JP2009137792A - Calcium phosphate based spherocrystal - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a calcium phosphate based spherocrystal, forming a porous body by complex entanglement of fibrous crystals, and to provide a method for easily producing such calcium phosphate based spherocrystal. <P>SOLUTION: The calcium phosphate spherocrystal characterized by having the automorphology which grows to form a porous body by complex entanglement of fibrous crystals having a specific elongation direction is provided. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a calcium phosphate spherulite that can be used as a biocompatible material, a specific atom / molecule adsorbing material, a standard material for measuring physical properties, and the like, and a method for producing the same.

  Conventionally, calcium phosphate materials have been used as biocompatible materials, adsorbent materials, or standard materials for measuring physical properties. In addition, as a method for producing calcium phosphate crystals, a solution method, a firing method, and the like have been proposed.

In the solution method, for example, it is known that a scaly crystal or a columnar crystal can be obtained by precipitating a crystal from an aqueous suspension of phosphoric acid and a calcium compound (Patent Document 1). In addition, as a method for producing phosphate apatite which is a kind of calcium phosphate crystal, surfactant-water-nonpolar organic liquid system or surfactant-water-alkanol nonpolar organic liquid system W / O microemulsion phase is used. A method for producing spherical apatite fine particles by solubilizing Ca (NO ₃ ) ₂ / ammonia aqueous solution and (NH ₄ ) ₂ HPO ₄ / ammonia aqueous solution and mixing these solubilized solutions is known (Patent Literature). 2).

  However, since the above-mentioned solution method has a high crystal growth rate, it is difficult to control crystal growth and particle size, and there is a problem that crystallinity is lowered. Since the solution is reacted by stirring, there is a problem that nuclei are generated in the crystal growth process, and the crystal is broken due to collision between the crystals, resulting in a decrease in quality. In addition, this method cannot produce calcium phosphate spherulites in which high-quality fibrous crystals are intertwined in an extremely complicated manner.

  On the other hand, the firing method in which the raw material powder of the calcium phosphate crystal is fired to produce crystals has a problem that, when fired for a long time, the crystal grains become coarse and the mechanical strength decreases. It is difficult to obtain quality crystals. Another problem is that only an anhydride crystal can be obtained because it is fired at a high temperature. Furthermore, in order to suppress the coarsening of the crystal grains, a method of firing in a short time using discharge plasma is disclosed in Patent Document 3, but even in this method, control of crystal growth is not sufficient, and the fibrous shape It is also impossible to produce calcium phosphate-based spherulites in which crystals are intricately intertwined.

  Also known are plate-like apatite (Patent Document 4) grown in the a- and b-axis directions by the hydrothermal method and plate-like apatite (Patent Document 5) in which the a-plane is preferentially grown. Since the period is extremely long, it is not suitable for industrialization and there is a problem that the apparatus is expensive. Furthermore, since by-products may be generated, it is difficult to obtain pure crystals. Even with this method, calcium phosphate spherulites in which fibrous crystals are intertwined in a very complicated manner cannot be produced.

  Furthermore, in the above solution method, firing is often performed after precipitation of crystals, and any of the above methods has a problem that a high temperature or high energy is required as a reaction condition. Further, since it is difficult to control crystal growth by the conventional solution method and firing method, it has been difficult to produce calcium phosphate spherulites in which fibrous crystals are intertwined in an extremely complicated manner.

JP-A-6-298505 JP-A-5-17111 JP-A-10-251057 JP-A-6-206713 Japanese Patent Laid-Open No. 10-45405

  The present invention has been made in view of the above problems, and provides a calcium phosphate-based spherulite in which fibrous crystals are extremely intertwined, and a production method capable of easily manufacturing such a calcium phosphate-based spherulite. The main purpose is to provide.

  In order to achieve the above object, the present invention provides a calcium phosphate spherulite characterized by having a self-form that forms a porous body by intricately intertwining fibrous crystals having a specific elongation direction. .

  Conventionally, calcium phosphate-based materials have been used as biomaterials, cell culture substrates, or adsorbing materials because of their poor physical properties due to their chemical composition and crystal structure, although they are poorly porous. However, according to the present invention, since the calcium phosphate spherulite is a spherulite composed of a large number of fibrous crystals, compared with conventional materials, for example, when used as a biomaterial or a cell culture substrate, It can be expected to have an advantageous effect on the growth of biological materials. It can also be expected to be suitable for use as a substrate that supports or adsorbs various substances.

  The calcium phosphate spherulite of the present invention is a porous body formed by entanglement of fibrous crystals in an extremely complicated manner, and the spherulite may be a single substance or a complex in which a plurality of spherulites are combined. preferable. This is because the calcium phosphate spherulites of the present invention form a porous body and can be used for various applications.

  Furthermore, the calcium phosphate spherulites of the present invention are preferably crystals represented by the following chemical composition formulas (1) to (8).

_{Ca 8 H 2 (PO 4)} 6 · 5H 2 O (1)
Ca ₁₀ (OH) ₂ (PO ₄ ) ₆ (2)
Ca ₁₀ Cl ₂ (PO ₄ ) ₆ (3)
Ca ₁₀ F ₂ (PO ₄ ) ₆ (4)
CaHPO ₄ (5)
_{CaHPO 4 · 2H 2 O (6} )
Ca ₃ (PO ₄ ) ₂ (7)
Ca ₃ (PO ₄ ) ₂ xH ₂ O (8)

  The present invention also provides a method for producing a calcium phosphate spherulite characterized by producing a calcium phosphate spherulite that forms a porous body by intricately intertwining fibrous crystals by a gel method.

  In the gel method, crystals grow by the reaction solution gradually diffusing into the gel, so the crystal growth rate can be controlled by the gel matrix density, and crystals with high purity and good crystallinity can be produced. Can do. Further, since the reaction field is in the gel, it is possible to suppress the destruction of the crystal due to the collision between the crystals, and it is possible to produce a high quality crystal. Furthermore, by adjusting the density and thickness of the gel matrix to be used, the diffusion permeation rate of the reaction solution in the gel can be controlled, the reaction rate in the gel can be controlled, crystal growth and In addition to controlling the particle size, the effect of controlling the crystal shape and the like can also be expected. In the gel method, crystals can be grown under low-temperature conditions, and crystal growth can be controlled, so that calcium phosphate crystals with few defects can be produced.

  In the present invention, the calcium phosphate spherulites are preferably crystals of a calcium phosphate compound represented by the following chemical composition formulas (1) to (8).

_{Ca 8 H 2 (PO 4)} 6 · 5H 2 O (1)
Ca ₁₀ (OH) ₂ (PO ₄ ) ₆ (2)
Ca ₁₀ Cl ₂ (PO ₄ ) ₆ (3)
Ca ₁₀ F ₂ (PO ₄ ) ₆ (4)
CaHPO ₄ (5)
_{CaHPO 4 · 2H 2 O (6} )
Ca ₃ (PO ₄ ) ₂ (7)
Ca ₃ (PO ₄ ) ₂ xH ₂ O (8)

  Calcium phosphate spherulites composed of crystals of the calcium phosphate compound are relatively easy to produce by the gel method.

  Furthermore, in the present invention, the gel used in the gel method is preferably an agar gel, gelatin gel, silica gel or cellulose gel. Since these gels can easily control the matrix density, the reaction solution can be efficiently diffused in the gel.

  Conventionally, calcium phosphate-based materials have been used as biomaterials, cell culture substrates or adsorbent materials because of their poor physical properties due to their chemical composition and crystal structure, although they are less porous than the present invention. However, according to the present invention, it is a calcium phosphate spherulite composed of fibrous crystals, and each fibrous crystal is intertwined in an extremely complicated manner to form a porous body. When used as a material or the like, it can be expected to have an effect that it has a good affinity with living bodies and cells and is advantageous for the growth of biological materials, compared to conventional materials. In addition, it can be expected to be suitable for use as a base material that supports or adsorbs various substances as compared with conventional materials.

  The present invention includes a calcium phosphate spherulite and a method for producing the same. Hereinafter, each will be described in detail.

A. First, the calcium phosphate spherulites of the present invention will be described.

  The calcium phosphate spherulites of the present invention are characterized in that they have a self-form that forms a porous body by intricately intertwining fibrous crystals having a specific elongation direction.

  In conventional solution method or firing method, it is difficult to control the crystal growth, and the crystal surface state is deteriorated due to the attachment of nuclei to the crystal due to the generation of secondary nuclei, the formation of twins, and the destruction of the crystal due to the collision between the crystals. Because of the roughening, the obtained crystal did not have a crystal face and did not have a crystal-specific outer shape. On the other hand, in the present invention, since it is a calcium phosphate-based spherulite that forms a porous body by intricately intertwining fibrous crystals, for example, when used as a biological material or a cell culture substrate, the living body or cell It can be expected to have an advantage that it has a good affinity for and is advantageous for the growth of biological materials. It can also be expected to be suitable for use as a substrate that supports or adsorbs various substances.

  The structure and form of crystals produced by the production method of the present invention are identified and observed using an X-ray diffractometer or various electron microscopes. In the X-ray diffraction method, if a sharp diffraction line caused by a calcium phosphate crystal is detected, it is determined that the crystal is high quality with few defects. In the transmission electron microscope, it is observed that each fibrous crystal extends in a specific direction of the crystal. Further, in the scanning electron microscope, the fibrous crystal is a porous spherulite intricately entangled. Can be observed.

  Furthermore, the calcium phosphate crystal of the present invention preferably has a self-form. In the present invention, having a self-form means that the calcium phosphate spherulites are spherulites composed of individual fibrous crystals elongated in a specific direction. Calcium phosphate spherulites having such self-forms are biocompatible materials such as biomaterials and bioforming materials, culture substrates such as cells, specific atom / molecule adsorbing materials, various substance carriers, phosphor materials, and physical property measurement. It can be used for various uses such as standard materials for use.

  Examples of SEM photographs of the calcium phosphate spherulites of the present invention are shown in FIGS. 1 (a), (b) and (c). 1 (a) and 1 (b) show that spherulites are porous. FIG. 1 (c) shows that spherulites are formed by intricately intertwining fibrous crystals. The calcium phosphate spherulites of the present invention have a good affinity with a living body as described above, and also have a large number of voids and a large surface area as shown in FIG. In addition, said self-form can be confirmed using a scanning electron microscope (SEM) and a transmission electron microscope (TEM).

  The crystal that forms the calcium phosphate-based spherulite is not particularly limited as long as it contains P—O bonds among the crystals containing phosphorus, oxygen, and calcium as main constituent elements. A crystal of a calcium phosphate compound represented by chemical composition formulas (1) to (8) is preferable.

_{Ca 8 H 2 (PO 4)} 6 · 5H 2 O (1)
Ca ₁₀ (OH) ₂ (PO ₄ ) ₆ (2)
Ca ₁₀ Cl ₂ (PO ₄ ) ₆ (3)
Ca ₁₀ F ₂ (PO ₄ ) ₆ (4)
CaHPO ₄ (5)
_{CaHPO 4 · 2H 2 O (6} )
Ca ₃ (PO ₄ ) ₂ (7)
Ca ₃ (PO ₄ ) ₂ xH ₂ O (8)

  In the present invention, the calcium phosphate spherulites are preferably prepared by a gel method. In the gel method of the present invention, various ions involved in crystal growth diffuse and react, and are included in the external reaction solution into the gel in the reaction field composed of the gel matrix capable of crystal growth and the external reaction solution. This is a method of promoting the generation and growth of crystal nuclei using the diffusion of ions as a driving force.

  The external reaction solution is a solution containing various ions involved in crystal growth, and is a solution for supplying the ions into the gel from the outside of the gel.

  Since the gel method of the present invention grows crystals by gradually diffusing various ions involved in crystal growth from an external reaction solution into the gel, the crystal growth rate can be controlled by the density of the gel matrix. It is possible to obtain crystals with high purity and good crystallinity, and further, it is advantageous in that the crystal grain size can be easily controlled. Moreover, since the crystal growth reaction is in the gel, it is possible to suppress the destruction of the crystal due to the collision between the crystals, and it is possible to obtain a high-quality crystal.

  In addition, about the manufacturing method of calcium-phosphate type | system | group spherulites, such as a gel method, since it describes in "B. Manufacturing method of a calcium-phosphate type crystal | crystallization" mentioned later, description here is abbreviate | omitted.

  Furthermore, in the present invention, the calcium phosphate spherulites can be made high in purity by producing the gel method described above, but the specific purity includes impurities contained in the calcium phosphate crystals of the present invention. Is preferably 20% by weight or less, more preferably 15% by weight or less, and particularly preferably 10% by weight or less.

  The content of the impurity is a value measured using X-ray photoelectron spectroscopy, energy dispersive X-ray fluorescence analysis, or electron probe microanalysis.

  The calcium phosphate spherulites of the present invention are preferably those with few defects. This is because, if there are defects in the crystal, the properties of the calcium phosphate spherulites may change and it may be difficult to use for the intended purpose. In the present invention, since the calcium phosphate spherulites are composed of fibrous crystals grown in a specific direction, the number of defects can be reduced.

  The fact that there are few defects can be specifically determined by the half width of the peak in the X-ray diffraction pattern. Here, it is assumed that the smaller the half width, the fewer defects in the crystal. It can also be determined from a diffraction pattern or a lattice image obtained by TEM observation.

  Since the generation of defects is generally an endothermic reaction, energy is required to generate defects in the crystal, and it can be said that more defects are introduced as the temperature is higher. The calcium phosphate crystal of the present invention is preferably produced by a gel method as described above, and the gel method allows growth of crystals under low temperature conditions and control of crystal growth. It can be developed.

B. Next, a method for producing a calcium phosphate spherulite according to the present invention will be described.

  The method for producing calcium phosphate spherulites of the present invention is characterized by producing calcium phosphate spherulites composed of fibrous crystals grown in a specific direction by a gel method.

  The gel method is a method of promoting crystal nucleation and growth by using the diffusion of each external reaction solution into the gel as a driving force in a reaction field composed of the gel and two or more external reaction solutions in contact with the gel. It is. However, the external reaction solution must not be in direct contact. In FIG. 2, an example of the manufacturing method of the calcium-phosphate type spherulite of this invention is shown. As shown in FIG. 2, an external reaction solution 1a containing a calcium supply material on one side and an external solution containing a phosphate supply material on the other side across an agar gel 2 present in the center of a U-shaped test tube 4 When the reaction solution 1b is injected, various ions involved in crystal growth diffuse in the agar gel 2 from the external reaction solutions 1a and 1b, and crystal nuclei of calcium phosphate compounds are generated inside the agar gel, and are in the form of fibers. Calcium phosphate spherulites 3 are formed by complex entanglement while growing.

  In this way, in the gel method, crystals are grown by the external reaction solution gradually diffusing into the gel, so the crystal growth rate can be controlled by the gel matrix density, and crystals with high purity and good crystallinity can be obtained. Can be manufactured. Further, since the reaction field is in the gel, it is possible to suppress the destruction of the crystal due to the collision between the crystals, and it is possible to produce a high-quality crystal having a crystal face. Furthermore, by adjusting the matrix density and gel thickness of the gel used, the diffusion permeation rate of the external reaction solution in the gel can be controlled, and the reaction rate in the gel can be controlled. Therefore, not only the control of crystal growth and grain size but also the effect that the shape of the crystal can be controlled can be expected.

  In general, since the generation of defects in the crystal is an endothermic reaction, energy is required to generate defects in the crystal, and more defects are introduced as the temperature is higher. In the conventional solution method and firing method, high temperature conditions are required, and since it is difficult to control crystal growth, there is a problem that defects are likely to occur, but the gel method used in the present invention may be under low temperature conditions, Since crystal growth can be controlled, calcium phosphate spherulites with few defects can be produced.

  Accordingly, the calcium phosphate spherulites produced according to the present invention have high purity, good crystallinity, and few defects. Therefore, biocompatible materials such as biomaterials and bioforming materials, culture substrates such as cells, specific atoms -It can be expected that it can be used for various applications such as molecular adsorption materials, carriers of various substances, phosphor materials, and standard materials for measuring physical properties.

The method for producing calcium phosphate-based spherulites of the present invention comprises an external reaction solution preparation step for preparing a gel or a plurality of external reaction solutions, contacting the gel and the external reaction solution, and diffusing the external reaction solution in the gel. A crystal growth step for growing spherulites, and a crystal separation step for separating the spherulites and the gel.
Hereinafter, each process of the manufacturing method of such a calcium-phosphate type spherulite is demonstrated.

1. First, the gel preparation step in the method for producing the calcium phosphate spherulites of the present invention will be described. In this invention, a gel preparation process is a process of producing the gel matrix which diffuses an external reaction solution.

  The gel used in the present invention is not particularly limited as long as it can support the external reaction solution, and a gel generally used as a support can be used. Among these, in the present invention, it is preferable to use agar gel, gelatin gel, silica gel or cellulose gel. This is because these gels are relatively easy to control the matrix density, and an external reaction solution described later can be efficiently diffused into the gel.

  Here, the agar gel can be obtained by dissolving a predetermined amount of agar powder in warm water and cooling the agar solution. Agar is a three-dimensional network-structured agar gel because the matrix density can be controlled by adjusting the concentration and cooling rate of the solution, and the gel matrix is formed by solution cooling.

  Next, the external reaction solution preparation step in the method for producing calcium phosphate spherulites of the present invention will be described. The external reaction solution preparation step in the present invention is a step of preparing an external reaction solution.

  The external reaction solution used in the present invention is not particularly limited as long as it does not have reactivity with the gel and can pass through the gel and contains a phosphoric acid supply material or a calcium supply material. .

  The material for forming calcium phosphate spherulites of the present invention can be divided into a phosphoric acid supply material and a calcium supply material, each of which is contained in a separate external reaction solution. Also, when using two or more raw materials as phosphoric acid or calcium feed materials, or when using additives or reaction modifiers for pH adjustment, it is necessary to prepare them as separate external reaction solutions There is. In that case, three or more kinds of external reaction solutions will be used.

  The phosphoric acid supply material of the present invention is a compound containing phosphorus and oxygen as main constituent elements, has a P—O bond, is water-soluble, and has no reactivity with the gel. For example, ammonium phosphate, diammonium hydrogen phosphate, ammonium dihydrogen phosphate, calcium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, potassium phosphate, dipotassium hydrogen phosphate, phosphoric acid Examples include potassium dihydrogen, sodium phosphate, sodium monohydrogen phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium ammonium hydrogen phosphate, magnesium phosphate, lithium phosphate, and hydrates thereof. . Moreover, said compound may be used independently and may use 2 or more types together. Among the above, ammonium phosphate, diammonium hydrogen phosphate, ammonium dihydrogen phosphate, sodium phosphate, sodium monohydrogen phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium ammonium hydrogen phosphate, and these It is preferable to use at least one selected from the group consisting of:

  The calcium supply material of the present invention is not particularly limited as long as it is a compound containing calcium as a main constituent element and is water-soluble and does not have reactivity with the gel. For example, calcium nitrate, Calcium chloride, calcium carbonate, calcium hydrogen phosphate, calcium phosphate, calcium dihydrogen phosphate, calcium diphosphate, calcium hydroxide, calcium oxalate, calcium acetate, calcium alginate, calcium citrate, calcium butyrate, calcium gluconate, calcium glypyrrolate , Calcium iodide, calcium lactate, calcium oxide, calcium pyrophosphate, calcium stearate, calcium sulfate, and hydrates thereof. Moreover, said compound may be used independently and may use 2 or more types together. Among the above, from the group consisting of calcium nitrate, calcium chloride, calcium carbonate, calcium hydrogen phosphate, calcium phosphate, calcium dihydrogen phosphate, calcium diphosphate, calcium hydroxide, calcium oxalate, calcium acetate, and hydrates thereof It is preferable to use at least one selected.

Further, as the external reaction solution for supplying hydroxide ions (OH ⁻ ), it is preferable to use at least one selected from the group consisting of water-soluble compounds such as sodium hydroxide, potassium hydroxide and ammonium hydroxide. , halide ions (Cl ^-, F ^-) as the external reaction solution supplying, sodium chloride, potassium chloride, ammonium chloride, hydrochloric acid, sodium fluoride, potassium fluoride, ammonium fluoride, water-soluble compounds such as hydrofluoric acid It is preferable to use at least one selected from the group consisting of:

  The solvent used in the external reaction solution is not particularly limited as long as it can dissolve or disperse the phosphoric acid supply material or the calcium supply material, but water is usually used.

  Furthermore, the solvent used in the gel solution is not particularly limited as long as it can dissolve or disperse the gel powder, but water is usually used. For example, it is possible to use a method in which an aqueous gel solution dissolved in a hot water bath is gelled by cooling or heating, or a matrix is formed by adding a pH adjuster to the gel solution.

  Further, the concentration of the phosphoric acid supply material or calcium supply material in the gel may be equal to or lower than the saturation concentration when these materials are dissolved in water. This is because crystals can be grown at a saturation concentration or less. Further, although it is considered that the concentration affects the crystal size and the number of nuclei generated, the lower limit value of the concentration is not particularly limited. This is because when the obtained crystal is fine, it has an advantage that it can be directly injected into a living body with a syringe or the like.

2. Crystal Growth Step Next, the crystal growth step in the method for producing the calcium phosphate spherulites of the present invention will be described. The crystal growth step in the present invention is a step of growing crystals by bringing the gel and two or more types of external reaction solutions into contact with each other and diffusing the external reaction solution into the gel.

  The method for bringing the gel and the external reaction solution into contact is not particularly limited as long as the gel is not destroyed. For example, as shown in FIG. 2, the external reaction solution is placed in a container 4 containing the gel 2. Examples thereof include a batch type production method for injecting 1a and 1b. Further, there is a continuous production method in which an external solution is brought into contact with a flowing gel and the gel or the external solution is continuously supplied.

  In this step, since the concentration of the phosphate supply material or calcium supply material to the gel matrix is constant, the crystal growth rate tends to decrease with time. Therefore, when it is desired to keep the crystal growth rate constant, the concentration of the external reaction solution may be adjusted appropriately, or the external reaction solution supply rate may be increased by keeping the concentration of the external reaction solution constant. May be.

  The temperature in this step is not particularly limited as long as the gel is not destroyed or does not hinder crystal growth, and is usually about room temperature.

3. Crystal separation step Next, the crystal separation step in the method for producing the calcium phosphate spherulites of the present invention will be described. The crystal separation step in the present invention is a step of separating the spherulites and the gel.

  Examples of the method for separating the spherulites and the gel include a method of dissolving the gel in warm water. The medium for dissolving the gel is not limited to warm water, but an aqueous medium is the most effective from the economical and environmental viewpoints. In addition to warm water, boiling water (hot water) can also be used as an aqueous medium.

  The average particle diameter of the calcium phosphate spherulites produced according to the present invention is not particularly limited. This is because crystals having a small particle size, for example, those having a particle diameter of less than 1 μm can be directly injected into a living body as nanoparticles, for example. Furthermore, since the surface area is remarkably increased, high performance as an adsorption / absorption material can be expected. Further, a crystal having a large particle diameter, for example, 1 μm or more is easy to process, and can be directly used as, for example, a bone forming material. Furthermore, one spherulite reaches a size that can be used as a cell culture substrate.

  In addition, since it is the same as that of what was described in the above-mentioned "A. artificial calcium phosphate spherulite" about the other point of the said calcium phosphate spherulite, description here is abbreviate | omitted.

  The present invention is not limited to the above embodiment. The above-described embodiment is an exemplification, and the present invention has substantially the same configuration as the technical idea described in the claims of the present invention, and any device that exhibits the same function and effect is the present invention. It is included in the technical scope of the invention.

  Hereinafter, the present invention will be specifically described with reference to Examples and Comparative Examples.

[Example 1]
60 ml of ion-exchanged water was put in a U-shaped test tube, agar powder (0.27 g) was added, and the agar powder was dissolved while boiling in 90 ° C. warm water. The test tube was cooled in water and gelled. After gelation, Ca (NO ₃ ) ₂ · 4H ₂ O aqueous solution (20 ml) adjusted to 0.25 M as an external reaction solution is gently poured from one inlet so that the gel is not destroyed, and from the other inlet (NH ₄ ) ₂ HPO ₄ aqueous solution (20 ml, 0.15 M) was poured in the same manner, and left standing in a constant temperature bath at 37 ° C. After crystal growth, the gel was dissolved in warm water to separate the grown spherulites. After 20 days of development, it could develop white _{Ca 8 H 2 (PO 4)} 6 · 5H 2 O spherulites reaching a maximum diameter of about 300 [mu] m. An SEM photograph of the obtained spherulite is shown in FIG. Moreover, when this crystal was observed by TEM, it was confirmed that individual fibrous crystals forming spherulites were <001> elongated.

[Example 2]
A Ca (NO ₃ ) ₂ .4H ₂ O aqueous solution adjusted to 0.25M was used as an external reaction solution containing a calcium ion source, and an Na ₂ HPO ₄ · adjusted to 0.15M was used as an external reaction solution containing a phosphate ion source. Crystals were grown in the same manner as in Example 1 except that NaOH (20 ml) adjusted to 0.05 M was used as an external reaction solution containing a 12H ₂ O, OH source, and white Ca ₈ H ₂ (PO ₄ ) ₆ · 5H ₂ O with _{Ca 10 (OH) 2 (PO} 4) was grown for ₆ spherulites.

[Example 3]
A Ca (NO ₃ ) ₂ .4H ₂ O aqueous solution adjusted to 0.25M was used as an external reaction solution containing a calcium ion source, and an Na ₂ HPO ₄ · adjusted to 0.15M was used as an external reaction solution containing a phosphate ion source. Crystals were grown in the same manner as in Example 1 except that NaCl (20 ml) adjusted to 0.05 M was used as an external reaction solution containing a 12H ₂ O, OH source, and white Ca ₈ H ₂ (PO ₄ ) ₆ · 5H ₂ O with _Ca 10 _Cl 2 _{(PO 4)} was grown for ₆ spherulites.

[Example 4]
A Ca (NO ₃ ) ₂ .4H ₂ O aqueous solution adjusted to 0.25M was used as an external reaction solution containing a calcium ion source, and an Na ₂ HPO ₄ · adjusted to 0.15M was used as an external reaction solution containing a phosphate ion source. Crystals were grown in the same manner as in Example 1 except that NaF (20 ml) adjusted to 0.05 M was used as an external reaction solution containing a 12H ₂ O, OH source, and white Ca ₈ H ₂ (PO ₄ ) ₆ · 5H ₂ O with _Ca 10 _F 2 _{(PO 4)} was grown for ₆ spherulites.

[Example 5]
A CaCl ₂ aqueous solution adjusted to 0.20M was used as an external reaction solution containing a calcium ion source, and Na ₂ HPO ₄ · 12H ₂ O adjusted to 0.15M was used as an external reaction solution containing a phosphate ion source. growing a crystal in the same manner as in example 1, was the resulting crystals were dried at 100 ° C. dryer, foster CaHPO ₄ spherulites with white _{Ca 8 H 2 (PO 4)} 6 · 5H 2 O did it.

[Example 6]
A CaCl ₂ aqueous solution adjusted to 0.20M was used as an external reaction solution containing a calcium ion source, and Na ₂ HPO ₄ · 12H ₂ O adjusted to 0.15M was used as an external reaction solution containing a phosphate ion source. When crystals were grown in the same manner as in Example 1, CaHPO ₄ · 2H ₂ O spherulites could be grown together with white Ca ₈ H ₂ (PO ₄ ) ₆ · 5H ₂ O.

[Example 7]
Using an aqueous Ca (NO ₃ ) ₂ .4H ₂ O solution adjusted to 0.15M as an external reaction solution containing a calcium ion source, Na ₂ HPO ₄ · adjusted to 0.10M as an external reaction solution containing a phosphate ion source. When except for using 12H ₂ O were grown crystals in the same manner as in example 1, a white _{Ca 8 H 2 (PO 4)} 6 · 5H 2 O with _Ca 3 _{(PO 4)} can train ₂ spherulites It was.

[Example 8]
A Ca (NO ₃ ) ₂ .4H ₂ O aqueous solution adjusted to 0.30M was used as an external reaction solution containing a calcium ion source, and Na ₂ HPO ₄ · adjusted to 0.15M was used as an external reaction solution containing a phosphate ion source. When except for using 12H ₂ O were grown crystals in the same manner as in example 1, a white _{Ca 8 H 2 (PO 4)} 6 · 5H 2 O with _{Ca 3 (PO 4) 2 ·} xH 2 O sphere I was able to grow crystals.

[Example 9]
Example 1 _Ca 8 _H 2 produced in _{(PO 4) 6 · 5H 2} O spherulites (0.2 g) or aqueous calcium phosphate prepared in Method spherulites (0.2 g), and methylene blue powder (0.25 mg) When 100 ml of ion-exchanged water was placed in a beaker and stirred, and the crystals were centrifuged, all of the spherulites prepared in Example 1 adsorbed methylene blue. Remained.

[Comparative Example 1]
When an external reaction solution containing a calcium feed material and an external reaction solution containing a phosphate feed material are mixed without using an agar gel matrix, very fine crystals are formed. The calcium phosphate-based spherulites that form a porous body cannot be obtained because the high-quality fibrous crystals unique to the present invention are intertwined in an extremely complicated manner.

[Comparative Example 2]
Crystals were grown in the same manner as in Example 1 except that the external reaction solution containing the calcium supply material was not added, and no crystals were produced.

[Comparative Example 3]
Crystals were grown in the same manner as in Example 1 except that the external reaction solution containing the phosphoric acid supply material was not added, and no crystals were produced.

It is a SEM photograph which shows an example of the calcium-phosphate type spherulite of this invention. It is process drawing which shows an example of the manufacturing method of the calcium-phosphate type spherulite of this invention.

Explanation of symbols

1a External reaction solution 1b External reaction solution 2 Agar gel 3 Calcium phosphate spherulite 4 U-shaped test tube

Claims (11)

  A calcium phosphate spherulite comprising a number of fibrous crystals, wherein the spherulite is porous.   2. The calcium phosphate spherulite according to claim 1, wherein a plurality of fibrous crystals are entangled to form a porous spherulite. The calcium phosphate spherulite according to any one of claims 1 and 2, wherein the calcium phosphate spherulite comprises a calcium phosphate compound represented by the following chemical composition formulas (1) to (8).
_{Ca 8 H 2 (PO 4)} 6 · 5H 2 O (1)
Ca ₁₀ (OH) ₂ (PO ₄ ) ₆ (2)
Ca ₁₀ Cl ₂ (PO ₄ ) ₆ (3)
Ca ₁₀ F ₂ (PO ₄ ) ₆ (4)
CaHPO ₄ (5)
_{CaHPO 4 · 2H 2 O (6} )
Ca ₃ (PO ₄ ) ₂ (7)
Ca ₃ (PO ₄ ) ₂ xH ₂ O (8)   The phosphate ion source solution and the calcium ion source solution are arranged on the surface side of the gel matrix where phosphate ions and calcium ions can diffuse without being in direct contact with each other, and the phosphate ion source solution and the calcium ions Contacting at least a portion of each of the source solution with the surface of the gel matrix, diffusing phosphate ions and calcium ions into the gel matrix from the contact surface of the phosphate ion source solution and the calcium ion source solution, The calcium phosphate spherulite according to any one of claims 1 to 3, wherein a calcium phosphate spherulite comprising fibrous crystals is produced by reacting phosphate ions and calcium ions in a gel matrix. Production method. Phosphate ion source capable of diffusing phosphate ions and calcium ions, and at least one ion of hydroxide ions or halide ions can be diffused without directly contacting each other on the surface side of the gel matrix A solution, a calcium ion source solution, and at least one solution of a hydroxide ion source solution or a halide ion source solution, and at least a portion of each ion source solution is in contact with the surface of the gel matrix Let
At least one ion of phosphate ion, calcium ion, hydroxide ion or halide ion is diffused in the gel matrix from each ion source solution, and in the gel matrix, phosphate ion, calcium ion, 5. A calcium phosphate spherulite composed of fibrous crystals is produced by reacting with at least one kind of hydroxide ion or halide ion. 6. A method for producing calcium phosphate spherulites. 6. The calcium phosphate spherulite formed of at least one of the calcium phosphate compounds represented by the following chemical composition formulas (1) to (8) is generated as the calcium phosphate spherulite. 2. A method for producing a calcium phosphate spherulite according to item 1.
_{Ca 8 H 2 (PO 4)} 6 · 5H 2 O (1)
Ca ₁₀ (OH) ₂ (PO ₄ ) ₆ (2)
Ca ₁₀ Cl ₂ (PO ₄ ) ₆ (3)
Ca ₁₀ F ₂ (PO ₄ ) ₆ (4)
CaHPO ₄ (5)
_{CaHPO 4 · 2H 2 O (6} )
Ca ₃ (PO ₄ ) ₂ (7)
Ca ₃ (PO ₄ ) ₂ xH ₂ O (8)   The method for producing calcium phosphate-based spherulites according to any one of claims 4 and 5, wherein an agar gel, gelatin gel, silica gel or cellulose-based gel is used as the gel matrix.   As phosphate ion source solution, ammonium phosphate, diammonium hydrogen phosphate, ammonium dihydrogen phosphate, sodium phosphate, sodium monohydrogen phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium ammonium hydrogen phosphate And a solution in which at least one selected from the group consisting of these hydrates is dissolved, The method for producing calcium phosphate-based spherulites according to any one of claims 4 to 7 .   The calcium ion source solution is composed of calcium nitrate, calcium chloride, calcium carbonate, calcium hydrogen phosphate, calcium phosphate, calcium dihydrogen phosphate, calcium diphosphate, calcium hydroxide, calcium oxalate, calcium acetate, and hydrates thereof. The method for producing calcium phosphate-based spherulites according to any one of claims 4 to 7, wherein a solution in which at least one selected from the group is dissolved is used. The hydroxide ion source solution is a solution in which at least one selected from the group consisting of sodium hydroxide, potassium hydroxide, and ammonium hydroxide is dissolved. A method for producing a calcium phosphate spherulite according to claim 1. As the halide ion source solution, a solution in which at least one selected from the group consisting of sodium chloride, potassium chloride, ammonium chloride, calcium chloride, sodium fluoride, potassium fluoride, and ammonium fluoride is dissolved is used. The method for producing a calcium phosphate spherulite according to any one of claims 4 to 9, wherein