JPH04144566A - Production of bioactive hydroxyl apatite film - Google Patents

Abstract

PURPOSE:To allow the extremely uniform and easy coating of the entire surface of a base material by allowing the base material and powder glass consisting essentially of CaO and SiO2 to coexist and immersing the base material into water or an aq. soln. contg. the phosphorus ion to form the nuclei of hydroxyl apatite on the surface of the base material. CONSTITUTION:Alumina balls 2 are used for the base material and are fixed to an alumina substrate by a cyanoacrylate adhesive. After a prescribed amt. of an extra-pure(EP) grade reagent is measured, this reagent is mixed and melted to prepare a soln. This soln. is poured into a steel plate and is vitrified; thereafter, the glass is ground and the powder glass 4 is removed. The powder glass is immersed together with the base material into an aq. soln. having an ion concn. P(V) 1 until the powder glass is completely covered with the soln. The aq. soln. 5 is obtd. by measuring the prescribed amt. of the EP grade reagent and dissolving the same in ion exchange water. The hydroxyl apatite film is formed over the entire surface of the base material when the base material is immersed into the aq. soln. having the ion concn. and is taken out.

Description

[Detailed Description of the Invention] (Industrial Application Field) This invention is applicable to bone repair materials, implantable medical devices,
This field relates to methods for manufacturing materials used in living organisms, such as medical supplies and various artificial organs. More specifically, this invention relates to inorganic materials,
The present invention relates to a method for producing a bioactive hydroxyapatite film having a composition and structure similar to bone on the surfaces of all materials of various shapes used in living organisms, regardless of whether they are metal or organic materials.

(Prior art) Methods for coating base materials with hydroxyapatite include: ■ Plasma spraying method (Japanese Patent Laid-Open No. 62-3455
9zu Publication, JP-A-62-57548, JP-A-63
-1-60663 Publication) ■Method of applying (2) sintering a solution or compound containing Ca and P to the surface of the base material (Japanese Unexamined Patent Publications No. 62-231゜669, No. 63-24952) Publication, JP-A-63-
46165 Publication), C) MONOKUTOKU” Opening and Closing by Spackling Method 58 10
Publication No. 9049) 1, ■Funome spraying method (8 Ceramics Association 1988 1st Autumn Symposium Lecture Proceedings ip, p, 4)
01-402), ■The baking dimensions of glass frits are legally required (Proceedings of the 9th Biomaterials Society Conference (1987) 11.
6) ■Through electrophoresis (Japan Ceramics Association 1)
988 1st Autumn Symposium Lecture Proceedings p, p. 41
'? -418) was announced.

(Problem that the invention seeks to solve) Each technology presents the following problems.

■Plasma melting U'U method/F) Nome spraying method requires complicated and expensive equipment, is difficult to make a dense film, and because the raw material hydroxyapatite is melted at high temperature, it is difficult to use in vivo. The sputtering method requires complicated and expensive equipment, and once the raw material hydroxyapatite is heated to high energy
・As it decomposes, a film of apatite different from the apatite in the living body is formed. ■Sintering method" ()Glass frit method requires heat treatment at around 850 degrees Celsius, so it has high heat resistance. J2, which can only be applied to the base material, and also in this case, the raw material hydroxyl Abakui I is once heat-treated at a high temperature, so that it can be applied to the in vivo γ Bakui I.
- different types of apatite films are formed, -, etc. In the electrophoresis method, the base material itself is used as the electrode and 17.
[2 or not applicable, raw material ε,
Because bisintered apatite is used, an apatite film that is different from the apatite in the body is formed.

First, the inventors have previously discovered that apatite and wollastonite have biological activity that naturally forms strong chemical bonds in living organisms by precipitating them in glass.
Furthermore, we have developed a crystallized glass that maintains high mechanical strength over a long period of time. In the process of pursuing the factors governing this bioactivity, the inventors discovered that the factors present in ceramics made by sintering and glass crystallization methods play an important role when ceramics fuse with bone. When they are implanted into the body, they react with surrounding body fluids.1. newly generated f! on the surface. 'It is a similar apatite layer, and furthermore, this apatite layer is similar to that of human body fluids. The inventors discovered that Ca and Si eluted from crystallized glass play an extremely important role in the formation of this apatite layer.Based on these findings, the inventors developed various base materials. I (This invention was completed as a result of extensive research into forming an apatite layer similar to bone on the surface.

That is, 1. - The purpose of the invention is to provide inorganic materials, metallic materials,
A film of bioactive apatite similar to bone in living bodies can be coated uniformly and extremely easily on all base materials of various shapes, regardless of organic materials, without heat treatment. The present invention seeks to provide a method.

(Means for Solving the Problems) That is, the first invention provides a base material and at least CaO and 5
Coexistence with a powder glass containing iOp as a main component is performed by immersing it in water or an aqueous solution containing at least phosphorus ions (from J. This is a method for producing an activated hydroxyapatite film.

Further, the second invention is characterized in that, following this operation, the base material is further immersed in an aqueous solution in which an amount of hydroxyapatite component is dissolved near or exceeding the saturation concentration, thereby forming an apatite film. This is a method for producing a bioactive hydroxyapatite film.

(Function) The mechanism by which a bioactive hydroxyapatite film is produced by the method of the present invention is briefly explained below.

In other words, when powder glass is immersed in an aqueous solution, its constituent components Ca2", 5i (IV) ions (H
8iOs- is a typical ion) etc. are eluted. Here, 5i(IV) ions are adsorbed to the substrate and provide favorable sites for the formation of apatite nuclei, and Ca''+ ions increase the degree of supersaturation of apatite in the aqueous solution.The degree of supersaturation increases. An apatite nucleus is formed at the part where 5i(IV) ions are adsorbed.In other words, when forming a ring, the important point is that 5i(IV) ions are adsorbed on the base material.
V) Ions are adsorbed and the degree of supersaturation locally increases near the base material. In this case, C which increases the degree of supersaturation
Both a ``'' ions and 5i (TV) ions may be supplied from glass, or P(V) ions (HP O4'- is a typical ion) may be contained in an aqueous solution and then supplied from glass. Ca2'' ions may be supplied from.

After apatite nuclei are formed by such a mechanism, when carrying out the second invention next, the base material in which the apatite nuclei have been formed is treated with a hydroxyapatite component in an amount close to or exceeding the saturation concentration. The glass powder is further immersed in an aqueous solution in which the powdered glass is dissolved, but the above-mentioned powder glass is not needed here. If powder glass is allowed to coexist, apatite will grow on the surface of the powder glass, resulting in the negative effect of consuming Ca'' and P (V) ions in the aqueous solution.

Hereinafter, the structure of the method of the present invention will be explained in detail along with its operation.

In order to carry out the method of the present invention efficiently, it is preferable to limit the composition and particle size of the powder glass coexisting with the substrate, and the ion concentration, pH, and temperature of the aqueous solution in which the substrate is immersed, respectively, to predetermined ranges. .

First of all, a powder glass suitable for the purpose of the present invention must contain at least CaO and 5i02 as main components.

Examples are shown in Table 1. In the same table, samples 1 to 3 are powder glasses containing only CaO and 5iOz.

Samples 4 to 10 are powder glasses containing PzOs in addition to CaO and 5iOi. Sample 11 is a powder glass having the same composition as bioglass. Sample 12 is a powder glass having the same composition as the bioactive crystallized glass previously developed by the present inventors. Samples 13 to 24 mainly contain CaO and 5ins, and also contain Na, 101K20, MgO1P20s, Ca
It is a powder glass containing various amounts of Fs and the like. All of these have the ability to form hydroxyapatite nuclei on various substrates.

However, if we look at the blending ratio of CaO and 5ins, C
If aO is less than 20 mo1%, the nucleation ability of the powder glass becomes too small, and if it is more than 70 mo1%, it becomes difficult to obtain glass. Furthermore, if SiOs is less than 30 mo1%, it is difficult to obtain glass (and if SiOs is more than 80 mo1%, the hydroxyapatite nucleation ability of the powder glass becomes too small. Furthermore, in the total amount of powder glass, CaO and SiO The total of * is 65mo
If it is less than 1%, the hydroxyapatite nucleation ability of the powder glass is significantly reduced. Therefore, CaO is 20-70mo
1%, 5ift is 30-80mo1%, and CaO
It is preferable that the total of SiOz and SiOz is 65mol% or more.

In addition, when P3O6 is further included in CaO and 5ins glass, looking at the blending ratio of CaO, SiO2 and P, 0°, if P2O6 is less than 0.1 mo1%, the ability of the glass to form an apatite film is extremely small. ,2
If it exceeds 5 mo1%, the glass itself cannot be formed. Therefore, in this case, in the total amount of powder glass, C
aO is 20-70m01%, StO□ is 30-80m
01%, and the total of CaO and 5iOa is 65mo1%
This is the above, and P2O is preferably 0.1 to 25 mol%.

(Hereinafter, blank spaces) Table 1 Next, the particle size of the powder glass is shown.As the particle size of the powder decreases, the specific surface area increases1, and the activity increases. In this method, when powdered glass is immersed in an aqueous solution, the rate at which glass components dissolve into the aqueous solution increases as the particle size decreases. As shown in Table 2, the particle size of powder glass is 0.5
When it is less than μm, the elution rate of ions from the glass increases rapidly, and at the same time as the elution, an apatite film is formed on the surface of the powder glass to suppress further elution.1. Mau. As a result, the nucleation of apatite that should occur selectively on the base material surface is inhibited, and the coverage rate (nucleation part surface @ / base material surface @)
decreased 1. , it ends up. In addition, if the particle size exceeds 10,000 μm, the distance between the base material and the powder glass becomes uneven, and the degree of supersaturation of apatite near the base material surface does not increase uniformly, causing nucleation to occur only sparsely, resulting in a reduction in coverage. It will drop. Therefore, the particle size of powder glass is 0
．． It is preferably in the range of 5 to 10,000 μm.

(Hereinafter, blank space) Table 2 (Relationship between particle size and coverage of powder glass) Next, the aqueous solution suitable for apatite nucleation is as follows:
It consists of water or an aqueous solution containing at least phosphorus ions.

More specifically, the following three aqueous solutions can be used. That is, (1) it is an aqueous solution containing at least the main constituent components of apatite at a substantially saturated or supersaturated concentration.

The expression "substantially saturated concentration" herein refers to a concentration that is close to the saturated concentration and exhibits an effect substantially equivalent to that of the saturated concentration.

■It is unsaturated with respect to apatite, but phosphorus ion (P
It is an aqueous solution containing a large amount of (V) ).

(2) It is an aqueous solution that is unsaturated with water or apatite and does not contain more than a certain amount of calcium ions (C, 9+) and phosphorus ions (P (V) ).

The aqueous solutions (■-■) described in "-" are closely related to the components of the powder glass.

In other words, apatite can be nucleated by combining powdered glass containing CaO, . CaO,Si
The specific composition of the powder glass whose main component is CaO is 20 to 70 mo1%, and SiO is 3 (1").
At 80mo1%, the total of caO and S i02 is 65
Powder glass containing 1% or more of XIIO is used. In addition,
N a *, 0, K, 0, M g O,, P %lQ
, etc. may be used.

Regarding powder glass containing CaO, 5iOs, and P2O as main components, apatite nuclei can be formed in any of the aqueous solutions (1) to (2). The specific composition of powder glass whose main components are CaO, SiO□, P, O,
O is 20-70mo1%, 5tOW is 30-80mo
1%, the total of CaO and 5i02 is 65 mo1% or more, and P2O is 0.1 to 25 mo1%. In addition, various amounts of Na, Q, K, 01Mg0, etc. may be contained.

The composition of the aqueous solution is shown in Table 3, in which Sample 1 is ion-exchanged water. Samples 2 to 6 are aqueous solutions containing only p(v) ions. Samples 7 to 15 are aqueous solutions containing Ca''+ ions and p(v) ions. Samples 16 to 1
9 does not contain Ca2+ ions and p(v) ions, and contains Na”
, K+, Mg! +, Cl-HCO1-1S Oa''-, etc. Samples 20 to 34 contain Ca ion and P(V) ion, and in addition, Na'',
K+ is an aqueous solution containing various amounts of Mg*, Cl-1HCO8-1so, "-, etc. Composition 35 is an aqueous solution having an ion concentration approximately equal to that of human plasma. It has the ability to form the nucleus of hydroxyapatite.

To explain specifically about the aqueous solution (2), Ca! If Ca'+ or p(v) ions are less than 0.1mM, the nucleation ability is too small, and if Ca''+ or p(v) ions exceed 10mM or 50mM, respectively, hydroxyapatite will precipitate everywhere in the aqueous solution. , there is a tendency for no nucleation and crystal growth. Therefore, Ca"+ is 0.1 to 10
p(v) ions are contained in the range of 0.1 to 50 mM.

Important ions as solutes in aqueous solutions are Ca”+ and P(V)
ion, but other than that, Na"K+, Mg
2 +, Cl-1HCOs-1so, "-, etc. ions may be included. However, in order for the aqueous solution to maintain a stable ionic state over a long period of time, the composition of the simulated body fluid of composition 35 is most desirable.

To explain specifically about the aqueous solution (①), p (v)
If the ion concentration is less than 0.1mM, the nucleation ability is too small, and if it exceeds 5000mM, it does not exist as an ion. Therefore, Ca” is 0-0゜1 mM!, :,p
(v) Ions are contained in a range of 0.1 to 500mM. There are two important ions as solutes in aqueous solutions: Ca"+ and p(v) ions, but other ions include Na", K"Mg"Cl-1Ht o 5-1s
It may contain ions such as o and "-".

To explain specifically about the aqueous solution (①), Ca″+,
p (v) ions are respectively 0-0. It is contained in a range of 1mM.

In addition, when carrying out the second invention of the present invention, after forming apatite nuclei on the surface of the base material, the aqueous solution of By dipping, a uniform apatite film is formed.

(Hereinafter, in the margins) Next, there is the pH of the aqueous solution.It is known that hydroxyapatite is unstable in an acidic region and stably precipitates in a neutral or alkaline region. When forming hydroxyapatite nuclei using the method of the present invention, the pH of the aqueous solution generally differs during preparation and after immersion, as shown in Table 4=j, and the pH changes due to elution of powder glass components during immersion. It changes in the direction of becoming larger. In order to form the nucleus of hydroxyl abatai I, it is preferable that the pH becomes 7 or more -1- after immersion. For this purpose, it is preferable to adjust the pH to 5 or higher. Also,
When the pH at the time of adjustment exceeds 9, hydroxyapatite precipitates occur in the aqueous solution17, and selective nucleation on the surface of the substrate results in round lighting. Therefore, I) H of a suitable aqueous solution is 5
-9 range. 1. The pH of the liquid is in the weakly alkaline range from the time of adjustment until the completion of hydroxyl abatai I/nucleation, and it is preferable that there is almost no change. (2
011) 3CNH2) 50 ynM and hydrochloric acid (HCI)
Add a buffer such as 45 mM to the aqueous solution to bring the pH to 7.
It is effective to keep it at -9.

Next, the pH of the aqueous solution in which the apatite nucleus is formed and the base material is immersed is as shown in Table 4-2. If it is smaller, the nucleus may disappear. 1. Taga-)
and l) H of a suitable aqueous solution is in the range 6-9.

Part 4-] Table (Relationship between pH, nucleation, and film formation area (36.5°C)) Part 4
Table 2 (Relationship between pH and growth rate of hydroxyapatite film) Next is the temperature of the aqueous solution in which the base material and powder glass are immersed.The solubility of hydroxyapatite decreases as the temperature rises. It has been known. The key point of the method of the present invention is that CaO and S are added to water or an aqueous solution containing at least P (V) ions.
IO! Powdered glass containing J as a main component is immersed, and the degree of supersaturation of the aqueous solution with respect to apatite is gradually increased by elution of the powdered glass component. When the temperature of the aqueous solution is lowered, the solubility increases, that is, the degree of supersaturation decreases, and the amount of elution of the glass component decreases. As shown in Table 5-3, when the temperature is lower than 5°C, the nucleation region becomes rapidly smaller. Also, when the temperature is raised, the degree of supersaturation tends to increase, but 7
When the temperature exceeds 0°C, the phase of the film is no longer a single phase of hydroxyapatite. Therefore, the preferred temperature of the aqueous solution is 5 to 70°C.

Next, regarding the temperature of the aqueous solution in which the base material in which the apatite nucleus has been formed is immersed, as shown in Table 5-2, when the temperature is less than 5℃, the film growth rate decreases, and when it exceeds 70℃, the hydroxyapatite It is no longer single phase. Therefore, the preferred temperature of the aqueous solution is also 5 to 70°C.

Table 5-1 (Relationship between temperature of aqueous solution, nucleation region, and film phase) HAp:
Hydroxyapatite OCP diphosphate calcium CC:
Calcium carbonate hexahydrate Table 5-2 (Relationship between aqueous solution temperature, film growth rate, and film phase) (Effects) According to the method for producing a bioactive hydroxyapatite film according to the method of the present invention, inorganic materials and metals A bioactive apatite film similar to bone in living bodies can be uniformly and extremely easily applied to all base materials of various shapes, regardless of material or organic material, without heat treatment. Can be coated.

(Example) Hereinafter, the present invention will be explained according to examples.

Example 1 Alumina balls having various diameters shown in Table 6 were used as the base material. Alumina balls having a diameter of 0.5 mm or less were fixed to an alumina substrate using a cyanoacrylate adhesive. Next, special grade reagents such as calcium carbonate, silicon dioxide, and
Predetermined amounts of magnesium oxide, calcium pyrophosphate, and silicon fluoride were weighed and mixed, and melted at 1450°C for 2 hours.
The melt was poured onto an iron plate and vitrified. The obtained glass was crushed in an agate mortar and classified using a sieve to obtain powder glass having various particle sizes. Among them, particle size 30
Weigh out 50 g of powder glass with a diameter of ~50 μm and place it together with the base material in 2000 ml of an aqueous solution having the ion concentration shown in Sample 35 in Table 3 so that the powder glass completely covers the surface of the base material as shown in Figure 1. and immersed at 36.5°C. In FIG. 1, 1 is a container, 2 is an alumina ball, 3 is an alumina substrate, 4 is powder glass, 5 is an aqueous solution, and 6 is a lid. The aqueous solution contains special grade reagents sodium chloride, sodium hydrogen carbonate, potassium chloride, dipotassium hydrogen phosphate trihydrate, magnesium chloride hexahydrate, calcium chloride,
A predetermined amount of sodium sulfate was weighed and dissolved in ion-exchanged water. 50mM of trishydroxymethylaminomethane and 45mM of hydrochloric acid were added as a buffer to adjust the pH to 7.25.
I kept it.

Two days later, the base material was taken out, and the base material alone was further immersed at 45°C in 2000 ml of an aqueous solution having the same ion concentration as Sample 35 in Table 3. When the substrate was taken out after 2, 4 and 6 days of immersion, the film thickness was 5, 10 and 15, respectively, in proportion to the number of days of immersion.
A μm-thick hydroxyapatite film was formed on the entire surface of the base material.

Table 6 Diameter of alumina ball as base material (mm) Example 2
゜An alumina ball with a diameter of 2 mm, which is the same as in Example 1, was placed in 5 g of powdered glass with a particle size of 5 to 10 μm having the composition of samples j and j in Table 1, as shown in Figure 2, lightly so as not to be buried. The sample was placed on the substrate and immersed in 20 Oynl of an aqueous solution having an ion concentration of Sample 33 in Table 3 at 30° C. for 2 days. In FIG. 2, J is a container, 2 is an alumina ball, 4 is a powder glass, 5 is an aqueous solution, and 6 is a lid. Powder glass is Example 1
．． It was prepared in the same manner as in Example 1, using the special grade reagent sulfur and lithium carbonate in addition to the reagent used in Example 1. After immersion, take out the alumina ball and prepare it as Sample 3 in Table 3.
It was further immersed in 50 ml of an aqueous solution having an ion concentration of 4 at 50°C. The aqueous solution is prepared by weighing the specified amounts of special grade reagents calcium hydroxide, calcium dihydrogen phosphate, sodium bicarbonate, magnesium chloride, thorium chloride, and potassium chloride and dissolving them in ion-exchanged water.1. Created again. In addition, 1-lishydroxymethylaminomethane and hydrochloric acid were added as Mtfai agents to the aqueous solution, and the pH was maintained at 7.25. When immersed for 2 days, it came into contact with the powder glass during the first immersion. An apatite film with a W width of about 5 μm was obtained on the entire surface of the alumina ball, regardless of whether it was visible or not.

Example 3 The alumina balls with a diameter of 0.5 mm used in Example] were mixed with 5 g of powder glass having the composition of Sample 17 in Table 1 with a particle size of 20 to 40 μm and a nylon mesh with an opening of 200 μm and a thickness of 100 μm. The specimens were then immersed in an aqueous solution 2001+111 having the ion concentration of Sample 22 in Table 3 at 40°C for 2 days. Powder glass is Example '36
．． In addition to the reagent used in Example 1, calcium carbonate, which is a special grade reagent, was used. Created using the same method. After soaking,
The alumina balls were taken out, and only the alumina balls were further immersed at 40° C. in an aqueous solution 200F111 having an ion concentration of Sample 33 in Table 3 as shown in FIG. In FIG. 3, 1 is a container, 2 is an alumina ball, 4 is a powder glass, 5 is an aqueous solution, 6 is a lid, and 7 is a nylon mesh. The aqueous solution was the same as in Example J1 with the addition of a special grade reagent, sodium hydrogen phosphate, and was prepared by weighing a predetermined amount and dissolving it in ion-exchanged water. In addition, trishydroxymethylaminomethane and hydrochloric acid were added to the aqueous solution after buffering, and the pH was maintained at 7.25. 6
After being immersed for several days, an apatite film having a thickness of approximately 5 μm was obtained uniformly over the entire surface of the alumina ball.

Example 4゜Alumina fibers, glass fibers, nylon threads, and stainless steel wires (hereinafter referred to as fibers) each having a length of 5 cm and having various diameters shown in Table 7 were 10=20
sample of Table 3 as shown in FIG.
It was immersed in 3000o+1 ion-exchanged water at 36°5°C. In Figure 4, 1 is a container, 4 is powder glass, 5 is an aqueous solution, 6 is a lid, 8 is alumina fiber, glass fiber, nylon thread among fibers, and 9 is stainless steel wire among fibers. It is.

After 2 days, take out the fiber and add only the fiber for 2 more times.
day, aqueous solution 3 having an ion concentration of sample 32 in Table 3
It was further immersed in 0θ0rni at 3665°C. The powder glass was prepared in Example 3. The reagents used in Example]. Created in the same way as 17. In addition, the aqueous solution was prepared in Example 1. [Also] was prepared in the same manner as in Example 1 using the reagent used in Example 1 with the addition of the special R reagent sodium hydrogen phosphate. Note that the ion-exchanged water and aqueous solution were as described in Example 1. Similarly, p
It was maintained at H7°25. 2 As a result, a hydroxyapatite film with a crotch thickness of about 5 μm was formed on the entire surface of all fibers.

Table 7 (Diameters of fibers in base material (in order)) Example 5 Alumina poles having various diameters shown in Table 6 were used as base materials. Alumina balls having a diameter of 0.5 mm or less were fixed to an alumina substrate using a cyanoacrylate adhesive. Next, predetermined amounts of calcium carbonate and silicon dioxide, which are special grade reagents, were weighed and mixed to obtain powder glass having the composition shown in Sample 1 in Table 1, and melted at 1600°C for 2 hours. 1. Powdered glass was created using the same method. Weigh out 50 g of powdered glass with a particle size of 30 to 50 μm, add it to 2000 ml of an aqueous solution having the ion concentration shown in Sample 35 in Table 3, and place it together with the base material. 36.
Immersed at 5°C. After 2 days, the base material was removed and only the base material was further treated with an aqueous solution 20 having an ion concentration of Sample 31 in Table 8.
00ml at 45°C. The aqueous solution was prepared in Example 1. It was prepared in a similar manner using the same reagents. Also, the pH is 7
The temperature was kept at 25°. When the substrate was taken out after 2.4.6 days of immersion, the film thickness was 5.10.1 in proportion to the number of days of immersion.
A 5 μm hydroxyapatite film was formed on the entire surface of the base material.

Example 6 Alumina balls with a diameter of 2 mm as in Example 5 were mixed with powder glass 5 having a particle size of 5 to 10 μm and having the composition of Sample 2 in Table 1.
Lightly place the aqueous solution 200 having the ion concentration of Sample 12 in Table 3 on top of g as shown in Figure 2 so as not to bury it.
ml for 2 days at 30'C. After immersion, the alumina balls were taken out and further immersed in 50 ml of an aqueous solution having an ion concentration of Sample 30 in Table 8 at 50°C.

The powder glass was prepared in Example 5. It was made using the same reagents and method.

The aqueous solution is Example 1. It was prepared in the same manner by adding ammonium hydrogen phosphate and sodium hydrogen phosphate to the same reagent. Further, the pH was maintained at 7.25. When immersed for 2 days, an apatite film with a thickness of approximately 5 μm was obtained on the entire surface of the alumina ball, regardless of whether the ball was in contact with the powder glass during the first immersion or not.

Example 7 The alumina balls with a diameter of 0.5 mm used in Example 5 were mixed with 5 g of powder glass having the composition of Sample 14 in Table 1 and having a particle size of 20 to 40 μm and a nylon mesh with an opening of 200 μm and a thickness of 100 μm. The specimens were placed facing each other and immersed in 200 ml of an aqueous solution having the ion concentration of Sample 8 in Table 3 at 40° C. for 2 days. After immersion, the alumina balls were taken out, and only the alumina balls were prepared as sample 2 in Table 3, as shown in Figure 3.
It was further immersed in 200 ml of an aqueous solution having an ion concentration of 9 at 40°C. The powder glass was prepared in Example 1. It was prepared in the same manner by adding sodium carbonate to the reagent. In addition, the aqueous solution was prepared in Example 1. and 6. It was prepared in the same manner using the same reagents. The pH was also maintained at 7.25. After 6 days of immersion, an apatite film with a thickness of about 5 μm was obtained uniformly over the entire surface of the alumina ball.

Example 8 Alumina fibers, glass fibers, nylon threads, and stainless steel wires with a length of 5 cm having various diameters shown in Table 7 were prepared with a particle size of 10 to 20 μm, Sample 19 in Table 1.
Along with 50 g of powdered glass having the composition of
1 at 36.5°C. After 2 days, the fiber was taken out and the fiber alone was further immersed for 2 days in 3000 ml of an aqueous solution having the ion concentration of Sample 28 in Table 3 at 36.5°C. The powder glass was prepared in Example 1. It was prepared in the same manner using the same reagent as above with addition of sodium carbonate and potassium carbonate. The aqueous solution was prepared in the same manner as in Example 1, using the same reagents plus ammonium phosphate and sodium hydrogen phosphate. As a result, the film thickness was 5μ
A hydroxyapatite film of m was formed on the entire surface of all fibers.

[Brief explanation of the drawing]

1 to 4 are schematic cross-sectional views of an apparatus for carrying out the method of the invention. 1 is a container, 2 is an alumina ball, 4 is a powder glass, 5 is an aqueous solution, and 6 is a lid.

Claims (6)

[Claims] (1) Forming hydroxyapatite nuclei on the surface of the substrate by making the substrate coexist with powder glass containing at least CaO and SiO_2 and immersing it in water or an aqueous solution containing at least phosphorus ions. A method for producing a bioactive hydroxyapatite film characterized by: (2) Bioactivity characterized by forming an apatite film by further immersing the base material in an aqueous solution in which a hydroxyapatite component is dissolved at a substantially saturated or supersaturated concentration following the operation of claim (1). A method for producing a hydroxyapatite film. (3) The particle size of the powder glass is 0.5 to 10,000 μm
The method for producing a bioactive hydroxyapatite film according to claim (1), which falls within the scope of the following. (4) Claim (1) wherein the aqueous solution has a pH range of 5 to 9.
) The method for producing a bioactive hydroxyapatite film. (5) Claim (2) wherein the aqueous solution has a pH range of 6 to 9.
) The method for producing a bioactive hydroxyapatite film. (6) The method for producing a bioactive hydroxyapatite film according to claim (1) or (2), wherein the aqueous solution has a temperature range of 5 to 70°C.