JP5509493B2 - Powder manufacturing method, powder, adsorption device - Google Patents

Description

  The present invention relates to a powder manufacturing method, powder, and adsorption device.

  Calcium phosphate compounds, which are a kind of ceramic material, are widely used as, for example, biomaterials, chromatographic fixed layer materials, and the like.

  When used as a biomaterial, the calcium phosphate compound is obtained by obtaining a powder from a slurry, etc., molding the powder into a desired shape to form a molded body, and further firing (sintering) the molded body. It is considered a tie. Such sintered bodies are clinically used as artificial bones, artificial tooth roots, and the like.

  In addition, when used as a material for a fixed layer of chromatography, the calcium phosphate compound is sintered by obtaining a powder in the same manner as in the case of using it as the biomaterial, and firing (sintering) the powder. Powder (hereinafter referred to as “sintered powder”). The sintered powder is used by filling a column or the like (for example, see Patent Document 1).

  However, a sintered body used as an artificial bone, an artificial tooth root, or the like has a problem that it is difficult to control the processing and porosity unless the strength of the powder obtained during the manufacturing process is sufficient (constant). Usually, when manufacturing the said sintered compact, it manufactures through the process of the following I-III.

  That is, I: The obtained powder is calcined and then pulverized by a pulverizer. II: The powder after pulverization is mixed with, for example, an aqueous methylcellulose solution. III: This mixture is gelled, hardened and blocked.

  However, in step I, if the strength of the powder is not constant, the pulverization conditions (for example, the particle size distribution of the pulverized powder) are not constant, and the porosity and strength of the obtained sintered body are unstable. There is a problem of becoming.

  In addition, with sintered powder used as a fixed bed for chromatography, if the strength of the powder before firing is not sufficient and constant, the sintered powder collapses during the column packing operation and clogs the filter. For example, there is a problem that the protein separation operation cannot be performed efficiently.

JP 2002-137910 A

  An object of the present invention is to produce a powder by which the strength of the obtained powder can be adjusted and the powder can be produced with uniform hardness, and by the method for producing such a powder. An object of the present invention is to provide a powder and an adsorption device including the powder.

Such an object is achieved by the present invention described in the following (1) to ( 3 ).
(1) The first liquid containing calcium hydroxide as the first raw material and the second liquid containing phosphoric acid as the second raw material are reacted with stirring to produce hydroxyapatite as a composite of these. A first step of obtaining a slurry containing aggregates of:
A second step of drying the slurry to obtain a powder of the composite,
In the first step, when the second liquid is dropped into the first liquid, the first raw material and the second raw material are reacted to obtain a slurry containing the aggregates. ,
Sintered powder obtained by firing the powder by setting the initial temperature of the first liquid to 0 to 20 ° C. and setting the temperature of the obtained slurry to 30 to 50 ° C. And classifying the compressed particle strength to 2.0 MPa or more when the compressed particle strength is measured,
Alternatively, the initial temperature of the first liquid is set to 30 to 40 ° C., and the temperature of the obtained slurry is set to 30 to 50 ° C., thereby sintering the powder. A method for producing a powder, wherein the powder is classified into an average particle size of 40 ± 4 μm, and the compressed particle strength when the compressed particle strength is measured is adjusted to 1.41 to 1.75 MPa.

  Thereby, while being able to adjust the intensity | strength of the obtained powder, this powder can be manufactured with uniform hardness.

(2) when dropping the second liquid to the first liquid, the powder according to (1) the temperature of the mixed solution of the second liquid and the first liquid increases gradually Production method.

  By synthesizing the synthesized product in the mixed solution under such conditions, the powder obtained in the second step has a particularly high bulk density.

( 3 ) The method for producing a powder according to (1) or (2) above, wherein the temperature of the atmosphere when the second liquid is dropped into the first liquid is normal temperature.
Thereby, the temperature of the liquid mixture of the first liquid and the second liquid can be gradually increased.

  According to the present invention, a slurry containing a compound such as a calcium phosphate compound is produced by reacting the first liquid containing the first raw material and the second liquid containing the second raw material while stirring. In the first step of obtaining, by setting an initial temperature for reacting the first liquid and the second liquid, the strength of the obtained powder can be adjusted, and the powder can be made uniform. Can be manufactured with hardness.

It is a figure which shows the particle size distribution of the aggregate comprised with the hydroxyapatite in a slurry. It is a figure which shows the change of the temperature while dropping phosphoric acid aqueous solution with respect to a calcium hydroxide dispersion. It is a figure which shows the change of pH during dropping the phosphoric acid aqueous solution with respect to a calcium hydroxide dispersion. It is a figure which shows the particle size distribution of the aggregate in the slurry containing the aggregate of a hydroxyapatite.

  Hereinafter, preferred embodiments of the method for producing powder, the powder, and the adsorption device of the present invention will be described in detail.

First, the manufacturing method of the powder of this invention is demonstrated.
In the production method of the present invention, a first liquid containing a first raw material is reacted with a second liquid containing a second raw material while stirring, and a slurry containing an aggregate of these synthesized products is obtained. A method for producing a powder comprising a first step of obtaining and a second step of drying the slurry to obtain a powder of the composite.

  Here, the powder is a concept including a granular material, a granule, and the like, and the shape, form, and the like are not particularly limited.

  The composite in the present invention may be either an organic material or an inorganic material, but an inorganic material is preferable, and a ceramic material is particularly preferable.

  Examples of ceramic materials include oxide ceramics such as alumina, silica, titania, zirconia, and yttria, calcium phosphate compounds, nitride ceramics such as silicon nitride, aluminum nitride, titanium nitride, and boron nitride, graphite, tungsten carbide, and the like. In addition, for example, ferroelectric materials such as barium titanate, strontium titanate, PZT, PLZT, and PLLZT.

  Here, the calcium phosphate compounds are used for biomaterials, chromatographic fixed layer materials, and the like, and specific examples thereof include apatites such as hydroxyapatite, fluorapatite, and carbonate apatite, and dicalcium phosphate. , Tricalcium phosphate, tetracalcium phosphate, octacalcium phosphate and the like.

  Among these, hydroxyapatite is rich in biocompatibility and is used for biomaterials, in particular, for medical and dental fillers, artificial bones, and artificial tooth roots. Hydroxyapatite is particularly excellent in the ability to adsorb proteins and the like.

  In the present embodiment, hydroxyapatite is typically described as a composite. However, it goes without saying that the composite is not limited to this.

  The method for producing a powder according to the present embodiment includes a step S1 for obtaining a slurry containing hydroxyapatite aggregates, and a step S2 for obtaining a hydroxyapatite powder by drying the slurry. Hereinafter, these steps will be sequentially described.

[S1: Step of obtaining slurry containing hydroxyapatite aggregates (first step)]
In this step, a calcium hydroxide dispersion (first liquid) containing calcium hydroxide (first raw material) and a phosphoric acid aqueous solution (second liquid) containing phosphoric acid (second raw material) While stirring, calcium hydroxide and phosphoric acid are reacted to obtain a slurry containing hydroxyapatite aggregates.

  Specifically, for example, while stirring the calcium hydroxide dispersion (first liquid) in a container (not shown), an aqueous phosphoric acid solution (second liquid) is dropped into the dispersion, A mixed solution of a calcium hydroxide dispersion and an aqueous phosphoric acid solution is mixed, and calcium hydroxide and phosphoric acid are reacted in this mixed solution to obtain a slurry containing hydroxyapatite aggregates.

  In this embodiment, a wet synthesis method using phosphoric acid (second raw material) as an aqueous solution is used. This makes it possible to synthesize hydroxyapatite (synthetic product) more easily and efficiently without requiring expensive production equipment.

  Moreover, by carrying out this reaction with stirring, the reaction between calcium hydroxide and phosphoric acid can proceed efficiently, that is, the efficiency of those reactions can be improved.

  Further, the stirring force for stirring the mixed solution containing the calcium hydroxide dispersion and the phosphoric acid aqueous solution is not particularly limited, but with an output of about 0.75 to 2.0 W with respect to 1 L of the mixed solution (slurry). It is preferable that the output is about 0.925 to 1.85 W. By setting the stirring force within such a range, the efficiency of the reaction between calcium hydroxide and phosphoric acid can be further improved.

  The calcium hydroxide content in the calcium hydroxide dispersion is preferably about 5 to 15 wt%, more preferably about 10 to 12 wt%. In addition, the content of phosphoric acid in the phosphoric acid aqueous solution is preferably about 10 to 25 wt%, and more preferably about 15 to 20 wt%. By setting the content of calcium hydroxide and phosphoric acid within this range, the opportunity for contact between calcium hydroxide and phosphoric acid when dropping the phosphoric acid aqueous solution while stirring the calcium hydroxide dispersion is increased. Therefore, calcium hydroxide and phosphoric acid can be reacted efficiently, and hydroxyapatite can be synthesized reliably.

  The rate of dropping the phosphoric acid aqueous solution is preferably about 1 to 40 L / hour, more preferably about 3 to 30 L / hour. By mixing (adding) the phosphoric acid aqueous solution into the calcium hydroxide dispersion at such a dropping rate, calcium hydroxide and phosphoric acid can be reacted under milder conditions.

  In this case, the time for dropping the phosphoric acid aqueous solution (addition time) is preferably about 5 to 32 hours, more preferably about 6 to 30 hours. Hydroxyapatite can be sufficiently synthesized by reacting calcium hydroxide and phosphoric acid with such a dropping time. Even if the dropping time is made longer than the above upper limit, further progress of the reaction between calcium hydroxide and phosphoric acid cannot be expected.

  Here, when the reaction between calcium hydroxide and phosphoric acid proceeds gradually, hydroxyapatite (synthetic) fine particles (hereinafter simply referred to as “fine particles”) are generated in the slurry. And between these fine particles, van der Waals force (intermolecular force) works between the positively charged portion of one fine particle and the negatively charged portion of the other fine particles, By aggregation, an agglomerate of hydroxyapatite (synthetic product) (hereinafter simply referred to as “aggregate”) is generated. As the aggregates are generated, the viscosity of the slurry gradually increases.

  Furthermore, when the reaction between calcium hydroxide and phosphoric acid proceeds, the ratio of positive charge to negative charge in the slurry approaches. At this time, in the slurry, the repulsive force acting on the fine particles is reduced, the aggregation of the fine particles is further accelerated, and an aggregate having a larger particle size is formed.

  Such an aggregate has a particle size distribution according to the size of the aggregate as shown in FIG. It has been found that it has two peaks, whose frequency of distribution is greater. In this specification, an aggregate having a peak with a smaller particle diameter is referred to as a primary aggregate, and an aggregate having a peak with a larger particle diameter is referred to as a secondary aggregate.

  By the way, after synthesizing the hydroxyapatite, the slurry is stirred, and by controlling the stirring force for stirring, the size of the primary aggregate and the secondary aggregate are further reduced. The abundance ratio with the secondary aggregate can be adjusted. Furthermore, the hydroxyapatite powder obtained by drying a slurry containing an aggregate having a larger abundance ratio of primary aggregates has a high particle strength.

  On the other hand, the present invention is characterized in that the strength of the hydroxyapatite powder is adjusted by setting the initial temperature at which the calcium hydroxide dispersion and the phosphoric acid aqueous solution are reacted.

  In the setting of the initial temperature when the calcium hydroxide dispersion and the phosphoric acid aqueous solution are reacted, the present ratio does not change the primary agglomerates and secondary agglomerates due to the inventors' investigation. In [S2], it is known that the bulk density of the dry powder obtained by drying the aggregates contained in the slurry changes. It is presumed that another factor different from the abundance ratio with the secondary aggregate contributes.

  Moreover, since the bulk density of the dry powder can be made uniform by setting the initial temperature when the calcium hydroxide dispersion and the phosphoric acid aqueous solution are reacted, the dry powder has a uniform particle strength. It can have.

  The initial temperature when the calcium hydroxide dispersion and the phosphoric acid aqueous solution are reacted is set by adding the phosphoric acid aqueous solution (second liquid) to the dispersion while stirring the calcium hydroxide dispersion (first liquid). ) Is dropped to react calcium hydroxide and phosphoric acid by setting the initial temperature of the calcium hydroxide dispersion.

  And when improving the bulk density of the dry powder obtained in the next step [S2] and improving the strength of the dry powder, the initial temperature of the calcium hydroxide dispersion is set to about 0 to 20 ° C. Is preferable, and it is more preferable to set to about 5-10 degreeC. By setting the initial temperature of the calcium hydroxide dispersion within such a range, the bulk density can be reliably improved.

  Moreover, the temperature of the atmosphere when dropping the phosphoric acid aqueous solution into the calcium hydroxide dispersion is not particularly limited, but is preferably about room temperature (25 ° C.).

  Under these conditions, when a phosphoric acid aqueous solution is dropped into the calcium hydroxide dispersion, the reaction between calcium hydroxide and phosphoric acid contained in these liquids is an exothermic reaction. The temperature of the mixed solution to which the acid aqueous solution is dropped is gradually increased from the initial temperature of the calcium hydroxide dispersion. By synthesizing hydroxyapatite fine particles in the mixed solution under such conditions, the fine particles can be made denser, and the dry powder obtained in the next step [S2] has a particularly high bulk density. It will be a thing.

  And since the temperature of the atmosphere is normal temperature, when the temperature of the mixed liquid exceeds 25 ° C., heat is dissipated from the mixed liquid into the atmosphere, and the gradient of gradually increasing the temperature of the mixed liquid is lowered. A slurry containing agglomerates of is obtained. The temperature of the slurry at this time is preferably about 30 to 50 ° C, and more preferably about 30 to 40 ° C. By making a slurry in such a temperature range, the above-mentioned effect can be exhibited more remarkably.

[S2: Step of drying slurry to obtain hydroxyapatite powder (second step)]
In this step, the slurry obtained in the step [S1] is dried to granulate hydroxyapatite to obtain a powder (dry powder) mainly composed of hydroxyapatite.

  The drying method is not particularly limited, but a spray drying method is preferably used. According to this method, a powder having a desired particle diameter can be obtained more reliably and in a short time.

  Moreover, it is preferable that the drying temperature at the time of drying a slurry is about 75-250 degreeC, and it is more preferable that it is about 95-220 degreeC. By setting within this range, a powder having excellent particle strength (mechanical strength) can be obtained.

  The particle size of the powder to be produced (target particle size of the powder) is not particularly limited, but is preferably about 3 to 300 μm, and more preferably about 10 to 120 μm.

  The method for producing a powder according to this embodiment is particularly suitable for producing a powder having a target particle size of about 10 to 80 μm (particularly about 15 to 43 μm).

  Such powder (dry powder) can be fired (sintered) into a sintered powder. Thereby, the particle | grain intensity | strength of powder (sintered powder) can be improved more.

In this case, the firing temperature for firing the powder is preferably about 200 to 800 ° C, and more preferably about 400 to 700 ° C.
Through the steps as described above, hydroxyapatite (synthetic) powder is obtained.

The particle strength of the obtained powder can be defined as follows, for example.
That is, the sintered powder obtained by sintering the dried hydroxyapatite powder is classified into an average particle size of 40 ± 4 μm, and the compressed particle strength measured by the classified sintered powder is measured. It can be defined by size.

  The compressed particle strength measured under such conditions is preferably as large as possible, specifically 2.0 MPa or more, and preferably about 2.5 to 4.5 MPa. It can be determined that the sintered powder having such a compressed particle strength has a high particle strength.

  Hydroxyapatite powder (dry powder) produced by the above powder production method or sintered powder obtained by firing this hydroxyapatite powder is adsorbent (fixed) provided in chromatography (adsorption device). Applied as phase).

  And, for example, when a liquid containing a plurality of proteins is passed through such chromatography, it is adsorbed on the powder (adsorbent), and further, when an eluate (buffer) is passed through the chromatography, Each protein is sequentially separated in the eluate based on the difference in adsorption between the protein and the powder.

  If these powders are used as an adsorbent for chromatography, it is possible to expand the range of selection of analyte (eg, protein) separation conditions and adsorption conditions. Therefore, such chromatography can be applied to a wider area (field).

  Further, such a powder is molded into a desired shape to obtain a molded body, and the molded body is sintered to form a sintered body, and the sintered body is an artificial bone such as a vertebral spacer or an ossicle. It is preferably used as an artificial tooth root or the like.

  As mentioned above, although the manufacturing method of the powder of this invention, the powder, and the adsorption | suction apparatus were demonstrated, this invention is not limited to this.

  For example, in the present invention, for any purpose, a step before step [S1], an intermediate step existing between steps [S1] and [S2], or a step after step [S2] is added. Also good.

  Moreover, in the said embodiment, the powder which obtains the objective (object of this invention) which sets the initial temperature which makes calcium hydroxide dispersion liquid (1st liquid) and phosphoric acid aqueous solution (2nd liquid) react. However, the object of the present invention is not limited to this.

  For example, a powder having a desired strength can be obtained by appropriately adjusting the initial temperature at which the calcium hydroxide dispersion (first liquid) and the phosphoric acid aqueous solution (second liquid) are reacted. Specifically, when the composite is hydroxyapatite, a powder having a relatively low strength can be obtained by setting the initial temperature in a range of about 30 to 40 ° C.

Next, specific examples of the present invention will be described.
1. Production of hydroxyapatite

Example 1
First, 5000 g of calcium hydroxide was dispersed in 40 L of pure water, and this calcium hydroxide dispersion was put in a tank and stirred, and 20 L of phosphoric acid aqueous solution (phosphoric acid concentration 19.8 wt%) was added to this at 3 L / hour. It was dripped at a speed. Thereby, 70 L of slurry containing 10 wt% hydroxyapatite was obtained.

Note that the initial temperature of the calcium hydroxide dispersion was set to 10 ° C. before dropping the phosphoric acid aqueous solution into the calcium hydroxide dispersion, that is, before starting the reaction.
Moreover, the temperature of the atmosphere during dripping was normal temperature (25 degreeC).

  Furthermore, the stirring force for stirring the mixed solution obtained by dropping the phosphoric acid aqueous solution into the dispersion was 1.7 W with respect to 1 L of the mixed solution (slurry).

  In addition, the temperature and pH of the liquid mixture (slurry) in which phosphoric acid aqueous solution was dripped were measured every 10 minutes. In addition, 500 mL of the obtained slurry was collected.

  Hydroxyapatite contained in the slurry is granulated by spray drying the slurry obtained as described above at 210 ° C. using a spray dryer (manufactured by Matsubo, “MAD-6737R”). A spherical dry powder was obtained, and the obtained dry powder (hydroxyapatite powder) was classified with a center particle size of about 40 μm.

  The dry powder was confirmed to be hydroxyapatite by powder X-ray diffraction.

(Example 2)
A dry powder (dried hydroxyapatite) was obtained in the same manner as in Example 1 except that the initial temperature of the calcium hydroxide dispersion was 30 ° C. before starting the reaction.

(Example 3)
A dry powder (dried hydroxyapatite) was obtained in the same manner as in Example 1 except that the initial temperature of the calcium hydroxide dispersion was 40 ° C. before the start of the reaction.

2. Evaluation 2-1. Evaluation of Slurry Temperature and pH The measurement results of the temperature and pH of the mixed solution (slurry) measured when obtaining the slurry containing the hydroxyapatite aggregate in Examples 1 to 3 are shown in FIGS. 2 and 3, respectively. Shown in

  As shown in FIG. 2, the temperature of the slurry of each Example was gradually increased from the initial temperature. In Example 3, the heat generation due to the reaction between calcium hydroxide and phosphoric acid and the heat release from the mixed solution to the atmosphere almost reach a steady state, and the gradual amplification that gradually increases from the initial temperature is the same as in Example 1 and It was small compared to Example 2.

  Moreover, as shown in FIG. 3, the change of the pH of the slurry of each Example hardly recognized between each Example. From this, it was found that no change was observed in the pH of the slurry by changing the initial temperature of the calcium hydroxide dispersion before the start of the reaction when obtaining hydroxyapatite.

2-2. Evaluation of Particle Size Distribution of Hydroxyapatite Aggregate About each of the slurry containing the hydroxyapatite aggregates obtained in Examples 1 to 3, using a particle size distribution measuring device ("MT3300" manufactured by Microtrac Co., Ltd.) The particle size distribution of the hydroxyapatite aggregates contained therein was determined.
The measurement results are shown in FIG.

  As shown in FIG. 4, the particle size distribution of the hydroxyapatite aggregates obtained in Examples 1 to 3 hardly changed between the examples. From this, it was found that there was no change in the particle size distribution of the hydroxyapatite aggregates by changing the initial temperature of the calcium hydroxide dispersion before starting the reaction when obtaining hydroxyapatite.

2-3. Evaluation of Strength and Bulk Density of Hydroxyapatite Powder The dry powders (Hydroxyapatite powders) of Examples 1 to 3 were each measured using a multi-tester (“MT-1001” manufactured by Seishin Enterprise Co., Ltd.). The density was determined.

  Moreover, about the dry powder of Examples 1-3, the compression particle intensity | strength was calculated | required using the micro compression tester (the Shimadzu Corporation make, "MCT-W200-J"), respectively.

Furthermore, the dry powders of Examples 1 to 3 were each fired in the air at 700 ° C. for 4 hours, and the obtained sintered powder (hydroxyapatite sintered body) was also similarly described above. The compression particle strength was determined using a compression tester. The compressed particle strength is an average value of 10 particles.
The measurement results are shown in Table 1.

  As is clear from Table 1, among the dry powders of Examples 1 to 3, the lower the initial temperature of the calcium hydroxide dispersion, the higher the bulk density tends to be. As a result, it became clear that the compressed particle strength of the dry powder and further the compressed particle strength of the sintered powder increased. That is, it was found that the compressed particle strength of the dry powder and the sintered powder increases in correlation with the initial temperature by setting the initial temperature of the calcium hydroxide dispersion low.

  Therefore, it was found that a dry powder and a sintered powder having a desired compressed particle strength can be produced by appropriately setting the initial temperature of the calcium hydroxide dispersion.

  In particular, the sintered powder obtained by sintering the dry powder of Example 1 in which the initial temperature of the calcium hydroxide dispersion is set to 10 ° C. has a compressed particle strength of 2.5 MPa or more, and is excellent. It was found to have a high particle strength.

Claims (3)

The first liquid containing calcium hydroxide as the first raw material and the second liquid containing phosphoric acid as the second raw material are reacted with stirring, and a hydroxyapatite aggregate as a synthesized product thereof A first step of obtaining a slurry comprising
A second step of drying the slurry to obtain a powder of the composite,
In the first step, when the second liquid is dropped into the first liquid, the first raw material and the second raw material are reacted to obtain a slurry containing the aggregates. ,
Sintered powder obtained by firing the powder by setting the initial temperature of the first liquid to 0 to 20 ° C. and setting the temperature of the obtained slurry to 30 to 50 ° C. And classifying the compressed particle strength to 2.0 MPa or more when the compressed particle strength is measured,
Alternatively, the initial temperature of the first liquid is set to 30 to 40 ° C., and the temperature of the obtained slurry is set to 30 to 50 ° C., thereby sintering the powder. A method for producing a powder, wherein the powder is classified into an average particle size of 40 ± 4 μm, and the compressed particle strength when the compressed particle strength is measured is adjusted to 1.41 to 1.75 MPa.   The method for producing a powder according to claim 1, wherein the temperature of the mixed liquid of the first liquid and the second liquid gradually increases when the second liquid is dropped into the first liquid. The method for producing a powder according to claim 1 or 2, wherein the temperature of the atmosphere when the second liquid is dropped into the first liquid is normal temperature .

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