JP2006044966A - Method for producing hydroxyapatite-calcium carbonate composite particle - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for efficiently easily producing hydroxyapatite-calcium carbonate composite particles (HAp-CaCO<SB>3</SB>) for utilizing various functions of hydroxyapatite (HAp). <P>SOLUTION: Carbon dioxide gas is introduced into a suspension, obtained by adding slaked lime into water in a ratio of 100-300 g per 1 L of water, at such a flow rate that the time until the pH of the suspension becomes 7-8 and the carbonation is finished is ≥4 h. After elapsing of a time of 50-70% of the preestablished time until finishing carbonation, mixing of phosphoric acid is started. When the pH of the suspension becomes 7-8, the introduction of carbon dioxide gas and the mixing of phosphoric acid are stopped. Otherwise, after elapsing of a time of 70-90% of the preestablished time until finishing carbonation, the introduction of carbon dioxide gas is stopped, and the mixing of phosphoric acid is continued until the pH of the suspension becomes 7-8. Thereby, it becomes possible to easily, efficiently produce the hydroxyapatite-calcium carbonate composite particles (HAp-CaCO<SB>3</SB>) by utilizing a usual production process of calcium carbonate, industrially produced by a carbon dioxide combining method. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention provides a new application by combining calcium carbonate, which is often used as a filler, a reinforcing material, etc. in various industrial fields, in particular by subjecting a substance having a function to calcium carbonate to precipitation, adhesion, impregnation and the like. The present invention relates to a method for producing composite particles expected to expand.

  Calcium carbonate is abundant in raw materials, can supply a sufficient amount stably, is inexpensive, non-toxic, odorless, non-inflammatory, highly safe for living organisms, has a wide range of particle sizes, and has a white and low refractive index It has many advantages such as rubber, plastics, paper, paint, etc., and is expected to play a role as an extender, and is used in large quantities as a filler. In addition to the properties inherently possessed by the material itself, imparting the desired form or material results in the appearance of many new functions. Taking advantage of the many advantages of calcium carbonate and providing the required shape and function is thought to lead to higher added value and expanded applications of calcium carbonate.

  Composite particles of calcium phosphate and calcium carbonate are useful for resin fillers, dental polishing / repairing agents, dentifrices, sustained release agents, antibacterial agents, food additives, cosmetics, papermaking materials, fluorine removal agents, etc. Has been promoted.

  For example, calcium carbonate whose surface is coated with calcium phosphate obtained by allowing dilute phosphoric acid to act while stirring a glycol slurry of calcium carbonate particles (Japanese Patent Laid-Open No. 3-281565), and water-soluble phosphoric acids are added to the calcium carbonate suspension. , A calcium carbonate-apatite complex obtained by coating treatment at a temperature of 5-250 ° C. under normal pressure or under pressure in a basic region (Japanese Patent Laid-Open No. 7-118011), and calcium carbonate and water-soluble phosphate are specified Calcium carbonate-calcium phosphate compound complex (JP-A-10-81514) comprising calcium carbonate produced by reacting under conditions and a plate-like or needle-like crystal layer of a calcium phosphate compound covering the surface thereof; Aqueous suspension dispersion and dilute aqueous solution of phosphoric acid and / or aqueous suspension dispersion of calcium hydrogen phosphate It has a petal-like porous structure with calcium carbonate as the core, which is prepared by mixing an aqueous suspension dispersion of calcium dihydrogen phosphate and / or an aqueous suspension dispersion under specific mixing conditions, aging under specific aging conditions and then drying. Calcium phosphate compound (JP-A-10-175833), fluorine adsorbent in which calcium carbonate is treated with a saturated potassium hydrogen phosphate solution and a zirconium solution and calcium phosphate and zirconium are coordinated on the surface (JP-A-2003-62457), etc. Calcium phosphate-calcium carbonate composite particles and a method for producing the same have been proposed.

JP-A-3-281565 JP 7-1118011 A JP-A-10-81514 JP-A-10-175833 JP 2003-62457 A

The object of the present invention is to combine the very fine hydroxyapatite (HAp) produced by the aqueous solution reaction with calcium carbonate particles having a median diameter of about 10 μm, which is excellent in handling such as dehydration, drying and pulverization. It is an object of the present invention to provide a method for efficiently and easily producing hydroxyapatite-calcium carbonate composite particles (HAp-CaCO ₃ ) for utilizing various functions of the present invention.

  Calcium carbonate is usually produced industrially by a carbon dioxide compounding method in which carbon dioxide gas is blown into lime milk prepared by adding quick lime to water. According to this production method, only calcium carbonate and water are produced, which is considered to be a useful method in terms of effective use of the environment and resources. In order to obtain calcium carbonate having the desired properties, the preparation conditions (digestion conditions) of lime milk in addition to the carbonation conditions are also important technical elements. The preparation of lime milk requires optimal setting of various conditions such as the reactivity (activity) of quick lime with water, quantity ratio, particle size distribution of quick lime, water quality and water temperature to be used, It is not easy to obtain lime milk that stably produces calcium carbonate.

  Instead of lime milk in which fine slaked lime particles prepared by reacting water and quicklime are suspended, by using a suspension prepared by adding water to what is already prepared as slaked lime, carbon dioxide gas is reduced. It is known that a nucleation and growth field of calcium carbonate crystals different from that of conventional lime milk can be introduced when blown (Japanese Patent Laid-Open No. 2003-73117).

The present invention prepares a suspension using, for example, granular slaked lime having a particle diameter of 0.5-5 mm, and introduces carbon dioxide into the suspension to generate calcium carbonate particles having a median diameter of about 10 μm. By mixing phosphoric acid into the suspension, HAp-CaCO ₃ is generated.

For example, carbon dioxide (or carbon dioxide-containing gas such as waste gas) is suspended in a suspension prepared by suspending granular slaked lime with a particle size of 0.5-5 mm in a ratio of 100-300 g per 1 L of water. Blow at a flow rate such that the time until carbonation at which the pH of the suspension becomes 7-8 is 4 hours or longer. When the introduction of carbon dioxide gas starts, mixing of phosphoric acid starts when 50-75% of the planned carbonation end time has elapsed, and when pH = 7-8, introduction of carbon dioxide gas and mixing of phosphoric acid are started. Stop and produce HAp-CaCO ₃ . In addition, after stopping carbonation gas introduction at 70-90% of the planned carbonation end time, phosphoric acid is mixed until pH = 7-8 to produce HAp-CaCO ₃ . In each of the above processes, HAp-CaCO ₃ having a higher HAp content can be generated by continuing the mixing of phosphoric acid even after pH = 7-8.

According to the present invention, HAp-CaCO ₃ can be easily produced by utilizing a normal production process of calcium carbonate that is industrially produced by a carbon dioxide compounding method.

  Both calcium carbonate and HAp are bioactive materials with high biocompatibility and are important as bone repair materials. Calcium carbonate is a resorbable material that is absorbed into the body as new bone is generated, or decomposes and is discharged outside the body, HAp is a surface active material that directly binds to bone and generally shows high binding strength at the interface It is positioned as. The composite particle according to the present invention can be expected to be applied as a biomaterial having a high bone repair function, such as a new bone cement material.

According to a preferred embodiment of the present invention, HAp-CaCO ₃ can be produced through the following steps.

  The granular slaked lime (particle size 0.5-5 mm) used as a starting material can be obtained from the following production process of powdered slaked lime, for example. After mixing and continuously digesting quicklime grains (particle size of 10mm or less) at a flow rate of about 5.5t / h and well water (water temperature 15-20 ° C) at about 3.3t / h, fine powder is removed with an air separator and sieved. Collect the desired size of granular slaked lime (particle size 0.5-5mm). By passing through such a selection process, granular slaked lime having a particle size of less than 0.5 mm is substantially removed (except for those generated by subsequent crushing), and granular slaked lime having a particle size of more than 5 mm is also removed.

  Suspended granular slaked lime (particle size 0.5-5mm) selected for 1L of water at 15-30 ° C agitated by turbine blades (circumferential speed approx. 1.4m / s) at a rate of 100-300g Prepare the solution. Next, a carbonation reaction by introducing carbon dioxide is performed. Carbon dioxide (or carbon dioxide-containing gas such as waste gas) is blown at such a flow rate that the time until carbonation at which the suspension becomes pH = 7-8 is 4 hours or longer.

  After the introduction of carbon dioxide gas, mixing of phosphoric acid is started when 50-90% of the planned carbonation completion time required until the carbonation of the suspension reaches pH = 7-8 has elapsed.

For example, if carbon dioxide is blown into a suspension (pH> 12) prepared with water and granular slaked lime at a flow rate that completes carbonation in 4 hours (pH = 7-8), start blowing for 2-3 hours (planned) After the carbonation end time = 50-75% of 4 hours: 2-3 hours), start mixing phosphoric acid, and when pH = 7-8, stop introduction of carbon dioxide gas and mixing of phosphoric acid HAp -CaCO ₃ is obtained. Also, carbon dioxide was blown in for 2 hours 50 minutes-3 hours 30 minutes (scheduled carbonation end time = 70-90% of 4 hours: 2 hours 50 minutes-3 hours 30 minutes) and the introduction of carbon dioxide gas was stopped. HAp-CaCO ₃ can also be obtained by mixing phosphoric acid until 7-8.

When the suspension reaches pH = 7-8, the mixing of phosphoric acid is not stopped. Subsequently, phosphorus within 0.5 mol (H ₃ PO ₄ /Ca≦0.5) is added to 1 mol of calcium in the suspension. By mixing the acid, HAp-CaCO ₃ with a higher HAp content is obtained. Mixing of 0.5 mol or more of phosphoric acid is not preferable because the calcium carbonate content in HAp-CaCO ₃ becomes too small.

  Phosphoric acid is preferably mixed at the time when 50-90% of the planned carbonation end time required until the carbonation of the suspension reaches pH = 7-8 after the start of carbon dioxide introduction. . If mixing of phosphoric acid is started before the introduction of carbon dioxide gas, at the same time, or at the time when only a short time has passed, the formation of calcium carbonate particles in the suspension is insufficient and there is a lot of slaked lime Therefore, composite particles composed of HAp and calcium carbonate and having a median diameter of about 10 μm cannot be efficiently produced. When phosphoric acid is mixed in a state where there is a large amount of slaked lime, a lot of fine HAp that does not complex with calcium carbonate will precipitate. On the other hand, even if phosphoric acid is added after the carbonation, plate-like calcium hydrogen phosphate dihydrate (DCPD) is produced from calcium carbonate and phosphoric acid, resulting in a mixed powder of calcium carbonate and DCPD. Particles cannot be generated.

  By blowing carbon dioxide in a suspension prepared at a rate of 100-300 g of granular slaked lime with a particle size of 0.5-5 mm per 1 L of water at a flow rate that makes the time until carbonation completes 4 hours or more. In addition, calcium carbonate particles having a median diameter of about 10 μm, which is the base of the composite particles, can be generated. When a suspension in which powdered slaked lime is added to water is used, calcium carbonate particles having a particle diameter of about 10 μm are hardly generated, and composite particles are also the same.

  If the amount of carbon dioxide blown is too large, there may be a case in which grains that remain as slaked lime remain inside the surface of the granular slaked lime, which is not preferable. The particle size of the granular slaked lime is preferably 0.5-5 mm, desirably 0.5-2 mm. The larger the particle size, the worse the production efficiency because carbon dioxide must be blown more slowly for the reasons described above.

  When the amount of granular slaked lime is less than 100 g with respect to 1 L of water, the production efficiency is inferior, and up to an amount of 300 g, predetermined composite particles can be obtained without inferior operability.

  Phosphoric acid is preferably mixed at a rate of 0.0017-0.006 mol / min (a flow rate of 1.7-6.0 ml / min with phosphoric acid having a concentration of 1 mol / L) with respect to 1 mol of calcium in the suspension. When concentrated phosphoric acid is added in a short period of time, a pH <7 region is created in the suspension, which may cause precipitation of DCPD and calcium hydrogen phosphate (DCP).

  The method for producing composite particles according to the present invention does not particularly require temperature adjustment and can be carried out at room temperature.

Examples of the method for producing HAp—CaCO _{3 according} to the present invention will be described below. The following description of the examples is for a better understanding of the present invention, and the present invention is not limited to the following examples.

The median diameter was measured with a laser diffraction particle size distribution analyzer LA-500 (Horiba Seisakusho). The morphology was observed with a scanning electron microscope (SEM) S-570 (Hitachi). For identification of the crystal phase, an X-ray diffraction pattern obtained with an X-ray diffractometer XRD-6100 (Shimadzu Corporation) was used. The P ₂ O ₅ content in the composite particles was measured with a fluorescent X-ray analyzer (FX) RIX3000 (Rigaku Denki Kogyo).

Example 1
After adding 222g (~ 3mol) of granular slaked lime (particle size 0.5-2mm) to 2L of water at 25 ° C, which is agitated by turbine blades (circumferential speed approx. 1.4m / s), carbon dioxide gas at a flow rate of 0.5L / min When blown, carbonation was completed in about 4 hours (pH = 7-8). When 2 hours and 30 minutes were blown, phosphoric acid having a concentration of 1 mol / L began to be dropped at a flow rate of 5 ml / min. When the suspension reached pH = 7-8, introduction of carbon dioxide gas and dropping of phosphoric acid were stopped. The amount of phosphoric acid added was 0.3 L. The product was collected by filtration and dried at about 105 ° C. to obtain Sample 1. FIG. 1 shows an SEM photograph of Sample 1. As shown in the X-ray diffraction pattern of FIG. 9 (a), in addition to the calcium carbonate (calcite) peak, a broad HAp peak was also observed. The P ₂ O ₅ content measured by FX was 9.5 wt%. Sample 1 which is HAp-CaCO ₃ composite particles having a median diameter of 11.6 μm in which fine particles are aggregated was obtained.

(Example 2)
In Example 1, when the suspension reached pH = 7-8, without stopping the introduction of carbon dioxide and mixing of phosphoric acid, carbon dioxide was supplied at a rate of 0.5 L / min and phosphoric acid was added at a rate of 5 ml / min. Continued to add. Both were stopped when the addition amount of phosphoric acid reached 1 L (H ₃ PO ₄ /Ca=0.33), and the product was collected by filtration and dried at about 105 ° C. to obtain Sample 2. FIG. 2 shows an SEM photograph of Sample 2. As shown in the X-ray diffraction pattern of FIG. 9 (b), the amount of HAp produced increased. The P ₂ O ₅ content measured by FX was 30 wt%. Sample 2 which was HAp-CaCO ₃ composite particles having a median diameter of 12.6 μm as coated with HAp was obtained.

(Example 3)
222 g (~ 3 mol) of granular slaked lime used in Example 1 is added to 2 L of water at 25 ° C. that is stirred by a turbine blade (circumferential speed of about 1.4 m / s), and carbon dioxide gas is supplied at a flow rate of 0.5 L / min. After stopping by blowing for 3 hours, phosphoric acid having a concentration of 1 mol / L was added dropwise at a flow rate of 5 ml / min until pH = 7-8. The amount added was 0.325L. The product was collected by filtration and dried at about 105 ° C. to obtain Sample 3. FIG. 3 shows an SEM photograph of Sample 3. As shown in the X-ray diffraction pattern of FIG. 10 (a), in addition to the calcium carbonate (calcite) peak, a broad HAp peak was also observed. The P ₂ O ₅ content measured by FX was 11 wt%. Sample 3 which is HAp-CaCO ₃ composite particles having a median diameter of 9.7 μm in which fine particles are aggregated was obtained.

Example 4
When the suspension reached pH = 7-8 in Example 3, phosphoric acid was continuously added at a flow rate of 5 ml / min without stopping the dropping of phosphoric acid. When the amount of phosphoric acid added reached 1 L (H ₃ PO ₄ /Ca≈0.33), the product was collected by filtration and dried at about 105 ° C. to obtain Sample 4. 4 and 5 show SEM photographs of Sample 4. As shown in the X-ray diffraction pattern of FIG. 10 (b), the amount of HAp produced increased. The P ₂ O ₅ content measured by FX was 29 wt%. Sample 4 which is HAp-CaCO ₃ composite particles having a median diameter of 11.8 μm as coated with HAp was obtained.

(Comparative Example 1)
222 g (~ 3 mol) of granular slaked lime used in Example 1 is added to 2 L of water at 25 ° C. that is stirred by a turbine blade (circumferential speed of about 1.4 m / s), and carbon dioxide gas is supplied at a flow rate of 0.5 L / min. After blowing for 4 hours to complete carbonation (pH = 7-8), 1 mol / L of phosphoric acid was started to be added dropwise at a flow rate of 5 ml / min. Both were stopped when the addition amount of phosphoric acid reached 0.5 L (H ₃ PO ₄ /Ca≈0.17), and the product was collected by filtration and dried at about 105 ° C. to obtain Sample 5. FIG. 6 shows an SEM photograph of Sample 5. As shown in the X-ray diffraction pattern of FIG. 11, in addition to the calcium carbonate (calcite) peak, a DCPD peak was also observed. Plate-like DCPD precipitated and HAp-CaCO ₃ was not obtained.

(Comparative Example 2)
Fine powdered slaked lime (special grade reagent: Kishida Chemical) instead of the granular slaked lime (particle size 0.5-2mm) used in Example 1 in 2L of water at 25 ° C stirred with a turbine blade (peripheral speed about 1.4m / s) After adding 222g (~ 3mol) of carbon dioxide, when carbon dioxide gas is blown in at a flow rate of 0.5L / min, carbonation is completed in 4 hours and 20 minutes (pH = 7-8), so carbon dioxide gas at a flow rate of 0.5L / min. After stopping by blowing for 3 hours and 20 minutes, phosphoric acid having a concentration of 1 mol / L was added dropwise at a flow rate of 5 ml / min until pH = 7-8. The amount added was 0.25L. The product was collected by filtration and dried at about 105 ° C. to obtain Sample 6. FIG. 7 shows an SEM photograph of Sample 6. As shown in the X-ray diffraction pattern of FIG. 12 (a), a broad HAp peak was also observed in addition to the calcium carbonate (calcite, aragonite) peak. HAp-CaCO ₃ having a non-uniform aggregation state and a particle size of about 10 μm could not be obtained.

(Comparative Example 3)
In Comparative Example 2, phosphoric acid was continuously added at 5 ml / min without stopping dropping of phosphoric acid when the suspension reached pH = 7-8. When the amount of phosphoric acid added reached 1 L (H ₃ PO ₄ /Ca≈0.33), the product was collected by filtration and dried at about 105 ° C. to obtain Sample 7. FIG. 8 shows an SEM photograph of Sample 7. As shown in the X-ray diffraction pattern of FIG. 12 (b), the amount of HAp produced increased. Since sample 6 was used as a base, HAp-CaCO ₃ having a good form could not be obtained.

  Although the embodiments and examples of the present invention have been described above, the present invention is not limited to the above-described embodiments and examples, and can be appropriately modified within the scope of the gist of the present invention. Needless to say.

FIG. 1 is a SEM photograph showing the composite particles obtained in Example 1. FIG. 2 is an SEM photograph showing the composite particles obtained in Example 2. FIG. 3 is an SEM photograph showing the composite particles obtained in Example 3. FIG. 4 is an SEM photograph showing the composite particles obtained in Example 4. FIG. 5 is an SEM photograph showing the composite particles obtained in Example 4. FIG. 6 is a SEM photograph showing the composite particles obtained in Comparative Example 1. FIG. 7 is an SEM photograph showing the composite particles obtained in Comparative Example 2. FIG. 8 is an SEM photograph showing the composite particles obtained in Comparative Example 3. FIG. 9 is an X-ray diffraction pattern of the composite particle shown in FIGS. FIG. 10 is an X-ray diffraction pattern of the composite particles shown in FIGS. FIG. 11 is an X-ray diffraction pattern of the mixed particles shown in FIG. FIG. 12 is an X-ray diffraction pattern of the composite particles shown in FIGS.

Claims (6)

Carbon dioxide gas is introduced into a suspension obtained by adding slaked lime at a ratio of 100-300 g to 1 L of water, and from the start of introduction of carbon dioxide gas to the end of carbonation where the suspension reaches pH = 7-8. A method for producing hydroxyapatite-calcium carbonate composite particles, characterized in that by starting mixing phosphoric acid, hydroxyapatite and calcium carbonate are produced and combined. The hydroxyapatite-carbonic acid according to claim 1, wherein the mixing of phosphoric acid is started when 50-90% of the planned carbonation completion time required for the suspension to reach pH = 7-8 has elapsed. How to produce calcium composite particles. The introduction of carbon dioxide gas was started at a flow rate at which the planned carbonation end time was 4 hours or more, and when 50-75% of the planned carbonation end time had elapsed, mixing of phosphoric acid was started, and the suspension had a pH of 7 The method for producing hydroxyapatite-calcium carbonate composite particles according to claim 2, wherein the introduction of carbon dioxide gas and the mixing of phosphoric acid are stopped when -8 is reached. The introduction of carbon dioxide gas was started at a flow rate where the planned carbonation end time was 4 hours or more, and when the introduction of carbon dioxide gas was stopped when 70-90% of the planned carbonation end time had elapsed, the suspension was adjusted to pH = The method for producing hydroxyapatite-calcium carbonate composite particles according to claim 2, wherein phosphoric acid is mixed until 7-8. In Claims 3 and 4, after the suspension reaches pH = 7-8, phosphoric acid within 0.5 mol (H ₃ PO ₄ /Ca≦0.5) is added to 1 mol of calcium in the suspension. A method for producing hydroxyapatite-calcium carbonate composite particles to be mixed. 6. The method for producing hydroxyapatite-calcium carbonate composite particles according to any one of claims 1 to 5, wherein a suspension is prepared using granular slaked lime having a particle size of 0.5 to 5 mm.