JP2756703B2 - Spherical apatite, method for producing the same, and molded article with porous structure - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to an apatite useful as a material for filling a bone defect, a column packing material for chromatography, an immobilizing material for microorganisms and enzymes, etc. The present invention relates to a novel hydroxyapatite having a spherical shape and a method for producing the same, and a porous structure molded article containing the spherical apatite as an active ingredient.

[Conventional technology]

Apatite, which is a sintered body of calcium phosphate, is a bioactive material because it has a good affinity for living bone tissue and exhibits excellent functions for inducing new bone and binding to bone tissue. Attention has been paid. In addition, hydroxy-based particles of apatite have been widely used in the field of separation and collection of trace components in order to efficiently adsorb useful organic substances such as nucleic acids and proteins.

Conventionally, many clinical cases have been reported regarding a filling material for a bone defect using apatite granules.A typical method for producing crystalline hydroxyapatite is to gradually drop phosphoric acid into slaked lime slurry. To produce low crystalline hydroxyapatite by the following reaction,
A method of growing a crystal by heating it to a temperature of 800 ° C. for 3 hours is known (Makishima, Aoki “Bioceramics” 7, Gihodo (1984)).

10Ca (OH) ₂ + 6H ₃ PO ₄ → Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ + 18H ₂ O However, the above-mentioned method based on the reaction between slaked lime and phosphoric acid requires Ca
The molar ratio of / P tends to fluctuate, and there are difficulties in controlling the reaction conditions.

Porous apatite sintered bodies are used for similar applications, but in this case, a foaming agent such as hydrogen peroxide is added in the manufacturing process to form a cellular structure [Dental Journal, 17 (5) ) 623-633 (1983)]. However, in this method, the cell diameter and pore size vary greatly depending on the type of the foaming agent, and the strength varies, making it difficult to control the quality.

As an improved method, a method of producing a porous apatite body in which a water-based slurry of apatite is subjected to hydrothermal treatment to form a cross-linked porous body of needle-like crystals, which is then sintered and fused at a cross-contact point (JP-A-60-90880) Publication).

In addition, as a method for producing hydroxyapatite particles for the purpose of packing for chromatography columns, Tiselius
(1956) is well known. This method makes the crystals of calcium hydrogen phosphate (CaHPO ₄ · 2H ₂ O) from the phosphate and calcium salts, which although is to convert the hydroxyapatite by hydrolysis by boiling in an alkaline solution, This type of crystal has a problem that it is easily broken down by pressurization to block the column. For this reason, in a field requiring high-performance liquid chromatography or column operation, improvement in crystal strength is desired.

[Problems to be solved by the invention]

As described above, conventional apatite does not sufficiently satisfy the requirements in terms of properties or manufacturing method for the purpose of use, and there is much room for improvement. The present invention has been developed for the purpose of solving the problems of the prior art, and provides a low-crystalline and high-crystalline dense spherical apatite obtained by a specified raw material composition and a simple manufacturing method. is there.

[Means for solving the problem]

That is, the present invention relates to calcium phosphate having a Ca / P molar ratio of 1.4 to 1.8, a specific gravity of 3.00 to 3.17, and a powder X-ray diffraction (CuKα) of 2θ = 33.0 ± 0.1 °. The ratio (H / W) of the half width (W) and the peak height (H) on the chart of 16 cm / dec and Full Scall 2000 csp at the indicated diffraction line peak.
Is in the range of 1 to 5.

Further, the present invention is a spherical apatite obtained by calcining a low crystalline spherical apatite, wherein the molar ratio of Ca / P is 1.4.
Calcium phosphate having a specific gravity of 3.00 to 3.17 and a relative intensity ratio (H ₂ ) of the diffraction peak height (H) indicated by 2θ = 33.0 ± 0.1 ° in powder X-ray diffraction (CuKα). / H ₁ )
Provide high crystalline spherical apatite characterized by having 1.1 or more (H ₁ = peak of low crystalline spherical apatite before firing, H ₂ = peak of high crystalline spherical apatite after firing) Is what you do.

These differences in crystallinity can also be visually grasped by, for example, electron micrographs shown in FIG. 2 and FIG.

Further, the spherical apatite of the present invention is, for example, as shown in FIG. 1, a true spherical fine particle having a particle size of 1 to several 100 μm by a microscopic observation method, and the individual particles are very dense. Therefore, the mechanical strength is also excellent.

The spherical apatite according to the present invention can be produced as follows.

That is, after preparing a raw material slurry mainly composed of calcium phosphate having a composition of Ca / P molar ratio of 1.4 to 1.8, it is spray-dried to obtain agglomerated particles, which are then flame-melted.

First, the raw material slurry is generally calcium phosphate within the above molar ratio, but may be a precursor thereof.

Further, for adjusting the molar ratio, phosphoric acid or / and a phosphate or calcium salt constituting calcium phosphate can be appropriately used.

Therefore, as a raw material, in addition to hydroxyapatite, for example, a phosphoric acid source such as phosphoric acid, polyphosphoric acid, phosphorus pentoxide, calcium orthophosphate, calcium hydrogen phosphate, calcium dihydrogen phosphate, ammonium phosphate, quicklime, slaked lime, calcium chloride, nitric acid Examples include calcium sources such as calcium and calcium glycerophosphate, which may be used alone or in combination of two or more.

Further, a small amount of a flux component or an auxiliary agent such as a modifying agent for modifying an apatite substance can be added to these raw materials as needed for the purpose of lowering the melting temperature.

These auxiliary agents include, for example, alkali metal salts such as Na, K and Li, alkaline earth metal salts other than calcium, fluorides, silica, boron-containing compounds, oxides such as Al, Zr or Ti, and hydroxides. And metal salts.

The reason that the raw material molar ratio Ca / P is limited to 1.4 to 1.8 is that it is necessary because apatite generated under the melting condition is stable.

In preparing the raw material slurry, the slurry concentration does not need to be particularly limited. Since the solubility of apatite is extremely small, a slurry can be formed even at a rare concentration, but the concentration may be as high as possible from the viewpoint of operation, considering the evaporation cost.

Next, the raw material slurry is dried by a conventional method to obtain fine aggregated particles of apatite primary particles.

The agglomerated particles may be pulverized particles of a dry cake, but as the industrially preferred embodiment of the present invention,
It is advantageous to adjust to spherical aggregated particles by spray drying.

In any case, since the size of the aggregated particles affects the size of the spherical particles of the product, it is necessary to adjust the size of the aggregated particles according to the application.

The resulting aggregated particles are then flame melted. The temperature for melting the raw material is not particularly problematic as long as it is usually equal to or higher than the melting point of the raw material component.
It is preferable to set the temperature higher by ° C.

Often, such temperatures are as high as 1500 ° C. or higher.

In this flame melting method, the dried powder is fed into a flame such as an oxyhydrogen burner, an oxygen-propane burner, or an air-propane burner to be melted. The melt is made spherical by its own interfacial tension and falls. Cool and solidify in the meantime. Therefore, by changing the particle size of the dried powder to be fed into the burner as described above, it is possible to adjust the particle size to a desired particle size of 1 to several hundreds μm. By adding a classification step, a sphere having a more uniform and sharp particle size distribution can be obtained.

It is sufficient that the falling length of the melt is equal to or longer than the length of the flame. However, considering the cooling efficiency, it is preferable that the falling length be twice or more, preferably five times or more. A method of dropping the melt into water for the purpose of quicker cooling can also be employed. In this case, the obtained hydroxyapatite has an extremely large amount of amorphous components.

The spherical apatite obtained in this way is an aggregate of low crystalline fine particles containing many amorphous parts due to the quenching effect in each case, and has a very dense It has structural characteristics with high mechanical strength. On the other hand, in order to obtain a high crystalline spherical apatite, the above low crystalline apatite must be 500 to 1
Baking in the temperature range of 400 ° C. If the temperature is lower than 500 ° C., the crystal growth rate is low, and if the temperature is higher than 1400 ° C., it is not necessary for crystallization. A more desirable set temperature range is 800 to 1400 ° C. By baking the low-crystalline apatite in this way, the crystal grows, so that it can be converted to high-crystalline.
The degree of crystallinity can be appropriately adjusted depending on the temperature and the processing time.

As described above, the present invention can produce a low-crystalline to high-crystalline dense spherical apatite. Further, the present invention provides a molded article characteristic of a porous structure including such a spherical apatite as an active ingredient. Can be.

That is, an initial adhesive such as an organic or inorganic water-soluble polymer is mixed with the spherical apatite particles, pressed and formed, and then baked at the above-mentioned temperature. A high-strength apatite molded article having a porous structure having continuous air holes having a bonded structure can be obtained.

(Operation)

The apatite according to the present invention has an excellent spherical shape, a dense and high mechanical strength.

For this reason, for example, when applied as a bone filler,
Not only can uniform and compact packing be easily achieved, but also uniform voids are formed between the grains, so that infiltration of bone cells is promoted and a strong callus formation function is exhibited. When used in the field of separation and recovery of active ingredients or in the field of chromatographic analysis, high mechanical strength does not cause particle disintegration due to pressurization. Use is guaranteed.

Further, those having a particle size adjusted to 120 to 180 μm can be used as a cell carrier for culturing animal cells, and cell culturing is possible without surface treatment due to excellent cell affinity.

〔Example〕

 Hereinafter, the present invention will be described based on examples.

Examples 1 to 4 Raw materials having the compositions shown in Table 1 were each made into a slurry having a solid content of 10%, and then spray-dried using a hot-air device at an inlet temperature of 300 ° C and an outlet temperature of 100 ° C to obtain granules. 10 g /
Hr was fed into an oxygen-propane flame (oxygen gas flow rate 45 l / min, propane gas flow rate 10 l / min) and melted by a flame melting method.

The spherical hydroxyapatite thus obtained had a dense spherical shape.

The physical properties of each of the obtained spherical apatites were measured, and the results shown in Table 2 were obtained.

Example 5 The low crystalline spherical apatite obtained in Example 1 was calcined in the air at a temperature of 1000 ° C. for 60 minutes. FIG. 2 is an electron micrograph (magnification: 10,000) showing the crystal state of each grain surface before firing and FIG. 3 after firing. The fact that the material was converted to highly crystalline by the calcination treatment was not only compared with these photographs, but also in the X-ray diffraction pattern 2θ = 33.0.
The peak relative intensity (H ₂ / H ₁ ) was 1.5 before and after firing.
It was confirmed that the height was doubled. The product had a density of 3.12 g / cm ³ and was a dense sphere.

In addition, 2 g of the spherical apatite was put into a 50 ml glass bottle with a lid, 45 g of water was added, and the mixture was shaken on a paint shaker (manufactured by Toyo Seiki Seisaku-sho) at 800 times per minute for 30 minutes. As a result, no disintegration of the particles was observed (SEM judgment), indicating that the particles were dense microcrystalline particles.

Example 6 2 g of 5% polyvinyl alcohol was added to 20 g of the spherical apatite of Example 1 and molded into a disk shape having a thickness of about 4 mm under a pressure of 2000 kg / cm ² . The molded body was fired at 1200 ° C. for 3 hours to produce a highly crystalline porous structure. Various physical properties were measured for a specimen cut out from the obtained porous structure into a size of 3.8 mm in thickness, 10 mm in width, and 48 mm in length, and the results are shown in Table 3.

[Effects of the Invention] As described above, the spherical apatite provided by the present invention has a uniform texture that is superior in shape and properties as compared with conventional products, and has a desired crystallinity and sphere by a simple manufacturing means. Since it is possible to stably obtain a material having a diameter range, a biological filler, a chromatographic filler,
It is expected to be useful for a wide range of applications such as adsorption and separation materials for various components.

[Brief description of the drawings]

FIG. 1 is an electron micrograph showing the crystalline state of the spherical apatite according to the present invention, and FIG.
FIG. 2 shows a low crystalline material before the calcination treatment with an increased magnification (magnification 10,000 times), and FIG. 3 shows a highly crystalline material after the calcination treatment (magnification 10,000 times).

──────────────────────────────────────────────────続 き Continuation of the front page (72) Eiji Miyoshi, Inventor Research and Development Department, 9-15-1, Kameido, Koto-ku, Tokyo (56) References JP-A-1-234308 (JP, A) Kaisho 64-76942 (JP, A) (58) Fields investigated (Int. Cl. ⁶ , DB name) C01B 25/32 C04B 38/00 G01N 30/48

Claims (4)

(57) [Claims] 1. A calcium phosphate having a molar ratio of Ca / P of 1.4 to 1.8, a specific gravity of 3.00 to 3.17, and a powder X-ray diffraction (CuKα) of 2θ = 33.0 ± 0.1 °. Low crystalline spherical apatite having a half width (W) and a peak height (H) ratio (H / W) of 1 to 5 on a chart of 16 cm / dec and Full Scall 2000 csp at the diffraction line peak. 2. A spherical apatite obtained by calcining a low crystalline spherical apatite, wherein the molar ratio of Ca / P is calcium phosphate of 1.4 to 1.8, and the specific gravity has a value of 3.00 to 3.17,
The relative intensity ratio (H ₂ / H ₁ ) of the diffraction peak height (H) indicated by 2θ = 33.0 ± 0.1 ° in powder X-ray diffraction (CuK α) is 1.1 or more (where H ₁ = low crystalline before firing) Spherical apatite peak, H ₂ = peak of highly crystalline spherical apatite after firing.) 3. A raw material slurry containing calcium phosphate as a main component having a Ca / P molar ratio of 1.4 to 1.8 is prepared, spray-dried to obtain aggregated particles, and then flame-melted. Quenched to obtain low crystalline spherical apatite,
A method for producing highly crystalline spherical apatite, comprising firing the low crystalline spherical apatite at 500 to 1400 ° C. to grow crystals. 4. A porous structure molded article comprising the spherical apatite according to claim 1 as an active ingredient.