JPS5830244B2 - Method for producing carbonated hydroxyapatite - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing carbonated hydroxyapatite.

Recently, phosphoric acid compounds, especially apatite, have been attracting attention as biomaterials, and various applications are being investigated for use in artificial bones and artificial teeth.

The manufacturing method for these artificial bones, etc., is based on powdered hydroxyapatite, tertiary calcium phosphate, MgO, K2
A method is known in which a small amount of additives such as O, CaF2°Al2O3, etc. are added and mixed, pressure molded, and then sintered.

The hydroxyapatite used in this method is synthesized by a solid diffusion reaction generally referred to as a dry method.

In the solid-state diffusion reaction, predetermined amounts of dibasic calcium phosphate and calcium carbonate are mixed, and 10
By firing at a high temperature of 00°C or higher, hydroxyapatite can be converted.

Such a dry method has the disadvantage that, as mentioned above, it requires long-time firing at a high temperature of <100° C. or higher, and it cannot remove hydroxyapatite containing carbonate.

On the other hand, a method called a wet method in which apatite is directly precipitated using ions in an aqueous solution is also known.

However, in such a wet method, the reaction rate is high and the precipitate obtained is colloidal.
It has not been put into practical use because it is inconvenient to handle and operate, and the composition ratio of the product changes even with slight differences in reaction conditions, making it difficult to obtain a constant product.

Furthermore, both the dry method and the wet method have the disadvantage that they cannot absorb hydroxyapatite containing carbonate, which has the same composition as bones and teeth in living organisms.

In other words, various chemical analyzes and infrared spectral analyzes have shown that bones and teeth in living organisms contain carbonic acid, and therefore, when used as biomaterials,
It is desirable to use hydroxyapatite that is compositionally similar to in-vivo bones and teeth as much as possible in order to be compatible with living organisms, shorten the acclimatization period, and reduce rejection reactions by living organisms.

The present inventors have conducted various studies to eliminate the above-mentioned drawbacks and obtain the desired carbonic acid-containing hydroxyapatite.
After adding dibasic calcium phosphate and calcium carbonate to aqueous ammonia at a molar ratio of 6:3 to 40,
By heating this to 60°C or higher to cause a solid-water reaction, we provide a completely new manufacturing method in which hydroxyapatite powder containing the desired carbonic acid can be easily produced in an extremely short period of time. They discovered that this is possible and completed the present invention.

That is, the method of the present invention consists of one solid phase (raw material powder) and one liquid phase (
It is carried out by dissolution, reaction, and precipitation in the reaction of the water)-solid phase (produced apatite powder) system, and basically the solubility product of dicalcium phosphate and calcium carbonate is about lXl0-8. Since the solubility product of hydroxyapatite is I x 10-110, this is carried out by taking advantage of the significant difference in solubility.

The method of the present invention is characterized by adding dibasic calcium phosphate and calcium carbonate to aqueous ammonia in the proportions described above, mixing and heating. This is done to improve the solubility of calcium phosphate and calcium carbonate and to shorten the reaction time.

That is, in the method of the present invention, the reaction time required is 4 to 5 days by heating the reaction solution to 60° C. or higher, whereas it takes several tens to hundreds of days without heating. It can be shortened in time.

In addition, in the present invention, by adding ammonia to water, a part of carbonic acid generated from calcium carbonate dissolved in water is combined with ammonia, and hydroxyapatite is generated as a result of carbonic acid being retained in the reaction solution. It contains carbonic acid.

Therefore, the carbonate content in the produced hydroxyapatite is mainly determined by the ammonia concentration in water.

The ammonia concentration varies depending on the carbonate content of the target hydroxyapatite, but usually the ammonia concentration is 1 to 5% (by weight, the same applies hereinafter).
It is preferable to use aqueous ammonia.

With this range of ammonia concentration, the carbonate content can be reduced to 1
．． 2 to 3.6 hydroxyapatite can be changed.

The reaction proceeds in the presence of ammonia water, and when the reaction is completed, the desired hydroxyapatite powder can be directly obtained by evaporating the ammonia water and drying it.

The amount of ammonia water in which the reaction is carried out is not particularly limited, but if a large amount of ammonia water is used, it is not preferable because a lot of time and energy are required for evaporation of the ammonia water.

Therefore, in the present invention, the amount of ammonia water to be added is reduced as much as possible, and the reaction vessel is provided with a lid or a reflux condenser to minimize evaporation of the ammonia water during the reaction. By removing the condenser and evaporating the ammonia water, the reaction operation can be carried out very efficiently.

However, the reaction may be carried out while aqueous ammonia is evaporated to such an extent that only a small amount of aqueous ammonia remains at the end of the reaction.

In the method of the present invention, it is necessary to use dibasic calcium phosphate and calcium carbonate, which are used as raw materials, at a molar ratio of 6:3 to 40.

When the dibasic calcium phosphate is smaller or smaller than this ratio, the produced apatite is mixed with other components such as calcium phosphate or calcium hydroxide, which is undesirable because the apatite production rate becomes low.

Next, the present invention will be described in detail with reference to Examples and Comparative Examples.

Example Second calcium phosphate 816P (6 moles) and calcium carbonate 40 (1 (4 moles)) were added to ammonia water obtained by dissolving 1001 parts of aqueous ammonia in 20001 water, and mixed well in a weighing reaction vessel.

This was covered with a lid and placed in a heating device set at 140°C.

As the liquid temperature rose, the generation of carbon dioxide gas was observed.

The temperature of the reaction solution in the heating device was 80 to 100°C, and it was heated in this state for 5 hours.

Then, the lid was removed and the ammonia water was evaporated under the above temperature conditions to obtain approximately 1100 f of dried carbonic acid-containing hydroxyapatite.
I got it.

By infrared absorption spectrum analysis, the wave number was 1400GIr.
It was confirmed that this product contained carbonic acid because it showed a unique absorption near L-'.

It was also confirmed by X-ray diffraction that this product was hydroxyapatite.

The measurement results of these infrared absorption spectra are shown in FIG. 1, and the measurement results of X-ray diffraction are shown in FIG. 2.

Comparative Example Hydroxyapatite was obtained by solid diffusion reaction, which is a dry method.

That is, the reaction requires 816 ft (6
mol) and calcium carbonate 300P (3 mol) were mixed in a ball mill, placed in a crucible, and burned in an electric furnace at 100 to 1200° C. for 2 to 5 hours in the presence of water vapor partial pressure.

Table 1 shows the results of comparing the properties of the hydroxyapatite powders obtained in these Examples and Comparative Examples.

The dispersion coefficient was calculated from the weight average diameter and the spread of distribution determined by the sedimentation method.

The larger the number, the wider the particle size distribution.

Also, is the carbon dioxide content 1-2f? 1oo in an oxygen stream
It was determined by heating to 0° C. and absorbing the generated carbon dioxide into an aqueous potassium hydroxide solution.

By changing the ammonia concentration of the ammonia water used, the hydroxyapatite obtained by the method of the present invention can be made to have a carbonic acid content comparable to that contained in natural bones and teeth. This can improve the compatibility between the artificial bones and teeth that have been removed and the natural bones and teeth.

In addition, in the present invention, in order to incorporate trace amounts of magnesium, potassium, fluorine or aluminum contained in natural bones and teeth into the hydroxyapatite product, appropriate amounts of these are added in advance to the reaction system. Alternatively, by adding and mixing these when firing the obtained carbonic acid-containing hydroxyapatite, apatite similar to natural bones and teeth can be obtained.

Therefore, the method of the present invention has the advantage that carbonate-containing hydroxyapatite having the same stoichiometric composition as the components forming natural bones and teeth can be easily produced with reproducibility.

Furthermore, in the method of the present invention, even if an acid such as hydrochloric acid or nitric acid is present in the reaction system, since the nucleic acid is neutralized by ammonia in the reaction solution, the apatite production reaction will not be affected. It also has the advantage that the reaction proceeds in a royal manner.

Thus, the carbonate-containing hydroxyapatite obtained by the method of the present invention has the same stoichiometric composition as natural bones and teeth, and has the advantage that it can be manufactured reproducibly and in an extremely short time. Therefore, it is suitably used as a raw material for manufacturing artificial bones and artificial teeth.

[Brief explanation of the drawing]

FIG. 1 shows the measurement results of the infrared absorption spectrum of carbonic acid-containing hydroxyapatite obtained by the method of the present invention, and FIG. 2 shows the measurement results of its X-ray diffraction.

Claims (1)

[Claims] 1 A carbonic acid-containing product characterized by adding and mixing dibasic calcium phosphate and calcium carbonate in a molar ratio of 623 to 40 to aqueous ammonia, and then heating the mixture to 60°C or higher to cause a solid-water reaction. Method for producing hydroxyapatite.