JPH0411483B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing hydroxyapatite. Hydroxyapatite has unique performance as an adsorbent for biopolymers, fluorine ions, heavy metal ions, etc., and in recent years, it has been used in chromatography to separate proteins, enzymes, etc. using its biocompatibility. It is a substance that is considered useful as a filler for E and is also attracting attention as a bioceramic material for artificial bones and artificial teeth. Conventionally, many methods for producing hydroxyapatite have been known for a long time, but if broadly classified, the following methods are exemplified. (1) A method using solid diffusion reaction called dry synthesis method. (2) A method of reaction under high pressure called hydrothermal synthesis. This method is mainly used for the purpose of obtaining large crystals. (3) Direct precipitation using aqueous ions, called wet synthesis. However, the dry synthesis method (1) requires a reaction at high temperatures for a long time, which consumes a lot of energy, and because it is a solid-solid reaction, it is difficult to obtain uniform composition. In addition, the hydrothermal synthesis method (2) involves problems such as expensive equipment and complicated operations because the reaction is carried out at high pressure. In the wet synthesis method (3), the apatite precipitate produced by the reaction must be separated, washed and dried, and many steps are required, resulting in complicated operations. have. Many wet synthesis methods for apatite have been proposed to date, but the common idea among these conventional wet synthesis methods is, for example, that a calcium salt aqueous solution and a phosphorus compound aqueous solution are heated at 90 to 100°C.
As can be seen in the example of the method of mixing in a decarboxylated atmosphere while maintaining the pH around 8 to form a precipitate, apatite is directly formed as a precipitate, and the apatite is extracted from an aqueous solution by filtration or other operations. This is based on the concept of separating and recovering the waste. However, according to this method, the process of mixing an aqueous solution of a calcium salt and an aqueous solution of a phosphorus compound, forming a precipitate through a direct reaction of ions, and crystallizing it into apatite depends on the type and concentration of the raw material salt, and the mixing procedure of the raw materials. It is difficult to obtain a precipitate with the exact composition as it is affected by many factors such as mixing rate, pH adjustment, etc., and the molar ratio of calcium and phosphorus (Ca/P) and the physical chemistry of the resulting powder. It has been extremely difficult to control the physical characteristics with good reproducibility. In addition, it requires multiple steps such as excessive washing, drying, and pulverization of the precipitate, as well as many devices, and its operation also requires training. The present inventors previously proposed a method for producing a novel calcium-phosphorus apatite using a flammable organic solvent that is compatible with water or a mixed solvent of a flammable organic solvent that is compatible with water and water. A soluble inorganic calcium compound and an organic phosphorus compound are dissolved in these solvents to prepare a solution with a uniform composition that does not cause precipitation, and this raw material solution is sprayed into a flame or heating zone to initiate a thermal decomposition reaction. It has been discovered that calcium-phosphorus apatite can be produced by (Refer to Japanese Patent Application Laid-Open No. 146704/1983), depending on the operating conditions, CaO, CaCO ₃ , etc. may be generated freely in the product, but the present inventors
Furthermore, subsequent research into the production of hydroxyapatite revealed that aqueous ammonia and amines were further added to the raw material solution in a system where CaO, _CaCO3 , etc. were produced freely, and by spray pyrolysis of this solution, CaO and CaCO3 were produced. It has been found that the free production of ₃ can be suppressed and the production rate of hydroxyapatite can be increased. The present invention has been made based on this knowledge. That is, the present invention provides a novel method for producing hydroxyapatite. In the method of the present invention, in order to achieve uniform mixing of raw materials,
It uses a raw material solution with a uniform composition dissolved in a flammable organic solvent that is compatible with water or a mixed solvent of a flammable organic solvent that is compatible with water and water, and that no precipitation occurs due to mixing. It has become one of its characteristics. Then, ammonia water or a soluble amine is contained in the solution within a range that does not cause precipitation, and the properties of the solution are adjusted from a neutral range to a weakly alkaline range to prepare a spray raw material solution. Next, this raw material solution is sprayed into a flame or a heating zone to cause a thermal decomposition reaction, thereby producing hydroxyapatite. By the method of the present invention, the synthesis reaction can be completed in an extremely short time of just a few seconds or less, compared to the conventional technology that requires a long time to synthesize hydroxyapatite, and in addition, it does not require complicated steps such as filtering, washing, and drying. Hydroxyapatite can be obtained directly without any additional steps. Furthermore, by adding aqueous ammonia or amine to the raw material solution, the production rate of hydroxyapatite is increased.
A special effect can be obtained in that free production of CaO, CaCO ₃ , etc. can be suppressed. The powder produced by the spray pyrolysis reaction according to the method of the present invention is usually obtained as a microspherical powder in which submicron particles are densely or coarsely fixed and sintered, and the type and combination of raw material compounds, Depending on the spray pyrolysis conditions, various phases can be obtained, including an amorphous phase and a phase containing both a hydroxyapatite crystalline phase and an amorphous phase, but all of them are highly reactive. It is a powder. Depending on the use and purpose, the degree of crystallinity can be further increased or the reaction activity can be slightly reduced by selecting conditions. That is, for example, by further heat-treating the powder produced by the spray pyrolysis reaction in various atmospheres at a desired temperature within the temperature range in which hydroxyapatite can stably exist without decomposing. , the above-mentioned physical properties can be controlled. For example, desired physical properties can be obtained by heat treatment at a desired temperature of 1400° C. or lower in an air atmosphere. A more specific explanation of the method of the present invention is as follows. In the method of the present invention, first, a soluble inorganic calcium compound and an organic phosphorus compound are added to a water-miscible organic solvent or a mixed solvent of a water-miscible organic solvent and water in proportion to the solubility. In addition, a raw material solution is prepared by adding ammonia water and/or an amine soluble in the above solution to the mixed and dissolved solution, and the liquid properties are made from a neutral range to a weakly alkaline range. The order in which these raw materials are mixed is not necessarily specified, and may be mixed in any order as long as the order does not cause precipitation. The time required for mixing will vary depending on the raw materials selected. When mixing, it is preferable to stir until a sufficiently uniform solution is obtained. Next, the solution prepared in this way is sprayed using a known method such as a pressurized nozzle or a rotating disk into a heating zone preheated to 700 to 1500°C in a flame such as a gas burner or in a gas furnace or electric furnace. In an extremely short period of time (less than a few seconds), the solvent in the solution evaporates and burns into a fine liquid cylinder, usually several tens of microns or less, and the solute solidifies.
Allow a thermal decomposition reaction to occur. The product is usually a fine powder in which submicron particles are tightly or coarsely fixed and sintered to form a spherical shape as a whole, and can be collected using a cyclone or the like. Furthermore, if necessary, the powder produced by the spray pyrolysis reaction is heated to a desired temperature in a temperature range in which hydroxyapatite does not decompose in various atmospheres such as air, air with water vapor added, and an inert atmosphere. By heat-treating, hydroxyapatite with controlled crystallinity, specific surface area, etc. can be obtained. The calcium inorganic compound and phosphorus organic compound used in the method of the present invention include:
Ca(NO ₃ ) ₂・4H ₂ O, (CH ₃ O) ₃ P, (C ₂ H ₅ O) ₃ P,
Examples include [CH ₃ (CH ₂ ) ₃ O] ₃ P, (C ₂ H ₅ O) ₂ POH, and the like. As the solvent, alcohols such as methanol and ethanol, or a mixed solvent of these organic solvents and water can be used. The amines added to a solution of an inorganic calcium compound and an organic phosphorus compound dissolved in these solvents are as follows:
trimethylamine, triethylamine, tri-n-
Butylamine and the like are preferably used. In order to include ammonia water in the solution, it may be added as ammonia water, or ammonia gas may be passed through the solution, resulting in the presence of ammonia water. None of these aspects are particularly specified, but
When preparing a raw material solution, a combination of raw materials must be used that allows a uniform solution state to be maintained without causing precipitation. Even when an organic solvent that is compatible with water is used alone as a solvent, depending on the combination of raw material compounds, the reaction system may mix with water and organic solvents due to residual moisture or crystal water in the raw material compounds. In some cases, the system uses a mixed solvent with a solvent, but even in this case, as long as the raw material solution can be prepared without causing precipitation, it can of course be used as a solvent in the method of the present invention. be able to. To explain the hydroxyapatite in the method of the present invention, the molar ratio of calcium and phosphorus in hydroxyapatite with a stoichiometric composition is usually
Ca/P is 5/3, but in the actual reaction in the method of the present invention, if a solution with a composition in which the molar ratio Ca/P of calcium and phosphorus in the raw material solution is in the range of 1.45 to 1.85, in any case A product whose main component is hydroxyapatite can also be obtained. Also Ca/
It has been experimentally confirmed that even when P is 1.45 or less or 1.85 or more, a product whose main component is hydroxyapatite can be obtained depending on the combination of raw materials. In this way, Ca/P
If the ratio deviates from 5/3, unreacted components and by-products may be mixed depending on the conditions, but such products may not have sufficient performance to be used depending on the use and purpose. The product thereof is naturally included in the scope of hydroxyapatite in the method of the present invention. EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto. Example 1 Tests were conducted using the following two embodiments (a) and (b) to confirm the effect obtained when aqueous ammonia was added to the raw material solution. Test (a): Ca (NO ₃ ) ₂・4H ₂ O36.90g, approximately 150ml
of methanol, add 11.63 g of (CH ₃ O) ₃ P to this solution, mix and dissolve, then add 16.7 ml of aqueous ammonia (28%) and mix, then add methanol until the total volume of the liquid is 250 ml. A uniform raw material solution was prepared. Next, this raw material solution was added at a rate of 10 ml per minute and compressed air was added at a rate of 10 ml per minute.
was supplied to a two-fluid spray nozzle and sprayed into the flame of a gas burner. The raw material solution, which had become fine droplets, was instantaneously heated in the flame by evaporation and combustion of the solvent, causing the thermal reaction. Test (b): A raw material solution was prepared and spray pyrolysis was performed under the same conditions as in (a) except that no ammonia water was added to the raw material solution. As a result of X-ray diffraction analysis of the powder produced in tests (a) and (b), it was found that both powders were mainly composed of hydroxyapatite. ) The diffraction intensity of the main peak of hydroxyapatite powder obtained by the test
Compared to that of the powder obtained by (b), approximately 4
It was twice the size. In addition to the peak of hydroxyapatite, the peak of CaO was only slightly observed in the test (a), but the peak of CaO was observed in the test (b).
A peak was clearly observed. In terms of intensity ratio, the diffraction intensity of the CaO peak obtained in test (a) is approximately 1/6 of that obtained in test (b).
It had decreased to These results clearly show that the addition of ammonia water increases the production rate of hydroxyapatite and has the effect of suppressing the free production of CaO. Example 2 The powder obtained by the method of test (a) of Example 1 was heated at a rate of 5°C/min in an air atmosphere, heat-treated at 600°C for 2 hours, and heated at 5°C/min. min
It was cooled at a rate of As a result of X-ray diffraction analysis of the product obtained by this heat treatment, only the peak of hydroxyapatite, which is the result of further crystal growth, was observed, and a trace amount was observed in the produced powder in test (a) of Example 1. The included CaO peak disappeared and was no longer recognized. Examples ₃ to 11 Ca( _{NO3 ) 2.4H2O} , ( _CH3O ) _3P , ( _C2H5O ) _3P ,
[CH ₃ (CH ₂ ) ₃ O] ₃ P, (C ₂ H ₅ O) ₂ POH, methanol, ethanol, ammonia water (28%), trimethylamine 30% aqueous solution, triethylamine, tri-n-butylamine, etc. as raw solution components A raw material solution was prepared according to the mixing ratio of each raw material shown in Table 1, and sprayed under the same conditions as in Example 1 except for the conditions shown in Table 1. A thermal decomposition operation was performed to synthesize hydroxyapatite. In both tests, it was confirmed that the production rate of hydroxyapatite was higher than when no ammonia water and/or amine were added to the raw material solution. Note that the number "250" in the alcohol column in Table 1 means that alcohol is added so that the total volume of the raw material solution is 250 ml.

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Claims (1)

[Claims] 1. Using a water-miscible organic solvent or a mixed solvent of a water-miscible organic solvent and water as a solvent, an inorganic compound of calcium and an organic compound of phosphorus that are soluble in the solvent are added. A raw material solution is prepared by adding ammonia water and/or an amine soluble in the above solution to the mixed and dissolved solution, and this raw material solution is sprayed into a flame or a heating zone to cause a thermal decomposition reaction. A method for producing hydroxyapatite, characterized by: 2 Using an organic solvent that is compatible with water or a mixed solvent of an organic solvent that is compatible with water and water as a solvent, add a soluble inorganic calcium compound and an organic compound of phosphorus to the solvent, and mix and dissolve. A raw material solution is prepared by adding aqueous ammonia and/or an amine soluble in the above solution to the solution consisting of A method for producing hydroxyapatite, which comprises further heating the obtained hydroxyapatite powder.