JPH0776082B2 - Method for producing tricalcium phosphate - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a new process for producing tricalcium phosphate.

Tricalcium phosphate (Tetiary Calcium Phosphat
e), Ca ₃ (PO ₄ ) ₂ is tricalcium phosphate (Tricalciu
m Phosphate), which is thermodynamically stable β type below 1180 ℃, α type stable from 1180 ℃ to 1430 ℃, and
The α'type is known to be stable at high temperatures above 1430 ° C. This tricalcium phosphate has been used for a long time as a glaze, an abrasive for ceramics, or a lubricant for casting by utilizing its high melting point. Further, in recent years, the β-type tricalcium phosphate porous body has excellent biocompatibility, and when it is embedded in a bone defect, it is absorbed by the bone that has penetrated into the pores, and eventually it becomes autogenous bone. It has been attracting attention as a bioactive implant ceramics because it has been clarified that it is completely replaced and does not leave a foreign substance in the living body.

Heretofore, the following methods have been known, roughly classified as to methods for producing tricalcium phosphate.

(1) A method of synthesizing tricalcium phosphate by a solid diffusion reaction called a dry synthesis method.

(2) Amorphous calcium phosphate is precipitated by a direct reaction of aqueous solution ions, which is called a wet synthesis method,
A method of converting to tricalcium phosphate by further heating at a high temperature after passing through steps such as filtration, washing and drying.

In the dry synthesis method of (1), for example, β-calcium pyrophosphate and calcium carbonate are mixed in equimolar amounts, and heated at 1100 ° C. for about 10 hours to synthesize tricalcium phosphate. However, there is a problem in that a large amount of energy is consumed because of the necessity of the reaction and that the composition is uniform because of the solid-solid reaction. Also, β
When type III tricalcium phosphate is used as a bone replacement material, it is necessary to control the rate of dissolution and absorption of β-type tricalcium phosphate in vivo, and therefore the method for synthesizing β-type tricalcium phosphate, the synthesis temperature Is one of the important factors, but β-type tricalcium phosphate by the dry synthesis method has already been subjected to a long thermal history at high temperature during synthesis, so there is almost no room to change the reaction activity. There are drawbacks. In the wet synthesis method (2), for example, an aqueous calcium nitrate solution and diammonium hydrogen phosphate are mixed in a decarboxylation atmosphere while maintaining the pH at around 10 to form a precipitate of amorphous calcium phosphate. , Wash with ammonia water, dry,
It is a method of converting into tricalcium phosphate by heat treatment at a temperature of about 600 ° C to 1300 ° C.

However, according to this method, the process of mixing an aqueous solution of calcium salt and an aqueous solution of phosphorus and producing a precipitate of amorphous calcium phosphate by a direct reaction of ions involves mixing with the type and concentration of the raw material salt and the mixing procedure of the raw material. As it is affected by so many factors such as speed and pH adjustment, it is difficult to obtain a precipitate having a desired composition, and many precipitates required for overwashing, drying, pulverizing etc. of the precipitate are required. There are difficulties in that it requires many steps and many devices, and its operation requires skill.

The present inventors have completed the present invention as a result of various studies on the method for producing tricalcium phosphate by a simple method which eliminates the above-mentioned drawbacks in the conventional technology and has a small number of steps. Was reached.

That is, the present invention provides a novel method for producing tricalcium phosphate. In the method of the present invention, in order to achieve uniform mixing of the raw materials, an alcohol compatible with water is used as a solvent, or a mixed solvent of alcohol and water compatible with water is used as a solvent and dissolved in the solvent. One of the features is that a raw material solution having a uniform composition is used and a precipitate due to mixing is not generated. Then, this solution is made to contain ammonia water or an amine soluble in the above solution within a range that does not cause precipitation, and the properties of the solution are changed from the neutral range to the weakly alkaline range to prepare a spraying raw material solution. Then, this raw material solution is sprayed into a flame or a heating zone to cause a thermal decomposition reaction to generate tricalcium phosphate.

Since the precipitate produced by the conventional wet synthesis method is amorphous calcium phosphate known as a precursor of wet-produced hydroxyapatite, it is necessary to convert the precipitate to the target crystalline tricalcium phosphate. Over
It is necessary to perform heat treatment after complicated steps such as washing and drying. On the other hand, in the method of the present invention, complicated steps such as excess, washing, and drying are not required at all, and the synthesis reaction can be performed in an extremely short time of only a few seconds or less, and further, directly. In addition, it has an excellent advantage that a desired powder containing crystalline tribasic calcium phosphate can be produced.

Further, in the method of the present invention, since the raw materials are mixed in a solution state, there is an advantage that it is easy to uniformly add and mix a trace amount of elements other than calcium and phosphorus as needed. For example, when using tricalcium phosphate as a powder for bioceramics, trace amounts of Na, Mg, Si, K, Fe, Cu, Zn, Sr, Ba, etc., which are usually contained in mammalian bone, are contained in tricalcium phosphate. When it is desirable to mix, to the raw material solution containing calcium and phosphorus,
The target product can be easily obtained by mixing a small amount of a compound soluble in it and containing these elements to prepare a uniformly dissolved solution, and subjecting it to spray pyrolysis.

As a first method, the present invention uses a water-compatible alcohol solvent or a mixed solvent of water-compatible alcohol and water as a solvent, wherein the soluble inorganic compound of calcium and the organic compound of phosphorus are used. Preparation of a raw material solution in which compounds are mixed and dissolved, and a soluble amine is further present in aqueous ammonia and / or a production solution, and the raw material solution is sprayed into a flame or a heating zone to cause a thermal decomposition reaction. Thus, the drawbacks of the prior art are eliminated, and a method for directly producing tricalcium phosphate powder is provided.

In the second method of the present invention, the powder obtained by the above-mentioned first method is further heat-treated at a temperature of about 400 ° C. or higher to control the powder characteristics such as reaction activity. The present invention provides a method for producing a desired type of tribasic calcium phosphate of the β-type or β-type.

According to the first method of the present invention, even in the spray pyrolysis reaction at a relatively low temperature of 1000 ° C. or lower, as the powder to be produced, the crystalline phase of the target tricalcium phosphate can be used depending on the conditions. Can contain an amorphous phase of tricalcium phosphate or a crystalline phase of hydroxyapatite. In any case, it was confirmed by X-ray diffraction analysis that the tricalcium phosphate in the produced powder was α-type tricalcium phosphate. Originally α
-Type tricalcium phosphate is considered to be a thermodynamically stable phase at high temperatures from 1180 ℃ to 1430 ℃ [DEC Corbridge,
“The Structural Chemistry of Phosphorus,” Elsevier
Scientific Pub. Co. (1974)], the α-type tricalcium phosphate produced under the above conditions is considered to be in a metastable state. Further, it goes without saying that the tricalcium phosphate powder can be directly obtained even in the synthesis at a higher spray pyrolysis temperature. Since it is not possible to directly obtain a crystalline powder of tricalcium phosphate by the conventional wet synthesis method, it is possible to directly synthesize the crystalline powder of tricalcium phosphate by the first method of the present invention as described above. Being able to do so can be said to be a special advantage.

According to the second method of the present invention, the powder produced by the above-mentioned first method is subjected to heat treatment at various temperatures to select the α-type or β-type crystal system and to react the powder. It is possible to control various characteristics of the tricalcium phosphate powder, such as the degree of activity, the degree of crystal growth, and the shrinkage rate during sintering. When the metastable α-type tribasic calcium phosphate is heated, the metastable α-type tribasic calcium phosphate is once transformed into β-type tribasic calcium phosphate. Depending on the type of raw material compound used and the synthesis conditions, the transition temperature from α-type to β-type is about 750 ° to 950 ° C, and from β-type to α-type.
The transition to mold was found to vary from approximately 1150 ° C to 1250 ° C. This means that by selecting the type of raw material compound and the synthesis conditions, the temperature range in which the desired type of tricalcium phosphate is present can be widened, and even with the same type of tricalcium phosphate, the heat treatment temperature can be changed to obtain high activity. This means that it is possible to obtain powders having low activity and low activity, which is extremely advantageous in the production of raw material powders for bioceramics and the like.

Further, as described above, the method of the present invention is not only a novel method for producing tricalcium phosphate that eliminates the drawbacks of the prior art, but also the property itself of the tricalcium phosphate produced is different from that of the tricalcium phosphate according to the prior art. It has the feature. That is, when the tricalcium phosphate obtained by the conventional technique is obtained by a dry synthesis method, it is usually obtained as a lump-shaped sintered body, and therefore, in order to obtain a raw material powder for use in various applications, The agglomerates must be ground. Moreover, the shape of the pulverized powder is indefinite and the particle size distribution has a wide range. Therefore, in order to obtain a powder having a particle size and particle size distribution that suits the purpose, further steps such as classification operation are required. Often. On the other hand, according to the method of the present invention, the produced tricalcium phosphate is obtained as a fine powder from the beginning, and is usually a submicron to tens of microns spherical powder. The particle size can be changed by selecting the type of raw material used for preparing the raw material solution, the concentration of the solution, and the spray pyrolysis conditions. Therefore, there is an advantage that there is no fear that the crushing process consumes time and that impurities are not mixed therewith.

When tricalcium phosphate is used as a raw material for ceramics, since a molded product of tricalcium phosphate is sintered at high temperature, the tricalcium phosphate raw material powder used for this must have excellent sinterability. However, since the dry synthesis method already reacts at high temperature during the synthesis of tricalcium phosphate,
Due to the heat history, when the powder is crushed and used as a raw material for ceramics, the activity for sintering the powder becomes small. Therefore, in order to obtain a dense sintered body, it is necessary to sinter at a higher temperature. On the other hand, the tricalcium phosphate powder produced by the method of the present invention is highly active in sintering.

Furthermore, according to the method of the present invention, various operating conditions are set according to the intended state of the tricalcium phosphate according to the intended use, and the tricalcium phosphate in that state is produced by a simple operation. be able to.

For example, when trying to obtain a product of only tricalcium phosphate, or when trying to mix crystal phases such as hydroxyapatite and calcium pyrophosphate in tricalcium phosphate, in various cases suitable for various other purposes, etc. Accordingly, according to the method of the present invention, tricalcium phosphate can be easily produced in a desired state.

The tricalcium phosphate obtained by the method of the present invention is suitable for use as a raw material for bioceramics such as artificial bone.

The method of the present invention will be described in more detail below. In the method of the present invention, first, to a mixed solvent of water-compatible alcohol or water-compatible alcohol and water, to the solvent, an inorganic compound of soluble calcium and an organic compound of phosphorus are added and mixed. In the solution that is dissolved,
Further, a raw material solution in which a soluble amine is present in ammonia water and / or the above solution is prepared, and the liquid property is changed from the neutral region to the weak alkaline region. The order of mixing these raw materials 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 homogeneous solution is obtained. Then, the solution thus prepared is sprayed by a known spraying method such as a pressure nozzle or a rotating disk in a flame such as a gas burner or a heating zone previously heated to 700 to 1500 ° C. by a gas furnace or an electric furnace. After spraying, the solvent in the solution, which is usually formed into fine droplets of several tens of microns or less, evaporates and burns, solidifies the solute, and causes a thermal decomposition reaction in an extremely short time of several seconds or less.
The product is usually spherical fine powder and can be collected by a cyclone or the like.

The powder produced by the spray pyrolysis reaction may contain both a crystalline phase of tribasic calcium phosphate and an amorphous phase depending on the kind and combination of raw material compounds and spray pyrolysis conditions. There are various other cases where unreacted components and by-products are mixed, but all of them are powders that are rich in reaction activity. It may be preferable to use it. In addition, depending on another use / purpose, the reaction activity may be decreased, the degree of crystallinity may be increased, the α-type or β-type tricalcium calcium phosphate crystal form may be converted into a desired form, and by-products may be generated. In some cases, it may be desirable to reduce or eliminate it, and in that case, the powder produced by the spray pyrolysis reaction is heat-treated at a desired temperature of about 400 ° C. or higher using, for example, an electric furnace. It is possible to obtain tricalcium phosphate whose various powder characteristics described above are controlled.

As the inorganic and organic compounds of phosphorus of the calcium used in the present invention _{method, Ca (NO 3) 2 ·} 4
H ₂ O, (CH ₃ O) ₃ P, (C ₂ H ₅ O) ₃ P, (C ₂ H ₅ O) ₂ POH and the like can be mentioned.

As the solvent, alcohols such as methanol and ethanol, or a mixed solvent of these organic solvents and water can be used. As the amine to be added to the solution in which the inorganic compound of calcium and the organic compound of phosphorus are dissolved in these solvents, 30% aqueous solution of trimethylamine, triethylamine, diethylamine and the like are preferably used. Further, in order to include the ammonia water in the solution, it may be added as ammonia water, or ammonia gas may be passed through the solution so that the ammonia water is present. None of these embodiments is particularly specified, but a combination of raw materials that can maintain a uniform solution state without causing precipitation when preparing a raw material solution must be used. Even when water-compatible alcohol alone is used as a solvent, depending on the combination of the raw material compounds, due to residual water or crystal water in the raw material compounds, the reaction system may result in water and alcohol. Although it may be a system using a mixed solvent with, even in this case, if the raw material solution can be prepared without causing precipitation, of course, as a solvent in the method of the present invention, to be used You can

Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

Example _{1 Ca (NO 3) 2 ·} 4H 2 O 34.73g is dissolved in ethanol to about 180 ml, the solution _{(C 2 H 5 O) 3} P 17.10g were mixed by stirring and further aqueous ammonia (28% ) 16.7 ml was added and mixed, and then ethanol was added to prepare a raw material solution having a total volume of 250 ml. Then, this raw material solution was supplied to a two-fluid spray nozzle at a rate of 10 ml / min and compressed air at a rate of 10 / min to be sprayed into the flame of a gas burner. The raw material solution in the form of fine droplets was instantaneously heated in the flame due to evaporation and combustion of the solvent, and a thermal decomposition reaction occurred. The generated powder is
It was collected by the cyclone method. Next, as a result of X-ray diffraction analysis of this powder, the powder obtained contains both the crystalline phase and the amorphous phase of α-type tricalcium phosphate, and the crystalline phase of hydroxyapatite. Was included in a trace amount.

Example 2 The powder obtained by the method of Example 1 was heated in an air atmosphere at a rate of 5 ° C./min, heat-treated at 750 ° C. for 1 hour, and cooled at a rate of 5 ° C./min. . The result of X-ray diffraction measurement of the product obtained by this heat treatment is shown in FIG. As is clear from FIG. 1, the crystalline phase of the product obtained in this example was only α-type tribasic calcium phosphate, and hydroxyapatite contained in the powder obtained in example 1 was used. The peak disappeared and was not recognized.

Example 3 The powder obtained by the method of Example 1 was heated in an air atmosphere at a rate of 5 ° C./min, heat-treated at 1000 ° C. for 1 hour, and cooled at a rate of 5 ° C./min. . The result of X-ray diffraction measurement of the product obtained by this heat treatment is shown in FIG. As is clear from FIG. 2, the product obtained in this example was completely phase-transposed to β-type calcium triphosphate.

Example 4 Ca (NO ₃₎ the _{2 ·} 4H 2 O 16.96g is dissolved in ethanol to about 180 ml, stirred and mixed by adding the solution to _{(C 2 H 5 O) 3} P 8.83g, further (C ₂ H ₅ ) ₂ NH2 (5.9 ml) was added and mixed, and then ethanol was added to prepare a raw material solution having a total amount of 250 ml. Next, this raw material solution was sprayed into a flame to be pyrolyzed in the same manner as in Example 1. As a result of X-ray diffraction analysis, the powder obtained by this method contained a crystalline phase of α-type tricalcium phosphate and a slight amount of an amorphous phase.

Example _{5~10 Ca (NO 3) 2 ·} 4H 2 O, (CH 3 O) 3 P, (C 2 H 5 O) 3 P, (C 2 H 5 O)
₂ POH, methanol, ethanol, ammonia water (28
%), Trimethylamine 30% aqueous solution, diethylamine,
Triethylamine and the like were used as raw material solution components, selected from these, raw material solutions were prepared according to the respective raw material blending ratios shown in Table 1, and conditions other than those shown in Table 1 Spray pyrolysis was performed under the same conditions as in 1 to synthesize tricalcium phosphate.

The number "250" in the alcohol column in Table 1 is
In each case, alcohol is added so that the total amount of the raw material solution becomes 250 ml.

[Brief description of drawings]

The attached drawings are all X-ray diffraction patterns of the products obtained in Examples of the present invention, and FIG. 1 is an X-ray diffraction diagram of α-type tricalcium phosphate obtained in Example 2. FIG. 2 is a view showing an X-ray diffraction diagram of β-type tricalcium phosphate obtained in Example 3.

Claims (2)

[Claims] 1. An alcohol compatible with water is used as a solvent, or a mixed solvent of alcohol and water compatible with water is used as a solvent, and an inorganic compound of calcium and an organic compound of phosphorus which are soluble in the solvent are mixed. A raw material solution in which an amine soluble in an aqueous solution and / or a product solution is dissolved and prepared, and the raw material solution is sprayed into a flame or a heating zone to cause a thermal decomposition reaction. A process for producing tricalcium phosphate. 2. An alcohol compatible with water is used as a solvent, or a mixed solvent of alcohol and water compatible with water is used as a solvent, and an inorganic compound of calcium and an organic compound of phosphorus which are soluble in the solvent are mixed. A raw material solution is prepared in which an amine soluble in an aqueous solution of ammonia and / or dissolved in the production solution is present, and the raw material solution is sprayed into a flame or a heating zone to carry out a thermal decomposition reaction to produce a product. A method for producing tricalcium phosphate, which comprises subjecting powder to heat treatment.