JPH03218911A - Method and device for producing hydroxyapatite - Google Patents

Abstract

PURPOSE:To continuously and automatically carry out the whole process and to obtain a high-purity and stabilized-quality product in the process in which a hydrolysis reaction is conducted in two stages without using an org. solvent by using an ion-exchange resin to remove the generated ions. CONSTITUTION:Sparingly water-soluble calcium phosphate 2 as the starting material and water sucked up from a tank 3 by a pump 4 through a solenoid valve 5 are charged into a first reaction vessel 1, and a pH regulator is added from a vessel 6. The vessel 1 is agitated, a reaction is carried out in the basic medium, and a suspension of hydroxyapatite having the non-stoichiometric composition and in which the molar ratio of Ca to P is controlled to <1.67 is produced. The suspension is successively introduced into chambers 9 and 10 respectively packed with anion and cation-exchange resin to remove the anion and cations, and then the suspension is supplied to a second reaction vessel 12. Ca<2+> is added to the suspension from a pH regulator container 16, a reactrion is carried out in the basic medium, the molar ratio of Ca to P is increased to 1.67, and the suspension is converted into a suspension of hydroxyapatite having a stoichiometric composition. The obtained suspension is supplied to a chamber 15 to remove Ca<2+>.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a method for producing hydroxyapatite and an apparatus therefor. [Prior art and its problems] Hydroxyapatite (Ca+e(PO4)i(OB)z), abbreviated as HAP, is a mineral that accounts for 60 to 70% of the components of teeth and bones, and has excellent biocompatibility. For this reason, it is attracting attention as a biological material. Specific uses include filling materials for teeth and bone defects, dental cement, toothpaste, artificial tooth crowns and roots, etc.In addition, the surface of hydroxyapatite particles is highly reactive and has adsorption capacity. Because it also has catalytic and catalytic abilities, it is increasingly being used as a column packing material for high-performance liquid chromatography, which separates and concentrates organic substances such as proteins with high efficiency. Conventional methods for producing hydroxyapatite include solid-phase reaction methods, hydrothermal synthesis methods, precipitation reaction methods, and hydrolysis methods. However, the solid phase reaction method contains many impurities such as arsenic^S and uses a closed pressure vessel for the reaction.
It's expensive. The hydrothermal synthesis method also uses a closed pressure vessel, and the resulting hydroxyapatite is single crystal and has a large particle size. In addition, hydroxyapatite obtained by the precipitation reaction method is
It is active and has good sinterability, but the precipitate is colloidal, making filterability poor, and composition control difficult. Furthermore, in the hydrolysis method, the reaction time can be shortened in the coexistence of an organic solvent (n-bentane), which generally requires a long reaction time.
There are disadvantages such as post-processing being troublesome. On the other hand, as a conventional method for producing hydroxyapatite, there is a method for producing hydroxyapatite in a short time by dividing the hydrolysis reaction into two stages without using an organic solvent.
It is disclosed in Publication No. 46908. In this method, a basic substance for pH adjustment (NH.O.
(H, etc.) and H3POs, which are reaction byproducts during hydrolysis, are present, and after the second stage reaction, along with hydroxyapatite of stoichiometric composition, excess calcium ion Ca''+ for pHtm adjustment is present. After the first stage reaction, the ions (NHa”,
or H*POn −, HPO4”−, P04, etc.), these ions must be removed from the aqueous solution in order to suppress the progress of the next second stage reaction.
Excess Ca2+ after the stepwise reaction also needs to be removed to obtain high purity hydroxyapatite. Therefore, in reality, at each reaction completion stage, the aqueous solution is a suspension of hydroxyapatite particles. ) and after the second stage reaction (Ca" addition), the suspension is repeatedly filtered and washed for about an hour. However, in this method, the suspension is removed from the reaction vessel. After that, the hydroxyapatite particles are separated by repeated filtration and washing.
It is necessary to collect the hydroxyapatite and transfer it to the next reaction vessel, etc., resulting in a discontinuous process, which is not suitable for industrial use in terms of productivity and quality stabilization of hydroxyapatite. [Means for Solving the Problems] The present invention has been made in view of the above circumstances, and the structure of the invention described in claim (1) is to hydrolyze poorly water-soluble calcium phosphate in a basic aqueous solution. A suspension of hydroxyapatite with a non-stoichiometric composition in which the Ca/P molar ratio is smaller than a predetermined value is made, and then calcium ions are added in a basic aqueous solution to bring the Ca/P molar ratio to a predetermined value. This is a method for producing hydroxyapatite in which generated anions or cations are removed using an ion exchange resin. Further, the structure of the invention described in claim (2) is such that barely water-soluble calcium phosphate is hydrolyzed in a basic aqueous solution, and Ca.
A first reactor containing a suspension of hydroxyapatite with a non-stoichiometric composition in which the /P molar ratio is smaller than a predetermined value; The chamber and the suspension are mixed through a cation exchange resin layer. a second chamber that removes cations, and the suspension that has passed through the first and second chambers is treated with calcium ions in a basic aqueous solution to
a second reaction vessel for increasing the a/P molar ratio to a predetermined value; and a third chamber for removing mixed calcium ions through a cation exchange resin layer that passes through the suspension that has passed through the second reaction vessel. This is a hydroxyapatite production equipment equipped with the following. Note that the first chamber may be filled with a cation exchange resin, and the second chamber may be filled with an anion exchange resin.

[Effect]

According to the method for manufacturing hydroxyapatite, poorly water-soluble calcium phosphate is made into a suspension of hydroxyapatite with a non-stoichiometric composition, and then the suspension is continuously processed until the final process. Anions or cations generated during the treatment process are removed by an ion exchange resin, the reaction is quickly completed, and highly pure hydroxyapatite is obtained.

According to the manufacturing apparatus, when hydrolyzing poorly water-soluble calcium phosphate in a basic aqueous solution in the first reaction vessel, anions such as P04 and NH. This anion is removed by an anion exchange resin in the first chamber, and the cation is rapidly removed by a cation exchange resin in the second chamber. The turbid liquid is introduced into the second reaction vessel, and calcium ions are added under a basic aqueous solution, so that the reaction is quickly completed and hydroxyapatite with a stoichiometric composition is obtained.Then, it is introduced into the third chamber, By removing excess calcium ions using a cation exchange resin, highly pure hydroxyapatite can be obtained quickly and automatically.The cations are removed in the first chamber, and the anions are removed in the second chamber. Even if it is removed, the effect is the same.

[Examples] Examples of the present invention will be described below with reference to the drawings. FIG. 1 shows an apparatus according to one embodiment of the present invention, and FIG. 2 shows the flow of the same process. In the figure, reference numeral 1 denotes a first reaction vessel, and inside the first reaction vessel l, there is a poorly water-soluble calcium phosphate (e.g., CaHPO4.2H!0) 2, which is a raw material (starting material) for hydroxyapatite, and water. It contains water pumped up from the tank 3 by the pump 4 and supplied through the NMi valve 5. 6 is a pH adjusting agent such as NH. This is a pHu4 preparation container containing 011. In the first step, the pH is adjusted by appropriately adding a pH adjusting agent from the pH adjusting agent container 6 to the first reaction container 1, and the inside of the first reaction container 1 is stirred by the stirrer 7a to make it basic. to produce hydroxyapatite (Ca+o-g (HPOa)g (POa)hm) with a non-stoichiometric composition in which the Ca/P molar ratio is less than 1.67.
(OH)z−*·nHzO) is generated. Here, n
represents θ~2.5, and 2 represents 0-1. This first stage reaction is carried out for about 1 hour at a temperature of 6°C, a pH value of 8, and a raw material of Ca}IPO4・2H!0.
The reaction formula of the first stage when using is shown below. (10-z)CaHPOn ・2HzO+ [(2-
z) +n) H! O → Ca+o-t (}IPO
a) g (POa)i-*(OR)z-++ 'II
HzO+(4-z)HsPOa+2(10-z)H
tO and after the completion of this reaction, NH40H for pH adjustment.
and H3PO. which is a reaction by-product during hydrolysis. are mixed. The accompanying ions (NH.”, or 11!PO.
HPO. ”- or PO. '-) is the second
These ions must be removed from the aqueous solution in order to inhibit the progress of the step reaction.

In addition, as poorly water-soluble calcium phosphate, CaHPO
In addition to a′ 2Hz, CaHPO4. Caz(P.O.
There are Jg etc. In the second step, the slurry pump 13a is driven, the electromagnetic valve 8 is opened, and a suspension of hydroxyapatite particles having a non-stoichiometric composition, which is a reaction product, in the first reaction vessel 1 is pumped into the first chamber. 9 and the second chamber 10 sequentially. The first chamber 9 is filled with anion exchange resin, so anions (PO4
”-) is removed. Also, in the second Changha-IO,
Since it is filled with cation exchange resin, mixed cations (NH4'') are removed.Pressure gauge 20a,
2Qb is for detecting clogging of each chamber 9, 10 as a pressure increase and washing each ion exchange resin with water. The time required for this second step is about 10 minutes. The non-stoichiometric suspension of hydroxyapatite that has passed through the second chamber 10 is supplied to the second reaction vessel 12 through the electromagnetic valve 11, and then proceeds to the third step. In the third step, the second
In the non-stoichiometric hydroxyapatite in the reaction vessel l2,
For example, supplying Ca (OH) z etc. from the pH adjuster container l6 and adding calcium ions Ca24,
The reaction was carried out in a basic state, and the molar ratio of Ca/P was 1.6.
7 to convert into a stoichiometric suspension of hydroxyapatite. This second stage reaction is carried out, for example, at a temperature of 60''C, a pH value of 11, and a period of about 1 hour. 7b is a stirrer.

The reaction formula for this second stage is shown below. CM+o-* (HPO4)g (POJ*-++(O
R) x-g'nHzo+Zca"◆10ZOH -
．． −Ca+e(POa)h(OR)z+zl{
”+nHzOAfter the completion of this reaction, surplus Ca” ◆ for pH adjustment exists along with hydroxyapatite of stoichiometric composition. Therefore, the suspension of hydroxyapatite in the second reaction vessel 12 is supplied to the third chamber 15 through the electromagnetic valve 14 by driving the slurry bomb 13b, and the process proceeds to the fourth step. The third chamber 15 is filled with cation exchange resin, and excess calcium ions (C
a1+) is removed, and a highly pure aqueous solution of hydroxyapatite is obtained. The time required for this fourth step is about 5 minutes. 20c is a pressure needle. The hydroxyapatite suspension that has passed through the third chamber 15 is stored in the HAP container 18 via the solenoid valve l7.
The hydroxyapatite suspension in the HAP container 18 is taken out to the outside by opening the magnetic valve 19 and dried. 7c is a stirrer.

In the second step, the first chamber 9 is filled with a cation exchange resin, and the second chamber 10 is filled with an anion exchange resin, whereby cations (
N.H. ↑) and anions (PO4'-) may be removed in the second chamber 10. [Effects of the Invention] As understood from the above explanation, according to the present invention, the following effects can be obtained.

(1). Since ions are removed using an ion exchange resin, the entire process can be carried out continuously and automatically while the hydroxyapatite remains as a suspension, reducing the total reaction time and allowing ions to be removed easily and quickly. This will greatly improve productivity.

(2). The production of hydroxyapatite is a closed cycle of the suspension throughout the entire process, which prevents the contamination of impurities during the filtration and washing processes that occur in conventional methods, and furthermore, the reaction conditions are accurately and uniformly controlled by continuous and automated processes. This stabilizes the quality of hydroxyapatite. (3). As a result of being able to obtain hydroxyapatite with stable quality and good productivity as described above, a method and apparatus for producing hydroxyapatite suitable for industrialization have been provided.

[Brief explanation of drawings]

FIG. 1 is a schematic diagram showing a manufacturing apparatus according to an embodiment of the present invention, FIG. 2 is a diagram showing a flow of the same manufacturing process, and FIG. 3 is a diagram showing a flow of a conventional manufacturing process. l: first reaction vessel, 2: poorly water-soluble calcium phosphate, 3
:Water tank, 4:Pump 5 8 1114,17,1
9: Solenoid valve, 6, 16: PH adjuster container, 9: First chamber. 10: second chamber, 12: second reaction vessel.
15: Third chamber. 18:l {AP container.

Claims (3)

[Claims] (1) Slightly water-soluble calcium phosphate is hydrolyzed in a basic aqueous solution to form a suspension of hydroxyapatite with a non-stoichiometric composition in which the Ca/P molar ratio is smaller than a predetermined value, and then under a basic aqueous solution. Add calcium ions to Ca/
1. A method for producing hydroxyapatite in which the P molar ratio is increased to a predetermined value, the method comprising removing generated anions or cations using an ion exchange resin. (2) a first reaction vessel in which poorly water-soluble calcium phosphate is hydrolyzed in a basic aqueous solution to form a suspension of hydroxyapatite with a non-stoichiometric composition in which the Ca/P molar ratio is smaller than a predetermined value; a first chamber that passes the suspension through an anion exchange resin layer to remove mixed anions; a second chamber that passes the suspension through a cation exchange resin layer to remove mixed cations; The suspension passed through the second chamber was passed through a second reaction vessel in which calcium ions were added to the suspension under a basic aqueous solution to increase the Ca/P molar ratio to a predetermined value. A hydroxyapatite production apparatus comprising: a third chamber for removing mixed calcium ions by passing the suspension through a cation exchange resin layer. (3) The apparatus for producing hydroxyapatite according to claim (2), wherein the first chamber is filled with a cation exchange resin and the second chamber is filled with an anion exchange resin.