JP3247896B2 - Method for producing hydroxyapatite - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing hydroxyapatite.

[0002]

2. Description of the Related Art Recently, hydroxyapatite (hereinafter abbreviated as HAP) is similar to minerals of bones and teeth, and has recently been used as a raw material for bioceramics and as a polymer such as proteins and nucleic acids. It is used as a packing material for chromatography for the purpose of separating substances. A method for producing HAP has been known in many documents and patents for a long time.

The main ones are as follows. (1) Wet method Generally, an aqueous slurry of calcium hydroxide or calcium oxide is reacted with an aqueous phosphoric acid solution to precipitate hydroxyapatite. (2) Hydrothermal synthesis A method in which calcium hydrogen phosphate anhydride and phosphoric acid are reacted in an autoclave at 100 to 500 ° C. and 1 to 500 atm for about 48 hours. (3) Dry synthesis method Ca ₈ H ₂ (PO ₄ ) ₆ disclosed in JP-A-53-111000
There is a method of producing crystalline apatite by mixing 5H ₂ O solids and one or more calcium compounds from a group of calcium compounds and subjecting them to a solid-phase reaction at 1000 to 1300 ° C.

[0004]

In both of the above methods (2) and (3), the reaction is carried out at a high temperature and a high pressure, so that the equipment is expensive, and the operation of the equipment is complicated, and the energy consumed is enormous. Disadvantages.

[0005] The above method (1) is generally carried out by a batch reaction method, but does not cause the above-mentioned problems in the apparatus. However, the batch reaction method of the wet method, that is,
For example, in a reaction method in which a phosphoric acid aqueous solution is dropped into an aqueous slurry of calcium hydroxide or calcium oxide to generate HAP, colloidal HAP is generated, so that a HAP having a desired Ca / P atomic ratio can be reproducibly prepared. There were drawbacks that could not be obtained. Further, as the reaction proceeds, the viscosity increases and stirring becomes difficult. Therefore, a powerful stirring device is required. Thus, in practice, only a small amount could be manufactured at a time.

The HAP obtained by this wet method has too small a secondary particle diameter when used as a packing material for chromatography, for example. Therefore, when used, the secondary particle diameter must be increased by a granulation method or the like, and a granulation step or the like is required, and there has been a problem that the process is complicated.

[0007] The batch type reaction method is a convenient means for producing a large number of varieties in a small amount, and HAP obtained from calcium hydroxide and phosphoric acid is free from impurities from by-products. It is an excellent manufacturing method.

However, as described above, HAP having a desired Ca / P atomic ratio cannot be obtained with good reproducibility, and the particle size cannot be controlled at the reaction stage.

An object of the present invention is to solve the above-mentioned drawbacks and to provide a batch-type production method of HAP having a desired Ca / P atomic ratio with good reproducibility and a desired particle size.

[0010]

Means for Solving the Problems In view of the above situation, the present inventors have conducted various studies. As a result, once a seed crystal is formed, the pH is kept constant, and the reaction is carried out.
It has been found that HAP having a desired Ca / P atomic ratio and a secondary particle diameter can be produced with good reproducibility while preventing the formation of AP, and the present invention has been completed.

[0011] That is, the present invention relates to CaO and / or Ca
In a method for producing hydroxyapatite from an aqueous slurry of (OH) _{2 and} an aqueous phosphoric acid solution by a batch reaction method, an aqueous phosphoric acid solution is dropped into the aqueous slurry to produce a fine hydroxyapatite slurry, and then the fine hydroxyapatite slurry is produced. In the apatite slurry, the aqueous slurry and the phosphoric acid aqueous solution are simultaneously dropped and reacted while keeping the pH of the reaction slurry constant. Finally, if necessary, the phosphoric acid aqueous solution has a desired Ca / P atomic ratio. This is a method for producing hydroxyapatite in which the reaction is completed by dropwise addition.

Hereinafter, the present invention will be described in more detail. The raw materials used in the present invention, CaO and Ca (OH) _2, can be used as they are commercially available. Alternatively, CaCO ₃ may be obtained by burning at a temperature of 800 ° C. or higher. As the other raw material, phosphoric acid, a commercially available product can be used as it is.

In the reaction method of the present invention, first, a phosphoric acid aqueous solution is dropped into an aqueous slurry of CaO and / or Ca (OH) ₂ , and a fine hydroxyapatite slurry (hereinafter, the generated slurry is referred to as a seed crystal slurry) Is generated. At this time, the concentration of the aqueous slurry of CaO and / or Ca (OH) ₂ is preferably 30% by weight or less. If the content is 30% by weight or more, the viscosity of the slurry becomes high and stirring becomes difficult, which is not preferable.
On the other hand, the concentration of the phosphoric acid aqueous solution is preferably 75% by weight or less.
When the content is 75% by weight or more, a high acid concentration portion tends to be generated in the reaction slurry, which is not preferable because a substance other than HAP such as dibasic calcium phosphate is generated. The dropping of the phosphoric acid aqueous solution is performed until the set pH value is reached.

Next, CaO and / or
An aqueous slurry of Ca (OH) _{2 and} an aqueous solution of phosphoric acid are simultaneously dropped while keeping the pH constant, to grow fine HAP crystals and increase the secondary particle diameter.

The set pH of the present invention is preferably from 7.0 to 12.0.
Particularly preferably, it is 9.0 to 12.0. Slurry pH 7.0
If it deviates from 112.0, H having the desired Ca / P atomic ratio
AP cannot be obtained with good reproducibility. This is because when the pH is 7.0 or less, a high acid concentration portion is easily generated in the reaction slurry,
This is because, for example, dibasic calcium phosphate other than HAP is generated. If the pH is 12.0 or more, the crystal growth is slowed, and the same colloidal HAP as in the conventional wet method is generated.

The size of the secondary particle diameter can be controlled by the set value of the pH. That is, the smaller the secondary particle size, the more the pH is set to be strongly basic. Further, as the pH is set to be more basic, a substance having a higher Ca / P atomic ratio is generated. Specifically, in the above pH range,
Average secondary particle size 1 ~ 10μm, Ca / P atomic ratio 1.4 ~ 1.75
Produces things. Therefore, the pH value at which the desired physical properties of HAP can be obtained may be selected.

If the charged Ca / P atomic ratio is larger than the desired Ca / P atomic ratio, finally, an aqueous solution of phosphoric acid is dropped into the obtained reaction slurry until the desired Ca / P atomic ratio is reached. To complete the reaction. The reaction temperature of the present invention is not particularly limited, but is preferably in the range of room temperature to about 100 ° C. In addition, the present invention can be carried out sufficiently with ordinary stirring without particularly strong stirring.

The reaction of the present invention is as described above, but the secondary particle size can also be controlled by changing the ratio of the seed slurry. That is, if the proportion of the seed crystal slurry is reduced, HAP having a large secondary particle size can be obtained.
HAP with a small secondary particle size
Can be generated. The proportion of the seed HAP is preferably not more than 60% by weight of the total amount of HAP formed. When the content is more than 60% by weight, the crystals do not grow sufficiently, so that colloidal HAP is formed and HA having poor reproducibility as in the conventional wet method is used.
It is not preferable because only P can be obtained.

The specific secondary particle size depends on the pH of the reaction as described above. For example, when the pH is 9.5 and the amount of seed crystals is 30%, HAP having an average particle size of about 5 μm is obtained. In order to obtain a powdered HAP from the reaction slurry obtained by the reaction method of the present invention, filtration, washing and drying in a usual manner may be performed after the reaction.

As described above, according to the present invention, the relationship between the conditions such as the pH and the amount of seed crystals and the physical properties such as the Ca / P atomic ratio and the secondary particle size are determined in advance to produce HAP having desired physical properties. It becomes possible.

Hereinafter, the present invention will be described in more detail with reference to specific examples. Hereinafter,% indicates weight% unless otherwise specified.

[0022]

【Example】

Example 1 10% was put into a reactor made of stainless steel with a stirrer and contained 15 liters.
A 3000 g aqueous Ca (OH) ₂ slurry is charged, and a 50% aqueous phosphoric acid solution is added at a speed of 4.7 g / min.
It was dropped until 9.5. At this time, the dripping amount of the 50% phosphoric acid aqueous solution was 467 g.

Subsequently, 10% Ca (OH) was added into the reaction slurry.
₍₂₎ Apply 7000 g of aqueous slurry at a speed of 35 g / min.
Both raw materials were simultaneously dropped while adjusting the dropping speed so that the pH of the reaction slurry was kept at 9.5 with a 0% phosphoric acid aqueous solution. The dropping time was 200 minutes, and the dropping amount of the 50% phosphoric acid aqueous solution was 1100 g. Finally, 18 g of a 50% aqueous phosphoric acid solution was added dropwise so that the charged atomic ratio Ca / P was 1.67, and the mixture was aged for 1 hour to complete the reaction. The reaction was performed at 50 ° C. The obtained reaction slurry was filtered, washed with water and dried in a usual manner to obtain a white powder.

Chemical analysis and particle size measurement of this powder (sedimentation method:
X-ray diffraction analysis revealed that it was a hydroxyapatite single phase with a Ca / P atomic ratio of 1.67 and an average particle size of 5.0 μm.

Example 2 The same operation as in Example 1 was carried out under the same conditions as in Example 1 except that the reaction pH was changed from 9.5 to 11.5. The amount of the 50% phosphoric acid aqueous solution dropped was 454 g at the time of the seed crystal slurry reaction, 1084 g at the time of the raw material simultaneous dropping reaction, and 47 g at the time of adjusting the Ca / P atomic ratio. The obtained white powder was a single phase of hydroxyapatite having a Ca / P atomic ratio of 1.67 and an average particle size of 1.2 μm.

Example 3 Except that the proportion of the seed crystal of Example 2 was changed from 30% to 10%,
The same operation was performed under the same conditions as in Example 2. The amount of the 50% phosphoric acid aqueous solution dropped was 151 g at the time of the seed crystal slurry reaction, 1384 g at the time of the simultaneous dropping reaction of the raw materials, and 50 g at the time of adjusting the Ca / P atomic ratio.
It became. As shown in Table 1, the obtained white powder was HAP in which only the average particle size was increased from 1.2 μm to 2.0 μm as compared with Example 2.

Example 4 The same operation was performed under the same conditions as in Example 1 except that the reaction pH of 9.5 was changed to 8.0. The amount of the 50% phosphoric acid aqueous solution dropped was 476 g during the seed crystal slurry reaction, 1290 g during the simultaneous raw material dropping reaction, and 50% for adjusting the Ca / P atomic ratio.
The dropping of the phosphoric acid aqueous solution was not performed. The resulting white powder had a Ca / P atomic ratio of 1.50 and an average particle size of 7.0 μm.
It was a single phase of defective hydroxyapatite.

Examples 5 to 6 The same operation as in Example 1 was carried out at the reaction temperature, Ca (OH) ₂ slurry concentration and phosphoric acid aqueous solution concentration shown in Table 1. The obtained white powder was the same as that of Example 1 as shown in Table 1. In Example 5, the amount of the phosphoric acid aqueous solution dropped was 467 g during the seed crystal slurry reaction, 1100 g during the simultaneous dropping reaction, and 18 g during the Ca / P atomic ratio adjustment. In Example 6, 389 g during the seed crystal slurry reaction, 917 g during the simultaneous dropping reaction, and Ca /
The weight was 15 g when the P atomic ratio was adjusted.

[0029]

[Table 1]

Comparative Example 1 10 kg of a 10% Ca (OH) ₂ slurry was placed in the same reactor as in Example 1.
And 1585 g of a 50% aqueous phosphoric acid solution in an amount corresponding to a Ca / P atomic ratio of 1.67 was added dropwise over 5 hours, and aging was performed for 1 hour to complete the reaction. The obtained reaction slurry is filtered by a conventional method,
After washing with water and drying, a white powder was obtained. Table 2 shows the reaction conditions and the analysis results of the products. As shown in Table 2, the charged Ca / P
Those obtained even when the atomic ratio was 1.67 were other than 1.67, and CaHPO ₄ was mixed in the X-ray analysis.

Comparative Examples 2 and 3 The same operation as in Comparative Example 1 was performed except that the Ca (OH) ₂ slurry concentration and the phosphoric acid aqueous solution concentration were changed as shown in Table 2.
The aqueous phosphoric acid solution was 1321 g in Comparative Example 2, and 2642 in Comparative Example 3.
g was dropped. As shown in Table 2, those obtained even when the charged Ca / P atomic ratio was 1.67 were other than 1.67, and CaHPO ₄ was mixed in the product of Comparative Example 2.

[0032]

[Table 2]

[0033]

As described above, according to the present invention, HAP having a desired Ca / P atomic ratio can be reproducibly obtained. Further, by changing the reaction conditions such as the ratio of seed crystals and the reaction pH, HAP having a desired Ca / P atomic ratio and an average particle diameter can be obtained. In addition, the method is advantageous in terms of operation, such that the stirring need not be particularly strong. The present invention provides a HAP having desired physical properties with good reproducibility without using any special apparatus or process.
And its significance is extremely large.

Claims (3)

(57) [Claims] 1. A method for producing hydroxyapatite from an aqueous slurry of CaO and / or Ca (OH) _{2 and} an aqueous phosphoric acid solution by a batch reaction method, comprising: (A) dropping an aqueous phosphoric acid solution into the aqueous slurry; And (B) successively dropping and reacting the aqueous slurry and the phosphoric acid aqueous solution into the fine hydroxyapatite slurry while simultaneously maintaining the pH of the reaction slurry constant. A method for producing hydroxyapatite. 2. A method for producing hydroxyapatite from an aqueous slurry of CaO and / or Ca (OH) _{2 and} an aqueous phosphoric acid solution by a batch reaction method, comprising: (A) dropping an aqueous phosphoric acid solution into the aqueous slurry; (B) Subsequently, the aqueous slurry and the phosphoric acid aqueous solution are simultaneously dropped and reacted in the fine hydroxyapatite slurry while keeping the pH of the reaction slurry constant. A method of producing hydroxyapatite, which comprises dropping an aqueous phosphoric acid solution into the reaction slurry until a desired Ca / P atomic ratio is reached, thereby completing the reaction. 3. The method according to claim 1, wherein the pH of the reaction slurry is in the range of 7.0 to 12.0.