JPH07206411A - Production of octacalcium phosphate - Google Patents

Abstract

PURPOSE:To produce high purity octacalcium phosphate at a low cost in large quantities. CONSTITUTION:Tetracalcium phosphate and/or tricalcium phosphate is mixed with at least one among phosphoric acid, calcium prim. phosphate and calcium sec. phosphate so that the molar ratio of Ca to P is regulated to 1.30-1.40 and the resulting mixture is ground in the presence of water and brought into a reaction.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing octacerium phosphate (hereinafter referred to as "OCP") useful as bioceramics (artificial bones, dental materials and raw materials for producing these), adsorbents and the like.

[0002]

2. Description of the Related Art OCP, that is, the general formula: Ca ₈ H ₂
(PO _{4) 6} · 5H compounds represented by ₂ O is one of the precursors of the apatite in the mineralization process in vivo, dental materials, Xin mainly in bioceramics related fields such as artificial bones Has attracted attention as a material.

The following (1) to (7) are mentioned as known methods for producing OCP.

(1) A method obtained by hydrolyzing CaHPO ₄ .2H ₂ O in 0.5 mol of CH ₃ COONa under the condition of pH <6.1.

(2) 0.04 mol Ca (NO ₃ ) ₂ and 0.03 mol Na ₂ HPO ₄ were simultaneously added to 0.2 mol CH ₃ COONa having a pH of 6.5 to 6.6, and the mixture was heated to 50 ° C.
Method obtained by aging at -60 ° C.

(3) A method of hydrolyzing Ca ₃ (PO ₄ ) ₂ at around pH 6.

[0007] (4) dilute _{CaO-P 2 O 5 -H 2} O system solution (Ca concentration 0.4 to 4 mM, P concentration 0.8
A method of recovering the product obtained by adding an alkali to 10 mmol).

(5) CaCl ₂ was added to a dilute H ₃ PO ₄ —NaOH solution (phosphoric acid concentration 5 mmol, pH = 7.5).
A method in which 2H ₂ O is added and the reaction is matured at about 40 ° C.

(6) A mixed solution of phosphoric acid and CaCl ₂ .2H ₂ O in demineralized water or a NaCl solution was added at pH = 5.
A method of collecting the product obtained by dropping at 0 for 5 hours.

(7) A method obtained by reacting a dicalcium phosphate slurry having an electrical conductivity of 300 μs / cm or less with a slaked lime slurry at pH <5.5.

However, any of the above methods (1) to (7) has various problems to be solved in terms of raw material cost, manufacturing cost and wastewater treatment.

More specific problems of these methods are, for example, that it is necessary to successively mix the raw materials, that it is necessary to control the pH from the start to the end of the reaction, and the heating of the reaction product. The need to remove unreacted substances and coexisting impurities, the need to separate the obtained OCP from a large amount of reaction water and to treat the wastewater, and the reaction time is long. , Low yield and the like.

That is, since there are many factors that complicate the manufacturing process, the raw material cost and the manufacturing cost are high, and special equipment is required for wastewater treatment. Under such circumstances, the industrial production method of OCP has not been established.

[0014]

SUMMARY OF THE INVENTION The main object of the present invention is to solve the problems of the prior art and to provide a method for inexpensively mass-producing high-purity OCP.

[0015]

In view of the above-mentioned state of the art, the present inventor has conducted diligent research on a method for simplifying the manufacturing process without lowering the yield or purity of OCP. Tetracalcium phosphate (Ca ₄ (PO ₄ ) ₂
O: hereinafter referred to as “4CP”) and / or tricalcium phosphate (Ca ₃ (PO ₄ ) ₂ : hereinafter referred to as “3CP”), mixed with at least one of phosphoric acid, monobasic calcium phosphate and dibasic calcium phosphate, It has been found that the problems of the prior art can be substantially eliminated or significantly reduced when the mixed raw materials are reacted while being milled in the presence of water.

That is, in the present invention, 4CP and / or 3CP are mixed with phosphoric acid, at least one of calcium phosphate monobasic and calcium phosphate dibasic at a Ca / P molar ratio of 1.30 to 1.40, and water is present. The present invention provides a method for producing octacalcium phosphate, which comprises subjecting it to a grinding treatment to react it.

In the present invention, 4CP and 3CP are
A product manufactured by a known method can be used.
The manufacturing method of 4CP and 3CP is not particularly limited, but for example, CaCO ₃ powder and CaHP
O ₄ · 2H ₂ and O powder were mixed, from 1,250 to 1,650 ° C.
Examples of the solid-state reaction method include the following reaction formula 1 (production method of 4CP) and reaction formula 2 (production method of 3CP).

Reaction formula 1: 2CaCO ₃ + 2CaHPO ₄
2H ₂ O → Ca ₄ (PO ₄ ) ₂ O + 2CO ₂ + 5H ₂ O Reaction formula 2: CaCO ₃ + 2CaHPO ₄ · 2H ₂ O → Ca ₃ (PO ₄ ) ₂ + CO ₂ + 5H ₂ O 4CP and / or 3CP has a purity of It should be as high as possible, preferably 90% or more.

4CP and / or 3CP are uniformly
It is preferable to pulverize beforehand so as to facilitate mixing and adjustment. The particle size of the 4CP and / or 3CP pulverized product is not necessarily limited, but is usually 0.1.
It is about 150 μm, and more preferably about 1 to 40 μm.

As phosphoric acid, monobasic calcium phosphate and dibasic calcium phosphate, those produced by known methods can be used. For example, commercially available reagents and food additives can be used. In the case of calcium phosphate, a particle size of about 0.1 to 90 μm, more preferably about 0.5 to 40 μm is usually used.

In the present invention, 4CP and / or 3CP
And at least one of phosphoric acid, monobasic calcium phosphate and dibasic calcium phosphate are mixed to obtain a reaction raw material of the present invention (hereinafter simply referred to as “mixed raw material”).

The Ca / P molar ratio in the mixed raw material is usually 1.
It is more preferably 30 to 1.40 and more preferably 1.33 to 1.36. However, when apatite or calcium phosphate other than OCP such as dicalcium phosphate may be mixed in the product, the Ca / P molar ratio of the mixed raw material may be 1.15 to 1.45.

In the present invention, a reaction product containing OCP as a main component is obtained by subjecting the above mixed raw material to a hydrolysis reaction in the presence of water in combination with a grinding treatment.

In the present invention, the milling treatment means a treatment in which 4CP and / or 3CP are brought into good contact with at least one of phosphoric acid, monobasic calcium phosphate and dibasic calcium phosphate in the presence of water.

The method for grinding the mixed raw material may be any method as long as the reaction material can be ground well. Examples of the grinding method include a grinding method by high-speed stirring, a grinding method by ultrasonic stirring, a grinding method using a vibrating mill, a grinding method using a ball mill, and the like.

The amount of water coexisted in the milling process during the reaction is usually 100 to 1 with respect to 100 parts by weight of the mixed raw material.
000 parts by weight, preferably 300 to 600 parts by weight. When phosphoric acid that is liquid at room temperature is used, it is more preferable to mix it with a required amount of water in advance.

The liquid phase pH of the reaction product changes with the progress of the reaction, but the range is usually within a range suitable for OCP production (pH 5 to 8). Therefore, it is not necessary to adjust the liquid phase pH during the reaction.

The reaction time is generally the same as that of the mixed raw material Ca / P.
It varies depending on the molar ratio, reaction temperature, and the like. In the present invention, the reaction is completed at room temperature in about 3 to 5 hours.

In the present invention, as described above, the reaction is usually completed in about 3 to 5 hours even at room temperature, so it is not particularly necessary to heat or keep the reaction product to promote the reaction.

In the present invention, since the amount of water required for the reaction is small (about 1/10 to 1/20 of the prior art), it is not necessary to filter the water after aging the reaction product after completion of the reaction. The reaction product can be dried as it is to obtain OCP.

In the present invention, the drying is usually completed in about 5 to 24 hours, but the drying time can be shortened by further filtering the product after the reaction.

The drying temperature is not particularly limited, but is 50 ° C.
It is preferably about -80 ° C. If the temperature is lower than 50 ° C, it takes a long time to dry, so that the productivity is lowered, whereas if the temperature is higher than 80 ° C, the OCP obtained is easily converted into apatite.

In the OCP thus obtained, Na ⁺ contained in the OCP obtained by the conventional technique,
Since no impurities such as K ⁺ , Cl ⁻ , NO ₃ ⁻ and CH ₃ COO ⁻ are contained at all, it is usually unnecessary to wash the reaction product.

When it is not necessary to separate or wash impurities due to the purpose of use of OCP, phosphates other than the above-mentioned compounds constituting the mixed raw materials and calcium salts of acids other than phosphoric acid should also be used as raw materials. Is possible.

Examples of these phosphates include sodium phosphate, calcium phosphate, sodium pyrophosphate, calcium pyrophosphate and the like.

As acids other than phosphoric acid used as the calcium salt, carboxylic acids and inorganic acids can be used.

Examples of the carboxylic acid include lactic acid, citric acid, tartaric acid and succinic acid.

Examples of the inorganic acid include hydrochloric acid, nitric acid, sulfuric acid and the like.

The qualitative properties of the OCP obtained by the above method are determined by powder X-ray diffraction.

[0040]

By the method of the present invention, high-purity OCP can be efficiently obtained by a simple operation. In particular,
The method of the present invention brings the following effects.

(1) Each raw material may be added at once at the beginning, and it is not necessary to mix the raw materials little by little over several hours.

(2) Since the reaction proceeds rapidly even at room temperature, it is not necessary to heat or keep it warm.

(3) It is not necessary to adjust the pH during the reaction process.

(4) Since no pH adjusting agent is used, the products are not contaminated by them and washing is not necessary.

(5) Basically, it can be synthesized with a raw material containing only calcium and phosphorus, so that impurities other than calcium phosphate are not mixed.

(6) Since the amount of water required for the reaction is 1/10 to 1/20 as compared with the conventional case, it is not necessary to separate the product and water by filtration.

(7) Since the wastewater is not polluted and the discharge amount is extremely small, it is substantially unnecessary to treat the wastewater.

[0048]

EXAMPLES Examples will be shown below. The invention is not limited to the following examples.

Example 1 183.1 g of 4CP powder and 100% 4.9% phosphoric acid aqueous solution
0 g was put into a beaker having a capacity of 3 liters (Ca / P molar ratio of mixed raw material = 1.33), and the contents were stirred at high speed by a mixer while applying ultrasonic waves.

After 4 hours, the contents were taken out and dried at 60 ° C.

The X-ray diffractogram of the product, shown as A in FIG. 1, showed a single phase of OCP.

Comparative Example 1 The same operation as in Example 1 was carried out except that no special milling treatment was carried out and the mixed raw materials were stirred to such an extent that sedimentation and aggregation did not occur.

The X-ray diffractogram of the product, shown as F in FIG. 2, was a mixture of OCP, dicalcium phosphate and hydroxyapatite.

Example 2 146.5 g of 4CP powder, 258.1 g of CaHPO ₄ .2H ₂ O powder, 1500 g of water and 5 kg of zirconia balls (10 mmφ) were placed in a 3.6 liter alumina pot and sealed ( Ca / P molar ratio of mixed raw material = 1.35).

After rotating the pot for 5 hours, the contents were taken out and dried at 60 ° C.

The X-ray diffractogram of the product, shown as B in FIG. 1, showed a single phase of OCP.

Comparative Example 2 The same operation as in Example 2 was carried out except that no special grinding treatment was carried out and the mixed raw materials were stirred to such an extent that they did not settle and aggregate.

The X-ray diffractogram of the product, shown as G in FIG. 2, was a mixture of OCP, hydroxyapatite and unreacted dicalcium phosphate.

Example 3 173.7 g of 3CP powder, Ca (H ₂ PO ₄ ) ₂ · H ₂
25.2 g of O powder and 1000 g of water were put into a beaker having a capacity of 3 liters (Ca / P molar ratio of mixed raw material = 1.
35), the contents were stirred at high speed with a mixer while applying ultrasonic waves.

After 4 hours, the contents were taken out and dried at 60 ° C.

The X-ray diffractogram of the product, shown as C in FIG. 1, showed a single phase of OCP.

Comparative Example 3 The same operation as in Example 3 was carried out except that no special milling treatment was carried out and the mixed raw materials were stirred to such an extent that they did not settle and aggregate.

The X-ray diffractogram of the product, shown as H in FIG. 2, was a mixture of OCP, dicalcium phosphate and unreacted 3CP.

Example 4 155.1 g of 3CP powder, 57.3 g of CaHPO ₄ .2H ₂ O powder, 1000 g of water and 5 kg of zirconia balls (10 mmφ) were placed in a 3.6 liter alumina pot and sealed ( Ca / P molar ratio of mixed raw material = 1.38).

After rotating the pot for 3 hours, the contents were taken out and dried at 60 ° C.

The X-ray diffractogram of the product, shown as D in FIG. 1, showed a single phase of OCP.

Comparative Example 4 The same operation as in Example 4 was carried out except that no special grinding treatment was carried out and the mixed raw materials were stirred to such an extent that they did not settle and aggregate.

The X-ray diffractogram of the product, shown as I in FIG. 2, was a mixture of OCP, unreacted dicalcium phosphate and unreacted 3CP.

Example 5 36.6 g of 4CP powder, 62.1 g of 3CP powder, CaH
81.6 g of PO ₄ powder, 1000 g of water, and 5 kg of zirconia balls (10 mmφ) were put into an alumina pot having a capacity of 3.6 liters, and the pot was sealed (Ca as a mixed raw material).
/ P molar ratio = 1.33).

After rotating the pot for 4 hours, the contents were taken out and dried at 60 ° C.

The X-ray diffractogram of the product, shown as E in FIG. 1, showed a single phase of OCP.

Comparative Example 5 The same operation as in Example 5 was carried out except that no special grinding treatment was carried out and the mixed raw materials were stirred to such an extent that they did not settle and aggregate.

The X-ray diffractogram of the product, shown as J in FIG. 2, was a mixture of OCP, dicalcium phosphate and unreacted 3CP.

[Brief description of drawings]

FIG. 1 is a chart showing the X-ray diffraction results of the products obtained in Examples 1 to 5 of the present invention.

[Explanation of symbols]

 A. The product of Example 1 B. The product of Example 2 C.I. The product of Example 3 D. The product of Example 4 E. Product of Example 5

FIG. 2 is a chart showing X-ray diffraction results of the products obtained in Comparative Examples 1 to 5 of the present invention.

[Explanation of symbols]

 F. Product of Comparative Example 1 G. The product of Comparative Example 2 Product of Comparative Example 3 I. Product of Comparative Example 4 Product of Comparative Example 5

Claims (1)

[Claims] 1. Tetracalcium phosphate and / or tricalcium phosphate are mixed with at least one of phosphoric acid, monobasic calcium phosphate and dibasic calcium phosphate at a Ca / P molar ratio of 1.30 to 1.40, and water is added. A process for producing octacalcium phosphate, which comprises reacting by milling in the presence of.