JPH11323570A - Method of forming hydroxyapatite film - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an easy method to form a hydroxyapatite film having excellent fixing property of the film on a metal base body to be used in a living body without decreasing the physical properties of the metal material. SOLUTION: When a hydroxyapatite film formed on a metal base material to be used in a living body, the metal base material is heated to 80 to 300 deg.C, then dipped in a first aq. soln. containing urea, calcium ion and phosphate ion, and then dipped in a second aq. soln. containing at least calcium ion and phosphate ion to form a hydroxyapatite film on the surface of the metal material.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for forming a hydroxyapatite film on the surface of a metal substrate used in vivo and imparting biocompatibility to the metal substrate.

[0002]

2. Description of the Related Art Metal materials such as titanium and Co-Cr-Ni are used as structural materials used in the body such as artificial joints and artificial roots. Since these metal materials are used in vivo for a long period of time, they are required to have not only toughness and light weight in physical properties, but also biocompatibility and durability capable of bonding to human body tissues. On the other hand, hydroxyapatite (Ca
_{Since 10} (PO ₄ ) ₆ (OH) ₂ ) is an inorganic component of the bone of a living body and has a high affinity and binding property with a living tissue, various attempts have been made to coat the metal substrate with the above. ing.

A method for forming a hydroxyapatite film on a metal substrate includes a physical method and a chemical method.
As a physical method, a plasma spraying method (for example,
-52471) and the like. As a chemical method, a nucleating substance of hydroxyapatite such as a glass component is first fixed to the surface of a metal substrate, and then immersed in a simulated body fluid containing calcium ions and phosphate ions to form hydroxyapatite as a film. (For example, JP-A-6-293506) or a method in which a metal substrate is heated to 600 ° C. or more in advance to form an oxide film on the surface, and then immersed in a simulated body fluid containing calcium ions and phosphate ions. For example, a method of forming a hydroxyapatite layer (for example, JP-A-5-176985) is known.

[0004]

However, in the plasma spraying method, metal components such as copper used for electrodes are mixed.
In addition, since hydroxyapatite is exposed to a high temperature of, for example, about 10000 ° C. for a short time, there is a fear that biodegradation is partially caused and biocompatibility is reduced. Also, in the chemical method, a method in which hydroxyapatite nuclei are formed on a metal surface in advance by using glass or the like and coating is performed has a low bonding strength of the obtained hydroxyapatite film to a metal substrate, and peeling is likely to occur. In the method of forming a metal oxide film, since the metal substrate is heated to a high temperature of 600 ° C. or higher, the fixing strength is improved, but the deterioration of the physical properties is inevitable in the case of a metal, particularly titanium. The present invention has been made in order to solve the above-mentioned problems, and accordingly, an object thereof is to form a hydroxyapatite film on a metal substrate used in vivo, and to improve the properties of the metal substrate. An object of the present invention is to provide a method for forming a hydroxyapatite film having a high fixing strength to a metal substrate without lowering the same.

[0005]

In order to solve the above-mentioned problems, the present invention provides the above-mentioned metal substrate heated at a temperature of 80 ° C. to 300 ° C. containing at least urea, calcium ions and phosphate ions. A method for forming a hydroxyapatite film is provided, wherein the method is immersed in a first aqueous solution and then immersed in a second aqueous solution containing at least calcium ions and phosphate ions to form a hydroxyapatite film on the surface of the metal substrate. Preferably, the metal substrate is titanium or a titanium alloy. The concentration of urea in the first aqueous solution is preferably in the range of 0.05 mol / liter to 2 mol / liter. In addition, the second aqueous solution is 30
It is preferable to keep the temperature in the range of 60C to 60C. This second aqueous solution is preferably a simulated body fluid containing calcium ions and phosphate ions.

[0006]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described in more detail with reference to preferred embodiments. In this example, as a metal substrate,
A biocompatible titanium substrate is used. The titanium substrate is first heated to a temperature in the range of 80C to 300C, for example, 200C. Next, this heated titanium base material is urea having the following composition,
It is immersed in, for example, 10 seconds in a first aqueous solution containing calcium ions and phosphate ions (hereinafter, referred to as “urea-containing aqueous solution”). Composition of urea-containing aqueous solution (example) Urea 0.5 mol / liter Ca (NO ₃ ) ₂ 0.167 mol / liter (NH ₄ ) ₂ HPO ₄ 0.100 mol / liter

Next, the titanium substrate is pulled up from the urea-containing aqueous solution, immersed in a second aqueous solution containing calcium ions and phosphate ions having the following composition, and kept at, for example, 50 ° C. for 14 days. Since this second aqueous solution has a so-called simulated body fluid composition, it is hereinafter referred to as a "simulated body fluid". Composition of simulated body fluid (example) Na ⁺ 142.0 × 10 ⁻³ mol / l K ⁺ 5.0 × 10 ⁻³ mol / l Ca ²⁺ 2.5 × 10 ⁻³ mol / l Mg ²⁺ 1.5 × 10 ^-3 mol / liter Cl ^- 147.8 × 10 ^-3 mol / l HCO ₃ ^- 4.2 × 10 ^-3 mol / l HPO ₄ ^2-1.0 × 10 ^-3 mol / l SO ₄ ^2- 0.5 × 10 ⁻³ mol / l Tris (human peroxymethyl) aminomethane 100 × 10 ⁻³ mol / l As a result, a hydroxyapatite film firmly adhered to the surface of the titanium base material is formed.

When the obtained hydroxyapatite-coated titanium substrate is examined by X-ray diffraction, it is particularly found that (100)
The generation of tabular hydroxyapatite crystals with developed (200) planes was remarkably observed. In addition, as a result of a tape method peel test, it was found that the hydroxyapatite film had extremely high bonding strength to the titanium substrate.

In the method of forming a hydroxyapatite film according to the present invention, the metal substrate heated in the range of 80 ° C. to 300 ° C. is contacted with calcium ions and phosphate ions in an aqueous solution in the presence of urea. Through the treatment step, a strong hydroxyapatite film is formed on the metal substrate. At this time, it was found that if the preheating temperature of the metal substrate was lower than 80 ° C., the hydroxyapatite film was not formed sufficiently. Preheating temperature is 300 ℃
If it exceeds, there is no problem in film formation, but the metal substrate may be deteriorated by oxidation or the like, and the strength may be reduced.

The urea concentration in the urea-containing aqueous solution is 0.05
It is preferable to be within the range of mol / liter to 2 mol / liter.
If it is less than 0.05 mol / liter, a hydroxyapatite film is not sufficiently formed on the metal substrate. A urea concentration exceeding 2 mol / liter is not preferable because not only does the film formation not increase, but urea may remain in the film.

The reason why a good hydroxyapatite film is formed by immersing a heated metal base material in an aqueous urea-containing solution is not clear, and the present invention is not limited by theory. When the metal substrate is immersed in a urea-containing aqueous solution, the urea in contact with the heated metal surface is decomposed into ammonia and carbonic acid, and the generated ammonia adjusts the pH of the contact interface to form hydroxyapatite nuclei on the metal surface. It is considered to have a promoting effect.

In the preferred embodiment of the present invention, the time for contacting the heated metal substrate with the aqueous urea-containing solution may be as short as about one second to several minutes. During this time, crystal nuclei are generated on the metal surface. Next, this is immersed in a simulated body fluid to grow hydroxyapatite crystals under mild conditions for a relatively long time. In this case, the simulated body fluid is preferably kept in the range of 30 ° C. to 60 ° C., and the crystal is grown for a relatively long time of several hours to several days, whereby the hydroxyapatite crystal grows in a plate shape. Entangled with each other on the metal surface to form a tough film.

[0013]

EXAMPLES (Example 1) Calcium nitrate 0.1 ml in 1 liter of water.
167 mol and 0.1 mol of ammonium monohydrogen phosphate were dissolved, and 0.5 mol of urea was added to the obtained aqueous solution (stock solution) to prepare a urea-containing aqueous solution. Diameter 14mm, thickness 1.
The surface of a 6 mm titanium base material is mirror-polished, heated to 200 ° C., immediately immersed in the above-mentioned urea-containing aqueous solution for 2 minutes, then kept in a simulated body fluid at 50 ° C. for 3 days, taken out, rinsed and dried, and the surface state is obtained. Was examined by X-ray diffraction. As a result of the inspection, as shown in FIG. 1, generation of hydroxyapatite crystals on the surface of titanium was recognized.

As a comparative example, an X-ray diffraction test was performed on a titanium base material of a comparative example obtained by treating in the same manner as in Example 1 except that the stock solution containing no urea was used.
Almost no hydroxyapatite crystals were formed on the surface of the titanium substrate. From these results, it was found that in the method of the present invention, the formation of the hydroxyapatite film on the surface of the metal substrate was promoted by bringing the heated metal substrate into contact with calcium ions and phosphate ions in the presence of urea. It is clear.

Example 2 The same titanium substrate as in Example 1 was heated to 80 ° C., 200 ° C., and 300 ° C., respectively.
For a sample obtained by immersing in a urea-containing aqueous solution for 5 seconds in the same manner as in Example 1 and then holding in a simulated body fluid at 50 ° C. for 3 days, the adhesion strength of the formed film was measured by a tape peeling method (1).
(0 division). In addition, the fixing strength of the deposited film was measured in the same manner in Comparative Examples in which the temperature at the time of immersing the titanium base material was 30 ° C. and 400 ° C. Table 1 shows the results.
The measurement result was represented by the number of peeled frames in 100 divisions.

[0016]

[Table 1]

The results of the tape peeling test showed that the comparative example in which the substrate heating temperature was 30 ° C. showed good adhesion strength except that the peeling was remarkable. However, in a bending strength test performed separately, a decrease in strength was observed in the comparative example in which the substrate was heated to 400 ° C. Therefore, as shown in Example 2, by setting the substrate temperature at the time of immersion in the range of 80 ° C. to 300 ° C., the hydroxyapatite-coated metal having excellent characteristics in both the film fixing strength and the physical properties of the metal substrate. It can be seen that a substrate is obtained.

Example 3 The same titanium substrate as in Example 1 was heated to 200 ° C., immersed in the same urea-containing aqueous solution as in Example 1 for 10 seconds, and immediately immersed in a simulated body fluid having the following composition. And kept at 50 ° C. for 14 days. Simulated body fluid composition Na ⁺ 142.0 × 10 ⁻³ mol / l K ⁺ 5.0 × 10 ⁻³ mol / l Ca ²⁺ 2.5 × 10 ⁻³ mol / l Mg ²⁺ 1.5 × 10 ⁻³ mol / liter Cl ^- 147.8 × 10 ^-3 mol / l _{^{HCO 3 - 4.2 × 10 -3 mol}} / l _{^{HPO 4 2- 1.0 × 10 -3 mol}} / liter SO ₄ ^2- 0.5 × 10 ⁻³ mol / l tris (human peroxymethyl) aminomethane 100 × 10 ⁻³ mol / l The obtained sample was subjected to X-ray diffraction, and the surface state was observed with a scanning electron microscope. An X-ray diffraction pattern is shown in FIG. 2 and a scanning electron micrograph is shown in FIG.

The X-ray diffraction diagram of FIG. 2 shows that the (100) and (200) planes of the hydroxyapatite crystal are particularly remarkably developed, and FIG. This shows a state in which flat hydroxyapatite crystals are developed and grown on the substrate surface.

[0020]

According to the method for forming a hydroxyapatite film of the present invention, a metal substrate heated to a temperature in the range of 80 ° C. to 300 ° C. is treated with calcium ions and phosphate ions in a first aqueous solution in the presence of urea. And then immersed in a second aqueous solution containing at least calcium ions and phosphate ions to precipitate hydroxyapatite on the surface of the metal substrate. , And a hydroxyapatite film having a high bonding strength to a metal substrate can be formed.

[Brief description of the drawings]

FIG. 1 is an X-ray diffraction diagram of a sample surface obtained according to one embodiment of the present invention.

FIG. 2 is an X-ray diffraction diagram of a sample surface obtained according to another embodiment of the present invention.

FIG. 3 is a scanning electron micrograph showing the fine structure of the surface and cross section of a sample obtained according to one embodiment of the present invention.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Akira Nozue 7-1 Kioicho, Chiyoda-ku, Tokyo Inside Sophia University Faculty of Science and Technology (72) Inventor Hiroyasu Takeuchi 1-297 Kitabukurocho, Omiya City, Saitama Prefecture Mitsubishi Materials Corporation Within the Research Institute

Claims (4)

[Claims] 1. A method for forming a hydroxyapatite film on a metal substrate used in a living body, comprising the steps of:
The metal substrate heated in the range of 00 ° C. is immersed in a first aqueous solution containing at least urea, calcium ions and phosphate ions, and then immersed in a second aqueous solution containing at least calcium ions and phosphate ions. And forming a hydroxyapatite film on the surface of the metal substrate. 2. The method for forming a hydroxyapatite film according to claim 1, wherein the metal substrate is titanium or a titanium alloy. 3. The concentration of urea in the first aqueous solution is set to 0.0
3. The method for forming a hydroxyapatite film according to claim 1, wherein the amount is in a range of 5 mol / liter to 2 mol / liter. 4. The method for forming a hydroxyapatite film according to claim 1, wherein the second aqueous solution is kept within a range of 30 ° C. to 60 ° C.