JPH04209711A - Production of hydroxyapatite - Google Patents

Abstract

PURPOSE:To improve reproducibility by controlling pH of reaction solution with a biochemical buffer solution such as tris buffer solution or Good buffer solution and making a specific theoretical composition ratio of Ca/P. CONSTITUTION:In order to maintain pH of Ca(OH)2 slurry approximately in neutrality during reaction in an inert gas atmosphere such as N2 gas while stirring, the slurry is mixed with a given amount of a biochemical buffer solution such as tris buffer solution comprising tris(hydroxymethyl)aminomethane and a strong acid or Good buffer solution comprising an aminopropanesulfonic acid derivative. Then the slurry is heated while stirring, a stoichiometric amount of phosphoric acid is dripped into the slurry, is reacted for a given time while maintaining the pH at 7-8 and the reaction product is aged. The reaction product is filtered, dried and calcined at >= about 1,000 deg.C to give hydroxyapatite shown by the chemical formula Ca10(PO4)6(OH)2, having 1.76 theoretical composition ratio of Ca/P.

Description

DETAILED DESCRIPTION OF THE INVENTION (Technical Field) The present invention relates to an improved method for producing hydroxyapatite, which has particularly good reproducibility and a theoretical composition ratio of Ca/P=1.6.
The present invention relates to a method for producing microcrystalline hydroxyapatite No. 7.

(Background Art) Hydroxyapatite (hereinafter abbreviated as HAp) has traditionally been suitably used as a biocompatible material.
Many proposals have been made regarding the starting materials and synthesis methods for wet synthesis methods for obtaining it.
Among these, the method of synthesis using calcium hydroxide and phosphoric acid is considered to be an industrially advantageous method because the raw material cost is low.

By the way, in such a method, the Ca/P ratio is easily influenced by the pH during the reaction, the dropping rate of phosphoric acid, the aging temperature, the aging time, and other factors, so it is important to synthesize with good reproducibility. In addition, since the solubility of HAp increases significantly in acidic solutions, it is necessary to maintain the pH during the reaction on the basic side.

Therefore, in order to deal with such a problem, (a) the reaction was divided into two stages, and the Ca-deficient type, that is, the Ca/P ratio was made smaller than the theoretical composition ratio of 1.67, and then the deficiency was (b) A method of finely controlling the rate of HAp production by dividing the dropping rate of phosphoric acid into several stages; (C) A method of adding an alkaline solution in advance to adjust the pH of the reaction solution.
Various methods have been proposed, such as methods to prevent the migration of ions to the acidic side, but these methods complicate the synthesis process, and the product tends to gel, making filtration and washing difficult. Problems have arisen, such as: Also,
A method using an organic compound that generates a base upon hydrolysis, such as urea or hexamethylenetetramine, has been considered, but in order to decompose such an organic compound, 10
A temperature of about 0° C. is required, and since urea decomposes and generates carbon dioxide gas, there are inherent problems such as the formation of carbonated apatite.

(Problem to be solved) The present invention has been made against this background, and the problem to be solved is to solve the problem of Ca/P in which all the above-mentioned problems are solved. The object of the present invention is to provide a method for producing HAp having a theoretical composition ratio of 1.67 with good reproducibility.

(Solution Means) In order to solve this problem, the present invention synthesizes hydroxyapatite by dropping a phosphoric acid aqueous solution into a calcium hydroxide slurry under stirring in an inert gas atmosphere and causing a reaction. At this time, the pH was controlled using a biochemical buffer such as Tris buffer or Gud's buffer to produce hydroxyapatite having a theoretical composition ratio of Ca/P = 1.67.
It has characteristics.

(Specific explanation/effect) By the way, hydroxyapatite (HAp)
10 (P 04) & (OH)! It has a chemical formula of 1.67, and its theoretical composition ratio of Ca/P is 1.67.

HAp, which constitutes biological hard tissues such as bones, has a concentration of Ca/P<
It is a so-called Ca-deficient HAp of 1.67. Therefore, when synthetic HAp is used for artificial bones or artificial tooth roots, Ca-deficient HAp is
It is said to have greater biocompatibility than p. However, in order to use synthetic HAp for artificial bones or artificial tooth roots, it is necessary to sinter it at a temperature of about 1000°C or higher.
When p is fired at a temperature of 800°C or higher, it partially decomposes and precipitates tricalcium phosphate. On the other hand, HAp with the theoretical composition ratio Ca/P=1.67 is 130
HAp is stable even after firing at 0°C.
In order to produce a sintered body, HAp powder with Ca/P=1.67 is required.

Generally, in order to generate HAp, when a stoichiometric amount of phosphoric acid is dropped into a calcium hydroxide suspension (slurry) in an inert atmosphere, the amount charged is 60%.
The pH value shows a constant value of 11.7 until ~70%, but after that, the pH value begins to decrease rapidly, and by the time the entire amount of phosphoric acid has been added, the pH value is around 4. (See Figure 1). And the solubility of such HAp is p
Strongly (depends on H) and increases significantly on the acidic side,
The generated HAp is Ca-deficient, and as mentioned above, 8
Calcination at a temperature of 00° C. or higher causes the transition to tricalcium phosphate, and if the pH is controlled to be on the basic side, it becomes Ca-excessive and precipitates CaO after firing. In this way, the composition of HAp varies depending on the pH, so in order to control the composition of HAp, in other words, to obtain HAp with a Ca/P ratio of 1.67, it is necessary to adjust the pH around neutrality. control is desirable.

Therefore, in the present invention, when synthesizing HAp by an aqueous solution reaction of calcium hydroxide and phosphoric acid, it is necessary to use a Tris buffer [tris(hydroxymethyl)aminomethane and a strong acid, pH = 7 to 9] or a gas buffer. By using a biochemical buffer such as (aminopropane sulfonic acid derivative, pH = 6 to 11), the pH of the reaction solution is in the neutral range,
Generally, it is controlled to be 7 or more and less than 8, preferably in the range of 7.0 to 7.8.

As is well known, these buffers have a buffering capacity near neutral pH, hardly react with metal ions, do not exhibit physiological activity themselves, do not pass through cell membranes, and do not contain carbon dioxide gas. It is widely used as a biochemical buffer because it does not absorb. In addition, when using Tris buffer, tris(hydroxymethyl)aminomethane CNH2C(CH20H)! , hereinafter abbreviated as Tris] and hydrochloric acid are generally combined as strong acids, but in the present invention, due to the presence of phosphoric acid,
The buffering effect of the combination of Tris and phosphoric acid will be utilized.

In the present invention, a phosphoric acid aqueous solution is added dropwise to a calcium hydroxide slurry while stirring in a predetermined inert gas atmosphere to cause a reaction, and a predetermined buffer solution as described above is added thereto. This allows the pH of the reaction solution to be adjusted. In addition, regarding the addition of such a biochemical buffer, in the calcium hydroxide suspension (slurry),
Prior to adding phosphoric acid, add it in advance in a predetermined amount, and then add phosphoric acid, or drop phosphoric acid first to reach the desired pH value within the above control range, and then add it. In either case, the pH can be maintained at a substantially constant value depending on the amount of the buffer solution added.
Ap can be generated with good reproducibility.

Thus, according to the present invention, HAp produced as described above with a theoretical composition ratio of Ca/P (1,67) while controlling the pH is then aged for an appropriate time,
Furthermore, it is prepared for various uses through various steps such as filtration, drying, and calcination according to conventional methods.

(Examples) Examples of the present invention are shown below to clarify the present invention more specifically, but the present invention is not limited in any way by the description of such examples. It goes without saying that.

In addition to the following embodiments and the above-described specific description, the present invention includes various changes and modifications based on the knowledge of those skilled in the art, as long as they do not depart from the spirit of the present invention. It should be understood that improvements and modifications may be made.

Example 1 Calcium oxide: 414.8 g was previously decarboxylated in a nitrogen stream. Water: 3. M! In addition, it was made into a calcium hydroxide suspension. Then, this suspension was heated to 60°C, and while stirring strongly, 4.421 of a 1 mol solution of phosphoric acid was slowly added dropwise, and when the pH value reached 7.2, 1 mol of Tris was added dropwise. Add the solution to 370 ml. In addition, phosphoric acid was further added dropwise. p at the time when the entire amount of phosphoric acid has been added
H was 7.2. Thereafter, aging continued for a predetermined period of time. The changes in aging time, pH value, and Ca/P ratio are shown in Table 1 below.

Table 1 Note that the average size of the HAp crystals after aging for 94 hours was 100n100n, 5nm.

After completion of such aging, the HAp powder was filtered and dried, and the resulting HAp powder was calcined at a temperature of 1100°C. In addition, the X-ray powder diffraction pattern (2-
a) is shown in Figure 2.

Example 2 All procedures were carried out except that before adding phosphoric acid to the calcium hydroxide suspension, enough Tris buffer was added to control pH = 7.2, and then phosphoric acid was added dropwise. HAp was synthesized under the same conditions as in Example 1. p due to aging
) (and the changes in Ca/P ratio are shown in Table 2 below.

G;=.

Table 2 Also, as in Example 1, the X-ray powder diffraction pattern (2-b) of HAp after firing at a temperature of 1100° C. was measured, and the results are shown in FIG.

Comparative Example 1 Phosphoric acid was added dropwise to a calcium hydroxide suspension, and when the pH value reached 6.0, a Tris buffer was added. Then, HAp was synthesized under the same conditions as in Example 1 except that the pH value was set to 6.0.

Changes in pH and Ca/P ratio due to aging are shown in Table 3 below.

Table 3 Then, in the same manner as in Example 1, the solid content (HAp) obtained by filtration was dried and calcined at a temperature of 1100°C.

The X-ray powder diffraction pattern (3-b) of the fired product is shown in FIG.

As is clear from this figure, in addition to HAp, a small amount of α
-TCP was found to coexist.

Comparative Example 2 Phosphoric acid was added dropwise to a calcium hydroxide suspension, and when the pH value reached 8.0, Tris buffer was added to lower the pH value to 8.0.
．． HAp was set to 0 in the same manner as in Example 1 except that it was set to 0.
was synthesized. Changes in pH and Ca/P ratio due to aging are shown in Table 4 below.

Table 4 Furthermore, the X-ray powder diffraction pattern (3-a) of the fired product after firing at 1100°C is shown in FIG.

As shown in this figure, in addition to HAp, a trace amount of Ca
The coexistence of O was observed.

Comparative Example 3 Ap was synthesized under the same conditions as in Example 1 except that no Tris buffer was added.
Changes in H value and Ca/P ratio are shown in Table 5 below.

Table 5 also shows the X-ray powder diffraction pattern (3-c) of the fired product after firing the obtained HAp powder at a temperature of 1100°C.
is shown in Figure 3. From this figure, it was recognized that all of the samples had changed to β-TCP.

(Effects of the Invention) As is clear from the above explanation, in the present invention, the pH of the reaction solution can be controlled using a biochemical buffer such as Tris buffer or Gud's buffer. Accordingly, Ca /
Since P is made to have a theoretical composition ratio (1,67), hydroxyapatite having a theoretical composition ratio of Ca/P can be produced without the need for complicated processes and with good reproducibility. You can get it.

[Brief explanation of the drawing]

FIG. 1 is a graph showing the relationship between the stoichiometric amount of phosphoric acid and pH for the hydroxyapatite composition;
The figure shows the X-ray powder diffraction pattern of the fired body obtained in Example 1.2, and FIG. 3 shows the X-ray powder diffraction pattern of the fired body obtained in Example 1 and Comparative Examples 1 to 3. It is a line figure. Applicant: Kyoritsu Ceramic Materials Co., Ltd. Niss TK Ceramics Research Institute, Ltd. Figure 1 0 20 40 60 80 X) 0 Hyde 0
Kishi7no? 411g of Rinsen that is perfect for tight charms
Fairy tale! (%) Figure 2 Figure 3

Claims (1)

[Claims] When synthesizing hydroxyapatite by dropping an aqueous phosphoric acid solution into a calcium hydroxide slurry under stirring in an inert gas atmosphere and causing a reaction, biochemical buffers such as Tris buffer and Good's buffer are used. 1. A method for producing hydroxyapatite, which comprises controlling the pH using a method of producing hydroxyapatite having a theoretical composition ratio of Ca/P=1.67.