JPS605009A - Preparation of hydroxy apatite - Google Patents

Abstract

PURPOSE:In preparation of hydroxy apatite (HAP) by an aqueous solution reaction, to prepare HAP economically under mild reaction conditions, by reacting CaHPO4(.2H2O) with Ca(OH)2 with adjusting pH to a specific value. CONSTITUTION:Ca(OH)2 is added to slurry of CaHPO4(.2H2O) with stirring in an inert gas atmosphere, and they are reacted at 5-100 deg.C. In the operation, (i) the reaction is carried out at <=10pH by regulating an amount of Ca(OH)2 added until Ca/P (molar ratio) becomes 1.6, and (ii) the reaction is done at 7-11pH after Ca/P (molar ratio) becomes >=1.6, to synthesize HAP having 1.67 theoretical Ca/P (molar ratio).

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing hydroxyapatite (hereinafter referred to as HAp).

In recent years, phosphoric acid compounds, especially HAp, have attracted attention as biomaterials, and have come to be used in artificial bones, artificial ambidextrous materials, and the like. This is because when HAp is implanted in a living body, it is safe and chemically stable, and moreover, it fuses with natural bone without causing a rejection reaction in the living body and is easily healed.

However, in order for artificial bones and the like to be safe and stable in vivo, the HAp constituting them must be of high purity. For example, if iron, zinc, lead, etc. are contained in excess of a paltry level, these ions may be eluted in vivo, making them unstable and toxic.

In general, there are two methods for synthesizing HAp: a wet method using an aqueous solution reaction and a hydrothermal reaction under atmospheric pressure, and a dry method using a solid phase reaction at high temperatures. Phase reactions require long-term calcination at high temperatures of 1000°C or higher;
The equipment is not expensive or industrial. In addition, as a method using an aqueous solution reaction, a method using phosphoric acid neutralization can be used, but the reaction rate is high and the precipitate that is mixed becomes colloidal, making handling and operation inconvenient. Since it is required to have very few impurities, it is extremely difficult to remove impurities when crude phosphoric acid is used as a raw material.

On the other hand, among the wet methods, as a method using a hydrothermal reaction, C
a1(PO4 or C1aHPO4-2H20 and Ca(
A method for producing HAp by the reaction of OH)2 has been proposed (JP-A-53-111000). In this method, each raw material is mixed solidly, and this mixture is heated at 100 to 500°C using an autoclave. Crystalline HA p'rH is produced by a hydrothermal reaction under hydrothermal conditions of 5 to 500 atm.

However, this method has the disadvantage that the reaction conditions are harsh, the reaction equipment is expensive, and the energy cost is not high.

The present inventors conducted intensive studies to eliminate the drawbacks of these conventional methods, and focused on the industrial advantages of aqueous solution reactions.
aHPOs or CaHPO4.2H2O and 0a(OH
) A completely new method for obtaining HAp'fc by an aqueous solution reaction of t has been achieved.

That is, the present invention provides 0aHPO4 or 0aHPO4
-2H,O and water slurry solution reaction temperature 5~100℃
The HAp production method is characterized by adding 0a(OR)1'i and allowing the reaction to occur while keeping the pH'(pH') below 10 until the Oa/p molar ratio is 1.6. Since it can be easily produced in a short time under suitable reaction conditions, it is an extremely economically advantageous method that does not require any expensive reaction equipment.

To explain the present invention in detail, the basic reaction formula between C1aHPO4 or OaHPO4-2, H20 and Oa(OH)z is shown below.

60aHPO4+40a(OH)2Cato (PO,
)s (0H)2↓+6H20・・・・・・・・・■6
(hHPO42H20+ 40a(OH)z 0alo
(F)4)s (OH)z↓8H,O-・-・■In this case, CaHPO4ma-rc is 0aHPO4-2H2
Even if a car's amount of Ch(OH)2 is added all at once to a slurry solution of Ch(OH)2 and water at a reaction temperature of 100°C or less, the reaction is extremely slow (H
AP is difficult to generate. However, as a result of research conducted by the present inventors, when Ca(OH)z is continuously or intermittently supplied to 0aHPO and slurry solutions within a range that does not exceed each reaction rate, specifically, when the PH value of the reaction solution is Adjust so that it does not exceed the value 0a (OH).

It has become clear that the reaction easily proceeds and is completed when the solution is supplied. Control of p and H is a major factor in this reaction, for example, starting material Q! aHPo◆Reaction temperature 85℃
In this case, the reaction solution charged Oa/P ratio ≦ molar ratio) is approximately 1.6.
'l: pH 10 or less, preferably I/1p) 18.
React in the region below 0. After that, prepare the reaction solution c a
When the /p ratio is from 1.60 to 1.67, the entire reaction is carried out at pH 7 to 11 and O, and HAp with a theoretical ca/P ratio of 67 is synthesized.

In this reaction, the pH during the reaction is an extremely important factor, and in order to complete the reaction, it is necessary to pay sufficient attention to pH control.
If not maintained below, unreacted CaHPO4 or 0
In some cases, aHPO4-2H20 remains and HAp cannot be obtained.

The reaction temperature is usually 5 to 100°C, but in order to make the reaction proceed quickly, the reaction temperature is 70 to 100°C for the 0aHPO4 raw material.
3 at 100℃, 0aHPO4・2H20 raw material
0 to ioo°C is preferred. At temperatures below 5°C, the progress of one reaction slows down, which is undesirable. At temperatures above 100°C, the reaction progresses easily in a short time, but it is not desirable for mass production of HAp because it requires an autoclave, etc. .

Also, the C! of the product HAp! The a/P ratio is 0a (p, 0a by changing the OJ2 supply amount (preparation ca/p ratio)
HPO4 raw material with ca/p ratio 1.56-1.67.0aH
Ca/P ratio 1.48-1.67 with PO4-2H2O raw material
HA p'i can be easily obtained.

Furthermore, in the present invention, Ca(OH)z used may be supplied in the form of powder or slurry.

Further, in order to suppress the incorporation of ao32- ions into the product f(Ap) as low as possible, it is desirable to carry out the reaction under an atmosphere surrounded by an inert gas (for example, an island).

As shown in Table 1, HAp obtained in the present invention is made of acicular powder in the form of acicular powder, molded or sintered as it is or with other organic matter such as cellulose or collagen, or composited with other organic or inorganic matrices. It can be used not only as a biological material but also as a chromatography packing system.

The present invention will be described in detail below with reference to Examples.

Examples 1 to 9 HAp was produced using the reaction apparatus shown in FIG.

That is, a 60It reactor made of 7' CSUS 304 was heated with hot water Jaquent 2, a stirrer 3, a pH meter 4, a thermometer 5,
Great technique 7 as a lid, reflux condenser 6 is placed, Oa inside
HPO4 or 0aHPO4-2B20'! il-
It is heated after being prepared with water to the composition shown in Table 2. When the reaction temperature reaches a predetermined value (Table 2), lime is preheated by a hot water jacket 9 from a separately arranged lime hole tank 8 with 10 stirrers, and supplied to the reactor 1 from a 1ζ10 lime hole pumping bong 11. (Examples 5 and 9 were added as powder)
Oa/P molar ratio ranged from 1,56 to t, 6 by sampling.
At pH 0, lime pores are supplied so that the pH becomes 1O or less, and then at pH 7 to 12, lime milk is completely supplied so that the Ea/P molar ratio becomes the total predetermined amount, and the reaction is carried out. , washed with water, and dried. The results are shown in Table 2. The relationships between the Oa/P molar ratio and pl at each reaction time are shown in Figures 4 to 12. (indicates pH.) In addition, the X-ray diffraction pattern of Example 1.6 is shown in Figures 2 (A) and (B), and the electron micrographs of Examples 1 and 6 are shown in Figures 5 (A) and (B). ).

Comparative Example 1 Ca(oH)2 slurry was entirely supplied to a CaHPO43,0Kp, -m2035Kpp reactor at a charging temperature of 85°C, and the charging Oa/P ratio i was adjusted to 1.67. reaction g
At pH 10.8 and reaction time 120 hours, all the product was removed, filtered, and dried. As a result of analyzing this with an X-ray diffraction device, no i(Ap) was observed. The entire X-ray diffraction pattern is shown in FIG. 2 (0).

Comparative example 2 aalHpo42H2O3,5Ky, H2O35Kp'
i (0a(OH)2 slurry was supplied at once to the reaction species at a charging temperature of 50°C, making the total charging ca/P ratio 1.67.Reaction?ffl 1?H"-', reaction time 72H
The product was removed with r, filtered and dried. Is this VX? N
As a result of analysis using a diffraction device, very little HAp was observed.

The entire Xi diffraction pattern is shown in FIG. 2(D).

Comparative Example 3 0aHPO43'9, 'H2O35ff At a charging temperature of 85°C, a portion of the Ca(OH)2 slurry was fed into the reaction tank in succession up to kpH 10.5, and then 0a(OH)
2. Slowly feed the slurry so that the f p H is in the range of 10.2 to 10.8, and make the charged Ca/P ratio 1.67. 3. After a reaction time of 50 Hr, the product is taken out, filtered, washed with water, and dried. did. As a result of analyzing this with an X-ray diffraction device, H
The relationship between Oa/P molar ratio and pH at each reaction time is shown in FIG. 13.

(In the figure, the solid line indicates the Ca/P molar ratio, and the broken line indicates the pH.

) Comparative Example 4 0aHPO4:5 I'I/, H2O351f)7. A part of the slurry (a (0H)) was charged into a reaction tank at 85°C until the pH reached 10.2, and then the pH
From the time when the pH dropped to 8.5, Oa(OH)2 slurry was fed again so that the Oa/P ratio was 1.581 and the pH was below 0, and the ca/p ratio was 1.60.

After a reaction time of 48 hours, the product was taken out, filtered, washed with water, and dried. As a result of analyzing this with an X-ray diffraction device, a small amount of OaHPO4 remained unreacted with HAp. The relationship between the Ca7'P molar ratio and pH at each reaction time is shown in FIG.

(In the figure, the solid line indicates the Oa/P molar ratio, and the broken line indicates the pH.

)

[Brief explanation of the drawing]

Figure 1 shows an example of the apparatus used to carry out the present invention, and Figure 2 shows the X-ray diffraction analysis of the products obtained in Example Process 6 and Comparative Example 1.2. It is. FIG. 5 is a micrograph of the product obtained according to Example 1.6. 4 to 14 are graphs showing the relationship between pH and Oa/P molar ratio at each reaction time in Examples 1 to 9 and Comparative Examples 3 and 4. Patent applicant Central Glass Co., Ltd. Agent Patent attorney Sakae Sakamoto - Fig. 2 2θ (6) 2θ (°) Reaction time (Meiji)

Claims (1)

[Claims] A slurry of 0aHPO4 or 0aHPO4.2H20 and water is dissolved at a reaction temperature of 5 to 100°C and a Ca/p molar ratio of 1.
A method for producing hydroxyapatite, in which the pH is maintained at 10 or less until the pH is maintained at 10 or less, and ca(OH)z is added to allow the reaction to occur.