JP6710410B2 - Inorganic crystal - Google Patents

Description

The present invention relates to an anisotropically shaped hydroxyapatite liquid crystal, a colloidal aqueous solution and an alignment film containing anisotropically shaped hydroxyapatite crystals, a method for preparing an aqueous colloidal solution containing anisotropically shaped hydroxyapatite crystals, and the colloidal aqueous solution. The present invention relates to a method for manufacturing an alignment film. The present invention also relates to a method for preparing an organic-inorganic composite in which the crystal orientation of hydroxyapatite is controlled.

Hydroxyapatite is a main component of teeth and bones, and is expected to be applied to biomaterials and medical materials as a highly biocompatible material. In teeth and bones, hydroxyapatite nanocrystals are arranged in the same direction, and an anisotropic structure with uniform crystal orientation is formed. Up to now, many attempts have been reported to control the crystal orientation of hydroxyapatite using an organic polymer in order to construct such a structure (Non-patent Documents 1 and 2). However, it is difficult for the hydroxyapatite crystals obtained by such a method to maintain a dispersed state in a solution for a long period of time, and it is also difficult to control the arrangement of these crystals.

Science, 2001, 294, 1684-1688. Nature Materials, 2010, 9, 1004-1009. Advanced Materials, 2008, 20, 1633-1637. Angewandte Chemie International Edition, 2008, 47, 2800-2803. MRS Bull, 2010, 35, 127-132.

It is an object of the present invention to provide a simple method for synthesizing anisotropically shaped crystals of hydroxyapatite whose dispersion state is stabilized in a solvent and a method for controlling the orientation of those crystals on a macroscopic scale. ..
Further, the present invention, by establishing a method of imparting a liquid crystallinity capable of simple molding processing and orientation control to a hard and brittle inorganic ceramics, the orientation of hydroxyapatite crystals on a macroscopic scale, which was conventionally difficult. It is intended to provide a method of control.

The present inventor, as a result of extensive studies to solve the above problems, stabilized amorphous calcium phosphate with an organic polymer, and by performing crystal growth via this, anisotropic crystal growth of hydroxyapatite was achieved. It was discovered that rod-shaped crystals were obtained. Furthermore, the present inventor has found that the adsorption of the polymer on the surface of the obtained composite can prevent aggregation between nanorod crystals by electrostatic repulsion and stabilize the colloidal state and the liquid crystal state.

That is, the present invention is
[1] An anisotropically shaped hydroxyapatite liquid crystal.
[2] A colloidal solution containing anisotropic hydroxyapatite crystals.
[3] The colloidal solution according to [2], wherein the organic polymer is adsorbed on the surface of the anisotropically shaped hydroxyapatite crystal.
[4] The colloidal solution according to [2] or [3], wherein the anisotropically shaped hydroxyapatite crystal has a volume fraction of more than 7.6 and less than 8.8 vol %.
[5] The colloidal solution according to [2] or [3], wherein the anisotropically shaped hydroxyapatite crystal has a volume fraction of 8.8 vol% or more.
[6] The colloidal solution according to [5], which exhibits liquid crystallinity.
[7] An alignment film containing anisotropic hydroxyapatite crystals.
[8] The alignment film according to [7], wherein the c-axis of anisotropic hydroxyapatite crystals is approximately aligned in the shear direction.
[9] The alignment film according to [7], wherein anisotropic hydroxyapatite crystals are radially aligned.
[10] Aligning the major axis of the hydroxyapatite crystals in one direction perpendicular to the magnetic field direction by applying a magnetic field to a colloidal solution containing anisotropic hydroxyapatite crystals exhibiting liquid crystallinity , A method for controlling the crystal orientation of hydroxyapatite.
[11] A composite containing anisotropic hydroxyapatite crystals and organic molecules.
[12] (1) A step of mixing a first solution containing calcium ions and an organic polymer with a second solution containing phosphate ions to prepare a mixed solution, and (2) a precipitate from the mixed solution. A method for preparing a colloidal solution containing anisotropically shaped hydroxyapatite crystals, which comprises a step of separating and collecting.
[13] The method according to [12], wherein the organic polymer is polyacrylic acid.
[14] The method according to [12] or [13], wherein the volume fraction of anisotropically shaped hydroxyapatite crystals in the colloidal solution is 8.8 vol% or more.
[15] The method according to any one of [12] to [14], which comprises a step of concentrating anisotropic hydroxyapatite crystals to a volume fraction of 8.8 vol% or more.
[16] The method according to [14] or [15], wherein the colloidal solution exhibits liquid crystallinity.
[17] A method for producing an alignment film, which comprises applying a liquid crystal colloidal solution containing an anisotropically shaped hydroxyapatite crystal to a substrate and applying shear to the solution.
[18] (1) A step of mixing a liquid crystalline colloidal solution containing an anisotropically shaped hydroxyapatite crystal and an organic molecule,
(2) orienting anisotropic hydroxyapatite crystals in the process of evaporating the solvent in the colloidal solution, and (3) photopolymerizing the organic molecules.
A method for preparing an organic-inorganic composite in which the crystal orientation of hydroxyapatite is controlled, comprising:
Is provided.

According to the present invention, it is possible to provide a simple method for synthesizing anisotropically shaped crystals of hydroxyapatite whose dispersion state is stabilized in a solvent and a method for controlling the orientation of these crystals on a macroscopic scale. A tooth or bone mainly composed of hydroxyapatite has a structure in which hydroxyapatite crystals are aligned in its nanostructure.Therefore, the orientation control technology of the hydroxyapatite crystal using the liquid crystalline hydroxyapatite according to the present invention is applied to an actual tooth or bone. Since a structure close to bone can be constructed, construction of a medical material having excellent biocompatibility and ability to repair an affected area can be expected as compared with conventional dental materials such as artificial bones and implants.
Further, by imitating the nanostructure of teeth and bones, it is considered possible to develop high-strength materials having excellent mechanical properties such as teeth and bones.
Further, according to the present invention, it is possible to provide an alignment film containing anisotropic hydroxyapatite crystals. The alignment film of the present invention may be applied as a scaffold for cell culture, and development of a scaffold material having an anisotropic structure can be expected, and there is a possibility that the morphology of cells growing on the scaffold can be controlled. Hydroxyapatite is also used as a packing material for column chromatography of peptides, nucleic acids, polysaccharides and the like. According to the present invention, it is possible to construct a packing material having a specific orientational structure, and it is possible to study its application to column chromatography having excellent separation ability in the purification of drugs.

Transmission electron micrograph of hydroxyapatite nanorod crystals of Example 1. Photograph of a colloidal aqueous solution of hydroxyapatite nanorod crystals of Example 1 having a volume fraction of 8.8 vol% Polarization micrograph of a colloidal aqueous solution of hydroxyapatite nanorod crystals of Example 1 having a volume fraction of 8.8 vol%. Phase diagram on liquid crystallinity of colloidal aqueous solution containing hydroxyapatite nanorod crystals Transmission electron micrograph of a non-limiting example of nanorod crystals in a liquid crystalline colloid solution Electron diffraction patterns of non-limiting examples of nanorod crystals in liquid crystalline colloidal solution Polarization micrograph and schematic diagram of hydroxyapatite nanorod aggregates uniaxially oriented by shearing Polarization microscopic image of hydroxyapatite nanorod aggregates radially aligned by spin coating and its schematic diagram Polarization microscopic image of a composite of hydroxyapatite nanorods and poly(2-hydroxyethylmethacrylate) oriented concentrically and its schematic diagram Polarization micrograph of liquid crystalline colloidal solution of hydroxyapatite nanorods before applying magnetic field Polarization micrograph of liquid crystalline colloidal solution of hydroxyapatite nanorods after applying 9.3T magnetic field

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.

One aspect of the present invention is an anisotropically shaped hydroxyapatite liquid crystal.
Moreover, one aspect of the present invention is an anisotropically shaped hydroxyapatite crystal.

Examples of anisotropic shapes of the hydroxyapatite liquid crystal and the hydroxyapatite crystal include nanoscale rod shapes (nanorods), peanut shapes, dumbbell shapes, and plate shapes.

As a non-limiting example of anisotropically shaped hydroxyapatite crystals of the present invention, a transmission electron micrograph of hydroxyapatite nanorod crystals is shown in FIG. 1a.

The anisotropic hydroxyapatite crystal size of the present invention is, for example, in the case of a nanorod crystal, the length thereof is usually 20 nm to 200 nm, preferably 50 nm to 150 nm. The width of the anisotropic hydroxyapatite crystal is usually 5 nm to 50 nm, preferably 5 nm to 30 nm.
In the present invention, the length and width of anisotropic hydroxyapatite crystals can be adjusted by changing adjustment conditions such as the concentration of polyacrylic acid.

Another aspect of the invention is a colloidal solution containing anisotropically shaped crystals of hydroxyapatite.
A preferred aspect of the present invention is a colloidal solution containing anisotropically shaped hydroxyapatite nanorod crystals.
Preferably, the colloidal solution is an aqueous colloidal solution.
Further, the colloidal solution of the present invention can contain an organic solvent such as ethylene glycol, dimethyl sulfoxide, dimethylformamide, tetrahydrofuran, dioxane, methanol, ethanol, butanol, etc. within a range that does not impair the effects of the present invention.

In the colloidal solution of the present invention, anisotropic hydroxyapatite crystals, preferably nanorod crystals, have a structure in which an organic polymer is adsorbed on the surface of the crystal. Although not intending to be bound by theory, it is possible to stabilize the colloidal state and liquid crystal state of the colloidal solution by preventing the aggregation of crystals by electrostatic repulsion by adsorbing the polymer on the surface of the crystal. Therefore, operations such as surface modification for stabilizing the liquid crystal state and solvent replacement can be omitted.

Examples of the organic polymer include polymers derived from amino acids such as polyacrylic acid, polyglutamic acid, and polyaspartic acid, polyvinylpyrrolidone, polyvinyl alcohol, and polyethylene glycol. Polyacrylic acid is preferable because it can stabilize the colloidal state.

In one example of the colloidal solution of the present invention, its liquid crystallinity was observed, and as shown in FIG. 2, when the volume fraction of hydroxyapatite nanorod crystals was 7.6 vol% or less, it was an isotropic phase and was larger than 7.6%. When it is less than 8.8 vol%, two phases of an isotropic phase and a liquid crystal phase coexist, and when it is 8.8 vol% or more, a liquid crystal phase appears.
That is, one embodiment of the present invention is a colloidal solution in which the volume fraction of anisotropically shaped hydroxyapatite crystals is greater than 7.6 vol% and less than 8.8 vol%.
Further, another embodiment of the present invention is a colloidal solution in which the volume fraction of anisotropically shaped hydroxyapatite crystals is 8.8 vol% or more.

Further, one aspect of the present invention is a liquid crystalline colloid solution in which the volume fraction of anisotropically shaped hydroxyapatite crystals is 8.8 vol% or more.

FIG. 3a shows a transmission electron micrograph of a non-limiting example of nanorod crystals in a liquid crystalline colloid solution. From FIG. 3a, it can be seen that this nanorod crystal has a secondary structure in which smaller needle-like crystals are oriented and gathered. Further, it is found from this transmission electron microscope observation that the c-axis of the hydroxyapatite crystal is oriented in the major axis direction of the nanorod crystal.
Moreover, FIG. 3b shows the electron diffraction pattern of this nanorod crystal. The arc-shaped pattern of the electron diffraction measurement shows that the hydroxyapatite crystals are oriented in the range of the transmission electron microscope image.
That is, the hydroxyapatite nanorod crystals in the liquid crystalline colloidal solution of the present invention have a crystallographically oriented structure although they are polycrystalline.

As a non-limiting example of the aqueous colloidal solution containing anisotropic hydroxyapatite crystals of the present invention, a photograph of a colloidal aqueous solution containing hydroxyapatite nanorod crystals is shown in FIG. 1b, and a polarization micrograph is shown in FIG. 1c. Here, the volume fraction of the nanorod crystal is 9.2 vol %.
Without intending to be bound by theory, anisotropic colloidal hydroxyapatite crystals, preferably colloidal aqueous solutions containing nanorod crystals, are dispersion stabilized by the polyacrylic acid present on the crystal surface, No precipitation or aggregation is seen even in concentrated solutions (Fig. 1b). Furthermore, the colloidal aqueous solution having a volume fraction of the nanorod crystals of 8.8 vol% or more exhibited optical anisotropy, and it was confirmed that the nanorods spontaneously aligned and exhibited a liquid crystal state (FIG. 1c).

Another aspect of the present invention is an alignment film containing anisotropically shaped hydroxyapatite crystals.
A preferred aspect of the present invention is an alignment film containing anisotropically shaped hydroxyapatite nanorod crystals.
The alignment film of the present invention can be obtained by applying shear to anisotropic hydroxyapatite crystals.

One embodiment of the present invention is an alignment film in which the c-axis of anisotropic hydroxyapatite crystals is approximately oriented in the shear direction. Specifically, such an alignment film is formed, for example, by sandwiching a colloidal solution containing anisotropic hydroxyapatite crystals showing a liquid crystal phase between substrates such as glass and applying shear in one direction. Can be obtained.

Further, another embodiment of the present invention is an alignment film in which anisotropic hydroxyapatite crystals are radially aligned. Such an alignment film can be obtained by spin coating a colloidal solution containing anisotropic hydroxyapatite crystals. Specifically, for example, an alignment film can be obtained by spin coating a colloidal solution containing anisotropic hydroxyapatite crystals showing a liquid crystal phase on a substrate such as glass.

A non-limiting example of an alignment film containing anisotropically shaped hydroxyapatite crystals of the present invention is shown in FIG. FIG. 4a shows a polarization micrograph of a hydroxyapatite nanorod aggregate uniaxially oriented by shearing and a schematic diagram thereof.
Further, FIG. 4b shows a polarization microscope image of a hydroxyapatite nanorod aggregate radially aligned by spin coating and a schematic diagram thereof.

Yet another embodiment of the present invention is to apply a magnetic field to a colloidal solution containing anisotropic hydroxyapatite crystals exhibiting liquid crystallinity, whereby the length of the hydroxyapatite crystals is increased in one direction perpendicular to the magnetic field direction. A method for controlling the orientation of hydroxyapatite crystals, which comprises orienting the axes.
Preferably, the anisotropic shaped hydroxyapatite crystals are anisotropic shaped hydroxyapatite nanorod crystals. Also preferably, the colloidal solution is an aqueous colloidal solution.
The applied magnetic field is usually 2 to 10 T, preferably 8 to 10 T.

As an example of this embodiment, a result of orienting the long axis of the nanorod crystal in one direction perpendicular to the magnetic field direction by applying a magnetic field of 9.3 T to a hydroxyapatite nanorod colloid aqueous solution showing a liquid crystal phase is shown. 5 (see Example 6). FIG. 5a. FIG. 5b is a polarization microscope photograph of a liquid crystalline colloidal solution of hydroxyapatite nanorods after applying a magnetic field of 9.3T, before applying a magnetic field.

Yet another aspect of the invention is a composite comprising anisotropically shaped crystals of hydroxyapatite and an organic molecule.
The composite of the present invention is a mixture of a colloidal solution containing anisotropic hydroxyapatite crystals exhibiting a liquid crystal phase and an organic molecule, and evaporating the solvent in the colloidal solution to form an anisotropic hydroxyapatite. Can be obtained by fixing the structure in which the crystals of hydroxyapatite are oriented by orienting the crystals of and the photopolymerization of the organic molecules.

A photopolymerizable molecule is preferably used as the organic molecule. Examples of the photopolymerizable molecule include 2-hydroxyethyl methacrylate, acrylamide, N-isopropylacrylamide, and N,N-dimethylacrylamide. Among them, 2-hydroxyethyl methacrylate is preferable because it does not hinder the dispersed state of nanorods.

A non-limiting example of a composite of anisotropically shaped hydroxyapatite crystals and organic molecules of the present invention is shown in Figure 4c. The figure is a polarization microscope image of a composite of hydroxyapatite nanorod crystals and poly(2-hydroxyethyl methacrylate) oriented concentrically, and a schematic view thereof.

Another aspect of the present invention is: (1) mixing a first solution containing calcium ions and an organic polymer with a second solution containing phosphate ions to prepare a mixed solution, and (2) the above It is a method of preparing a colloidal solution containing anisotropic hydroxyapatite crystals, which includes a step of separating and collecting a precipitate from a mixed solution.

The method for preparing the colloidal solution of the present invention is as follows. First, a complex having an amorphous structure containing water together with an organic polymer such as polyacrylic acid, calcium ions, and phosphate ions, that is, a precursor of amorphous calcium phosphate. It is characterized by forming a body and crystallizing it in the same reaction vessel. By having such a step, it is possible to prepare a hydroxyapatite nanorod crystal and a colloidal solution containing the nanoapatite crystal, which could not be obtained conventionally.

Examples of the organic polymer include polymers derived from amino acids such as polyacrylic acid, polyglutamic acid, and polyaspartic acid, polyvinylpyrrolidone, polyvinyl alcohol, and polyethylene glycol. Polyacrylic acid is preferable because it can stabilize the colloidal state.

The concentration range of polyacrylic acid in the first solution is 40 mM or more, preferably 60 mM or more, and about 150 mM is suitable. If it is 40 mM or more, nanorod crystals are formed.

The polyacrylic acid having an average molecular weight of about 2000 can be used.

In addition to polyacrylic acid, polyglutamic acid, polyaspartic acid, polyvinylpyrrolidone, and polyethylene glycol can be added to the first solution, and they are 50 mol%, 50 mol%, and 20 mol% or more, respectively, with respect to polyacrylic acid. A transparent and amorphous composite can be obtained even when added in an amount of 10 mol% or less and 10 mol% or more and 100 mol% or less.

Calcium chloride can be preferably used as the compound that generates calcium ions in the first solution. The concentration of calcium ions in the first solution is 80 mM or more, preferably 80 mM or more and 120 mM or less. If it is 80 mM or more, a sufficient amount of amorphous calcium phosphate is formed.
Further, as the compound that generates calcium ions in the first solution, the portion corresponding to X of CaX may be other as long as it has a solubility of about 100 mM. Examples thereof include acetic acid, and calcium acetate (Ca(CH ₃ COO) ₂ ) can also be preferably used. Similar transparent/amorphous solids can be obtained at 80 mM or more, but at 70 mM, not a solid but a cloudy colloidal dispersion. By using this colloid, a complex can be obtained. Even if the amount is 70 mM or less, the colloid can be obtained if the amount is 50 mM or more, although the yield varies.

As the compound that generates phosphate ions in the second solution, tripotassium phosphate (K ₃ PO ₄ ) is preferable. Further, trisodium phosphate (Na ₃ PO ₄ ) and triammonium phosphate ((NH ₄ ) ₃ PO ₄ ) can also be used.
The concentration of phosphate ions in the second solution is 80 mM or more, preferably 80 mM or more and 120 mM or less. If it is 80 mM or more, a sufficient amount of amorphous calcium phosphate is formed.

The mixing ratio of the first solution and the second solution is usually about 1:1 by volume.

A mixed solution obtained by mixing the first solution and the second solution at room temperature is usually stirred at 60° C. for about 3 to 7 days.
The mixed solution is usually prepared at room temperature and atmospheric pressure, and the stirring is usually performed at 60° C. and atmospheric pressure. However, if the temperature is 40° C. or lower, the progress of crystallization may be slowed down, but if there is no change in the water that is the solvent, a precipitate of the same structure is obtained within the range of 20° C. or higher and 90° C. or lower. Conceivable.

After stirring the mixed solution for 10 to 30 minutes, a polyacrylic acid, a phosphate ion, and a calcium ion are contained together with water, and a complex having an amorphous structure is formed. The complex can be precipitated as a transparent/amorphous solid, or can be present in a cloudy colloidal dispersion rather than as a solid.

A colloidal solution containing anisotropic hydroxyapatite crystals can be prepared by stirring the composite dispersion as it is for about 3 to 7 days at 60°C. Further, it is possible to separate the precipitate generated by the crystallization of the above complex after stirring to obtain anisotropic hydroxyapatite crystals. In addition, the precipitation may be recovered by another method as long as the precipitation can be recovered, instead of the centrifugal separation.

When a colloidal solution containing anisotropic hydroxyapatite crystals is concentrated so that the volume fraction of crystals is in the range of more than 7.6 vol% and less than 8.8 vol %, two phases, an isotropic phase and a liquid crystal phase, are formed. It will coexist.
Further, when a colloidal solution containing anisotropic hydroxyapatite crystals is concentrated to a crystal volume fraction of 8.8 vol% or more, liquid crystallinity is exhibited. An alignment film can be manufactured by applying a colloidal solution having such liquid crystallinity to a substrate and applying shear to the solution.

The material of the substrate is not particularly limited as long as it can be coated with a glass substrate, a plastic film or the like.

As a coating method, a coating method used for forming a thin film such as spin coating, reverse coating, gravure coating, micro gravure coating, dip coating, or flow coating can be appropriately used.

The shearing can be applied, for example, by applying a colloidal solution to a glass substrate, stacking the glass substrates on top of it, sandwiching the colloidal solution, and applying shearing in one direction. When shearing is applied by such a method, an oriented film in which the c-axis of anisotropic hydroxyapatite crystals is approximately oriented in the shearing direction can be suitably obtained.

Further, for example, an alignment film can be obtained by spin-coating a colloidal solution containing anisotropic hydroxyapatite crystals showing a liquid crystal phase on a substrate such as glass. In this case, an oriented film in which anisotropic hydroxyapatite crystals are oriented radially can be suitably obtained.

The thickness of the alignment film is usually 2 μm to 10 μm.

Another aspect of the present invention is: (1) a step of mixing a colloidal solution containing anisotropic hydroxyapatite crystals with an organic molecule, (2) a step of evaporating a solvent in the colloidal solution, A method for preparing a complex containing anisotropic hydroxyapatite crystals and organic molecules, comprising the steps of orienting anisotropically shaped hydroxyapatite crystals, and (3) photopolymerizing the organic molecules. ..

A photopolymerizable molecule is preferably used as the organic molecule. Examples of the photopolymerizable molecule include 2-hydroxyethyl methacrylate, acrylamide, N-isopropylacrylamide, and N,N-dimethylacrylamide. Among them, 2-hydroxyethyl methacrylate is preferable because it does not hinder the dispersed state of nanorods.

Preparation of a complex containing anisotropically shaped hydroxyapatite crystals and organic molecules is performed, for example, by combining a colloidal aqueous solution containing hydroxyapatite nanorod crystals with a photopolymerizable molecule such as 2-hydroxyethyl methacrylate to form a cylindrical shape. In the process of evaporating water in the glass container, the nanorods are aligned concentrically, and the alignment structure can be fixed by photopolymerizing a photopolymerizable molecule such as 2-hydroxyethyl methacrylate. ..

Hereinafter, the present invention will be described in more detail with reference to Examples, but the scope of the present invention is not limited to the following Examples.

[Example 1]
Preparation of Colloidal Aqueous Solution Containing Hydroxyapatite Nanorod Crystals A 100 mM calcium chloride aqueous solution containing 7.2×10 ⁻¹ wt% of polyacrylic acid having a molecular weight of 2.0×10 ³ was prepared, and an equal volume of 100 mM triphosphate was prepared. An aqueous potassium solution is prepared. After mixing the prepared two kinds of aqueous solutions at room temperature, the mixture is stirred in a constant temperature bath at 60° C. for 7 days. The precipitate is recovered from the aqueous solution by centrifugation. The collected product is not dried but redispersed in water for washing, and the precipitate is recovered again by centrifugation.

The observation result of the precipitate of hydroxyapatite nanorods obtained above by a transmission electron microscope (JEM-2800, JEOL) is shown in FIG. 1a.
Moreover, the observation result of one hydroxyapatite nanorod crystal by a transmission electron microscope is shown in FIG. 3a. From FIG. 3a, rod-shaped crystallites having a size of about 10-40 nm are confirmed. Moreover, the measurement result of the electron beam diffraction (JEM-2800, JEOL) of the hydroxyapatite nanorod crystal is shown in FIG. 3b. From FIG. 3b, it can be seen that the c-axis of the hydroxyapatite crystal is aligned in the long axis direction of the nanorod crystal. That is, the nanorod crystal has a crystallographically oriented structure although it is a polycrystalline body.

[Example 2]
Next, FIG. 1c shows the results of observing a colloidal aqueous solution containing 9.2 vol% of hydroxyapatite nanorod crystals (FIG. 1b) with a polarization microscope (BX51, Olympus). The colloidal solution exhibited liquid crystallinity with a fluid texture shown in the photograph of FIG. 1c. A phase diagram regarding liquid crystallinity is shown in FIG. When the volume fraction of hydroxyapatite nanorod crystals in the aqueous colloid solution is 7.6 vol% or less, an isotropic phase is present. When the volume fraction of hydroxyapatite nanorod crystals is more than 7.6 vol% and less than 8.8 vol%, two phases of an isotropic phase and a liquid crystal phase coexist, 8.8 vol%. The liquid crystal phase developed above.

[Example 3]
A colloidal solution containing 9.2 vol% hydroxyapatite nanorod crystals was sandwiched between glass substrates, and shear was applied in one direction. When this crystal was observed with a polarizing microscope (BX51, Olympus), as shown in FIG. 4a, bright and dark were repeated every 45 degrees under the observation with the polarizing microscope, and macroscopic uniaxial orientation of the c-axis of the hydroxyapatite crystal was observed. It was

[Example 4]
When a colloidal solution containing 7.3 vol% hydroxyapatite nanorod crystals was placed on a glass substrate and spin-coated at 2000 rpm for 30 seconds, a macroscopic radial arrangement of hydroxyapatite nanorods was observed by a polarization microscope as shown in FIG. 4b. ..

[Example 5]
90 μL of 2-hydroxyethyl methacrylate, 4 mg of N,N′-methylenebisacrylamide and 2 mg of 2,2-dimethoxy-2-phenylacetophenone were added to 250 μL of a colloidal solution containing 7.1 vol% hydroxyapatite nanorod crystals, and the mixture was allowed to stand at room temperature. After water was evaporated, UV irradiation (SP-9, Usio) was performed for 1 hour, and concentric alignment of the hydroxyapatite nanorods was observed by a polarization microscope as shown in FIG. 4c.

[Example 6]
When a magnetic field of 9.3 T was applied to a colloidal solution containing 8.8 vol% hydroxyapatite nanorod crystals by a nuclear magnetic resonance apparatus (JNM-LA400, JEOL), as shown in FIG. A uniaxial orientation perpendicular to the axial magnetic field direction was observed.

Claims (18)

A colloidal solution containing anisotropically shaped hydroxyapatite crystals in which an organic polymer is adsorbed on the surface , wherein the organic polymer is a polymer derived from an amino acid selected from polyacrylic acid, polyglutamic acid or polyaspartic acid. The colloidal solution selected from the group consisting of polyvinylpyrrolidone, polyvinyl alcohol and polyethylene glycol . The colloidal solution according to claim 1 , wherein the anisotropic shaped hydroxyapatite crystals have a volume fraction of more than 7.6 and less than 8.8 vol %. Volume fraction of hydroxyapatite crystals of the anisotropic shape is not less than 8.8vol%, colloid solution according to claim 1 or 2. The colloidal solution according to claim 3 , which exhibits liquid crystallinity. An anisotropically shaped hydroxyapatite crystal in which an organic polymer is adsorbed on the surface, wherein the organic polymer is a polymer derived from an amino acid selected from polyacrylic acid, polyglutamic acid or polyaspartic acid, polyvinylpyrrolidone, The hydroxyapatite crystals selected from the group consisting of polyvinyl alcohol and polyethylene glycol. A liquid crystal containing an anisotropically shaped hydroxyapatite crystal in which an organic polymer is adsorbed on the surface, wherein the organic polymer is a polymer derived from an amino acid selected from polyacrylic acid, polyglutamic acid or polyaspartic acid, The liquid crystal selected from the group consisting of polyvinylpyrrolidone, polyvinyl alcohol and polyethylene glycol. An alignment film containing the anisotropic hydroxyapatite crystals according to claim 5 . The alignment film according to claim 7, wherein the c-axis of the anisotropic hydroxyapatite crystal is approximately oriented in the shear direction. The alignment film according to claim 7, wherein the anisotropic hydroxyapatite crystals are radially aligned. A method for controlling the orientation of hydroxyapatite crystals, which comprises applying a magnetic field to the colloidal solution according to claim 1 to orient the major axis of the hydroxyapatite crystals in one direction perpendicular to the magnetic field direction. .. A complex comprising anisotropic hydroxyapatite crystals according to claim 5 and an organic molecule. (1) A step of preparing a mixed solution by mixing a first solution containing calcium ions and an organic polymer with a second solution containing phosphate ions, and (2) separating a precipitate from the mixed solution. A method for preparing a colloidal solution containing anisotropically shaped hydroxyapatite crystals in which an organic polymer is adsorbed on the surface, comprising the step of recovering , wherein the organic polymer is polyacrylic acid, polyglutamic acid or polyacrylic acid. The method selected from the group consisting of polymers derived from amino acids selected from aspartic acid, polyvinylpyrrolidone, polyvinyl alcohol and polyethylene glycol . The method according to claim 12, wherein the organic polymer is polyacrylic acid. The method according to claim 12 or 13, wherein a volume fraction of anisotropically shaped hydroxyapatite crystals in the colloidal solution is 8.8 vol% or more. The method according to any one of claims 12 to 14, comprising a step of concentrating the hydroxyapatite crystals having an anisotropic shape such that the volume fraction of the hydroxyapatite crystals is 8.8 vol% or more. The method according to claim 14 or 15, wherein the colloidal solution exhibits liquid crystallinity. Applying a liquid crystalline colloidal solution containing anisotropically shaped hydroxyapatite crystals to the substrate,
A method for producing an alignment film, which comprises applying shear to the solution. (1) A step of mixing an organic molecule with a liquid crystalline colloidal solution containing an anisotropically shaped hydroxyapatite crystal in which an organic polymer is adsorbed on the surface ,
(2) orienting anisotropic hydroxyapatite crystals in the process of evaporating the solvent in the colloidal solution, and (3) photopolymerizing the organic molecules.
A method for preparing an organic-inorganic composite in which the crystal orientation of hydroxyapatite is controlled , wherein the organic polymer is an amino acid-derived polymer selected from polyacrylic acid, polyglutamic acid or polyaspartic acid, and polyvinyl. The method selected from the group consisting of pyrrolidone, polyvinyl alcohol and polyethylene glycol .

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