JP4366105B2 - Granular apatite aiming at DDS and its production method - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
In relation to hydroxyapatite, which is a typical bioactive ceramic, which has been put to practical use as a bone filler and is also expected as a scaffold for tissue engineering in recent years, it relates to granular apatite aimed at DDS and a method for producing the same. Technology.
[0002]
[Prior art]
Hydroxyapatite (Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ : hereinafter abbreviated as HA) is a typical bioactive ceramic and has been put into practical use as a bone filler. In recent years, it is also expected as a scaffold for tissue engineering. In the conventional fabrication technique, an aqueous solution containing Ca and an aqueous solution containing P are mixed to form a calcium phosphate precipitate, and the precipitate is heated to a high temperature of about 900 ° C. or higher to form HA, or Ca and P are mixed. The contained solid is mixed and heated to about 900 ° C. or higher to make HA. HA heated at a high temperature is a polycrystal, and it has become necessary to have adsorption characteristics, particularly selectivity, higher than that of HA according to the prior art.
[0003]
Ioku et al. (Non-Patent Document 1) has a unique structure (acicular particles, control of crystal plane, bipolarization of pore size distribution), which is expected to be used as a scaffold for highly functional artificial bones and cultured bones. HA porous material having selenium and its production method have been reported (Non-patent Document 1). The method for producing the porous apatite is as follows. In order to create pores that are easy for cells to enter, α-TCP powder is coated with glycine (H ₂ NCH ₂ COOH, particle size of about 200 μm, Wako Pure Chemicals) or sodium chloride (NaCl, particle size of about 200 μm, Wako Pure Chemicals). 50-75 mass% was added. This mixed powder was pressure-molded to 8 mmφ × 5 mmL, and the compact was placed in a small autoclave (FIG. 1) and steam-treated at 30 to 200 ° C., 5 to 20 hours, and under saturated vapor pressure. The starting material and the prepared sample are subjected to chemical analysis by inductively coupled plasma mass spectrometry (ICP-MS), powder X-ray diffraction measurement (XRD), Fourier transform infrared spectroscopy (FT-IR), transmission electron microscope Evaluation was made by observation (TEM), scanning electron microscope observation (SEM), mercury intrusion pore size distribution measuring device (MIP), universal testing machine, and the like. The case where glycine is used as an additive to α-TCP will be described. Glycine was eluted by hydrothermal steam treatment at 200 ° C. for 5 hours. As a result, the crystal phase in the material was only HA. This HA was a Ca-deficient HA and Ca / P = 1.54. As the porosity of the porous material and the amount of glycine added increased, it was possible to control to about 70 to 90%. From SEM observation, the shape of the particles was needle-like, the long axis length was about 10 μm, and the aspect ratio was 30 or more. From MIP and SEM observations, the pore size distribution was bipolar, and it was composed of large pores of 100 μm or more in which cells could enter and fine pores of about 0.1 μm. The shape and size of the large pores are almost the same as those of the glycine particles, which suggests that pores were formed by elution of glycine. On the other hand, it is considered that fine pores were formed by entanglement of the generated HA needle-like particles. It can be inferred that this acicular particle has selectivity for the adsorption and desorption of a substance because a lot of the a-plane is exposed. When NaCl was used as an additive to α-TCP, a porous structure having a bipolar pore diameter was formed under the same conditions as in the previous experiment in which glycine was added. However, the shape of pores of about 100 μm was clearly different from that of glycine, and pores reflecting the shape of NaCl crystals were formed. Therefore, it may be a material for investigating the influence of pore shape on cell activity.
[0004]
Since HA is excellent in adsorbing proteins and amino acids, research on chromatographic packing materials and DDS (Drug Delivery System) is also underway. As an example of a patent relating to DDS, a patent entitled “Porous Hydroxyapatite Particles as a Drug Substance Carrier” has been published (Patent Document 1). The HA ceramics used in this method are polycrystalline, and the adsorption selectivity and adsorption control are not performed.
[0005]
[Patent Document 1]
Special table 2001-524513
[Non-Patent Document 1]
Ioku, Misumi, Fujimori, Sanaki, Goto; Proceedings of the 15th Autumn Symposium (sponsored by the Ceramic Society of Japan), p. 110, 2002
[0006]
[Problems to be solved by the invention]
In the present invention, a granular high-functional material having a controlled particle shape and crystal plane for constructing a material structure, and a method for producing the same, for the purpose of producing a material having better adsorption characteristics than the current HA sintered porous body Development is the issue.
[0007]
[Means for Solving the Problems]
The granular apatite of the present invention is mainly a granular apatite suitable for use as a DDS or chromatographic filler. It is also a granular apatite that is useful as a scaffold for bone filler and tissue engineering. Compared with HA produced by conventional high-temperature heating, the granular apatite of the present invention is a granular apatite having better adsorption characteristics, particularly selectivity, than HA according to the prior art, and particularly for DDS and chromatography. Suitable for use as a filler.
[0008]
Granular apatite having good adsorption characteristics, particularly selectivity, over HA according to the prior art is a granular apatite in which the crystal phase in the sample is composed only of HA, and the size of the HA granule is about 100 μm. , HA granules are characterized by being constructed of acicular particles. In particular, the long axis length of the acicular particles is about 10 to 100 μm, the aspect ratio is 20 or more, and the HA acicular particles are controlled in crystal plane, and in particular, granules in which many a-planes are exposed as crystal planes. Apatite is preferable from the viewpoint of the selectivity of adsorption and desorption of substances.
[0009]
Compared with the polycrystalline HA prepared by conventional high-temperature heating, the HA of the present invention, which is excellent in selectivity of adsorption and desorption of substances, can be prepared by a hydrothermal method. α-Tricalcium phosphate (α-TCP) powder is added to an aqueous gelatin solution to form a slurry. The slurry is added dropwise to vegetable oil, stirred, recovered, and heated to produce α-TCP granular particles. The α-TCP granules can be produced by steam treatment under conditions of saturated vapor pressure using a small autoclave.
[0010]
In the production of granular apatite, crystals were grown under hydrothermal conditions in order to make the constituent particles acicular with a specific crystal plane exposed. That is, α-tricalcium phosphate (α-Ca ₃ (PO ₄ ) ₂ : α-TCP, Taihei Chemical Industry) powder is added to a gelatin (Wako Pure Chemical Industries) 3 to 30% aqueous solution at 30 to 90 ° C. It was made into the slurry form. This slurry was dropped into vegetable oil and stirred for 1 hour. After collecting the sample, it was heated at 1190 to 1300 ° C. for 30 minutes to 3 hours to produce α-TCP granular particles. This α-TCP granule was steam-treated using a small autoclave shown in FIG. 1 at 30 to 200 ° C. for 5 to 20 hours under the conditions of saturated vapor pressure.
[0011]
DETAILED DESCRIPTION OF THE INVENTION
DESCRIPTION OF THE PREFERRED EMBODIMENTS Embodiments of the present invention will be described with reference to the drawings based on examples.
[0012]
【Example】
An example of the method for producing the granular apatite of the present invention will be described. α-Tricalcium phosphate (α-Ca ₃ (PO ₄ ) ₂ : α-TCP, Taihei Chemical Industry) powder was added to a gelatin (Wako Pure Chemical Industries) 10% aqueous solution to form a slurry at 80 ° C. This slurry was added dropwise to vegetable oil and stirred for 1 h. After collecting the sample, it was heated at 1200 ° C. for 3 hours to produce α-TCP granular particles. This α-TCP granule was steam-treated using a small autoclave shown in FIG. 1 under the conditions of 200 ° C., 10 hours, and saturated vapor pressure.
[0013]
The starting material and the prepared sample are subjected to chemical analysis by inductively coupled plasma mass spectrometry (ICP-MS), powder X-ray diffraction measurement (XRD), Fourier transform infrared spectroscopy (FT-IR), transmission electron microscope Evaluation was made by observation (TEM), scanning electron microscope observation (SEM), mercury intrusion pore size distribution measuring device (MIP), universal testing machine, and the like.
[0014]
It was possible to control the sample size by adjusting the concentration of the α-TCP / gelatin slurry and the stirring speed of the vegetable oil. When the sample was heated at 1190-1300 ° C. for 30 minutes to 3 hours, the gelatin disappeared and α-TCP granular particles were obtained. This α-TCP granule was treated with water vapor at 120 to 200 ° C. for 5 to 20 hours, so that the crystal phase in the sample was only HA.
[0015]
A scanning electron microscope (SEM) photograph of the HA granular particles obtained by steam treatment at 200 ° C. for 20 hours is shown in FIG. The size of the HA granules was about 100 μm (FIG. 2 (a)), and the HA granules were constructed by acicular particles (FIG. 2 (b)). The acicular particles had a major axis length of about 50 μm and an aspect ratio of 40 or more. Moreover, HA needle-like particle | grains exposed many a surface.
[0016]
【The invention's effect】
Granular hydroxyapatite constructed from acicular particles was produced by a hydrothermal process. Since the crystal plane is controlled and the pore diameter is controlled, the material is expected to be applied as a highly functional material having excellent adsorption characteristics.
[Brief description of the drawings]
FIG. 1 is a diagram showing an outline of a small autoclave for reaction (the internal volume of a chamber is about 100 cm ³ ).
FIG. 2 is a view showing an SEM image of granular apatite.

Claims (4)

Granular apatite whose crystal phase in the sample is only hydroxyapatite (HA) ,
HA granules are constructed of acicular particles,
Granular apatite having a long axis length of about 10 to 100 μm and an aspect ratio of 20 or more, and HA needle-like particles have a lot of a-faces, so that they have selectivity in adsorbing and desorbing substances . Granular apatite according to claim 1 size of HA granules is about 100 [mu] m. A method for producing granular apatite in which a crystal phase in a sample is only hydroxyapatite (HA),
α-Tricalcium phosphate (α-TCP) powder is added to an aqueous gelatin solution of 3 to 30% to form a slurry. The slurry is dropped into vegetable oil, stirred for 1 hour, sample recovered, 1190 to 1300 ° C., 30 min and heated to 3 hours to produce alpha-TCP granular particles, the alpha-TCP granules, using a small autoclave, 30 to 200 ° C., 5～20H, condyle you steamed at the conditions of saturated vapor pressure Production method of granular apatite. A method for producing granular apatite in which a crystal phase in a sample is only hydroxyapatite (HA),
α-Tricalcium phosphate (α-TCP) powder is added to a gelatin 10% aqueous solution to form a slurry, and the slurry is dropped into vegetable oil, stirred for 1 hour, and after sample collection, 1190-1300 ° C., 30 minutes- and heated for 3 hours to prepare alpha-TCP granular particles, the alpha-TCP granules, using a small autoclave, 30 to 200 ° C., 5～20H, condyle granular apatite you steamed at the conditions of saturated vapor pressure Manufacturing method.

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