JPH0415165B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing calcium-phosphorus apatite. Calcium-phosphorus apatite has unique performance as an adsorbent for biopolymers, fluorine ions, heavy metal ions, etc., and in recent years, it has been used for the separation of proteins, enzymes, etc. using its biocompatibility. It is considered to be useful as a filler for chromatography, and is also attracting attention as a bioceramic material for artificial bones and teeth. Conventionally, many methods have been known for producing apatite, and the following methods are exemplified if broadly classified. (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 temperature for a long time, which consumes a lot of energy, and because it is a group-group 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. The present inventors have completed the present invention as a result of various research into a method for producing calcium-phosphorus apatite using a simple operation that eliminates the drawbacks of the above-mentioned conventional technology and requires fewer steps. I came to the conclusion. That is, the present invention provides a novel method for producing calcium-phosphorus apatite. In the method of the present invention, as a starting material, a flammable organic solvent that is compatible with water or a flammable organic solvent that is compatible with water is mixed with water in order to achieve uniform mixing of raw materials at the atomic and molecular level. It uses a raw material solution with a uniform composition dissolved in a solvent, and one of its characteristics is that no precipitate is generated due to mixing. So far, many wet synthesis methods for apatite have been proposed, but the common idea among these conventional wet synthesis methods is that, for example, a calcium salt aqueous solution and a phosphorus compound aqueous solution are
As seen in the example of a method in which apatite is formed as a precipitate by mixing in a decarboxylated atmosphere while maintaining the pH around 8 at 100℃, apatite is directly formed as a precipitate, and the filtrate is removed from an aqueous solution. Basically, it is separated and recovered through operations. Therefore, the calcium compounds and phosphorus compounds used in the conventional wet synthesis method include, for example, Ca(NO ₃ ) ₂ , CaCl ₂ , Ca(OH) ₂ , CaF ₂ ,
_H3PO4 , _{CaHPO4 ・ 2H2O} , ( _NH4 ) _{2HPO4 ,}
Inorganic compounds of calcium and phosphorus have been used, such as NH ₄ H ₂ PO ₄ , KH ₂ PO ₄ , Na ₂ HPO ₄ . By the way, according to such a conventional method, an aqueous solution of a calcium salt and an aqueous solution of a phosphorus compound are mixed,
The process of forming a precipitate through a linear reaction of ions and crystallizing it into apatite has various results depending on a large number of factors such as the type and concentration of raw salt, mixing procedure and mixing speed, and pH adjustment. As a result, it is difficult to obtain a precipitate with a composition that matches the blending ratio, and it is extremely difficult to control the molar ratio Ca/P of calcium and phosphorus and the physicochemical properties of the resulting powder with good reproducibility. In addition, it required multiple steps such as excessive cleaning, drying, and pulverization of the precipitate, as well as many devices, and its operation required skill. In contrast to such conventional methods, one technical feature of the method of the present invention is that, in order to solve the difficulties in the precipitation formation and crystallization process in the wet synthesis method of the conventional technology, a flammable organic solvent that is compatible with water or a water-compatible combustible organic solvent is used. Using a mixed solvent of a soluble flammable organic solvent 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. The purpose is to make it into a raw material solution. In the method of the present invention, in order to maintain the uniformity of the composition of this raw material solution all the way to the product, the volume in which the components in the solution are segregated is made extremely fine by the spray pyrolysis method, and the solvent evaporates. This was achieved by performing combustion rapidly and minimizing the segregation of components within the droplets. 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 apatite. A special effect is obtained in that linear powder can be obtained without any complicated process. Furthermore, the method of the present invention has the advantage that apatite containing halogens such as chlorine and bromine can be easily synthesized. For example, in the past, chlorapatite was synthesized only by high-temperature solid phase reaction or pressurized hydrothermal reaction, and not by normal pressure wet method, but in the method of the present invention, CaCl ₂ .
By using raw materials containing chlorine such as 2H ₂ O and NH ₄ Cl, chlorapatite and solid solution apatite of chlorapatite and hydroxyapatite can be easily synthesized. Bromine apatite and bromine solid solution apatite can also be tested using CaBr ₂ 2H ₂ O, NH ₄ Br, or the like. The powder produced by the spray pyrolysis reaction according to the method of the present invention is usually obtained as a fine powder in which submicron particles are densely or coarsely fixed and sintered to form a hollow spherical shape as a whole. Depending on the type, combination, and spray pyrolysis conditions, some may be amorphous, some may contain both apatite crystalline phase and amorphous phase, and some may contain free forms in addition to apatite.
There are various cases such as those containing CaO and by-products, but all have a large specific surface area and
It is a powder rich in reaction activity. Depending on the application and purpose, it may be desirable to use powders with high reaction activity, or powders with high reaction activity may be used to reduce reaction activity, increase crystallinity, or reduce unreacted components and by-products. , or it may be desirable to eliminate it. In that case, the powder produced by the spray pyrolysis reaction is further heat-treated in various atmospheres at a desired temperature within the temperature range in which apatite can stably exist without decomposing. , the above-mentioned physical properties can be controlled. For example, desired physical properties can be obtained from hydroxyapatite by heat-treating it at a desired temperature of 1400° C. or lower in an air atmosphere. For example, regarding salt crude apatite, by selecting the preparation conditions of the raw material solution and the spray pyrolysis conditions, calcium chloride phosphate ( It is also possible to obtain a product that changes into chlorapatite (Ca ₂ PO ₄ Cl) and then changes back to chlorapatite at high temperatures of 1000°C or higher. Therefore, in this case as well, chloroapatite can be obtained by heat treatment by selecting appropriate temperature conditions. Regarding calcium chloride phosphate, the following facts can be found from the above facts. That is,
In preparing the above-mentioned raw material solution of the method of the present invention, a soluble phosphorus organic compound and calcium chloride are used, their concentrations in the solution are appropriately selected, and the raw material solution is subjected to the above-mentioned spray pyrolysis treatment, then
Calcium chloride phosphate can be produced by heat treatment at 500 to 1000°C. In addition, when the apatite produced by the method of the present invention contains free produced CaO, etc., if it is desirable to sufficiently remove them for the use of the target substance, a well-known method,
For example, pure apatite can be obtained by extraction and removal using an aqueous ammonium chloride solution. A more specific explanation of the method of the present invention is as follows. In the method of the present invention, first, a soluble phosphorus organic compound, calcium nitrate, calcium chloride, and One or two calcium compounds selected from calcium chloride and, if necessary, one selected from ammonium chloride and ammonium bromide are added, mixed, and dissolved to produce a homogeneous solution. A raw material solution with a specific composition is prepared, but the order in which these raw materials are mixed is not necessarily specified, and may be mixed in any order as long as it 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 in advance in a flame such as a gas burner or in a gas furnace or electric furnace by a known spraying method using a pressurized nozzle or a rotating disk.
By spraying into a heating zone heated to 700-1500℃,
In an extremely short period of time of several seconds or less, the solvent in the solution is evaporated and burned, the solute is solidified, and the thermal decomposition reaction takes place, usually in the form of fine droplets of several tens of microns or less. The product is usually a fine powder in which submicron particles are tightly or coarsely fixed and sintered to form a hollow 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 in various atmospheres such as air, air with water vapor added, and an inert atmosphere at a desired temperature within the temperature range in which apatite does not decompose. By heat treatment, apatite with controlled crystallinity, specific surface area, etc. can be obtained. Examples of the above-mentioned phosphorus organic compounds used in the method of the invention include (CH ₃ O) ₃ P,
(C ₂ H ₅ O) ₃ P, [(CH ₃ ) ₂ CHO] ₃ P, [CH ₃
(CH ₂ ) ₃ O〕 ₃ P, (C ₆ H ₅ ) ₃ P, (C ₂ H ₅ O) ₂ POH,
Examples include (C ₆ H ₅ ) ₃ PO. Examples of the flammable organic solvent used include alcohols such as methanol, ethanol, and isopropanol, and acetone. None of these are particularly limited, and as mentioned above, one selected from calcium nitrate, calcium chloride, and calcium bromide.
Any combination of a species or two types of calcium salts and an organic compound of phosphorus or an organic solvent that can form a solution with a uniform composition may be used. Calcium nitrate, calcium chloride, and calcium bromide usually contain water of crystallization, so even if a mixed solvent with water is not used, a small amount of water will be present in the system. The raw materials to be used may be selected depending on the desired calcium urin apatite. For example, when synthesizing hydroxyapatite, Ca(NO ₃ ) ₂ .
Calcium nitrate salts such as 4H ₂ O may be used. In addition, when synthesizing chlorapatite,
_CaCl2・_2H2O , Ca( _NO3 ) ₂・_4H2O and _CaCl2・
Chloroapatite or solid solution apatite of hydroxyapatite and chlorapatite can be obtained by combined use with 2H ₂ O, Ca(NO ₃ ) _{2.4H 2} O and NH ₄ Cl, etc. Similarly, for bromine apatite, CaBr ₂ 2H ₂ O, Ca(NO ₃ ) ₂ 4H ₂ O
Combination of CaBr ₂ 2H ₂ O, Ca(NO ₃ ) ₂ 4H ₂ O
By using NH ₄ Br in combination, brominated apatite or solid solution apatite of brominated apatite and hydroxyapatite can be obtained. The molar ratio Ca/P of calcium and phosphorus in calcium-phosphorus apatite with stoichiometric composition is 5/3.
However, in the actual reaction in the method of the present invention, the molar ratio of calcium to phosphorus in the raw material solution is
When a solution with a composition in the Ca/P range of 1.25 to 1.75 is used, in each case a product is obtained in which the main component is apatite. Depending on the conditions, free generated CaO may remain, but depending on the application and purpose, the performance is sufficient to use it, and such products can also be treated with the calcium-phosphorus based method of the present invention. Naturally, it is included in the range of apatite. Also, if Ca/P is less than 1.25 or
Even if it is 1.75 or more, depending on the combination of raw materials,
It has been experimentally confirmed by the present inventors that a product whose main component is apatite can be obtained.
Although specifically explained, the present invention is not limited thereto. Example 1 Dissolve 36.90 g of Ca(NO ₃ ) ₂ 4H ₂ O in approximately 200 ml of ethanol, add 15.58 g of (C ₂ H ₅ O) ₃ P to this solution, stir, mix and dissolve, and then add ethanol was added to prepare a uniform raw material solution with a total volume of 250 ml.
Next, this raw material solution was supplied at a rate of 10 ml per minute and compressed air at a rate of 10 per minute to the liquid supply side and the gas supply side of the two-fluid spray nozzle, and sprayed into the flame of the gas burner. The raw material solution, which had become fine droplets, was instantaneously heated by evaporation and combustion of the solvent in the flame, causing a thermal decomposition reaction. The temperature during the thermal decomposition reaction was 1050-1105°C. The powder thus generated is collected using a cyclone method,
As a result of observation with an electron microscope, it was found to be a hollow spherical fine powder consisting of densely sintered particles of 0.2 to 0.5 microns.
Next, as a result of X-ray diffraction analysis of this produced powder,
The obtained powder contained both a crystalline phase and an amorphous phase of hydroxyapatite, and the unreacted component CaO remained. Example 2 The powder obtained by the method of Example 1 was heated at a rate of 5°C/min in an air atmosphere, heat-treated at 1300°C for 1 hour, and cooled at a rate of 5°C/min. The results of X-ray diffraction measurements of the product obtained by this heat treatment are shown in FIG. As is clear from FIG. 1, the product obtained in this example was hydroxyapatite (hexagonal crystal) with well-grown crystals, and no decomposition of hydroxyapatite was observed at high temperatures. Example 3 Dissolve 045.94 g of CaCl ₂ 2H ₂ in approximately 200 ml of ethanol, add 31.16 g of (C ₂ H ₅ O) ₃ P to this solution, stir to mix and dissolve, and further add ethanol. A uniform raw material solution with a total volume of 250 ml was prepared.
Next, this raw material solution was subjected to spray pyrolysis in the same manner as in Example 1. The results of X-ray diffraction measurements of this produced powder are shown in FIG. As is clear from FIG. 2, it was confirmed that the produced powder contained both a crystalline phase and an amorphous phase of chlorapatite. Example 4 (a): The powder obtained by the method of Example 3 was heated at a rate of 5°C/min in an air atmosphere, held at a constant temperature for 1 hour, and cooled at a rate of 5°C/min. In the heat treatment method, 400, 600, 800, 1000
Experiments were conducted at each temperature of °C. As a result of measuring X-ray diffraction of the product heat-treated at 400°C, it showed a diffraction pattern of chlorapatite similar to that shown in Fig. 2, and the diffraction intensity increased slightly, indicating the growth of crystallites. However, at 600℃ and
The results of X-ray diffraction measurements of the product heat-treated at 800°C all agreed with the characteristic diffraction peak of calcium chloride phosphate (Ca ₂ PO ₄ Cl) described in ASTM Card 19-247. Figure 3 shows the results of X-ray diffraction measurements of the product heat-treated at 800°C.
As a result of measuring X-ray diffraction of the product heat-treated at 1000°C, the diffraction peak due to calcium chloride phosphate decreased, and the diffraction pattern showing the diffraction line due to the formation of chlorapatite disappeared. Through this series of experiments, it was found that when a powder containing both chlorapatite and an amorphous phase (powder obtained by the method of Example 3) was heat-treated, it remained as chlorapatite at 400°C, but It was confirmed that it changes to calcium chloride phosphate at temperatures above 1000°C, and then changes back to chlorapatite at temperatures above 1000°C. (b): The powder obtained by the method of Example 3 was heated in an air atmosphere at a rate of 5°C/min, held at 1200°C for 1 hour, and cooled at a rate of 5°C/min.
By this heat treatment, the obtained product was dissolved in nitric acid and a cloudiness test was performed using a silver nitrate solution.
It was confirmed that silver chloride was precipitated. The results of X-ray diffraction measurement of the above product are shown in FIG. As is clear from Figure 4, this product is chlorapatite, and the main peaks are the (211) diffraction peak at the diffraction angle 2θ = 31.4° and the diffraction peak at 2θ = 31.4°.
Overlapping diffraction peaks of (112) and (300) were measured at 32.3°. Example 5 36.90 g of Ca(NO ₃ ) 2.4H _{2 O} was dissolved in about 180 ml of ethanol, and 15.58 g of (C ₂ H ₅ O) ₃ P was added to this solution and mixed and dissolved with stirring. Next, an aqueous solution of ammonium bromide prepared by dissolving 4.90 g of NH ₄ Br in 25 ml of water was added to this solution and mixed well, and ethanol was further mixed to prepare a uniform raw material solution with a total volume of 250 ml. . Then, this raw material solution was subjected to spray pyrolysis in the same manner as in Example 1. The obtained powder was heat treated under the same conditions as in Example 4. As a result of measuring X-ray diffraction of the obtained product, it showed a hydroxyapatite-type (hexagonal) diffraction pattern similar to that shown in FIG. 1, and the peak of freely generated CaO remained. When this product was dissolved in nitric acid and bromine was detected using a silver nitrate solution, silver bromide precipitated, confirming the presence of bromine. Therefore, it can be seen that the product obtained in this example is a solid solution apatite of hydroxyapatite and bromine apatite. Example 6 Dissolve 36.87 g of CaBr ₂ 2H _{2 O} in approximately 180 ml of ethanol, add 15.58 g of (C ₂ H ₅ O) ₃ P to this solution, stir to mix and dissolve, and then add ethanol. A uniform raw material solution with a total volume of 250 ml was prepared.
Next, this raw material solution was subjected to spray pyrolysis in the same manner as in Example 1. The obtained powder was heat treated under the same conditions as in Example 4(b). As a result of measuring X-ray diffraction of the obtained product, it showed the same diffraction pattern as in FIG. 4, and the presence of bromine was confirmed by the silver nitrate solution. Therefore, it can be seen that the above product is brominated apatite. Examples 7 to 18 Ca( _NO3 ) ₂・_4H2O , _CaCl2 , _CaCl2・_2H2O ,
_CaBr2 ... _2H2O , _NH4Cl , ( _CH3O ) _3P ,
(C ₂ H ₅ O) ₃ P, [(CH ₃ ) ₂ CHO] ₃ P, [CH ₃
(CH ₂ ) ₃ O〕 ₃ P, (C ₆ H ₅ O) ₃ P, (C ₆ H ₅ ) ₃ PO,
(C ₂ H ₅ O) ₂ POH, methanol, ethanol, isopropanol, acetone, H ₂ O, etc. were used as raw material components and prepared according to the mixing ratio of each raw material shown in Table 1. With respect to conditions other than those shown, various calcium-phosphorus apatites were synthesized by performing a spray pyrolysis operation under the same conditions as in Example 1.

【table】

【table】 [Brief explanation of drawings]

FIG. 1 is an X-ray diffraction diagram of hydroxyapatite obtained in Example 2, and FIG. 2 is an X-ray diffraction diagram of chlorapatite obtained in Example 3. Figure 3 is an X-ray diffraction diagram of calcium chloride phosphate obtained by heat treatment at 800°C in Example 4(a), and Figure 4 is an X-ray diffraction diagram of calcium chloride phosphate obtained in Example 4(b). It is an X-ray diffraction diagram of apatite.

Claims (1)

[Claims] 1. Calcium nitrate, calcium chloride, and calcium bromide for a water-compatible flammable organic solvent or a mixed solvent of a water-compatible flammable organic solvent and water. Add one or two types of calcium compounds and an organic compound of phosphorus soluble in the above solvent, and further add or not add one type selected from ammonium chloride and ammonium bromide, mix and dissolve uniformly. Prepare a raw material solution with a composition,
Calcium, which is characterized by spraying this raw material solution into a flame or a heating zone to cause a thermal decomposition reaction.
Method for producing phosphorus apatite. 2. The method according to claim 1, wherein a phosphorus alkoxide is used as the organic phosphorus compound. 3. The method according to claim 1, characterized in that triethyl phosphite is used as the organic compound of phosphorus. 4. One or two selected from calcium nitrate, calcium chloride, and calcium bromide for a water-compatible flammable organic solvent or a mixed solvent of a water-compatible flammable organic solvent and water. A calcium compound and an organic phosphorus compound soluble in the above solvent are added, and one selected from ammonium chloride and ammonium bromide is added or not mixed and dissolved to obtain a raw material solution with a uniform composition. Prepare,
A method for producing calcium-phosphorus apatite, which comprises spraying this raw material solution into a flame or a heating zone to cause a thermal decomposition reaction, and heat-treating the resulting powder. 5. The method according to claim 4, wherein a phosphorus alkoxide is used as the organic phosphorus compound. 6. The method according to claim 4, characterized in that triethyl phosphite is used as the organic compound of phosphorus.