JP2696345B2 - Calcium phosphate ceramic sintered body - Google Patents

Description

The present invention relates to a calcium phosphate-based ceramics sintered body having excellent acid resistance.

“Prior art and its problems” Hydroxyapatite Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ sintered body is
Because it has excellent biocompatibility, conventionally, artificial roots,
It was used in clinical settings as a biomaterial such as an artificial bone. However, hydroxyapatite lacks acid resistance, and has a disadvantage that it is easily dissolved and eroded under acidic conditions. This means that when a material consisting of hydroxyapatite ceramics is implanted in a living body,
It indicates that erosion from the surface may result in a significant reduction in the mechanical strength of the material. Further, even when used in other fields, in a humid atmosphere, a part of ceramics may be dissolved, which may cause deterioration of material properties.

On the other hand, it is already known that fluorapatite has lower solubility than hydroxyapatite, for example,
For many years, attempts have been made to apply a solution containing a fluorine compound to the surface of human teeth containing hydroxyapatite as a main component and increase the acid resistance by changing the surface to fluorapatite, thereby preventing corrosion. Has been confirmed.

However, conventionally, a fluorapatite sintered body that can be used as bioceramics such as artificial teeth and bones has not been known.

[Object of the Invention] An object of the present invention is to provide a calcium phosphate-based ceramics sintered body having excellent acid resistance and mechanical strength.

[Constitution of the Invention] The calcium phosphate-based ceramics sintered body according to the present invention has a main component represented by the general formula (I) Ca ₁₀ (PO ₄ ) ₆ (OH) _2-2x F _2x (I) wherein x is 0.1 to 1.0 Fluorapatite represented by the formula:
0% by weight, primary particles constituting the ceramic having a size of 0.1 μm to 30 μm, and a porosity of 5% or less, and a porosity of 20 to 80%. %, Having a pore diameter of 1 μm to 2000 μm.

The sintered body according to the present invention contains tricalcium phosphate in addition to the fluorapatite represented by the general formula (I).
It may contain 1 to 50% by weight. However, if the amount of tricalcium phosphate exceeds 50% by weight, the solubility increases, which is not preferable.

Further, the calcium phosphate-based ceramics sintered body according to the present invention is manufactured by sintering a powder containing fluorapatite represented by the above general formula (I) as a main component at 800 to 1100 ° C.

The fluorapatite represented by the general formula (I) is preferably produced by using ammonium hydrogen fluoride as a fluorine source as proposed in Japanese Patent Application No. 63-93191. That is, a method of dropping an aqueous solution of phosphoric acid to which ammonium hydrogen fluoride is added into a calcium hydroxide slurry, a method of dropping an aqueous solution of phosphoric acid to a slurry of calcium hydroxide to which ammonium hydrogen fluoride is added, or a method of adding phosphoric acid to a slurry of calcium hydroxide It is preferable to produce the hydroxyapatite by dropping an aqueous solution, then dropping an aqueous solution of ammonium hydrogen fluoride, drying, and then performing a heat treatment. In addition to such a wet method, a fluorine compound can be produced by a dry synthesis method in which a phosphorus compound, a calcium compound, and a fluorine compound are mixed at a predetermined ratio and reacted at a high temperature. Fluoroapatite produced by either method may be used, but one that does not contain impurities that hinder sintering should be used.

In the synthesis of fluorapatite, calcium /
By setting the phosphorus ratio to be Ca / P <1.666, a compound containing tricalcium phosphate [Ca ₃ (PO ₄ ) ₂ ] can be obtained. Furthermore, by changing the content of fluorine,
Hydroxyapatite in which hydroxyl groups are substituted with fluorine at an arbitrary ratio can be obtained. In the present invention, those in which x in the general formula (I) is 0.1 to 1.0 are used.
When x is less than 0.1, no improvement in acid resistance is observed.

The liquid containing fluorapatite as a main component obtained by the above wet method is powdered by a known drying method using a spray drier, a band drier, a vacuum freeze drier, etc., to obtain a ceramic raw material powder. Can be.

The ceramic raw material powder used for producing the sintered body of the present invention is fine particles of 100 to 1000 mm or secondary particles in which they are bonded to each other, and the average particle size of the secondary particles is 0.5 to 20 μm. It is desirable that This is because sintering activity is inferior when the primary particles exceed 1000 °.

The obtained ceramic raw material powder is calcined and pulverized, if necessary, and molded by a known ceramic molding method.
A sintered body can be obtained by sintering at a temperature of 800 to 1100 ° C.

As the dry molding method, compression molding using, for example, an isostatic press is used, and as the wet molding method, cast molding, extrusion molding, injection molding, sheet molding, or the like is used. Generally, the molded article obtained by these methods is:
It becomes a dense sintered body by firing, but if a porous structure such as a biomaterial or a sensor is desired, a foaming step is incorporated at the time of molding, or a substance that decomposes and burns and burns out by firing in the molded body. It is molded by a known method for producing a porous body, such as mixing at a predetermined ratio.

These molded bodies are fired after finishing processing such as secondary processing as necessary. The firing may be performed in the air, or may be performed in an atmosphere of an inert gas such as argon or nitrogen. Further, the firing can be performed under vacuum, normal pressure, high pressure (200 MPa) or the like.

Fluorine in fluorapatite is liable to volatilize by heating, and it is considered that the vaporization rate of fluorine is increased by the following reaction formula, particularly when water vapor is present.

Ca ₁₀ (PO ₄ ) ₆ F ₂ + 2H ₂ O → Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ + 2HF Further, the hydroxyapatite generated by this reaction may be decomposed by the following formula.

Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ → 3Ca ₃ (PO ₄ ) ₂ + CaO + H ₂ O Therefore, in order to obtain the sintered body mainly containing fluorapatite according to the present invention, an inert gas atmosphere containing no water vapor is required. It is preferable to perform calcination in medium, dry air, or vacuum, but even if calcination is performed in air containing water vapor, calcium oxide and / or calcium fluoride is only generated on the surface. Is not at all,
Or less.

The firing temperature is preferably in the range of 800 to 1100 ° C. Below 800 ° C, sufficient sintering does not occur, and
If the temperature exceeds 0 ° C., the amount of calcium oxide tends to be too large, and the strength tends to decrease.

When manufacturing a dense sintered body by the above method,
A dense sintered body with a relative density of 95% or more can be obtained.

Conventionally, in the case of hydroxyapatite, the relative density
It has been common knowledge that in order to obtain a dense sintered body of 95% or more, it is usually necessary to perform sintering at least at 1000 ° C. or more. However, it has been found that, according to the method of the present invention, a sintered body of fluoroapatite having the same crystal structure and physicochemical properties as hydroxyapatite can be obtained even at 1000 ° C. or lower.

The size of the primary particles constituting the sintered body of the present invention is 0.1
It is preferably in the range of 〜30 μm. Those having a particle size of less than 0.1 μm are difficult to synthesize, and those having a particle size of more than 30 μm cause a problem of reduction in the strength of the sintered body due to grain growth.

Further, when mechanical strength is required, it is preferable that the porous body is denser than the porous body, and the porosity at that time is preferably 5% or less. If the porosity exceeds 5%, the strength is significantly reduced.

However, when the sintered body of the present invention is used for a bioceramic, a sensor, or the like, a porous body having a pore diameter and a porosity is desirable depending on the purpose. In the case of bioceramics, at least the surface or overall porosity
It is desired that the pore diameter is 1 μm to 2000 μm at 20 to 80%. More preferably, the pore diameter is from 10 μm to 500 μm. In the case of a gas sensor, etc.,
Those having pores of 000 ° are preferred.

"Examples of the Invention" Next, the present invention will be described in more detail based on examples, but the present invention is not limited to these examples.

Example 1 10 l of a 0.3 M phosphoric acid aqueous solution in which 28.5 g of ammonium hydrogen fluoride was dissolved was stirred into 10 l of a 0.5 M calcium hydroxide slurry at a rate of 5 ml / min using a roller pump.
At a speed of. The stirring was stopped 24 hours after the completion of the dropwise addition, and the mixture was aged for 48 hours in a stationary state. The product was dried with a spray dryer under the following conditions and granulated.

Drying conditions Inlet temperature 200 ° C Outlet temperature 80 ° C Drying speed 1.6l / h Spray method Disc type atomizer Rotation speed 30000rpm After calcining the granulated powder at 700 ° C and press-molding in a mold, pressure of 200kg / cm ² And pressed with a hydrostatic press to obtain a green molded body. This compact was fired at 860 ° C. for 4 hours in air using a box-type electric furnace, to obtain a dense sintered body having a relative density of 99%.

The surface of the obtained sintered body was analyzed by X-ray diffraction without pulverization, and it was found that the a-axis length was 9.365 ° and the c-axis length was 6.883 angstroms, which was consistent with the data of the ASTM card. I was able to confirm that there was. Also, a peak of calcium oxide was detected. The result is shown in FIG. FIG. 2 shows the results of measuring the infrared reflection spectrum on the surface of the sintered body. No absorption by the hydroxyl group near 630 cm ⁻¹ observed in hydroxyapatite was observed, confirming that the hydroxyapatite was a fluoroapatite in which the hydroxyl group was substituted by fluorine. When the surface of the sintered body was observed with a scanning electron microscope, the size of the primary particles was about 0.3 μm. When the sintered body was pulverized and the powder was analyzed by X-ray diffraction, no calcium oxide was detected.

Example 2 In Example 1, the amount of ammonium hydrogen fluoride was changed to 14.2.
After synthesizing in the same manner as 5 g, drying, calcining and molding, the molded body was fired in air at 1100 ° C. for 4 hours,
A dense sintered body with a relative density of 99.9% was obtained.

FIG. 3 shows the results of X-ray diffraction of the surface of the sintered body. A small amount of calcium oxide is generated on the surface by the decomposition of apatite. On the other hand, when the sintered body was pulverized and subjected to powder X-ray diffraction analysis, no calcium oxide peak was detected. Thus, it is believed that the degradation occurred only on a portion of the surface. When the lattice constant was determined from the X-ray diffraction data, the a-axis length was 9.388 ° and the c-axis length was 6.874 °.
Met. Since the a-axis length was an intermediate value between hydroxyapatite and fluorapatite, and the fluorine content determined by elemental analysis was 1.85%, the sintered body was about 1% of the hydroxyl group of hydroxyapatite. / 2 was found to be hydroxy-fluorapatite substituted with fluorine.

The lattice constant data in Example 1 and Example 2
Shown in the figure.

Example 3 The molded body produced in Example 1 was vacuumed in a vacuum furnace at a degree of vacuum of 4 × 10 4.
^-6 torr, heating rate 200 ° C / hour, firing temperature 900 ° C, 950 ° C
And baked under the condition of 1000 ° C, diameter about 5mm, length 2
A 2 mm sintered body was obtained.

For each sintered body, measure the relative density and bending strength,
The results are shown in Table 1 below.

The above-mentioned fluorapatite (noted as FAp) fired in vacuum at 1000 ° C. and hydroxyapatite (noted as HAp) fired in air at 1020 ° C. were each dissolved in 200 ml of distilled water and pH.
After immersion in the acetate buffer of No. 5 for 10 days, the dissolved calcium concentration and phosphorus concentration were measured to examine the solubility, and the results are shown in Table 2.

From the results of the above examples, in the case of hydroxyapatite, in order to obtain a dense sintered body with a relative density of 99% or more, in the case of normal pressure sintering, 1050 ° C or more, and even in the case of high pressure sintering, 1000 ° C Although the above temperature was required, it was found that according to the present invention, a high-density sintered body having a relative density of 99% or more can be obtained at a temperature of 1000 ° C. or less regardless of whether it is in air or vacuum.

In addition, hydroxyapatite showed high solubility in an acetate buffer, while fluorapatite showed low solubility in an acetate buffer as in distilled water. That is, the sintered body of the present invention has high acid resistance. Further, when the fluorapatite sintered body fired in vacuum was analyzed by X-ray diffraction, it was confirmed that calcium oxide was not present even on the surface.

Example 4 100 g of the fluorapatite powder obtained by the method shown in Example 1 was dispersed in 3% aqueous hydrogen peroxide to prepare a slurry having a viscosity of 40 cp (centipoise). The slurry was transferred to a glass container and foamed and dried in a thermostat set at 120 ° C. for 48 hours to obtain a dry foam. 1200 dry foam
Calcination was performed at 4 ° C. for 4 hours. Heating rate up to 800 ° C, 200 per hour
The temperature was set to 100 ° C./hour from 800 ° C. to 1200 ° C. Cut the sintered body with a diamond cutter while pouring distilled water,
A rectangular parallelepiped block of 10 × 20 × 30 mm was obtained. The block had a porosity of about 40%, and the pores consisted of micropores of 100 μm to 2000 μm in diameter and micropores of about 2 μm comprising secondary particle gaps. All pores were continuous with each other and had an ideal structure as a bioceramic.

Example 5 28.5 g of ammonium hydrogen fluoride was dissolved in 10 l of 0.5 M calcium hydroxide slurry while stirring. 0.3
10 liters of phosphoric acid solution with M concentration per minute using a roller pump
It was dropped at a rate of 5 ml. After completion of the dropwise addition, 0.45 l of a 0.3 M phosphoric acid aqueous solution was added, and the mixture was stirred for 24 hours and then left to stand for 48 hours for aging. The resulting slurry is dried under the same conditions as in Example 1,
After granulation and molding, baking is performed at 1050 ° C for 4 hours to obtain a relative density of 96.
% Of a compact was obtained.

When the sintered body was analyzed by the powder X-ray method, it was confirmed that the sintered body was composed of fluorapatite and β-calcium triphosphate. The main peak ratio of these components is about 7: 3
Met. When Ca / P, which is the ratio of calcium to phosphorus, was determined by chemical analysis, the value was about 1.59.

[Effect of the Invention] The calcium phosphate ceramic sintered body according to the present invention is excellent in acid resistance and mechanical strength, and is a material for replacing and supplementing hard tissues such as artificial tooth roots and artificial bones, as well as artificial trachea, artificial blood vessels, and percutaneous transdermal membrane for CAPD. Not only is it suitable as a soft tissue replacement / repair material for devices and the like, but also useful as a substrate for immobilized enzymes such as substrates for electronic materials such as IC package substrates, temperature sensors, heat-resistant components, and bioreactors.

Further, when the ceramic sintered body of the present invention containing tricalcium phosphate as the second component is used as an isoplant material, the tricalcium phosphate is dissolved and absorbed, and is promptly replaced with newly generated new bone. It is an ideal bio-ceramic that forms a tight bond with the bone and the other non-absorbable part (fluorapatite part) maintains the shape of the implant site and maintains the load applied to it. .

[Brief description of the drawings]

1 is an X-ray diffraction diagram of the surface of the sintered body obtained in Example 1, FIG. 2 is an infrared reflection spectrum of the surface of the sintered body obtained in Example 1, and FIG. And FIG. 4 is a graph showing the relationship between the degree of fluorination and the lattice constant of apatite crystals.

Claims (3)

(57) [Claims] 1. A method for _preparing tricalcium phosphate from 0.1 to 0.1 together with a fluorapatite represented by the general formula: Ca ₁₀ (PO ₄ ) ₆ (OH) _2-2x F _{2x wherein} x is a number from 0.1 to 1.0. 50% by weight
A calcium phosphate-based ceramics sintered body characterized by containing. 2. A ceramic containing a fluorine apatite represented by the general formula: Ca ₁₀ (PO ₄ ) ₆ (OH) _2-2x F _2x (where x represents a number from 0.1 to 1.0) as a main component. A calcium phosphate-based ceramics sintered body, wherein the size of the primary particles constituting the sintered body is 0.1 μm to 30 μm and the porosity is 5% or less. 3. A fluorinated apatite represented by the general formula: Ca ₁₀ (PO ₄ ) ₆ (OH) _2-2x F _{2x wherein} x is a number from 0.1 to 1.0. Is 20-80% and the pore size is 1μ
A porous calcium phosphate-based ceramics sintered body having a diameter of from m to 2000 μm.