JPH01168872A - Formation of hydroxyapatite coating film - Google Patents

Abstract

PURPOSE:To easily form a hydroxyapatite coating film having high bonding strength even on a substrate having a complex surface shape by coating the substrate with hydrosol prepd. by mixing an aq. Ca(OH)2 soln. with an aq. phosphoric acid soln. in the presence of protective colloid, drying the hydrosol and making the resulting film insoluble. CONSTITUTION:An aq. Ca(OH)2 soln. is mixed with an aq. phosphoric acid soln. in 1.50-2.0atomic ratio of Ca to P in the presence of protective colloid such as gelatin to prepare hydrosol. A substrate such as a metal or glass substrate is coated with the hydrosol by application, dipping or other conventional method and the hydrosol is dried. The resulting film is made insoluble by calcining under proper conditions or other method to form a hard hydroxyapatite coating film. This coating film having high bonding strength can easily be formed on the substrate having a complex surface shape or a large area at a high rate of film formation.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a method for forming a hydroxyapatite film on the surface of a substrate.

[Conventional technology]

Since hydroxyapatite has excellent biocompatibility and high adsorption capacity, various applications have been investigated. In particular, active research is being carried out on its use as an implant material for the replacement or repair of biological hard tissues. Implant materials are required to have biomechanical strength in addition to biocompatibility. However, hydroxyapatite itself is insufficient in strength even in a sintered body. Therefore metallic materials,
The most promising method for practical use is to form a hydroxyapatite film on the surface of a substrate or core material such as ceramics or glass.

Various methods have been proposed so far for forming hydroxyapatite films. For example, JP-A-5
No. 2-82893 describes a plasma spraying method,
-109049 publication describes the sputtering method,
9-111753 discloses PVD and CVD methods, JP-A-53-128190 discloses electrophoresis method, JP-A-53-128190 describes
JP-A-118411 discloses each coating method.

[Problem that the invention seeks to solve]

However, plasma spraying, sputtering, CVD
In the method and PVD method, it is difficult to form a film on the surface of a substrate with a complex shape, such as inside a porous body, and in the electrophoresis method, it is difficult to form a film on a substrate that is non-conductive. have. The coating method is easy to operate, and JP-A-53-118411 discloses a method in which fine powder of apatite is suspended in water, and this suspension is coated on the surface of a substrate and fired. However, it is generally difficult to make fine powder into finer particles, agglomerated particles are likely to exist, and the size of the dispersed particles is generally 0.
Because the thickness is 1 μm or more, the adhesion strength of apatite to the substrate surface is weak (and it is easily peeled off).

Measures for Solving Problems] In view of the above circumstances, the present inventors have determined that in order to form a film with high adhesion strength by the coating method, the film thickness should be 1 to 2 μm or less without cracking, and the film should be resistant to agglomeration. As a result of intensive study based on the idea that it is important to apply fine particles in a dispersed state, the present invention was completed by discovering that a good hydroxyapatite film could be formed by using a hydrosol.

That is, in the present invention, a calcium hydroxide aqueous solution and a phosphoric acid aqueous solution are mixed with Ca/P=1.50 to 2.0 in the presence of a protective colloid.
The present invention provides a method for forming a hydroxyapatite film, which comprises coating a substrate with a hydrosol mixed and adjusted at a ratio of 0 (atomic ratio), followed by drying and insolubilization treatment.

The present invention will be explained in detail below.

Hydrosol herein refers to a colloid that uses water as a dispersion medium, and has smaller dispersed particles compared to emulsions and suspensions. Generally, the size of colloid particles is 0.
It is 1 to 0.001 μm.

Regarding the general preparation method of hydroxyapatite hydrosol, please refer to the following document:
h der Anorganischen Che+w
ie) No. 28 to B-3, 1158-1159 (1
961) discloses the following three methods.

(2) A precipitate formed by mixing an aqueous phosphoric acid solution and an aqueous calcium hydroxide solution is stirred with the mother liquor to produce a hydrosol of hydroxyapatite.

■ Phosphate aqueous solution and calcium salt aqueous solution Ca/P=1
．． A hydrosol of hydroxyapatite is produced by double decomposing a precipitate of tricalcium phosphate produced by mixing at a ratio of 50% to 0.0016N at a concentration of o,oos to 0.0016N.

■Produce a hydrosol of hydroxyapatite from calcium phosphate, which is produced when a trisodium phosphate solution is added to a calcium chloride solution in the presence of gelatin. However, this depends on the concentrations of calcium phosphate and gelatin.

However, according to experiments conducted by the present inventors, the precipitate produced without the addition of a protective colloid such as gelatin did not turn into a sol even with continued stirring, making it impossible to reproduce the above methods ① and ②. . In addition, although the method (2) produces a hydrosol, sodium chloride is produced as a by-product, and since the crystals of sodium chloride are large, when this hydrosol is coated on a substrate, etc., it adversely affects the properties of the film, which is not preferable.

The hydrosol in the present invention is prepared by mixing a calcium hydroxide aqueous solution and a phosphoric acid aqueous solution in the presence of a protective colloid with Ca/P=1.
They are mixed and adjusted at a ratio of 50 to 2.0 (hereinafter referred to as atomic ratio). Especially the Ca/P ratio is 1.50-1.67
A range of is preferred.

When Ca/P is less than 1.50, calcium diphosphate is produced and hydroxyapatite is not produced, and when it exceeds 2.0, calcium hydroxide remains too much and the proportion of hydroxyapatite produced is slightly unfavorable. .

When a calcium hydroxide aqueous solution and a phosphoric acid aqueous solution are mixed in the range of Ca/P=1.50 to 1.67, the pH of the mother liquor ultimately changes to 6 to 8. On the other hand, Ca/P=1.6
If it exceeds 7, unreacted calcium hydroxide will remain in the mother liquor, and the pH of the mother liquor will be 8 to 11 even after the reaction is completed. In this case, it may be neutralized with an acid if necessary.

If an aqueous calcium hydroxide solution and an aqueous phosphoric acid solution are mixed with Ca no P in the range of 1.50 to 1.67, the calcium phosphate produced remains in the mother liquor at the beginning of the reaction. If this is kept under stirring or without stirring, the calcium hydroxide in the mother liquor will be gradually consumed, the Ca/P value of calcium phosphate will increase, and the pl() in the mother liquor will decrease.

When the pH reaches 6-8, most of the calcium hydroxide is consumed and the metathesis reaction is terminated. At this time, the Ca/P ratio of calcium phosphate is equal to the mixing ratio of the raw materials. Furthermore, analysis of the powder recovered from the mother liquor and air-dried by powder X-ray diffraction revealed that it contained low-crystalline hydroxyapatite.

Calcium hydroxide used in the present invention may be produced by a conventional method and is not particularly limited, and the concentration of the aqueous solution is not particularly limited as long as it is below the solubility of calcium hydroxide. However, it is desirable that the solubility be approximately 1/100 or more so that the thickness of the formed film does not become too thin.

Further, the phosphoric acid used in the present invention may be produced by a conventional method and is not particularly limited.The concentration in the aqueous solution is also not particularly limited, but is the same as the concentration of calcium hydroxide. It is preferable to set it as a standard.

Common protective colloids used in the present invention include gelatin, albumin, gum arabic, protalbic acid, and resalbic acid. It can be dissolved in either or both of an aqueous calcium hydroxide solution and an aqueous phosphoric acid solution.

The concentration of the protective colloid is preferably 0.5 to 10 times the weight of the hydroxyapatite to be produced.
If the amount is more than 0 times, the concentration of hydroxyapatite in the film is diluted, making it difficult to form a continuous hydroxyapatite layer, and if the amount is less than 0.5 times, the effect of the protective colloid is small and the formation of hydrosol is inhibited. I don't like it because it's difficult.

Next, as a method for coating a substrate with the hydrosol obtained according to the present invention, conventional methods such as coating, spraying, and dipping can be employed.

The substrate to be used may be metal, ceramics, glass, etc., but it is difficult to apply this method to hydrophobic materials such as plastics, so it is preferable to surface-treat the surface to make it hydrophilic.

The present invention is particularly applicable to substrates whose surfaces have an ixm shape. For example, it can be applied to an implant material whose surface is made porous.

Such implant materials include metals such as titanium alloys, ceramics such as alumina, and glasses such as bioglass.

The hydrosol coated on the substrate is dried and further subjected to an insolubilization treatment.

This insolubilization is a necessary treatment to make the hydroxyapatite film stronger. Specific insolubilization treatments include a method of producing a stable and strong film by coating or spraying an insolubilizing agent such as a crosslinking agent, such as formaldehyde, glutaraldehyde, tannic acid, etc. on the film, and a method of manufacturing a stable and strong film by baking to remove the protective colloid. There is a method that uses only a strong film. When firing is performed as an insolubilization treatment, a protective colloid that does not produce a firing residue may be selected.

The firing conditions may be determined by considering the burnout temperature of the protective colloid used and the heat resistance temperature of the substrate. However, since hydroxyapatite undergoes significant thermal decomposition at temperatures above 1200°C, it is desirable to keep the temperature below this temperature.

〔Effect of the invention〕

According to the present invention, the adhesion strength of the film is stronger than that of conventional coating methods, and it is also possible to easily form a hydroxyapatite film even on a substrate with a complicated surface shape. It is a fast and inexpensive method that can form a film, and the obtained substrate can be used for various purposes, and is particularly useful as an implant material, an interlocking separation material, and a catalyst.

(Examples) The present invention will be described below with reference to Examples, but the present invention is not limited thereto.

Note that % used in the examples represents weight %.

Example 1 1.0 g of purified gelatin was dissolved in 500 g of 0.055% calcium hydroxide aqueous solution, and 0.0 g of purified gelatin was dissolved in the solution without stirring.
365 g of 60% phosphoric acid aqueous solution was added over 4 minutes. (C
a/P-1,66) At this time, the liquid 91 (was initially 12.3
When this liquid was allowed to stand still for 7 days, p)I decreased to 8.0. As a result, a hydrosol was produced without any precipitate.

A portion of this hydrosol was taken out, and sodium sulfate as a flocculant was added thereto to flocculate it, which was then filtered. When the resulting slurry was air-dried and subjected to powder X-ray diffraction, it was found to be hydroxyapatite with low crystallinity as shown in FIG.

Base: N25III11, width 25mm, depth ll1
Vertical 40 II 111 horizontal 40 III 11 with 11 recesses
1 Alumina dense sintered body with a thickness of 5a++w (purity 99.9
%) was prepared in which alumina beads having a diameter of 1 m11 were bonded in a layer in a recess.

The above-mentioned hydrosol was injected until the inside of the recessed part of the base body was completely filled, and then air-dried and fired. The firing conditions range from room temperature to 8
The temperature was raised to 00°C at a rate of 100°C/Hr and held at 800°C for 1 hour.

The film after firing was shiny and had interference fringes.

As a result of measuring the thickness of the film with a film thickness meter, the thickness was approximately 0.
．． It was 3 μm.

The obtained substrate was immersed in physiological saline for one week, but the film remained strong without any change.

Example 2 Ca/P = Ca/P =
A hydrosol of 1.50 was prepared. The pH at the time of preparation initially decreased from 12.3 to 10.8, and when this solution was allowed to stand for 7 days, the pu decreased to 8.0. As a result, a hydrosol was produced without any precipitate.

When this hydrosol was confirmed in the same manner as in Example 1, it was found to be hydroxyapatite with low crystallinity.

The base material was an alumina substrate with surface roughness Ra = 0.05 μm (purity 99.9%, length 10 mm, width 10 mm, thickness 0.
hm) washed with acetone was prepared.

The above hydrosol was dropped onto the surface of this alumina substrate to form a liquid film with a thickness of 111 Im. Thereafter, it was air-dried and fired in the same manner and under the same conditions as in Example 1.

The film after firing was glossy and had interference fringes, similar to the example work.

As a result of measuring the thickness of the film with a film thickness meter, the thickness was approximately 0.
．． It was 3 μm.

The obtained substrate was immersed in physiological saline for one week in the same manner as in Example 1, but the film remained strong without any change.

Example 3 Using the same hydrosol and alumina dense sintered body as in Example 1, the hydrosol was injected into the recesses of the sintered body and air-dried in the same manner as in Example 1.

Subsequently, the sintered body was immersed in a 5% glutaraldehyde solution for 20 hours to be insolubilized.

The sintered body was immersed in physiological saline for one week in the same manner as in Example 1, but the film remained strong without any change.

Example 4 A titanium plate (J
Type I52, length 1011111, width 10mm, thickness 1mm
) was prepared by washing it with acetone.

The hydrosol used in Example 1 was dropped onto the surface of the titanium plate to form a liquid film with a thickness of 11 mm. Thereafter, it was air-dried and fired in the same manner and under the same conditions as in Example 1.

The film after firing was glossy and had interference fringes as in Example 1.

As a result of measuring the thickness of the film with a film thickness meter, the thickness was approximately 0.
．． It was 3 μm.

The obtained titanium plate was immersed in physiological saline for one week in the same manner as in Example 1, but the film remained strong without any change.

Comparative Example 1 Ammonium diphosphate aqueous solution and calcium nitrate water? g
When 0.50 g of hydroxyapatite (unfired product) prepared by mixing Wl was added to 1000 g of a 0.1% gelatin aqueous solution and stirred, all of the mixture precipitated after one day. This was stirred again and the suspension was filled into the recesses of the same dense alumina sintered body as in Example 1, and air-dried to form a white film. Subsequently, the film was fired under the same firing conditions as in Example 1, but the resulting film peeled off easily when touched.

Comparative Example 2 When a calcium hydroxide aqueous solution and a phosphoric acid aqueous solution were mixed in the same concentration and amount as in Example 1 except that they were not in the presence of gelatin, the change in pH was the same, but immediately after mixing, a precipitate was formed and a hydrosol was formed. There was no.

The obtained precipitate was collected by filtration, air-dried, and subjected to powder X-ray diffraction, which showed a pattern exactly similar to that shown in FIG. 1, indicating that it was hydroxyapatite with low crystallinity.

The alumina dense sintered body used in Example 1 was used as a base, and the precipitate was filled into the recesses of the sintered body, and then air-dried and fired in the same manner and under the same conditions as in Example 1.

The resulting film peeled off easily when touched.

Comparative Example 3 The same material as Example 1 was used except that 434 g of 0.060% phosphoric acid aqueous solution was used, and Ca/P-
A hydrosol of 1,40 was prepared. A portion of this hydrosol was collected by adding sodium sulfate as a flocculant to flocculate it and filtering it out. After air-drying the obtained slurry, powder X-ray diffraction was performed in the same manner as in Example 1, and the result showed that it was a mixture of low-crystalline hydroxyapatite and calcium diphosphate.

Comparative Example 4 The same material as Example 1 was used except that 243 g of 0.060% phosphoric acid aqueous solution was used, and Ca/P=
A hydrosol of 2.50% was prepared. A portion of this hydrosol was collected by adding sodium sulfate as a flocculant to flocculate it and filtering it out. After air-drying the obtained slurry, powder X-ray diffraction was performed in the same manner as in Example 1, and the result showed that it was a mixture of low-crystalline hydroxyapatite and low-crystalline calcium hydroxide.

[Brief explanation of the drawing]

FIG. 1 shows a powder X-ray diffraction pattern after the hydrosol obtained according to the present invention was aggregated, filtered, and air-dried. Procedural amendment (voluntary) 1. Indication of the case 1988 Patent Application No. 327727 2. Name of the invention Method for forming a hydroxyapatite film 3. Person making the amendment Relationship to the case Patent applicant address 5 Kitahama, Higashi-ku, Osaka 15-chome name (
209) Sumitomo Chemical Co., Ltd. Representative: Hideo Mori 4, Agent address: 5-15-5 Kitahama, Higashi-ku, Osaka City, “Detailed description of the invention” column 6 of the specification subject to the amendment, Contents of the amendment (1) ) In the 7th line of page 3 of the specification, ``It is 0.16 m or more'' is corrected to ``It is more than 0.5 μm.'' (2) Change “Done” on page 5, line 12 of the specification to “
It was difficult. ” he corrected. that's all

Claims (1)

[Claims] A substrate is coated with a hydrosol prepared by mixing an aqueous calcium hydroxide solution and an aqueous phosphoric acid solution at a ratio of Ca/P=1.50 to 2.0 (atomic ratio) in the presence of a protective colloid, and then dried and insolubilized. A method for forming a hydroxyapatite film characterized by