JP2775644B2 - Wet production of α-type tricalcium phosphate cement - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a method for producing medical and dental cements such as bone substitutes, and more particularly, to an improvement in a wet production method for α-type tricalcium phosphate cement. Things.

[Conventional technology]

It is well known that tribasic calcium phosphate reacts with water and hydrates and hardens, and the hydroxyapatite produced by this hydration reaction is considered to have almost the same structure as bone in vivo. It is extremely important as a medical or dental cement such as a bone filling material.

On the other hand, for tricalcium phosphate, 1180 ° C to 1430
Α-type is stable at 1 ° C. and β-type is stable at 1180 ° C. or lower. Among them, α-type has higher hydration activity, so α-type is exclusively used for the tricalcium phosphate cement.

The method for producing the α-type tricalcium phosphate cement includes a dry method and a wet method.

In the dry method, dibasic calcium phosphate is heated at 550 ° C. for about 2 hours to be converted into γ-calcium pyrophosphate, and calcium carbonate is uniformly mixed with the calcium phosphate.
It is a method of baking for more than an hour, taking out into the outside air and quenching. Conventionally, it has been considered that the strength of the hydrated hardened product of the tricalcium phosphate cement by the wet method is low, and therefore, the dry method has been mainly employed.

The wet method is a method in which calcium ions and phosphate ions are directly reacted in an aqueous solution to precipitate amorphous calcium phosphate, which is filtered, washed, dried, and heat-treated at a high temperature. In order to improve the disadvantage that the strength of the hydrated hardened product of the tricalcium phosphate cement by the wet method is low, the following various improvements have been attempted.

JP-A-63-100008 discloses that condensed phosphoric acid or a salt thereof is heated at 100 ° C.
A method is disclosed in which a reaction is performed below and a heat treatment is performed at 700 ° C. or lower (therefore, β-type).

JP-A-1-100048 discloses that hydroxyapatite is heated at 1150 ° C.
A method for producing a cement comprising α-type tricalcium phosphate and tetracalcium phosphate, which is fired under reduced pressure at 4501450 ° C., is disclosed.

[Problems to be solved by the invention]

In the dry method that has been conventionally employed, since the raw materials are mixed with powders, it is difficult to achieve uniform mixing, and there is a problem in the uniformity of the product, and the conversion to hydroxyapatite during hydration hardening was not sufficient. In addition, after calcination at 1180 ° C. or more, unless quenched (10 ° C./min or more), the whole product could not be retained in α-type tribasic calcium phosphate. Therefore, it was necessary to press and compress to about 1000 kg / cm ² by a rubber press method or the like, and then to fire again at 1200 ° C. to 1300 ° C. for 1 hour or more.

On the other hand, the drawback that the hydrated hardened product of the tricalcium phosphate cement produced by the conventional wet method has a low compressive strength is not sufficiently solved by the inventions disclosed in the above-mentioned JP-A-63-100008 and JP-A-1-100048. Has not been resolved.

The invention disclosed in JP-A-63-100008 is for producing β-type tribasic calcium phosphate, and is not always sufficient in terms of hydration activity.

The invention disclosed in Japanese Patent Application Laid-Open No. 1-100048 relates to a method for producing a cement comprising a mixture of α-type tricalcium phosphate and tetracalcium phosphate. It has not been.

The problem to be solved by the present invention is to solve the above-mentioned problems by producing a novel calcium phosphate cement having uniform product quality, easy hydration hardening, and high compressive strength of the hardened material. Is to develop a law.

[Means for solving the problem]

Means for Solving the Problems To solve the above-mentioned problems, the present inventors reacted a calcium hydroxide suspension with a phosphoric acid aqueous solution, and obtained a product by calcining the obtained precipitate of calcium phosphate to obtain a product by wet production of a calcium phosphate cement. At a temperature of 50 ° C.
A mixture of hydroxyapatite and dicalcium phosphate by reacting at a temperature of not less than 100 ° C. and a final reaction product concentration of not less than 5% and not more than 25%, and firing the mixture. We propose a method for wet production of α-type tricalcium phosphate cement.

In the present invention, setting the reaction temperature to 50 ° C. or higher prevents the crystallinity of hydroxyapatite itself from becoming high, and at the same time, suppresses the crystal of dibasic calcium phosphate from becoming too large. This is to obtain a mixture of calcium diphosphate.

However, the reason why the reaction temperature exceeds 100 ° C. is that
Not only is a pressurized container required, but also the operation becomes complicated, which is not economically preferable.

The reason why the final reaction product concentration is set to 5% or more is to prevent the crystallinity of hydroxyapatite itself from increasing and to suppress the crystal of dibasic calcium phosphate from becoming too large.

In addition, to make the final reaction product concentration 25% or less, 25%
%, Stirring becomes difficult and a wet reaction becomes impossible.

[Action]

In the present invention, if the reaction temperature is set to 50 ° C. or higher, the effect of generating a mixture of hydroxyapatite and dicalcium phosphate is unknown, but it is considered as follows.

Hydroxyapatite is a very stable compound, and it is known that the higher the pH and the higher the temperature, the easier it is to form.The lower the pH of the dibasic calcium phosphate and the lower the temperature, It is known to be easy to produce and stable.

Therefore, when phosphoric acid is dropped into a calcium hydroxide suspension at a high temperature of 50 ° C. or higher, hydroxyapatite is first generated, and then, as the pH decreases, other calcium phosphate compounds are generated. Also, it is considered that hydroxyapatite changes into stable hydroxyapatite with the hydroxyapatite already formed as a nucleus. Then, when the addition of phosphoric acid is continued and the solution becomes acidic, it is considered that acidic and stable dibasic calcium phosphate is generated.

In addition, although the details of why the α-type tricalcium phosphate cement obtained by calcining a mixture of hydroxyapatite and dicalcium phosphate has high hydration activity are unknown, microcrystalline hydroxyapatite and dicalcium phosphate are It is thought that when baking the mixed crystal of the above, phosphorus and calcium of dibasic calcium phosphate diffuse on the surface of hydroxyapatite to generate α-type tribasic calcium phosphate with high purity.

The details of how the α-type tribasic calcium phosphate cement thus obtained produces a hydrated hardened product having high compressive strength are unknown, but are presumed as follows.

The hydration hardening reaction of tribasic calcium phosphate is said to form non-stoichiometric hydroxyapatite according to the following formula.

(10−z) Ca ₃ (PO ₄ ) ₂ +3 (2 + nz) H ₂ O → 3Ca _10−z (HPO ₄ ) _z (PO ₄ ) _6−z (OH) _2-z · nH ₂ O + 2 ( 1-z) H ₃ PO ₄ and, it is said that the strength appears by entanglement coupling microcrystalline projecting around this way non-stoichiometric hydroxyapatite particles generated.

From these facts, it is presumed that in the α-type tribasic calcium phosphate cement of the present invention, tribasic calcium phosphate derived from dibasic calcium phosphate acts as an effective adhesive for this entangled bond.

〔Example〕

Example 1 A stainless beaker containing 3 l of ion-exchanged water was heated to 80 ° C.
, And 215 g of calcium oxide (CaO) was added to the ion-exchanged water, followed by stirring for 30 minutes to emulsify.

After adjusting the liquid temperature to 50 ° C., 1002 g of a 25% phosphoric acid solution was dropped using a microtube pump over 2 hours to cause a reaction. The concentration of the final reaction solution was 9.4%.

After leaving still at 50 ° C. for 1 hour, the mixture was filtered and dried at 150 ° C. for 2 hours. The X-ray diffraction pattern of the obtained crystal (hereinafter, referred to as “crystal I”) was as shown in FIG.

In this figure, ○ indicates a peak specific to hydroxyapatite, and ▽ indicates a peak specific to dicalcium phosphate.

After firing this crystal I at 1300 ° C. for 1 hour,
Cooled down to room temperature over time. This is crushed and the average particle size is 5 μm
(Hereinafter referred to as “powder I”).

The powder I was subjected to X-ray diffraction analysis with a CuKα ray using a Ni filter under the conditions of 35 KV, 15 mA, and slit width (1, 0.15, 1). As a result, the diffraction angle was 30.8 ° 34.2 ° 24.1 °.
, And coincided with the characteristic diffraction pattern of α-type tricalcium phosphate described in JCPD S- Card 9-348.

Chemical analysis of Powder I resulted in a Ca / P ratio of 1.51,
It almost coincided with the theoretical Ca / P ratio of 1.50.

Example 2 A reaction was performed under the same conditions as in Example 1 except that the reaction temperature was 70 ° C. The concentration of the final reaction solution was 9.4%. From this, a crystal (hereinafter referred to as “crystal II”) was obtained under the same conditions as in Example 1. The X-ray diffraction pattern of this crystal II was as shown in FIG.

A powder having an average particle size of 5 μm (hereinafter referred to as “powder II”) was obtained from the crystal II under the same conditions as in Example 1.

The result of X-ray diffraction analysis of the powder II was in agreement with the characteristic diffraction pattern of α-type tricalcium phosphate.

As a result of a chemical analysis of Powder II, the Ca / P ratio was 1.50.

Example 3 A reaction was performed under the same conditions as in Example 1 except that the reaction temperature was set to a boiling condition of 98 ° C. or higher. The concentration of the final reaction solution was 9.3%. From now on, the crystal (hereinafter referred to as “crystal”
III "). The X-ray diffraction pattern of this crystal III is
It was as shown in the figure.

A powder having an average particle size of 5 μm (hereinafter referred to as “powder III”) was obtained from the crystal III under the same conditions as in Example 1.

As a result of X-ray diffraction analysis of the powder III, the powder III agreed with the characteristic diffraction pattern of the α-type tribasic calcium phosphate.

As a result of a chemical analysis of Powder III, the Ca / P ratio was 1.51.

Comparative Example 1 The reaction was carried out under the same conditions as in Example 1 except that the reaction temperature was changed to 40 ° C. The concentration of the final reaction solution was 9.4%. From this, a crystal (hereinafter, referred to as “crystal IV”) was obtained under the same conditions as in Example 1. The X-ray diffraction pattern of this crystal IV was as shown in FIG.

A powder having an average particle size of 5 μm (hereinafter referred to as “powder IV”) was obtained from the crystal IV under the same conditions as in Example 1.

The result of X-ray diffraction analysis of the powder IV was consistent with the characteristic diffraction pattern of α-type tricalcium phosphate.

As a result of a chemical analysis of Powder IV, the Ca / P ratio was 1.50.

Comparative Example 2 A stainless steel beaker containing 12 liters of ion-exchanged water
This was placed in a thermostat set at a temperature of ℃, and 215 g of calcium oxide (CaO) was added to the ion-exchanged water, followed by stirring for 30 minutes to emulsify.

After adjusting the liquid temperature to 70 ° C., 1002 g of a 25% phosphoric acid solution was added dropwise over 2 hours using a microtube pump to cause a reaction. The concentration of the final reaction solution was 3.0%.

Thereafter, the same operation as in Example 1 was performed to obtain a crystal (hereinafter, referred to as “crystal V”). The X-ray diffraction pattern of this crystal V was as shown in FIG.

A powder having an average particle size of 5 μm (hereinafter referred to as “powder V”) was obtained from the crystal V under the same conditions as in Example 1.

As a result of X-ray diffraction analysis of the powder V, the powder V contained a small amount of hydroxyapatite according to the characteristic diffraction pattern of α-type tribasic calcium phosphate.

As a result of a chemical analysis of Powder V, the Ca / P ratio was 1.50.

Comparative Example 3 Conventional wet method Calcium nitrate C was added to 500 ml of ion-exchanged water in a 2 l beaker.
a (NO ₃ ) ₂ 4H ₂ O 354 g was dissolved, and into this, with stirring, 500 ml of ion-exchanged water was added to diammonium phosphate (NH ₃ ) ₂ HPO ₄
A solution in which 132 g was dissolved was added dropwise over 2 hours using a microtube pump to cause a reaction, and the mixture was further stirred for 24 hours. The concentration of the final reaction solution was 10.4%.

This was filtered, dispersed and stirred with about 1500 ml of ion-exchanged water, allowed to stand for 1 hour, and then filtered. Such washing operation was performed 5 times, and dried at 150 ° C. for 2 hours to obtain a crystal (hereinafter referred to as “crystal VI”). The X-ray diffraction pattern of this crystal VI was as shown in FIG.

This crystal VI was fired at 1300 ° C. for 1 hour, taken out into the open air, quenched, and pulverized to obtain a powder having an average particle size of 5 μm (hereinafter referred to as “powder VI”).

The result of X-ray diffraction analysis of the powder VI was consistent with the characteristic diffraction pattern of α-type tricalcium phosphate.

As a result of a chemical analysis of Powder VI, the Ca / P ratio was 1.50.

Comparative Example 4-Dry Method 344 g of dicalcium phosphate CaHPO ₄ 2H ₂ O was calcined at 500 ° C. for 5 hours to obtain γ-calcium pyrophosphate γ-Ca ₂ P ₂ O ₇ , mixed with 100 g of CaCO ₃ , and placed in an automatic mortar. The mixture was homogenized by mixing for 5 hours, calcined at 1200 ° C. for 2 hours, taken out into the open air, quenched, crushed, and passed through a 350 mesh sieve.

Further, the powder was pressed to 1000 kg / cm ² using a rubber press, baked at 1300 ° C. for 1 hour, and then pulverized to obtain a powder having an average particle size of 5 μm (hereinafter referred to as “powder VII”).

The powder VII was subjected to X-ray diffraction analysis, and the result was consistent with the characteristic diffraction pattern of α-type tricalcium phosphate.

As a result of a chemical analysis of Powder VII, the Ca / P ratio was 1.51.

Powders I to VII obtained as described above were
In accordance with the method of IS-6602, using a physiological saline solution as a solution, the solution was pulverized to a powder-liquid ratio (P / L) of 2.0, and the curing time and the compressive strength after 24 hours were measured. .

Further, the crystal seeds were identified from the X-ray diffraction diagrams of the crystals I to VI (FIGS. 1 to 6).

 The results are shown in Table 1.

Table 1 shows cured products (powder I) using α-type tricalcium phosphate cement produced by the method according to the present invention.
-III) shows that the compressive strength is much higher than that of a cured product using a conventional cement.

The hydration activity was determined by measuring the peak height (Iα-TCP) of 30.8 ° which is the main peak of the characteristic diffraction line of α-type tribasic calcium phosphate in the X-ray diffraction diagram and 25.9 ° which is the main peak of the characteristic diffraction line of hydroxyapatite. From the peak height (I-HAP), the conversion was determined by the following equation and is shown in FIG.

From FIG. 7, it was found that the conversion rate from α-type tricalcium phosphate to hydroxyapatite showing the hydration activity of α-type tricalcium phosphate cement produced by the method according to the present invention was faster than that of the conventional cement. .

〔The invention's effect〕

The method for producing the α-type tribasic calcium phosphate cement according to the present invention has the above-described configuration and operation, and thus has the following effects.

In the dry method, homogeneous mixing is difficult and there is a problem in the uniformity of the product.
In addition, it was necessary to bake again at 1200 ° C. to 1300 ° C. for 1 hour or more after compression and compression to about 1000 kg / cm ² by a rubber press method or the like. However, in the method according to the present invention, a homogeneous product is obtained Therefore, there is no need for rapid cooling, and no need for pressure re-firing.

Cement manufactured by the conventional wet method has a disadvantage that the compressive strength of the hydrated hardened product is low. However, the cement manufactured by the method according to the present invention has a very low compressive strength of the hydrated hardened product. By the method according to the present invention, it is possible to obtain a product having a compressive strength that surpasses that of a dry-processed product re-fired under pressure.

[Brief description of the drawings]

1 to 6 show Examples 1 to 3 and Comparative Example 1, respectively.
7 is an X-ray diffraction diagram of crystals I to VI obtained in the production of α-type tribasic calcium phosphate cement, and FIG. 7 shows the change over time of the conversion rate from α-type tribasic calcium phosphate to hydroxyapatite. FIG. In FIGS. 1 to 5, ○ indicates a peak specific to hydroxyapatite, and ▽ indicates a peak specific to dicalcium phosphate.

Claims (1)

(57) [Claims] 1. A method for producing a calcium phosphate cement by reacting a suspension of calcium hydroxide with an aqueous phosphoric acid solution and calcining the resulting precipitate of calcium phosphate to obtain a product. A mixture of hydroxyapatite and dibasic calcium phosphate is formed by reacting a phosphoric acid aqueous solution at a temperature of 50 ° C. or more and 100 ° C. or less and a final reaction product concentration of 5% or more and 25% or less. Characterized by firing
-Type method for producing tribasic calcium phosphate cement.