obtained by dissolving solid diammonium phosphate in water A solution containing calcium ions may be mixed with a solution containing calcium ions, or an aqueous phosphate solution containing water as a solvent in the phosphate ion-providing material itself may be mixed with a solution containing calcium ions.

In addition, a process of forming a mixed solution containing a first phosphate material (S10), a process of forming a mixed solution containing a second phosphate material (S20), and a first phosphate material and a second In the process of aging a solution containing a phosphate material (S40), when a solution containing phosphate ions is mixed, it may be mixed by a Pouring method. The pouring method is a method different from the dropwise method, and refers to a method of adding substantially all of the volume of the solution to be added within a very short time at once. For example, in the conventional method for producing whitlockite, a solution containing phosphate ions was continuously mixed in a dropwise manner at a volume flow rate of 12.5 ml/min. On the other hand, according to an embodiment of the method for manufacturing whitlockite disclosed in the present application, a solution containing phosphate ions can be mixed at a time at a volume flow rate of 2 ml/sec (120 ml/min) to 130 ml/sec (7800 ml/min). . The time for mixing the solution containing phosphate ions may be shortened, and thus the time for manufacturing whitlockite may be shortened.

That is, the second time, the fifth time, or the eighth time may be a substantially very short time (eg, within about 1 second). However, even by the pouring method, the second time, the fifth time, or the eighth time may be extended from several seconds to several tens of seconds depending on the volume of the solution containing phosphate ions to be added.

The volume of the solution containing phosphate ions mixed in the process of forming a mixed solution containing the first phosphate material (S10) and the process of forming a mixed solution containing the second phosphate material (S20) is the purpose, respectively. It can be determined in consideration of the stoichiometric ratio for forming the phosphate material and the pH of the mixed solution.

For example, in the first container, a phosphate ion supply material containing an amount of phosphate ions in consideration of a stoichiometric ratio for forming hydroxyapatite, one of the first phosphate substances, by mixing and reacting with calcium ions is provided. Can be mixed. In addition, a phosphate ion supply material including phosphate ions may be added in consideration of the pH of the mixed solution for stably forming the first phosphate material and maintaining a stable state. For example, when phosphoric acid is used as a phosphate ion supply material, the amount of phosphate ions to stably generate hydroxyapatite and the pH at which hydroxyapatite can be stably maintained are provided. The first volume of phosphoric acid may be mixed in consideration of the amount of hydrogen ions for which it is used. Alternatively, in the case of using phosphoric acid as a phosphate ion supply material, after adding a volume of phosphoric acid in consideration of the mole of phosphate ions for stably generating hydroxyapatite, hydroxyapatite A substance other than phosphoric acid may be additionally mixed in order to provide (or adjust) a pH at which is stably maintained.

At this time, preferably, the ratio of the amount of phosphate ions to the amount of calcium ions mixed in the step (S10) of forming a mixed solution containing the first phosphate material is in the range of 0.6 or more and 1.4 or less. May be applicable. If the ratio is outside this range, substances other than whitlockite may be formed in the resulting product.

Similarly, in the second vessel, a phosphate ion supply material containing phosphate ions in consideration of a stoichiometric ratio for mixing and reacting with magnesium ions to form a second phosphate material, preferably dimagnesium phosphate (MgHPO4). Can be added. In addition, in order to stably generate the second phosphate material and maintain a stable state, a phosphate ion-providing material including phosphate ions may be mixed in consideration of the pH of the mixed solution. For example, the amount (mole) of phosphate ions for stably producing dimagnesium phosphate from magnesium ions and phosphate ions and the amount of hydrogen ions (mole) to provide a pH at which dimagnesium phosphate can be stably maintained. Taking into account a second volume of phosphoric acid can be mixed. Alternatively, in the case of using phosphoric acid as the phosphate ion supply material, dimagnesium phosphate is added after adding the amount of phosphoric acid in consideration of the amount of phosphate ions for stably generating dimagnesium phosphate. A substance other than phosphoric acid may be additionally mixed in order to provide (or adjust) a pH at which is stably maintained.

At this time, preferably, the ratio of the amount of phosphate ions to the amount of magnesium ions mixed in the step (S20) of forming a mixed solution containing the second phosphate material is in the range of 0.6 or more and 5 or less. May be applicable. If the ratio is outside this range, substances other than whitlockite may be formed in the resulting product.

In this case, the first volume of phosphoric acid and the second volume of phosphoric acid may be the same, but preferably, the first amount and the second amount may be different.

The volume of the solution containing phosphate ions mixed in the process of aging the solution containing the first phosphate material and the second phosphate material (S40) is obtained from the first phosphate material and the second phosphate material. The pH conditions under which locite can be produced or the desired amount of whitlockite produced can be considered and determined. For example, the amount of the solution containing the phosphate ion may be determined in consideration of a pH condition for preparing whitlockite through ion exchange between the hydroxyapatite and the magnesium phosphate. However, since substances other than phosphoric acid for pH control may be mixed, phosphoric acid is mixed to supply phosphate ions in consideration of the target amount of whitlockite produced, and substances other than phosphoric acid for pH adjustment are additionally mixed. I can.

When a feed material other than Phosphoric acid (e.g., diammonium hydrogen phosphate, ammonium phosphate, and phosphate) is used as the phosphate ion supply material, Along with the solution, a solution containing hydrogen ions for adjusting the pH may be additionally added. For example, when solid diammonium hydrogen phosphate is dissolved to prepare a solution containing phosphate ions and added to a mixed solution containing a first phosphate substance and a second phosphate substance, Whitlock A solution containing hydrogen ions (or a solution for adjusting pH) may be additionally added so that the mixed solution is aged at a pH for stably generating kite.

In addition, the volume of the solution containing phosphate ions mixed in the process of aging the solution containing the first phosphate material and the second phosphate material (S40) is the total amount of cations mixed to form whitlockite. It can be mixed in consideration of the ratio of the total sum of and anions.

For example, the volume of the phosphoric acid solution containing phosphate ions required to form a certain amount of phosphate ions is the third amount, and mixing in the process (S10) of forming a mixed solution containing the first phosphate material When the volume of the phosphoric acid solution is the first amount, and the volume of the phosphoric acid solution mixed in the process (S20) of forming a mixed solution containing the second phosphate material is the second amount, the first phosphate material And the volume of the phosphoric acid solution mixed in the process (S40) of aging the mixed solution containing all of the second phosphate material can be viewed as the amount obtained by subtracting the sum of the first amount and the second amount from the third amount. have.

Preferably, the ratio of the amount of the phosphoric acid solution mixed in the process (S40) of aging the mixed solution containing both the first phosphate material and the second phosphate material to the sum of the first amount and the second amount is 0.3 or more. It may be in the range of 0.55 or less. If the ratio is outside this range, substances other than whitlockite may be formed in the resulting product.

According to the exemplary embodiment disclosed in the present application, since it is possible to prepare whitlockite by adding a predetermined amount of phosphate ions three times without the need to finely control the pH, it is much simpler than the conventional method for producing whitlockite. It has the advantage of being able to manufacture whitlockite in an intuitive and clear way.

Again, referring to FIGS. 7 and 8, as the solution containing phosphate ions is mixed by the Pouring method, the terminal point of the third time may be located at a later point than the terminal point of the second time.

In other words, the mixing process (S11) of the solution containing calcium ions and the solution containing phosphate ions is completed before the time when the reaction for forming the first phosphate material is completed (the terminal point of the third time). For example, if a solution containing phosphate ions and a solution containing calcium ions are mixed within a short period of time within 1 second by the Pouring method, the first phosphate material is also mixed after the completion of mixing (terminal point of the second time). The resulting reaction can proceed.

Likewise, the terminal point of the sixth time may be located later than the terminal point of the fifth time. In other words, the mixing process (S21) of the solution containing the second cation and the solution containing phosphate ions is completed before the time when the reaction for forming the second phosphate material is completed (terminal point of the sixth time). For example, when a solution containing a phosphate ion and a solution containing a second cation are mixed within 1 second by the Pouring method, the second phosphate material is generated even after the time when the mixing is completed (terminal point of the fifth time). The reaction can proceed.

Similarly, the terminal point of the ninth time may be located at a later point than the terminal point of the eighth time. In other words, when the mixing process (S41) of the mixed solution containing the first phosphate substance and the second phosphate substance and the solution containing phosphate ions is completed to form whitlockite (terminal point of the ninth hour) It can be done earlier. For example, when a solution containing phosphate ions is mixed within 1 second by a Pouring method in a mixed solution containing a first phosphate substance and a second phosphate substance, the time when mixing is completed (terminal point of the eighth hour) Even after that, a process of aging to form whitlockite may proceed.

In addition, according to an embodiment according to the present application, a process of forming a mixed solution containing a first phosphate material (S10), a process of forming a mixed solution containing a second phosphate material (S20), and a first phosphate material And in the process (S40) of aging the solution containing the second phosphate material, a solution containing phosphate ions is mixed.

At this time, the solution containing phosphate ion ions may be mixed three times at a predetermined time interval.

In other words, the initial point of the eighth time may be located later than the terminal point of the second time and the terminal point of the fifth time. For example, after a predetermined time has elapsed from the time when the process (S11) of mixing the solution containing calcium ions and the solution containing phosphate ions is completed (terminal point of the second time), the first phosphate material and the second A process (S41) of mixing a solution containing a phosphate material and a solution containing a phosphate ion may be started.

In addition, after a predetermined time elapses from the time when the process (S21) of mixing the solution containing the second cation and the solution containing the phosphate ion is completed (terminal point of the fifth time), the first phosphate material and the second phosphate A process (S41) of mixing a solution containing a substance and a solution containing phosphate ions may be started.

However, the process of mixing the solution containing calcium ions and the solution containing phosphate ions (S11) and the process of mixing the solution containing the second cation and the solution containing phosphate ions (S21) are performed simultaneously on the time axis. Therefore, the terminal point of the second time and the terminal point of the fifth time may be completely the same on the time axis, regardless of their precedence and succession, on the time axis.

In the process of aging the solution containing the first phosphate material and the second phosphate material (S42), the second cation contained in the liquid phase of the mixed solution or the second cation derived from the solid second phosphate material is the first phosphate material. Some atoms of is substituted with and bonded in an atomic form, and some of the atoms substituted in the first phosphate material may be in the form of ions in a liquid phase. At this time, as the first phosphate material in which the second cation is partially substituted is aged, the crystal structure changes through phase shift to form whitlockite.

For example, the crystal structure of hydroxyapatite before some calcium atoms of hydroxyapatite are substituted in the form of magnesium atoms is a hexagonal structure. As some of the calcium atoms are substituted and aged with magnesium atoms, the structure of hydroxyapatite is changed to a Rhombohedral structure, so that whitlockite may be formed. In other words, hydroxyapatite has a hexagonal structure, and whitlockite has a different structure with a rhombohedral structure, and as hydroxyapatite in which some calcium atoms are substituted with magnesium atoms is aged, the crystal structure changes through phase shift to form whitlockite. Can be.

According to a preferred embodiment of the present invention, a process of forming a mixed solution containing a first phosphate material (S10), a process of forming a mixed solution containing a second phosphate material (S20), and combining into one mixed solution At least one of the process (S30) and the process (S40) of aging a solution including the first phosphate material and the second phosphate material may be performed at 50°C or more and 95°C or less.

According to an embodiment disclosed by the present application, the method of manufacturing whitlockite is the process of forming a mixed solution containing the first phosphate material (S10), forming a mixed solution containing the second phosphate material. In at least one of the process (S20), the process of combining into one mixed solution (S30), and the process of aging the solution containing the first phosphate material and the second phosphate material (S40), an oxidizing agent is additionally added ( Or mixed). For example, in the process of forming a mixed solution containing the first phosphate material (S10), the oxidizing agent may be added together in the process of mixing the solution containing the first cation and the solution containing phosphate ions (S11). have.

Alternatively, the oxidizing agent may be added prior to a point earlier than the initial point of the first time, which is the start point of the process (S10) of forming the mixed solution containing the first phosphate material. For example, an oxidizing agent may be added to the first container before the process (S10) of forming a mixed solution containing the first phosphate material is started.

Alternatively, the oxidizing agent may be added at a point earlier than the initial point of the fourth time, which is the start point of the process (S20) of forming the mixed solution containing the second phosphate material. For example, the oxidizing agent may be added to the second container before the process (S20) of forming a mixed solution including the second phosphate material is started.

In other words, the method of manufacturing whitlockite by spatial separation according to the present application further includes a fifth process of mixing an oxidizing agent for a tenth time, wherein the initial point of the tenth time is the first time or the fourth time. It may be positioned at a time point prior to the initial point, or may overlap at least a portion of the first to ninth times on a time axis.

By adding an oxidizing agent, it is possible to shorten the manufacturing time it takes to prepare whitlockite crystals.

Preferably, the oxidizing agent may be hydrogen peroxide.

In addition, in order to manufacture whitlockite, filtering, washing, oven drying, ball milling, and sieving processes may be further included.

Whitlockite made according to the present manufacturing method can be used as a raw material for products such as artificial bone inserted into the body for regeneration or treatment of human tissues, dental restorations, bone cement, oral compositions, and fillers.

2.1 Experimental example

In the experiment (first experiment) related to the method for preparing whitlockite by spatial separation (Example 1), the content of magnesium ions was set to about 26 mol% with respect to the total cations, and the molar ratio of total phosphate ions to the total cations was It was set to about 1 and aged at 80°C to synthesize whitlockite.

6.85g(약 0.0924mol)을 증류수(125ml)에 용해시켜, 칼슘 이온을 포함하는 용액(0.74M

수용액 125mL)을 제조하고, 인산 이온을 포함하는 85% 인산용액(

) 3.81mL(107.19ml DW, 즉 0.5M

수용액 111mL)과 혼합하였다. 이후 80℃ 에서 1시간 동안 스터링(stirring)하여 칼슘 포스페이트 물질을 형성하도록 반응시켰다. Solid calcium hydroxide in the first container

6.85 g (approximately 0.0924 mol) was dissolved in distilled water (125 ml), and a solution containing calcium ions (0.74 M

125 mL of aqueous solution) was prepared, and an 85% phosphoric acid solution containing phosphate ions (

) 3.81 mL (107.19 mL DW, i.e. 0.5 M

111 mL of aqueous solution) and mixed. Thereafter, the mixture was stirred at 80° C. for 1 hour to form a calcium phosphate material.

) 1.90g(약 0.032579mol)을 증류수(125ml)에 용해시켜, 마그네슘 이온을 포함하는 용액(0.26M

수용액 125mL)을 제조하고, 인산 이온을 포함하는 85% 인산용액(

) 2.23mL(62.77ml DW, 즉 0.5M

수용액 65mL)과 혼합하였다. 이후 80℃ 에서 1시간 동안 스터링(stirring)하여 마그네슘 포스페이트 물질을 형성하도록 반응시켰다. 이 때, 마그네슘 이온의 몰 수는 마그네슘 이온과 칼슘 이온의 몰 수의 합인 전체 양이온의 몰 수의 26몰%이다. 제1 용기와 제2 용기에서 혼합되는 각각의 인산 이온의 양(mole) 또는 인산 이온을 포함하는 인산 용액의 양(Volume)은 1.7:1의 비율로 상이하게 혼합하였다. In the second container, solid magnesium hydroxide (

) 1.90 g (about 0.032579 mol) was dissolved in distilled water (125 ml), and a solution containing magnesium ions (0.26 M

125 mL of aqueous solution) was prepared, and an 85% phosphoric acid solution containing phosphate ions (

) 2.23 mL (62.77 mL DW, i.e. 0.5 M

65 mL of aqueous solution) and mixed. Thereafter, stirring was performed at 80° C. for 1 hour to form a magnesium phosphate material. In this case, the number of moles of magnesium ions is 26 mole% of the total number of moles of cations, which is the sum of the number of moles of magnesium ions and calcium ions. The amount (mole) of phosphate ions or the amount of phosphate solution containing phosphate ions mixed in the first container and the second container was differently mixed at a ratio of 1.7:1.

Thereafter, the mixed solution of the first container and the mixed solution of the second container were combined into one mixed solution to form a mixed solution containing a calcium phosphate material and a magnesium phosphate material.

) 2.54mL(71.46 ml DW, 즉 0.5M

수용액 74mL)을 혼합하였다. 이후 80℃ 에서 23시간 동안 스터링(stirring)하여 숙성시켰다. 이 때 인산 이온이 포함된 용액이 첨가될 때, 적하 방식(Dropwise)이 아니라 세 번에 걸쳐 각각 해당하는 양의 인산을 한꺼번에 첨가하는 Pouring 방식을 이용하여 첨가하였다. After that, an 85% phosphoric acid solution containing phosphate ions in a mixed solution containing a calcium phosphate material and a magnesium phosphate material (

) 2.54 mL (71.46 ml DW, i.e. 0.5M

74 mL of aqueous solution) were mixed. After that, it was aged by stirring at 80° C. for 23 hours. At this time, when the solution containing phosphate ions was added, it was added using a Pouring method in which a corresponding amount of phosphoric acid was added all at once, not dropwise, but three times.

After aging the mixed solution for 23 hours, the mixed solution was filtered, washed, oven dried, ball milled, and sieved to prepare a dried powder.

Subsequently, the synthesized powder was analyzed through SEM and XRD, and referring to FIGS. 9 and 10, it can be seen that high purity whitlockite having a variety of shapes and fine size was synthesized through this experiment. The SEM data of FIG. 9 is the data obtained by magnifying the prepared crystal by 50000 times.

3. Method for manufacturing whitlockite by temporal separation (second embodiment)

Referring to FIG. 11, the manufacturing method of whitlockite according to an embodiment of the present application is a process of making a mixed solution containing a first phosphate material (S100), a process of making a mixed solution containing a second phosphate material ( S200), a process of aging a mixed solution including all of the first phosphate material and the second phosphate material (S300) may be included.

3 and 11, the manufacturing method of whitlockite according to an embodiment of the present application is different from the above-described first embodiment, the process of preparing a mixed solution containing a first phosphate material (S100) and 2 The process (S200) of making a mixed solution containing a phosphate material is performed in the same container. However, unlike the first embodiment, in which the manufacturing time of whitlockite is significantly shorter than that of the prior art through spatial separation, the present embodiment can shorten the manufacturing time of whitlockite through temporal separation.

See Figs. 11 and 12. According to an embodiment of the present application, the process of preparing a mixed solution containing a first phosphate material (S100) is a process of mixing a solution containing calcium ions and a solution containing phosphate ions for a first time (hereinafter, The first step, S101) and a step of forming a mixed solution by reacting the result of the first step for a second time so that the first phosphate material is formed (hereinafter, the second step, S102) may be included.

After the process (S100) of making a mixed solution containing the first phosphate material is performed, a process (S200) of making a mixed solution containing the second phosphate material may be sequentially performed.

11 and 13, the process of preparing a mixed solution containing a second phosphate material (S200) is a process of mixing a solution containing phosphate ions and other cations other than calcium ions, which is a second cation, for a third time. (Hereinafter, a third process, S201) and a process in which the result of the third process is reacted for a fourth time to form a second phosphate material to form a mixed solution (hereinafter, a fourth process, S202) may be included.

According to the method of manufacturing whitlockite disclosed by the present application, preferably, the mixing of the first step (S101) and the reaction of the second step (S102) may be preferably carried out in the same container, but must be the same. It doesn't have to be done out of courage.

Likewise, the mixing of the third step (S201) and the reaction of the fourth step (S202) may preferably be performed in the same container, but do not have to be performed in the same container.

In other words, according to the present application, if the mixed solution containing the first phosphate material is made in the first container, and the mixed solution containing the second phosphate material is also made in the same first container, the object of the present application can be sufficiently achieved. There will be.

Unlike the first embodiment, since the process of making a mixed solution containing the first phosphate material (S100) and the process of making a mixed solution containing the second phosphate material (S200) in one container can be sequentially performed, the above The mixed solution resulting from the fourth process may contain both a first phosphate material and a second phosphate material.

In addition, there is a difference from the first embodiment in that a mixed solution including both the first phosphate material and the second phosphate material can be formed without the process of combining into one mixed solution (FIG. 3, S30).

After the process (S200) of making a mixed solution containing the second phosphate material is performed, a process (S300) of aging a mixed solution including both the first phosphate material and the second phosphate material may be sequentially performed.

11 and 14, the process of aging the mixed solution containing both the first phosphate material and the second phosphate material (S300) includes both the first phosphate material and the second phosphate material as a result of the fourth process. Including the process of mixing a solution containing phosphate ions in the mixed solution for 5 hours (hereinafter, the 5th process, S301) and the process of aging the result of the 5th process for the 6th hour (hereinafter, the 6th process, S302). can do.

In the conventional method for producing whitlockite, calcium ions and a second cation are mixed together from the beginning, and the reaction proceeds by adding a phosphoric acid supply material to an aqueous solution in which the two cations exist together, and the produced first phosphate and second cation are mixed together. Whitlockite was prepared depending on the thermodynamic stability according to the pH of phosphate.

However, in the conventional method of manufacturing whitlockite, phosphate ions must be supplied dropwise in order to precisely control the pH, and the supply rate and amount of phosphate ions must be closely controlled. There is a problem that it is extended and the manufacturing method is complicated.

According to a preferred embodiment of the present application, the process of forming a mixed solution containing the first phosphate material (S100) and the process of forming a mixed solution containing the second phosphate material (S200) may be temporally separated.

The meaning of separating in time means that after applying the first reaction conditions to make a mixed solution containing the first phosphate material, and after a predetermined time interval elapses, the second reaction to make a mixed solution containing the second phosphate material. It can mean applying conditions.

For example, in the process of forming a mixed solution containing a first phosphate material (S100), a solution containing calcium ions and a solution containing a first amount of phosphate ions are mixed and reacted to generate the first phosphate material. I can. After a predetermined time has elapsed, in the process of forming a mixed solution containing a second phosphate material (S200), a solution containing a second cation and a solution containing a second amount of phosphate ions are prepared to generate a second phosphate material. It can be mixed and reacted.

Through such temporal separation, a desired intermediate product can be formed in each process, and whitlockite can be manufactured simply and intuitively because it is not necessary to complicatedly control the pH to form the desired intermediate product.

In addition, since it is not necessary to precisely control the pH, the phosphate ion supply material can be added in a pouring method rather than a dropwise method, so that the manufacturing time of whitlockite can be considerably shortened. In other words, according to the method of manufacturing whitlockite disclosed in the present application, a method of manufacturing whitlockite having a short manufacturing time, a simple manufacturing method, and an intuitive high purity may be provided.

Hereinafter, each process will be described in more detail with reference to FIGS. 11 to 16.

According to an embodiment of the present application, the process of preparing a mixed solution containing a first phosphate material (S100) is a process of mixing a solution containing calcium ions and a solution containing phosphate ions for a first time (first process , S101) and a process of forming a mixed solution by reacting the result of the first process for a second time so that the first phosphate material is formed (second process, S102).

The first phosphate material may be a phosphate material containing calcium ions. That is, it may be a calcium phosphate material. For example, it may be a material containing a calcium phosphate substance such as hydroxyapatite, dicalcium phosphate dehydrate (DCPD), brushite, monetite, or a combination thereof. have. However, it is not limited to the exemplified material, and a material in which calcium ions and phosphate ions are combined may be regarded as a calcium phosphate material. Preferably, the first phosphate material may be hydroxyapatite, and may exist in a solid state in the mixed solution.

The solution containing calcium ions may be prepared by dissolving in water a material that contains calcium atoms and is well ionized when dissolved in water. That is, the solution containing the first cation may be prepared by dissolving a calcium ion-providing material in water. The calcium ion-providing material may be calcium hydroxide, calcium carbonate, calcium nitrate, calcium acetate, or the like.

As described above, it was described that the step of forming a mixed solution containing the first phosphate material (S100) includes mixing a solution containing phosphate ions and a solution containing calcium ions with each other. If a solution in which ions coexist in the solution can be prepared, the calcium ion providing material is directly mixed with the phosphate ion providing material, or the phosphate ion providing material and the calcium ion providing material are mixed with water at once. Could be done.

15 and 16, the first time refers to a time from when the solution containing calcium ions and the solution containing phosphate ions are started to be mixed, and the second time is Denotes the time from the time when the solution containing calcium ions and the solution containing phosphate ions start to react to the time when the reaction is completed.

At least a part of the first time and at least a part of the second time may overlap on a time axis. That is, the mixing process (S101) of the first process may proceed, and the reaction (S102) of generating the first phosphate material of the second process may proceed. For example, as soon as mixing of a solution containing calcium ions and a solution containing phosphate ions is started, a reaction to generate the first phosphate material may occur.

According to an embodiment of the present application, when the mixing process (first process) of the solution containing calcium ions and the solution containing phosphate ions is completed, that is, at the terminal point of the first time, calcium ions and phosphate ions are aqueous solutions. Can be included within. However, since the first process S101 and the second process S102 to be described later may partially occur at the same time, a calcium phosphate material, which is a first phosphate material, may be further included at the terminal point of the first time.

According to a preferred embodiment of the present application, in the second process (S102), a mixed solution including a calcium phosphate material, which is a solid first phosphate material formed by reacting calcium ions and phosphate ions, may be formed. Therefore, when the second process is completed, that is, at the terminal point of the second time, a solid calcium phosphate material may be included in the mixed solution.

According to an embodiment of the present application, the process (S102) of reacting at least the solution containing calcium ions and the solution containing phosphate ions may be performed at 50°C or more and 100°C or less. The process of mixing the solution containing calcium ions and the solution containing phosphate ions (S101) may also be performed at 50°C or more and 100°C or less, but the reaction process for forming the first phosphate (S102) is 50°C or more and 100°C or less If it proceeds, the object of the present application can be achieved.

According to an exemplary embodiment of the present application, after the process of making a mixed solution containing the first phosphate material (S100) is performed, the process of making the mixed solution containing the second phosphate material (S200) is sequentially performed.

In the process of making a mixed solution containing a second phosphate material (S200), a solution containing a second cation (or a cation other than calcium ions) and a solution containing phosphate ions are mixed with the result of the second process for a third time. A process of mixing during (3rd process, S201) and a process of forming a mixed solution by reacting the result of the 3rd process for a fourth time so that the second phosphate material is formed (4th process, S202) may be included.

The second cation is a cation other than a calcium ion, for example, at least one of Mg, Co, Sb, Fe, Mn, Y, Eu, Cd, Nd, Na, La, Sr, Pb, Ba, and K It may be in the form of ions. Preferably, the second cation may be a magnesium ion.

The second phosphate material is a phosphate material containing the second cation. That is, the second phosphate material may be regarded as a material in which the second cation and phosphate ion are combined.

), 디마그네슘 포스페이트(Dimagnesium phosphate,

), 뉴베리아이트(Newberyite), 트리마그네슘 포스페이트(Trimagnesium phosphate,

) 또는 이들의 조합을 포함하는 물질로 볼 수 있다. 다만, 예시된 물질로 제한되지 않으며, 마그네슘 이온과 인산 이온이 결합된 물질이라면 마그네슘 포스페이트 물질로 볼 수 있을 것이다. For example, if the second cation is a magnesium ion, the second phosphate material is a magnesium phosphate material, and monomagnesium phosphate (Monomagnesium phosphate,

), Dimagnesium phosphate (Dimagnesium phosphate,

), Newberyite, Trimagnesium phosphate,

) Or a combination thereof. However, it is not limited to the exemplified material, and a material in which magnesium ions and phosphate ions are combined may be regarded as a magnesium phosphate material.

)일 수 있다.In addition, if the second cation is a cobalt ion, the second phosphate material is cobalt (II) phosphate hydrate,

) Can be.

), 아이언(III) 포스페이트 테트라하이드레이트(Iron(III) phosphate tetrahydrate,

) 또는 이들의 조합을 포함하는 물질일 수 있다.In addition, if the second cation is an iron ion, the second phosphate material is iron (III) phosphate dihydrate,

), Iron (III) phosphate tetrahydrate,

) Or a combination thereof.

)일 수 있다.In addition, if the second cation is a sodium ion, the second phosphate material is sodium phosphate (Sodium phosphate,

) Can be.

)일 수 있다.In addition, if the second cation is a potassium ion, the second phosphate material is potassium phosphate tribasic (Potassium phosphate tribasic,

) Can be.

)일 수 있다.In addition, if the second cation is a strontium ion, the second phosphate material is strontium phosphate (Strontium phosphate,

) Can be.

)일 수 있다.In addition, if the second cation is a barium ion, the second phosphate material is barium phosphate (Barium phosphate,

) Can be.

However, the second phosphate material is not limited to the exemplified material, and any material that can exist in an aqueous solution by combining the above-described second cation and phosphate ions may be regarded as the second phosphate material.

The solution containing the second cation may be prepared by dissolving in water a material that contains the atomic form (X) of the second cation and is well ionized when dissolved in water. That is, the solution containing the second cation may be prepared by dissolving the second cation-providing material in water. The second cation-providing material may be X hydroxide, X carbonate, X nitrate, and X acetate.

For example, when the second cation is magnesium ions, magnesium ions including at least one selected from magnesium hydroxide, magnesium carbonate, magnesium nitrate, and magnesium acetate It may be supplied by a feed material and preferably, may be supplied by magnesium hydroxide.

As described above, the process of forming a mixed solution containing a second phosphate material (S200) has been described as mixing a solution containing a phosphate ion and a solution containing a second cation with the result of the second process, If a solution in which a phosphate ion and a second cation can coexist in a mixed solution can be prepared, the second cation providing material is directly mixed with the phosphate ion providing material and mixed with the result of the second process, or the It may be performed by mixing the phosphate ion providing material and the second cation providing material together in the result of the second process.

For example, if the second cation is magnesium ions, a solution containing the second cation may be prepared by dissolving solid magnesium hydroxide in water, and the result of the second process and a solution containing phosphate ions Can be mixed. Alternatively, it may be carried out by directly mixing the solid magnesium hydroxide material with the phosphate ion providing material and then mixing it with the result of the second process, or by mixing the phosphate ion providing material and magnesium hydroxide in the result of the second process at once. There will be

15 and 16, the third time refers to a time from the start of mixing of the third process (S201) to the time of completion of the mixing, and the fourth time refers to the fourth process ( It means the time from the time when the reaction of S202) starts to the time when the reaction is completed.

According to a preferred embodiment of the present application, at least a part of the third time and at least a part of the fourth time may overlap on a time axis. That is, the mixing process (S201) of the third process may proceed, and the reaction (S202) of generating the second phosphate material of the fourth process may proceed. For example, as soon as mixing between a solution containing magnesium ions and a solution containing phosphate ions and a result of the second process is started, a reaction to form a second phosphate material may proceed.

According to an embodiment of the present application, since the mixed solution of the resultant of the second process contains a solid calcium phosphate material, a solution containing a cation other than calcium ions, which is the second cation, and phosphate ions are included. When the solution is mixed with the result of the second process, that is, at the terminal point of the third time, a calcium phosphate material, a second cation, and a phosphate ion may be included in the mixed solution. However, since the third process S201 and the fourth process S202 to be described later may partially occur at the same time, the second phosphate material may be further included at the terminal point of the third time.

According to the exemplary embodiment of the present application, in the fourth process (S202), a mixed solution including a solid second phosphate material generated by reacting a second cation and a phosphate ion may be formed. Therefore, when the fourth process is completed, that is, at the terminal point of the fourth time, the mixed solution may contain a solid second phosphate material.

In addition, in the fourth process, since the solid first phosphate material formed in the second process remains, the mixed solution at the terminal point at the time when the fourth process is completed, that is, the fourth time, may further contain the first phosphate material. have. In other words, the mixed solution at the terminal point of the fourth time may contain the first phosphate and the second phosphate material.

According to an exemplary embodiment of the present application, a process (S202) of reacting a solution containing a cation other than the calcium ion and a solution containing a phosphate ion (S202) may be performed at 50°C or more and 100°C or less. The process of mixing a solution containing a cation other than calcium ions and a solution containing phosphate ions (S201) may also be performed at 50°C or more and 100°C or less, but the reaction process of forming the second phosphate (S202) is 50°C. If it proceeds at more than 100 ℃ can achieve the object of the present application.

According to a preferred embodiment according to the present application, after the mixed solution containing the solid calcium phosphate material is formed preferentially in the second process (S102), the fourth process (S202) in which the second phosphate material is formed is performed. It is characterized in that a mixed solution containing both a solid calcium phosphate material and a solid second phosphate material can be formed only from the initial point of the fourth process.

There is a difference from the first embodiment in that a mixed solution including both the first phosphate material and the second phosphate material is formed without the process of combining into one mixed solution (FIG. 3, S30).

After the mixed solution including both the first phosphate material and the second phosphate material is formed by the fourth process, the process of aging the mixed solution including both the first phosphate material and the second phosphate material (S300) proceeds. do. In this case, conditions for sufficient transformation may be provided so that whitlockite is formed from the mixed solution containing the first phosphate material and the second phosphate material.

According to an embodiment of the present application, the process of aging the mixed solution containing both the first phosphate material and the second phosphate material (S300) comprises a first phosphate material and a second phosphate material as a result of the fourth process. Including the process of mixing a solution containing phosphate ions in the all-inclusive mixed solution for a fifth time (step 5, S301) and a process of aging the result of the fifth step for a sixth time (step 6, S302) can do.

Referring to FIGS. 15 and 16, the fifth time period is from the time when the mixing of the solution containing phosphate ions and the mixed solution containing the first phosphate material and the second phosphate material starts to the time when the mixing is completed. Means time.

The sixth time refers to a time from the start of aging of the mixed solution including the first phosphate material and the second phosphate material to the completion of aging to form whitlockite.

At least a portion of the fifth time and at least a portion of the sixth time may overlap on a time axis on a time axis. That is, the mixing process (S301) of the fifth process may be performed, and the aging process (S302) of the sixth process may be performed.

For example, as soon as the solution containing phosphate ions is mixed with the mixed solution containing hydroxyapatite and dimagnesium phosphate, the aging of the mixed solution containing hydroxyapatite and dimagnesium phosphate may proceed.

According to an embodiment of the present application, when the mixing process (the fifth step, S301) of the mixed solution containing the first phosphate material and the second phosphate material and the solution containing phosphate ions is completed, that is, the fifth time At the terminal point, the first phosphate material, the second phosphate material, and phosphate ions may be included in the mixed solution. However, since the fifth process and the aging process (sixth process, S302) to be described later may partially occur at the same time, whitlockite may be further included at the terminal point of the fifth time.

According to an embodiment according to the present application, in the'aging' process (6th process, S302) of a mixed solution containing a first phosphate material and a second phosphate material and a solution containing phosphate ions, aging for a sixth time is performed. It goes on. In this step (S302), the second cation contained in the liquid phase of the mixed solution or the second cation derived from the solid second phosphate material is substituted with some atoms of the first phosphate material and bonded in an atomic form. Some of the atoms substituted in the phosphate material can be in the form of ions in the liquid phase. At this time, as the first phosphate material in which the second cation is partially substituted is aged, the crystal structure changes through phase shift to form whitlockite.

For example, the crystal structure of hydroxyapatite before some calcium atoms of hydroxyapatite are substituted in the form of magnesium atoms is a hexagonal structure. As some of the calcium atoms are substituted or aged with magnesium atoms, the structure of hydroxyapatite changes to a Rhombohedral structure, and thus whitlockite may be formed. In other words, a calcium phosphate material, preferably hydroxyapatite, has a hexagonal structure, and whitlockite has a different structure with a Rhombohedral structure. As it changes, whitlockite can form.

Therefore, the mixed solution at the terminal point of the sixth time may contain solid whitlockite.

According to an embodiment of the present application, the'aging' process (S302) of the mixed solution containing the first phosphate material, the second phosphate material, and phosphate ions may be performed at 50°C or more and 100°C or less. The'mixing' process (S301) of the mixed solution containing the first phosphate material and the second phosphate material and the solution containing phosphate ions may also be performed at 50°C or more and 100°C or less, but the first phosphate material and the second phosphate material And if the'aging' process (S302) of the mixed solution containing phosphate ions is performed at 50°C or more and 100°C or less, the object of the present application may be achieved.

According to an embodiment of the present application, a process of forming a mixed solution containing a first phosphate material (S100), a process of forming a mixed solution containing a second phosphate material (S200), and a first phosphate material and a first 2 In the process of aging a solution containing a phosphate material (S300), a solution containing phosphate ions is mixed.

를 의미한다고 볼 수 있으나, 이에 제한되지는 않으며, 수용액 상에서 인산(Phosphoric acid)가 존재할 수 있는 형태를 모두 포함할 수 있다. 예를 들어,

,

,

,

모두 상기 인산 이온으로 볼 수 있다.The phosphate ions may include all forms of phosphate ions that may exist depending on the pH of the aqueous solution. Generally speaking of phosphate ion,

Although it may be regarded as meaning, it is not limited thereto, and all forms in which phosphoric acid may exist in an aqueous solution may be included. E.g,

,

,

,

All can be seen as the phosphate ions.

The phosphate ion may be supplied by a phosphoric acid supply material containing at least one selected from phosphoric acid, diammonium hydrogen phosphate, ammonium phosphate, and phosphate, preferably It can be supplied by phosphoric acid.

The solution containing phosphate ions may be prepared by dissolving a phosphate ion-providing material (eg, diammonium phosphate, ammonium phosphate, phosphate) present as a solid at room temperature in water or an aqueous solution. Alternatively, a phosphate ion-providing material such as phosphoric acid may contain phosphate ions in the phosphate ion-providing material itself because water is present as a solvent.

For example, when a solution containing calcium ions and a solution containing phosphate ions are mixed in the process of forming a mixed solution containing a first phosphate material (S100), an aqueous solution obtained by dissolving a solid diammonium phosphate in water A solution containing calcium ions may be mixed with a solution containing calcium ions, or an aqueous phosphate solution containing water as a solvent in the phosphate ion providing material itself may be mixed with a solution containing calcium ions.

In addition, a process of forming a mixed solution containing a first phosphate material (S100), a process of forming a mixed solution containing a second phosphate material (S200), a first phosphate material and a second In the process of aging a solution containing a phosphate material (S300), when a solution containing phosphate ions is mixed, it may be mixed by a pouring method. The pouring method is a method different from the dropwise method, and refers to a method of adding all the solutions to be added in a substantially very short time at once. For example, in the conventional method for producing whitlockite, a solution containing phosphate ions was continuously mixed in a dropwise manner at a volume flow rate of 12.5 ml/min. On the other hand, according to an embodiment of the method for manufacturing whitlockite disclosed in the present application, a solution containing phosphate ions can be mixed at a time at a volume flow rate of 2 ml/sec (120 ml/min) to 130 ml/sec (7800 ml/min). . The time for mixing the solution containing phosphate ions may be shortened, and thus the time for manufacturing whitlockite may be shortened.

That is, the first time, the third time, or the fifth time may be a substantially very short time (eg, within about 1 second). However, even by the pouring method, the first time, the third time, or the fifth time may be extended from several seconds to several tens of seconds depending on the volume of the solution containing phosphate ions added.

The amount (Volumne) of the solution containing phosphate ions mixed in the process of forming a mixed solution containing the first phosphate material (S100) and the process of forming a mixed solution containing the second phosphate material (S200) is It can be determined in consideration of the stoichiometric ratio for forming the phosphate material and the pH of the mixed solution.

For example, in the process (S100) of forming a mixed solution containing a first phosphate material, a stoichiometric ratio for forming a first phosphate material and hydroxyapatite by mixing and reacting with calcium ions is considered. It is possible to mix a phosphate ion supply material containing a mole of one phosphate ion. In addition, in consideration of the pH of the mixed solution for stably forming the first phosphate material and maintaining a stable state, a phosphate ion supply material including phosphate ions may be added. For example, in the case of using phosphoric acid as a phosphate ion supply material, the amount of phosphate ions to stably produce hydroxyapatite, and to provide a pH condition in which hydroxyapatite can be stably produced and maintained. The first volume of phosphoric acid may be mixed in consideration of the amount of hydrogen ions for. Alternatively, in the case of using phosphoric acid as a phosphate ion supply material, after adding a volume of phosphoric acid in consideration of the mole of phosphate ions for stably generating hydroxyapatite, hydroxyapatite A substance other than phosphoric acid may be additionally mixed in order to provide (or adjust) a pH at which is stably maintained. At this time, preferably, the ratio of the amount of phosphate ions to the amount of calcium ions mixed in the step (S100) of forming a mixed solution containing the first phosphate material (mole) is in the range of 0.6 or more and 1.4 or less. May be applicable. If the ratio is outside this range, substances other than whitlockite may be formed in the resulting product.

In addition, in the process (S200) of forming a mixed solution containing a second phosphate material, a stoichiometric method for forming a second phosphate material, preferably dimagnesium phosphate (MgHPO4) by mixing and reacting with magnesium ions. It is possible to add a phosphate ion supply material containing the moles of phosphate ions taking into account the ratio. In addition, in order to stably generate the second phosphate material and maintain a stable state, a phosphate ion supply material including phosphate ions may be mixed in consideration of the pH of the mixed solution. For example, in consideration of the amount of phosphate ions to stably produce dimagnesium phosphate from magnesium ions and phosphate ions, and the amount of hydrogen ions to provide a pH condition in which dimagnesium phosphate can be stably produced and maintained, phosphoric acid The second volume of can be mixed. Alternatively, in the case of using phosphoric acid as the phosphate ion supply material, dimagnesium phosphate is added after adding the amount of phosphoric acid in consideration of the amount of phosphate ions for stably generating dimagnesium phosphate. A substance other than phosphoric acid may be additionally mixed in order to provide (or adjust) a pH at which is stably maintained.

At this time, preferably, the ratio of the amount of phosphate ions to the amount of magnesium ions mixed in the process (S200) of forming a mixed solution containing the second phosphate material may fall within the range of 0.6 or more and 5 or less. have. If the ratio is outside this range, substances other than whitlockite may be formed in the resulting product.

The volume of the solution containing phosphate ions mixed in the process of aging the solution containing the first phosphate material and the second phosphate material (S300) is obtained from the first phosphate material and the second phosphate material. The pH conditions in which locite can be produced or a target amount of whitlockite produced can be considered and determined. For example, the volume of the phosphoric acid solution containing phosphate ions may be determined in consideration of the pH condition for preparing whitlockite through ion exchange between the hydroxyapatite and the magnesium phosphate. However, if phosphoric acid is mixed in consideration of the pH condition, substances other than phosphoric acid to adjust the pH may be mixed. Therefore, phosphoric acid is mixed to supply phosphate ions in consideration of the target amount of whitlockite produced, and the pH Substances other than phosphoric acid for control may be further mixed.

When a feed material other than Phosphoric acid (e.g., diammonium hydrogen phosphate, ammonium phosphate, and phosphate) is used as the phosphate ion supply material, Along with the solution, a solution containing hydrogen ions for adjusting the pH may be additionally added. For example, when solid diammonium hydrogen phosphate is dissolved to prepare a solution containing phosphate ions and added to a mixed solution containing a first phosphate substance and a second phosphate substance, Whitlock A solution containing hydrogen ions (or a solution for adjusting pH) may be additionally added so that the mixed solution is aged at a pH at which kite can be stably generated.

In addition, the volume of the solution containing phosphate ions mixed in the process of aging the solution containing the first phosphate material and the second phosphate material (S300) is the total amount of cations mixed to form whitlockite. It can be determined by taking into account the ratio of the total sum of and anions.

For example, the amount of phosphoric acid solution required to form a certain amount of whitlockite is the third volume, and the amount of phosphoric acid solution mixed in the process (S100) of forming a mixed solution containing the first phosphate material If this is the first volume and the amount of the phosphoric acid solution mixed in the process (S200) of forming a mixed solution containing the second phosphate material is the second volume, the first phosphate material and the second phosphate The volume of the phosphoric acid solution mixed in the process (S300) of aging the mixed solution containing all substances may be viewed as an amount obtained by subtracting the sum of the first amount and the second amount from the third amount.

Preferably, the amount of the phosphoric acid solution mixed in the process (S300) of aging a mixed solution containing both the first phosphate material and the second phosphate material with respect to the sum of the first amount and the second amount is 0.3 or more and 0.55 or less. It can be a range. If the ratio is outside this range, substances other than whitlockite may be formed in the resulting product.

In addition, preferably, the ratio of the first amount, the second amount, and the third amount may be 0.44 (±0.05): 0.26 (±0.05): 0.30 (±0.05).

According to the exemplary embodiment disclosed in the present application, since it is possible to prepare whitlockite by adding a predetermined amount of a solution containing phosphate ions three times without the need to finely control the pH, the conventional method for preparing whitlockite It has the advantage of being able to manufacture whitlockite in a much simpler, more intuitive, and clearer way.

Again, referring to FIGS. 15 and 16, as the solution containing phosphate ions is mixed by the Pouring method, the terminal point of the second time may be located at a later point than the terminal point of the first time. In other words, the mixing process (S101) of the solution containing calcium ions and the solution containing phosphate ions is completed before the time when the reaction for forming the first phosphate material is completed (terminal point of the second time). For example, when a solution containing phosphate ions and a solution containing calcium ions are mixed within 1 second by the Pouring method, the reaction to generate the first phosphate material even after the time when the mixing is completed (terminal point of the first time) This can be done.

Likewise, the terminal point of the fourth time may be located later than the terminal point of the third time. In other words, the mixing process (S201) of the solution containing the second cation and the solution containing phosphate ions may be completed before the time point when the reaction for forming the second phosphate material is completed (the terminal point of the fourth time). For example, when a solution containing a phosphate ion and a solution containing a second cation are mixed within 1 second by the Pouring method, the second phosphate material is generated even after the time when the mixing is completed (terminal point of the third time). The reaction can proceed.

Likewise, the terminal point of the sixth time may be located later than the terminal point of the fifth time. In other words, when the mixing process (S301) of the mixed solution containing the first phosphate material and the second phosphate material and the solution containing phosphate ions is completed to form whitlockite (terminal point of the sixth time) It can be done earlier. For example, when a solution containing phosphate ions is mixed within 1 second by a Pouring method in a mixed solution containing a first phosphate substance and a second phosphate substance, the time when mixing is completed (terminal point of the fifth time) Even after that, a process of aging to form whitlockite may proceed.

As described above, while the solution containing phosphate ions is mixed in a substantially short time in the pouring method, it is possible to significantly shorten the manufacturing time of whitlockite.

In addition, according to an embodiment according to the present application, a process of forming a mixed solution containing a first phosphate material (S100), a process of forming a mixed solution containing a second phosphate material (S200), and a first phosphate material And in the process of aging the solution containing the second phosphate material (S300), a solution containing phosphate ions may be mixed three times in total.

At this time, the solution containing phosphate ion ions may be mixed three times at a predetermined time interval.

In other words, the initial point of the fifth time may be located later than the terminal point of the first time and the terminal point of the third time. In addition, the initial point of the third time may be located later than the terminal point of the first time.

For example, after a predetermined time has elapsed from the time when the process (S101) of mixing the solution containing calcium ions and the solution containing phosphate ions is completed (terminal point of the first time), the second phosphate material is formed. , A process (S201) of mixing a solution containing phosphate ions with a solution containing a cation other than calcium ions and a mixed solution containing a first phosphate material may be started.

In addition, after a predetermined time elapses from the time when the process of mixing the solution containing the second cation and the solution containing phosphate ions (S201) is completed (the terminal point of the third time), the first phosphate material and the second phosphate A process (S301) of mixing a solution containing a substance and a solution containing phosphate ions may be started.

In sum, the initial point of the fifth time may be located later than the terminal point of the third time, and the terminal point of the third time may be located later than the terminal point of the first time. In other words, the solution containing phosphate ions may be mixed three times at a predetermined time interval.

As described above, as the solution containing phosphate ions is mixed three times in a specific amount, it is possible to prepare whitlockite without the need to finely control the pH, so it is much simpler than the conventional method of preparing whitlockite. It is possible to manufacture whitlockite in a simple, intuitive, and clear way.

According to a preferred embodiment of the present application, at least one or more processes in the first to sixth processes may be performed at 50° C. or more and 95° C. or less.

According to an embodiment disclosed by the present application, the method of manufacturing whitlockite is the step of forming a mixed solution containing the first phosphate material (S100), forming a mixed solution containing the second phosphate material In at least one of the process S200 and the process of aging the solution including the first phosphate material and the second phosphate material (S300), an oxidizing agent may be additionally added (or mixed). For example, in the process of forming a mixed solution containing a first phosphate material (S100), an oxidizing agent may be added together in the process of mixing a solution containing a first cation and a solution containing phosphate ions (S101). I can.

Alternatively, the oxidizing agent may be added before the initial point of the first time, which is the start point of the process (S100) of forming the mixed solution containing the first phosphate material. For example, before the process (S100) of forming a mixed solution containing the first phosphate material is started, an oxidizing agent may be added first.

In other words, the method for manufacturing whitlockite by temporal separation disclosed by the present application further includes a seventh process of mixing an oxidizing agent for a seventh time, wherein the initial point of the seventh time is the initial point of the first time It may be positioned at an earlier point in time, or may overlap on a time axis with at least a portion of the first to sixth times.

By adding an oxidizing agent, it is possible to shorten the manufacturing time it takes to prepare whitlockite crystals.

Preferably, the oxidizing agent may be hydrogen peroxide.

In addition, in order to manufacture whitlockite, filtering, washing, oven drying, ball milling, and sieving processes may be further included.

Whitlockite made according to the present manufacturing method can be used as a raw material for products such as artificial bone inserted into the body for regeneration or treatment of human tissues, dental restorations, bone cement, oral compositions, and fillers.

3.1 Experimental example

In the experiment (hereinafter referred to as the first experiment) related to the method for producing whitlockite by temporal separation (hereinafter, the first experiment), the content of magnesium ions was set to 26 mol% with respect to the total cations, and the molar ratio of the total phosphate ions to the total cations was It was set to about 1 and aged at 80°C to synthesize whitlockite.

)을 6.85g(약 0.0924mol)을 증류수(112.5ml)에 용해시켜, 칼슘 이온을 포함하는 용액(0.74M

수용액 125mL)을 제조하고, 인산 이온을 포함하는 85% 인산용액(

) 3.81mL(107.19ml DW, 즉 0.5M

111mL)과 혼합하였다. 이후 80℃에서 제1 반응시간 동안 스터링(stirring)하여 칼슘 포스페이트 물질을 형성하도록 반응시켰다. 제1 실험에서는 상기 제1 반응시간은 1h로 실험하였다. 30% hydrogen peroxide aqueous solution (25 ml) and solid calcium hydroxide (

) 6.85 g (approximately 0.0924 mol) was dissolved in distilled water (112.5 ml), and a solution containing calcium ions (0.74 M

125 mL of aqueous solution) was prepared, and an 85% phosphoric acid solution containing phosphate ions (

) 3.81 mL (107.19 mL DW, i.e. 0.5 M

111 mL). Thereafter, the mixture was stirred at 80° C. for the first reaction time to form a calcium phosphate material. In the first experiment, the first reaction time was 1 h.

) 1.90g(약 0.032579mol)을 증류수(112.5ml)에 용해시켜, 마그네슘 이온을 포함하는 용액(0.26M

수용액 125mL)을 제조하여, 인산 이온을 포함하는 85% 인산용액(

) 2.23mL(62.77ml DW, 즉 0.5M

65mL)과 함께 상기 칼슘 포스페이트 물질이 포함된 혼합용액에 혼합하였다. 이후 80℃에서 제2 반응시간 동안 스터링(stirring)하여 마그네슘 포스페이트 물질을 형성하도록 반응시켰다. 제1 실험에서는 상기 제2 반응시간은 1h로 진행하였다. Sequentially solid magnesium hydroxide (

) 1.90 g (about 0.032579 mol) was dissolved in distilled water (112.5 ml), and a solution containing magnesium ions (0.26 M

125 mL of aqueous solution) was prepared, and an 85% phosphoric acid solution containing phosphate ions (

) 2.23 mL (62.77 mL DW, i.e. 0.5 M

65 mL) and mixed in the mixed solution containing the calcium phosphate material. Thereafter, the mixture was stirred at 80° C. for a second reaction time to form a magnesium phosphate material. In the first experiment, the second reaction time was 1 h.

) 2.54mL(71.46 ml DW, 즉 0.5M

수용액 74mL)을 혼합하였다. 이후 80℃에서 제3 숙성시간 동안 스터링(stirring)하여 숙성시켰다. 제1 실험에서는 상기 제3 숙성시간은 5h로 진행하였다. 85% phosphoric acid solution containing phosphate ions in a mixed solution containing a calcium phosphate substance and a magnesium phosphate substance sequentially (

) 2.54 mL (71.46 ml DW, i.e. 0.5M

74 mL of aqueous solution) were mixed. Thereafter, it was aged by stirring at 80° C. for the third aging time. In the first experiment, the third aging time was performed at 5 h.

At this time, when the solution containing phosphate ions was added, it was added using a Pouring method in which a corresponding amount of phosphoric acid was added all at once, not dropwise, but three times.

The ratio of the amounts of phosphate ions added three times or the ratio of the phosphate solutions containing phosphate ions was mixed at a ratio of 0.444:0.260:0.296.

After aging the mixed solution for 5 h, the mixed solution was filtered, washed, oven dried, ball milled, and sieved to prepare a dried powder.

Subsequently, the synthesized powder was analyzed through SEM and XRD, and referring to FIGS. 17 and 18, it was confirmed that various shapes and high purity whitlockite were synthesized through this first experiment. The SEM data of FIG. 17 is the data obtained by magnifying the prepared crystal by 5000 times.

In the first modified experiment (hereinafter, referred to as the second experiment or the first modified example) of the first experiment, the third aging time was fixed to 5 hours, and then the experiment was conducted using the first reaction time as a variable. The experiment was performed while changing the first reaction time to 5min, 15min, 30min, and 60min, and other experimental conditions were carried out in the same manner as in the first experiment to prepare whitlockite powder. Subsequently, the synthesized powder was confirmed through SEM and XRD, and referring to FIGS. 19 to 21, it was confirmed that the production time was significantly shortened to within 7 hours through the second experiment to synthesize high purity whitlockite. The SEM data of FIG. 19 is the data obtained by magnifying the prepared crystal by 10000 times, and FIG. 19 (a) shows the first reaction time of 5 min, (b) the first reaction time of 15 min, and (c) the second reaction time. 1 reaction time is 30min, (d) is SEM data when the first reaction time is 60min. In Figure 20 (a), the first reaction time is 5 min, (b) is the first reaction time is 15 min, (c) is the first reaction time is 30 min, (d) is the first reaction time is 60 min. This is XRD Data in the case of.

In the second modified experiment (hereinafter, referred to as the third experiment or the second modified example) of the first experiment, the first reaction time was fixed at 60 min, and the experiment was conducted with the third aging time as a variable. The experiment was performed while changing the third aging time to 5h and 10h, and other experimental conditions were carried out in the same manner as in the first experiment to prepare whitlockite powder.

Subsequently, the synthesized powder was analyzed through SEM and XRD, and referring to FIGS. 22 and 23, it was confirmed that the preparation time was significantly shortened to within 12 hours through the third experiment to synthesize high purity whitlockite. The SEM data of FIG. 22 is the data obtained by magnifying the prepared crystal by 50,000 times. Figure 22 (a) is the third aging time is 5h, (b) is the SEM data when the third aging time is 10h.

In the third modified experiment (hereinafter, referred to as the fourth experiment or the third modified example) of the first experiment, the first reaction time was fixed at 15 min, and the experiment was conducted with the third aging time as a variable. The experiment was performed while changing the third aging time to 30min, 1h, 3h, and 5h, and other experimental conditions were carried out in the same manner as in the first experiment to prepare whitlockite powder.

Subsequently, the synthesized powder was analyzed through SEM and XRD, and referring to FIGS. 24 to 26, it can be seen that the preparation time was synthesized within 6 hours, particularly within 2 hours, through the fourth experiment. Thus, it was confirmed that the manufacturing time of whitlockite was considerably shortened. The SEM data of Fig. 24 is the data obtained by magnifying the prepared crystal by 10000 times, and Fig. 24 (a) shows the third aging time is 5h, (b) is the third aging time is 3h, 3 The aging time is 1h, (d) is SEM data when the third aging time is 30min. Figure 25 (a) shows the third aging time is 5h, (b) is the third aging time is 3h, (c) is the third aging time is 1h, (d) is the third aging time is 30min This is XRD Data in the case of.

In the above, the configuration and features of the present invention have been described based on the embodiments and drawings according to the present invention, but the present invention is not limited thereto, and various changes or modifications can be made within the spirit and scope of the present invention. It will be apparent to those skilled in the art to which it belongs, and therefore, such changes or modifications are found to belong to the appended claims.

Claims (13)

A first step of mixing a first solution containing calcium ions and a second solution containing a first amount of phosphate ions for a first time-
A second process of forming a first mixed solution in which the result of the first process is reacted for a second time so that the first phosphate material is formed-the terminal point of the second time is at a later time than the terminal point of the first time Located;
A third process in which a third solution containing a cation other than calcium ions and a fourth solution containing a second amount of phosphate ions are mixed with the first mixed solution for a third time-the initial point of the third time is Located at a later point than the terminal point of the first time;
A fourth process in which the result of the third process is reacted for a fourth time to form a second phosphate material to form a second mixed solution-the terminal point of the fourth time is at a later point than the terminal point of the third time Located;
A fifth process in which a fifth solution containing a third amount of phosphate ions is mixed for a fifth time in the second mixed solution-the initial point of the fifth time is located at a later point than the terminal point of the third time ; And
A sixth process of aging the result of the fifth process for a sixth time-the terminal point of the sixth time is located at a later point than the terminal point of the fifth time; Containing,
Wheatlockite manufacturing method. The method of claim 1,
At least a part of the first time and at least a part of the second time overlap,
At least a part of the third time and at least a part of the fourth time overlap,
Characterized in that at least a part of the fifth time and at least a part of the sixth time overlap,
Wheatlockite manufacturing method. The method of claim 1,
Characterized in that the ratio of the amount of phosphate ions contained in the fifth solution to the sum of the amount of phosphate ions contained in the second solution and the fourth solution is in the range of 0.3 or more and 0.55 or less,
Wheatlockite manufacturing method. The method of claim 1,
The phosphate ions are supplied by a phosphate ion supply material including at least one selected from phosphoric acid, diammonium hydrogen phosphate, ammonium phosphate, and phosphate. doing,
Wheatlockite manufacturing method. The method of claim 1,
The calcium ions are supplied by a calcium ion supply material including at least one selected from calcium hydroxide, calcium carbonate, calcium nitrate, and calcium acetate. Made by,
Wheatlockite manufacturing method The method of claim 1,
The cation other than the calcium ion is a magnesium ion, and the magnesium ion is at least one selected from magnesium hydroxide, magnesium carbonate, magnesium nitrate, and magnesium acetate. Characterized in that supplied by a magnesium ion supply material containing,
Wheatlockite manufacturing method. The method of claim 1,
It further comprises a seventh process of mixing the oxidizing agent for a seventh time, wherein the initial point of the seventh time is located at a time earlier than the initial point of the first time, or at least part of the first to sixth time Characterized in that overlapping,
Wheatlockite manufacturing method The method of claim 1,
Cations other than the calcium ions are magnesium ions,
The ratio of the amount of phosphate ions contained in the second solution to the amount of calcium ions contained in the first solution of the first step is in the range of 0.6 or more and 1.4 or less,
Characterized in that the ratio of the amount of phosphate ions contained in the fourth solution to the amount of magnesium ions contained in the third solution in the third process is in the range of 0.6 or more and 5 or less,
Wheatlockite manufacturing method. The method of claim 1,
The first mixed solution contains a solid first phosphate material,
The second mixed solution contains both a solid first phosphate material and a solid second phosphate material,
The second mixed solution is formed as the third solution and the fourth solution are additionally added to the first mixed solution after the first mixed solution is formed,
Wheatlockite manufacturing method. The method of claim 7,
The oxidizing agent is characterized in that hydrogen peroxide,
Wheatlockite manufacturing method. The method of claim 9,
The first phosphate material is a material comprising hydroxyapatite, dicalcium phosphate dehydrate (DCPD), brushite, monetite, or a combination thereof. ,
Wheatlockite manufacturing method. The method of claim 9,
The second phosphate material is monomagnesium phosphate (Monomagnesium phosphate,

), Dimagnesium phosphate (Dimagnesium phosphate,

), Newberyite, Trimagnesium phosphate,

) Or a material comprising a combination thereof,
Wheatlockite manufacturing method. The method according to any one of claims 1 and 12,
At least one process in the first to sixth processes is characterized in that to proceed at 50 ℃ or more and 95 ℃ or less,
Wheatlockite manufacturing method.

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