JPH01290513A - Preparation of hydroxyapatite - Google Patents

Abstract

PURPOSE:To obtain a product having high purity from inexpensive raw materials easily and with sufficient reproducibility by adding H3PO4 to an aq. slurry of CaCO3 powder under specified conditions, aging the mixture by heating while causing a reaction, and proceeding a reaction by mixing Ca(OH)2 under specified conditions and heating. CONSTITUTION:An aq. slurry of CaCO3 powder having 5-15% concn. is admixed slowly with H3PO4 at 20-80 deg.C in ca.1.5molar ratio of Ca to P to cause a reac tion, then aged at 40-80 deg.C for 1-5hr. Ca(OH)2 is added thereto in a proportion of about 1.67 ca/P. The mixture is allowed to react at 60-100 deg.C by heating for 1-5hr, and filtered. The filter cake is dried to obtain thus a product compris ing fine particles. If the concn. of the slurry is <5% in this process, the practi cality is insufficient. It if is >15%, a uniform reaction product is not obtd. If the reaction temp. of H3PO4 exceeds 80 deg.C, the reactivity of generated tricalcium phosphate with Ca(OH)2 becomes extremely inferior, so the aging at high temp. for a long time becomes necessary.

Description

[Detailed description of the invention] [Industrial application field] The present invention relates to a method for packaging hydroxyapatite.

Hydroxyapatite (hereinafter abbreviated as HAP) is a type of calcium phosphate expressed by the general formula % (where n represents 0 to 6.2, O to 1), and is the main component of natural bones and teeth. Because it has the same chemical composition as the other components, it is a useful compound that has attracted particular attention in recent years as a raw material for bioceramics such as artificial bones and artificial tooth roots.

In addition, as a packing material for column chromatography, HAP has excellent separation ability for biological substances such as proteins, enzymes, and nucleic acids, and has recently become indispensable for the separation and purification of useful substances in the biotechnology field. It is something. Furthermore, H.A.
P is expected to be used as an adsorbent for harmful inorganic ions, a phosphor material, a catalyst for chemical reactions, etc., and the present invention relates to a method for producing HAP.

[Prior Art] Various methods for producing HAP have been studied and many methods have been proposed. For example, (1): Add a calcium salt to the calcium phosphate precipitate produced by the solution reaction to adjust the calcium to phosphorus molar ratio Ca/P to 1.67, and then carry out the reaction at high temperature and high pressure in an autoclave. The hydrothermal synthesis method and ■.

(b) A dry method of firing at a high temperature of 00°C or higher, or a wet method: (2): Precipitation reaction method using a soluble salt; (3):
A neutralization method in which the reaction between Ca(Oll)2 and )(3PO4 is carried out while grinding), and (4): a hydrolysis method are known.

[Problem to be solved by the invention] These manufacturing methods have advantages and disadvantages. For example, the hydrothermal synthesis method and dry method (1) require long-term firing at high temperatures, and therefore require expensive equipment. However, there are problems with industrial mass production, such as complicated operations and high energy costs.

The wet method does not require special equipment and is suitable for mass production, but in the precipitation reaction (2), the product becomes a colloid, which not only makes filtering and washing difficult and inconvenient to handle, but also makes the reaction difficult. The molar ratio Ca/P of calcium and phosphorous easily changes even with slight changes in conditions, resulting in poor reproducibility. or,(
3) The neutralization method is industrially advantageous in that it uses inexpensive raw materials, but it requires grinding to make the composition of the product homogeneous, requires special equipment, and is complicated to operate. There are drawbacks. Furthermore, the hydrolysis method (4) can be applied to, for example, CaHPO4.
Since hydrolysis is carried out by adding an alkali to the aqueous slurry of 2H20, there are many problems such as the alkali being adsorbed into the product and difficult to remove.

Therefore, we solved the above-mentioned problems of the conventional technology and produced fine, high-purity hydroxyapatite, which is suitable for raw materials for bioceramics such as artificial bones and has excellent separation ability as a chromatography packing material, by using inexpensive raw materials and simple operations. A technical problem arises that must be solved in order to facilitate manufacturing, and the present invention aims to solve this problem.

[Means for Solving the Problems] The present invention was proposed to achieve the above-mentioned object.
A 15% slurry is produced and the slurry is heated to a temperature of 20-8.
At 0°C, H3PO4 was gradually added and reacted at a ratio such that the molar ratio Ca/P of calcium and phosphorus was around 1.5, followed by heating at a temperature of 40 to 80°C for 1 to 5 hours, Next, Ca(OH)2 is added and mixed at a ratio such that the molar ratio Ca/P of calcium and phosphorus is around 1.67, and the mixture is heated and reacted at a temperature of 60 to +00°C for I to 5 hours. The present invention aims to provide a method for producing hydroxyapatite.

[Examples and Effects] Examples of the present invention will be described in detail below. First, H and PO4 are added to an aqueous slurry of CaCO3 for reaction, and tricalcium phosphate of the specific formula Ca3 (PO4)2 .nl,, O, which is produced by ripening, is mixed with Ca(Oll)2.

In such cases, it is a stable compound that easily absorbs calcium and has a calcium to phosphorus molar ratio Ca/P close to the stoichiometric value of hydroxyapatite, 1.67, and whose composition does not change even after washing. Changes to HAP.

Furthermore, as another example, H3PO4 is gradually added to a slurry of CaCO3 powder and water at a temperature of 20-80°C, and the mixture is aged to produce tricalcium phosphate having the characteristic formula Ca3(PO4)2.nlI20. Then, Ca(011)2 was added at a ratio such that the molar ratio of calcium to phosphorus, Ca/P, was 1.67, and the mixture was heated at a temperature of 60 to 10.
After heating the reaction to 0°C, it is filtered and dried to obtain fine particles of HA.
produced P.

Therefore, embodiments of the present invention will be described in more detail.

The raw material CaCO3 powder is mixed with water to give a concentration of 5 to 15% by weight (
(hereinafter simply referred to as %), and stirred to form a slurry of 1 to 1%.
Using H3PO4 diluted 0 times in a ratio such that the molar ratio Ca/P of calcium and phosphorus is around 1.5,
The reaction is carried out by gradual addition over a period of 0.5 to 2 hours at a temperature range of 80°C, and then at 40 to 80°C, preferably 60 to 8°C.
Aging at 0°C for 1-5 hours. Therefore, if the CaCO3 slurry concentration is less than 5%, the concentration is too low to be practical, and if it is more than 15%, the concentration is too high and the reaction becomes heterogeneous. A compound is generated, and the subsequent reactivity with Ca(011)2 becomes poor, making it impossible to obtain homogeneous HAP. Furthermore, if H3PO4 is diluted 10 times or more, the concentration of the reaction solution becomes too low to be practical.

The reaction temperature is preferably room temperature or higher, but if it exceeds 80°C, the generated tricalcium phosphate will have extremely poor reactivity with Ca(Oll)2, and the absorption rate of calcium will become slow, making it difficult to complete the reaction. Since it is necessary to heat the reaction mixture to a higher temperature or for a longer period of time, the reaction can be carried out at a temperature of 80° C. or lower. Aging is carried out at a temperature of 40°C or higher, preferably 60°C or higher. If the temperature is below 40°C, the effect of ripening will be slow, and for the same reason as in the reaction, it is possible to carry out the aging at below 80°C.

1 (There is no particular restriction on the time for adding 3PO4, but if it is added at -300°C, it will not only generate a large amount of CO□, but also become locally strongly acidic and produce CaHPO4, 2II20, etc., resulting in heterogeneity. This is not desirable, so at least 0.
Do this gradually over a period of 5 hours or more.

However, no particular effect can be expected even if the treatment exceeds 2 hours, so it is preferable to use the treatment for about 2 hours. In this way, the reaction is carried out in a slightly acidic region around 11116.

In this reaction, particles of ClCO3 come into contact with H3PO4 and C
As a result of progressing while firing O2, the product tends to become fine particles, and unreacted particles are not incorporated into the core of the produced particles. In addition, it is characterized by good filterability despite being homogeneous and fine particles.

The slurry-like product thus obtained may be used as it is, or after filtering and washing to remove impurities, it may be made into a slurry again, and the molar ratio of calcium to phosphorus, Ca/P, may be 1.
Calculation amount Ca(011)2 so that it becomes 67 or something excessive
The mixture is added and mixed, heated and reacted at 60 to 100°C for 0.5 to 5 hours, filtered, excess Ca(011)2 removed by washing with water, and dried at 50 to 200°C. According to the method of the present invention, fine and homogeneous particles with a molar ratio of calcium to phosphorus of H
[■] AP, which is close to the calculated value of AP 1.67, can be easily obtained with reproducibility. The dry powder thus obtained was confirmed to be HAP by X-ray diffraction method.
The sample fired for one hour showed a clear diffraction pattern. This will be specifically explained below using experimental examples.

Experimental example 1 50 g of CaCO3 powder and 285 ml of water were placed in a beaker and mixed with stirring to prepare a slurry with a concentration of 15%.
heated to ℃.

Separately, 83110438.4 g of 85% and 287 m of water
A 10% H3PO4 aqueous solution was prepared by adding CaC
A slurry of O3 was gradually added over 2 hours with stirring to react, and the mixture was heated and aged at 80° C. for 1 hour. The molar ratio of calcium to phosphorus is 1.50.

Next, it is filtered, washed with water, and dried at 80°C to obtain a white fine powder 5.
7.0g was obtained. This was determined by chemical and thermal analysis.
: 35.13%, P:I8.09% Ca/P molar ratio is 1°50, and the specific formula Ca3(P Oa )2
・1.8 H20 tricalcium phosphate.

Next, 57 g of this powder and 5 ml of water were charged into a sealed reactor and mixed with stirring to make a 10% slurry.
11) 24.9 g was added and mixed with stirring. The molar ratio of calcium to phosphorus is 1.70. Next, the temperature was raised to 80°C, heated for 2 hours, filtered, and washed with water, initially at 100°C.
Subsequently, it was dried at 200°C to obtain 59.3 g of white fine powder. From chemical analysis Cl: 37.57%, P
: 17.38%, and the Ca/P molar ratio was 1.67.

Furthermore, it was confirmed to be HAP by X-ray diffraction. Furthermore, those fired at 800° C. for 1 hour showed a clear diffraction pattern.

Experimental Example 2 By the same operation as Experimental Example 1, 50g of CaCO3 powder was prepared.
Prepare a 5% slurry from 950 ml of water and 85%
438.4 g of H3P0 was added and reacted at 20°C over 1 hour, and the mixture was heated and aged at 40°C for 5 hours. This was filtered and washed with water, and then added to a reactor with 500 ml of water to give a concentration of approximately 10%.
A slurry was prepared, 4.9 g of Ca(Oll)2 was added thereto, and the mixture was reacted by heating at 95° C. for 0.5 hour. Reaction mixture Ca
/P molar ratio is 1.70 - then filtered and washed with water +
It was dried at 00°C to obtain 61.6 g of white fine powder. Chemical analysis results Ca: 3B, 06%, P:I6.74
It was a fine powder with a Ca/P molar ratio of 1.66% and was confirmed to be HAP by X-ray diffraction.

Experimental Example 3 By the same operation as Experimental Example 1, 50g of CaCO3 powder was
Prepare a 10% slurry from 450 ml of water and 60 ml of water.
Warmed to ℃. Separately, a 50% solution was prepared from 85% H3PO438.4 g and 27 ml of water, added and reacted over 0.5 hours, and further heated and aged at 60'C for 3 hours.

This was transferred to a reactor, and then Ca(011)2
After adding 4.9 g of 60.degree.
5g was obtained. From chemical analysis, this product has Ca: 35.
66%.

P: 16.66%, Ca/P molar ratio 1.66,
It was confirmed by line diffraction that it was HAP.

The white powders obtained in Experimental Examples 1 to 3 are all fine powders with particle diameters of several microns or less.

Comparative Example CacOl powder 5 [1 g and 10% from 450 ml of water
A 25% H3po4 aqueous solution was prepared from a slurry of 38.4 g of 85% H:l POn and 92 ml of water in the same manner as in Experimental Example 1, and after addition reaction at 85°C for 2 hours, the mixture was heated to 95°C. The mixture was heated and aged for 5 hours. This was transferred to a reactor, the temperature was lowered to 80°C, and 4.9
g was added, reacted by heating for 5 hours, filtered and washed with water, and then heated to 100°C.
The mixture was dried to obtain 1.4 g of white fine powder 5'. CaC
Except for the reaction temperature of O2 and H3PO4 and the aging temperature, all other conditions are within the range of the experimental examples. This white powder is C
a: 37.18%.

P: 17.95% and Ca/P molar ratio was 1.60.

[Effects of the Invention] According to the present invention, high-purity hydroxyapatite (HAP), which is composed of fine particles with a Ca/P molar ratio of approximately 67 and is useful as a raw material for bioceramics, a filler for chromatography, etc., can be produced at low cost. It can be easily produced from raw materials at low temperatures with good reproducibility.

It should be noted that the present invention can be modified in various ways without departing from the spirit of the invention, and it goes without saying that the present invention extends to such modifications.

Claims (1)

[Claims] CaCO_3 powder and water are mixed to form a chiller with a concentration of 5-15%, and H_3PO_4 is added to the chiller at a temperature of 20-80°C with a molar ratio of calcium to phosphorus Ca
The reaction was gradually added at a ratio such that /P was around 1.5, followed by heating at a temperature of 40 to 80°C for 1 to 5 hours, and then Ca(OH)_2 was added to the molar ratio of calcium to phosphorus. A method for producing hydroxyapatite, which comprises adding and mixing Ca/P at a ratio of around 1.67, and heating and reacting at a temperature of 60 to 100°C for 1 to 5 hours.