JP2000093498A - Bone substitution material and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To impart bioaffinity which may be obtd. by a simple method equivalent to the case of an alkali treatment and heat treatment method (a method for subjecting the surface of titanium or titanium alloy to an alkali treatment, then to a heat treatment) and is better than in the case of the alkali treatment and heat treatment method to a base body consisting or titanium on titanium alloy. SOLUTION: This bone substitution material has the base body consisting of the titanium or titanium alloy and an amorphous alkali titanate layer formed on the surface of the base body. The alkali titanate layer contains calcium and the concn. of the calcium is 5 to 20 atm.% on the extreme surface of the alkali titanate layer. The alkali titanate layer has a thickness of 0.3 to 5 μm and has a three-dimensional network structure.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention belongs to the technical field of a bone substitute material and a method for producing the same, and more specifically, a bone substitute material using titanium or a titanium alloy as a base material (substrate) and a method for producing the same. In particular, the present invention belongs to a technical field related to a technique for imparting biocompatibility to a substrate made of titanium or a titanium alloy.

[0002]

2. Description of the Related Art Since titanium and titanium alloys have excellent mechanical properties, have corrosion resistance to body fluids, and have extremely low toxicity to living organisms, titanium and titanium alloys have been used as metals for bone substitute materials. ing. However, titanium and titanium alloy have a problem that affinity with living bone is low. That is, the bone substitute material is required to have biocompatibility to directly bond with living bone, but titanium and titanium alloy have a low affinity for living bone and require a long time to bond with living bone. is there.

[0003] The condition for titanium and titanium alloy to show affinity for living bone is to form a hydroxyapatite (hereinafter referred to as HAP) layer which is a main component of bone on the surface.
The role of HAP in affinity for living bone is essential. That is, HAP has excellent biocompatibility and has the property of directly binding to living bone.

[0004] As technology utilizing the characteristics of such HAP,
A technique of coating titanium or a titanium alloy with a material having biocompatibility including HAP and thereby imparting affinity to living bone (hereinafter referred to as a biocompatible material coating method) has been proposed.

[0005] However, in such a biocompatible material coating method, it is difficult to increase the bonding strength between the coating layer and the underlying metal. Further, there is a problem in that a processing process becomes complicated and an expensive apparatus is required to form a highly reliable coating layer, so that the manufacturing cost is increased.

Studies have been made for the purpose of solving such a problem, and as a result, a simple method of treating the surface of a substrate made of titanium or a titanium alloy with an aqueous alkali solution and then performing a heat treatment (hereinafter referred to as an alkali treatment / treatment). It has been found that the biocompatibility can be imparted by the heat treatment method), and is described in Kim et al., J. Biomed. Mater. Res, vol.
2, P409-417 (1996) "and Japanese Patent Publication No. 7-813100 (republished patent publication).

[0007]

[Problems to be Solved by the Invention]
The method described in Japanese Patent No. 3100 (alkaline treatment / heat treatment method) can provide biocompatibility more easily than the biocompatible material coating method. However, the bone replacement material obtained by this alkali treatment / heat treatment method has a lower HAP forming ability on the surface than the bone replacement material obtained by the biocompatible material coating method,
Biocompatibility, that is, affinity with living bone is not sufficient.

The present invention has been made in view of such circumstances, and its object is to make it as simple and easy as in the case of the alkali treatment / heat treatment method. An object of the present invention is to make it possible to impart a better biocompatibility to a substrate made of titanium or a titanium alloy. That is, it is a bone substitute material using titanium or a titanium alloy as a base (substrate) of a constituent material, and can be obtained by a method as simple as the alkali treatment / heat treatment method. An object of the present invention is to provide a bone substitute material having a higher HAP forming ability on the surface than that of a bone substitute material obtained by a heat treatment method and having excellent biocompatibility, and a method for producing the same.

[0009]

In order to achieve the above-mentioned object, a bone substitute material and a method for producing the same according to the present invention are described as the bone substitute material according to claims 1 and 2, and the bone substitute material according to claims 3 to 5. A method for manufacturing an alternative material is as follows.

That is, the bone substitute material according to the first aspect is a bone substitute material comprising a base made of titanium or a titanium alloy, and an amorphous alkali titanate layer formed on the surface of the base. The alkali titanate layer contains calcium, the calcium concentration is 5 to 20 atomic% at the outermost surface of the alkali titanate layer, and the alkali titanate layer has a thickness of 0.3 μm. It is a bone substitute material having a size of super 5 μm or less and having a three-dimensional network structure (first invention).

[0011] In the bone substitute material according to the second aspect, the scratch strength of the alkali titanate layer is 10 gf or more.
(A second invention).

[0012] The method for producing a bone substitute material according to claim 3 is as follows.
A substrate made of titanium or a titanium alloy is immersed in an aqueous solution of sodium hydroxide or potassium hydroxide, and then immersed in one type of aqueous solution selected from an aqueous solution of calcium hydroxide, an aqueous solution of calcium phosphate, and an aqueous solution of calcium nitrate. This is a method for producing a bone substitute material to be replaced (third invention).

[0013] The method for producing a bone substitute material according to claim 4 is as follows.
4. The method for producing a bone substitute material according to claim 3, wherein the one selected aqueous solution is a calcium hydroxide aqueous solution (a fourth invention). The method for producing a bone substitute material according to claim 5, wherein the substrate is immersed in an aqueous solution of sodium hydroxide or potassium hydroxide, before immersion in the aqueous solution of the selected one, or in the selected aqueous solution. The method according to claim 3 or 4, wherein the substrate is heated at 400 to 800 ° C after being immersed in one kind of aqueous solution (fifth invention).

[0014]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention is embodied, for example, in the following modes. After cleaning and drying a substrate made of titanium or a titanium alloy having a required shape and size, the substrate is immersed in an aqueous solution of sodium hydroxide or potassium hydroxide. For example, 60 ° C
Immersed in a 5 M (molar concentration) aqueous sodium hydroxide solution held for 24 hours. Then, an amorphous alkali titanate layer having a three-dimensional network structure is formed on the surface of the substrate. At this time, the thickness of the alkali titanate layer is 0.3
It should be more than 5 μm and less than 1 μm, for example.

Next, after washing the substrate after the immersion, the substrate is immersed in one kind of aqueous solution selected from an aqueous solution of calcium hydroxide, an aqueous solution of calcium phosphate and an aqueous solution of calcium nitrate. For example, 10 mM (mmol concentration) maintained at 60 ° C
For 24 hours. Then, the alkali titanate layer on the substrate surface contains calcium. At this time, the concentration of calcium is usually the highest on the outermost surface of the alkali titanate layer,
As the layer becomes deeper in the thickness direction, it gradually decreases. The concentration of calcium is adjusted to 5 to 20 atomic% at the outermost surface of the alkali titanate layer. After this immersion, it is washed and dried.

In this manner, the method for producing a bone substitute material according to the present invention is performed, and the bone substitute material according to the present invention is obtained.

The substrate is heated at 400 to 800 ° C. before or after immersion in one of the selected aqueous solutions.
For example, by heating at 600 ° C. for 1 hour, the scratching strength of the alkali titanate layer can be set to 10 gf or more, and thus the bone substitute material according to the second aspect of the present invention is obtained.

Hereinafter, the function and effect of the present invention will be mainly described.

According to the alkali treatment / heat treatment method,
An amorphous alkali titanate layer is formed on the surface of a substrate made of titanium or a titanium alloy. This alkali titanate layer has a HAP-forming ability and has a function of imparting biocompatibility to a substrate made of titanium or a titanium alloy.

The bone replacement material according to the present invention is, as described above,
An amorphous alkali titanate layer is provided on the surface of a substrate made of titanium or a titanium alloy. Therefore, first, the alkali titanate layer imparts the same degree of biocompatibility to a substrate made of titanium or a titanium alloy as in the case of the alkali treatment / heat treatment method. It may have the same biocompatibility as in the method.

[0021] In addition, the bone substitute material according to the present invention further includes, as described above, wherein the alkali titanate layer contains calcium, and the concentration of calcium is 5 to 5 at the outermost surface of the alkali titanate layer. 20 atomic%, and the thickness of the alkali titanate layer is more than 0.3 μm and 5 μm.
m or less and has a three-dimensional network structure.

Calcium in such an alkali titanate layer has a remarkably high HAP-forming ability, rapidly forms the HAP layer, and gives a substrate made of titanium or a titanium alloy an extremely excellent biocompatibility. Work well.
That is, the calcium in the alkali titanate layer having a three-dimensional network structure with the above thickness and containing calcium at the high concentration as described above is applied to the surface of the substrate made of titanium or a titanium alloy (the alkali titanate layer). Quickly and in large quantities as calcium ions in the body fluid near the surface of the substrate, and rapidly increase and supersaturate the calcium ion concentration in the body fluid near the surface of the substrate, whereby HAP is rapidly and abundantly increased. Precipitates (HAP crystals are formed) and adheres firmly to the surface of the substrate, thereby forming a HAP layer and imparting biocompatibility. This HAP-forming ability (and, consequently, biocompatibility) is extremely superior to that of the alkali treatment / heat treatment method.

The bone substitute material according to the present invention has such excellent biocompatibility in addition to the biocompatibility provided by the alkali titanate layer. Therefore, the bone substitute material according to the present invention has a biocompatibility extremely superior to that of the alkali treatment / heat treatment method given to a substrate made of titanium or a titanium alloy.
That is, the HAP forming ability on the surface is remarkably higher than that of the bone substitute material obtained by the alkali treatment / heat treatment method, and the biocompatibility is extremely excellent.

On the other hand, in the method for producing a bone substitute material according to the present invention, as described above, a substrate made of titanium or a titanium alloy is immersed in an aqueous solution of sodium hydroxide or potassium hydroxide, and then an aqueous solution of calcium hydroxide and phosphoric acid. It is immersed in one kind of aqueous solution selected from a calcium aqueous solution and a calcium nitrate aqueous solution (third invention). According to such a method, the bone substitute material according to the present invention can be obtained.

That is, by dipping the substrate in an aqueous solution of sodium hydroxide or potassium hydroxide (hereinafter referred to as alkali treatment), an amorphous alkali titanate layer having a three-dimensional network structure is formed on the surface of the substrate. Can be formed. At this time, the thickness of the alkali titanate layer is 0.3 μm
It can be made to be super 5 μm or less.

The substrate after the alkali treatment is immersed in one kind of aqueous solution selected from an aqueous solution of calcium hydroxide, an aqueous solution of calcium phosphate, and an aqueous solution of calcium nitrate (hereinafter referred to as a calcium introduction treatment), whereby the alkali titanium on the surface of the substrate is treated. The acid salt layer contains calcium. At this time, the concentration of calcium is usually highest at the outermost surface of the alkali titanate layer, and gradually decreases as the layer becomes deeper in the thickness direction of the layer. The calcium concentration is 5 to 5 at the outermost surface of the alkali titanate layer.
It can be 20 atomic%.

Therefore, according to the method for producing a bone substitute material according to the present invention, the bone substitute material according to the present invention can be obtained.

This production method is as simple as the above-mentioned alkali treatment / heat treatment method. The bone substitute material according to the present invention can be manufactured by such a simple manufacturing method.

As can be seen from the above, the bone substitute material according to the present invention can be obtained by a method as simple as the above-mentioned alkali treatment / heat treatment method, and can be obtained by the above-mentioned alkali treatment / heat treatment method. The HAP forming ability on the surface is remarkably higher than that of the bone substitute material, and it is extremely excellent in biocompatibility. Further, according to the method for producing a bone substitute material according to the present invention, a bone substitute material having such excellent characteristics can be easily obtained.

In the bone substitute material according to the present invention, the thickness of the alkali titanate layer is determined to be more than 0.3 μm and 5 μm or less when the thickness is 0.3 μm or less. Since the absolute amount of calcium contained is small, the amount of calcium eluted into the body fluid near the surface of the substrate (the surface of the alkali titanate layer) is small, and is insufficient to increase the calcium concentration in the body fluid. Therefore, HAP precipitation is unlikely to occur, and as a result, HA
P-forming ability is small, bioaffinity becomes insufficient,
If the thickness is more than 5 μm, a defect such as a crack is easily generated in the alkali titanate layer, and when bonded to living bone, there is a possibility that the defect becomes a starting point of destruction.

The calcium concentration at the outermost surface of the alkali titanate layer is defined as 5 to 20 atomic%. When the calcium concentration is less than 5 atomic%, the calcium is contained in the alkali titanate layer. Because the absolute amount of calcium is small,
The amount of calcium eluted into the body fluid near the surface of the substrate (the surface of the alkali titanate layer) is reduced, and as a result, HAP is hardly precipitated, and the HAP forming ability is small,
This is because the biocompatibility becomes insufficient, and the content cannot exceed 20 atomic%. Calcium concentration 20
The reason that it cannot be more than atomic% is that the calcium in the alkali titanate layer exists in the form of calcium titanate (CaTiO ₃ ), and the entire outermost surface of the alkali titanate layer
This is because even in the case of CaTiO ₃ , the calcium concentration is 20 atomic%, and thus does not exceed 20 atomic%.

Hereinafter, the present invention will be described in more detail.

[0033] The biocompatibility is an affinity with living bone (ie, bone affinity). A material having excellent biocompatibility forms a HAP layer on the surface of the material during immersion in a simulated body fluid having an inorganic ion concentration close to that of a human body fluid. The rate of layer formation can be used as an indicator of biocompatibility.

It is already known that a biocompatibility can be imparted by forming an amorphous alkali titanate layer on the surface of titanium or a titanium alloy (for example, Japanese Patent Laid-Open Publication
No. 7-813100). However, the ability of this alkali titanate layer to form HAP, which governs the bone affinity, is inferior to bone substitute materials such as bioglass. Although the cause is not fully understood, bone substitute materials such as bioglass
It is considered that the alkali titanate layer does not contain these components while the calcium and phosphate components which are the HAP components are contained.

The present inventor has performed various alkali treatments and the like on titanium and titanium alloys and investigated the HAP forming ability of the obtained material. As a result, the amorphous alkali titanate layer containing calcium contained It was found that it had excellent HAP-forming ability. And they found that such a material can be obtained by an alkali treatment and a calcium introduction treatment.

As an attempt to impart biocompatibility to titanium or a titanium alloy, a layer containing calcium has been formed on the surface by ion implantation. However, an apparatus for performing this treatment is large and expensive. It is complicated and requires a high vacuum. Furthermore, biocompatibility is also inferior to the case where an amorphous alkali titanate layer is formed. For example, JP-A-9-308681 discloses a metal material having osteoconductivity (bone affinity) in which calcium is present as an oxide or hydroxide on the surface of a base metal material,
Further, a method for manufacturing the same by an ion implantation method or an ion mixing method is disclosed. However, calcium as this oxide or hydroxide is highly alkaline in vivo and is not preferred in terms of osteoblast proliferation.

On the other hand, it is considered that calcium in the alkali titanate layer formed by the alkali treatment and the calcium introduction treatment is present in the form of calcium titanate, and the oxide or hydroxide It is thought to be less alkaline than calcium and not inhibit osteoblast proliferation.

In the ion implantation method or the ion mixing method, as described in JP-A-9-308681, only calcium can be implanted to a depth of about 30 nm from the surface. It takes a long time. Furthermore, it is difficult to uniformly inject calcium into the surface of an implant member having a complicated shape.

In the bone substitute material according to the present invention, since the alkali titanate layer contains calcium and has a three-dimensional network structure, the HAP layer is quickly formed as described above. The concentration of calcium is 5 to 20 atomic% at the outermost surface of the alkali titanate layer, but is desirably 10 to 20 atomic% in order to ensure a high level of HAP forming ability.

In the method for producing a bone substitute material according to the present invention, calcium treatment is performed after alkali treatment. By this alkali treatment, an amorphous alkali titanate layer having a three-dimensional network structure is formed. After this,
By the calcium introduction treatment, calcium is taken into the alkali titanate layer. At this time, the concentration of calcium is usually highest at the outermost surface of the alkali titanate layer, and gradually decreases as the layer becomes deeper in the thickness direction of the layer.

Titanium and titanium alloys generally have excellent corrosion resistance. In addition, calcium compounds such as calcium hydroxide have low solubility in water. For example, the solubility of calcium hydroxide is 0.12 (g / 100 g water) at 60 ° C. Therefore, an aqueous solution containing calcium ions such as an aqueous solution of calcium hydroxide has an alkaline strength. Is low. Therefore, even if titanium and a titanium alloy are directly treated with an aqueous solution containing calcium ions, an amorphous alkali titanate layer containing a sufficient concentration of calcium cannot be formed. Also, such treated titanium and titanium alloys do not have the ability to form HAP.

On the other hand, sodium hydroxide and potassium hydroxide are strongly alkaline compounds and have high solubility in water, so that a highly concentrated aqueous solution can be prepared (sodium hydroxide: 114 g / 100 g water, potassium hydroxide: 118g / 100g
water). Therefore, first, when a titanium or titanium alloy is alkali-treated with a high-concentration aqueous solution of sodium hydroxide or potassium hydroxide, an amorphous alkali titanate layer having a three-dimensional network structure and a sufficient thickness is formed. Can be done. Next, when calcium is introduced with an aqueous solution containing calcium ions, calcium ions can be efficiently introduced into the alkali titanate layer, and the calcium concentration on the outermost surface of the alkali titanate layer is 5 to 20.
Atomic%.

Generally, when a calcium compound reacts with sodium hydroxide or potassium hydroxide, it becomes calcium hydroxide and precipitates. Since calcium hydroxide hardly dissolves in sodium hydroxide of 1M or more, calcium ions hardly exist in the solution. When calcium ions coexist in an alkaline aqueous solution as described in Japanese Patent Publication No. 7-813100, it is considered that the calcium ion concentration is extremely low and sufficient calcium cannot be introduced into the treatment layer. In addition, since the proper conditions for forming an amorphous alkali titanate layer having a three-dimensional network structure on the surface of titanium or a titanium alloy and the proper conditions for introducing calcium are slightly different, the alkali treatment and the calcium introduction are performed simultaneously. It is not considered appropriate to do so.

On the other hand, as described above, first, an amorphous alkali titanate layer having a three-dimensional network structure is formed by alkali treatment, and then calcium introduction treatment is performed with an aqueous solution containing calcium ions. Calcium ions can be efficiently introduced into the inside of the salt layer.

In the method for producing a bone replacement material according to the present invention, the concentration of the alkali solution (aqueous sodium hydroxide solution or potassium hydroxide solution) during the alkali treatment is less than 2M, and the treatment temperature is lower than 40 ° C. In addition, when the treatment time is shorter than 1 hour, the reaction is difficult to proceed, so that it is difficult to form an alkali titanate layer having a three-dimensional network structure with a sufficient thickness. Further, the concentration of the alkaline solution is more than 10M, the processing temperature is higher than 70 ° C, and the processing time is 24 hours.
If the time is exceeded, the reaction will be excessive, and the alkali titanate layer having a three-dimensional network structure may be cracked and collapsed (the alkali titanium having such a crack may be formed). An example of the acid salt layer is shown in FIG. 6). Further, when the concentration of the alkali solution is high, for example, when the alkali treatment is performed with a 15 M aqueous solution of sodium hydroxide, an alkali titanate layer having a three-dimensional network structure is not formed, and a titanium oxide layer having a smooth appearance is formed. (An example of such a smooth titanium oxide layer is shown in FIG. 7). From these points, the concentration of the alkali solution during the alkali treatment is 2 to 10 M, and the treatment temperature is 40 M
7070 ° C. and the treatment time are desirably 1-24 hours.

When the concentration of the aqueous solution containing calcium ions (aqueous solution of calcium hydroxide, aqueous solution of calcium phosphate and aqueous solution of calcium nitrate) is less than 0.1 mM during the calcium introduction treatment, it is difficult to introduce calcium into the alkali titanate layer. It is also difficult to make the calcium concentration at the outermost surface of the layer 5 atomic% or more. In the case of an aqueous solution of calcium hydroxide, the saturation concentration is around 15 mM.
Above M, precipitation occurs and the efficiency of calcium introduction does not increase further. When the processing temperature is lower than 30 ° C. or the processing time is shorter than 1 hour, the reaction is difficult to proceed.
It becomes difficult to introduce calcium sufficiently. Further, even if the processing temperature exceeds 100 ° C. or the processing time exceeds 24 hours, the efficiency of calcium introduction does not increase any more. From these points, the concentration of the aqueous solution containing calcium ions during the calcium introduction treatment is 0.1 to 15 mM, and the treatment temperature is 30 to 10 mM.
It is desirable that the treatment time is 0 ° C. and the treatment time is 1 to 24 hours. In particular, in order to efficiently introduce calcium, the concentration of the calcium ion-containing aqueous solution is desirably 2.5 to 15 mM, preferably 10 to 15 mM, and the treatment temperature is 80 to 100 ° C. It is desirable to do.

In the case of using a calcium hydroxide aqueous solution among calcium ion-containing aqueous solutions, calcium can be most effectively introduced (the fourth invention).

As described above, when the concentration of the alkali solution in the alkali treatment is high, a smooth titanium oxide layer is formed. Even if such a material is immersed in a simulated body fluid, its surface
HAP is not formed. From this, it can be said that having a three-dimensional network structure on the surface is important for HAP formation in body fluids. By having a three-dimensional network structure, the surface area is dramatically increased, so that HAP-forming components are efficiently eluted into body fluids, and as a result, HAP precipitation and
It is considered that the formation of the HAP layer is likely to occur.

[0049] The bone substitute material according to the present invention is more effective than the bone substitute material obtained by the alkali treatment / heat treatment method.
It has a remarkably high ability to form HAP on the surface and is extremely excellent in biocompatibility. For example, in the case of a bone substitute material obtained by the above-mentioned alkali treatment / heat treatment method, two to two layers are required to form the HAP layer.
Although it takes three weeks, the time required for the bone replacement material according to the present invention to form the HAP layer is 1 to 5 days.

By the way, the alkali titanate layer having a three-dimensional network structure formed by the alkali treatment has a very large surface area, but has a low strength, and may be peeled off from the substrate in some cases during the operation of implantation into a living body. There is fear.
In general, a shear strength or a peel strength is used to evaluate the strength of a biomaterial coating layer. These reflect the joining strength after joining with the living bone in the living body, but do not reflect the strength for handling at the time of the operation for implantation into the living body.
Therefore, the strength for handling at the time of implantation into a living body was evaluated using the scratching strength as an index, and means for improving this strength were examined. The details will be described below.

Titanium or titanium alloy treated with alkali and then treated with calcium, treated with alkali and treated with heat, treated with calcium, and treated with alkali and treated with calcium and treated with heat Using these as a sample, the scratching strength was measured using a surface property measuring device (HEIDON-14S / D). That is, as shown in FIG.
A scratch needle with a needle tip of 200 μm is vertically applied to the surface of the sample, and the vertical load (applied load) on the scratch needle is changed stepwise to form a layer (alkali titanate layer) on the titanium or titanium alloy surface. The state of the peeling was confirmed using a microscope, and the vertical load at the time when the peeling occurred was determined as the scratching strength.

As a result of the above-mentioned measurement of the scratching strength, a heating treatment at 400 to 800 ° C. after the alkali treatment and before the calcium introduction treatment or after the calcium introduction treatment enhances the scratching strength of the alkali titanate layer. It has been found that strength can be provided for handling at the time of an implantation operation in a living body (fifth invention).

When the temperature at the time of the above-mentioned heat treatment is lower than 400 ° C., the scratching strength is low, and there is a possibility that the alkali titanate layer may be peeled off due to handling during implantation into a living body. When the temperature is higher than 800 ° C., the amorphous alkali titanate layer changes to a titanium oxide layer, and the biocompatibility is lowered and becomes insufficient. From this point, the heating temperature was set to 400 to 800 ° C. in the above heat treatment. In order to maintain a high level without decreasing biocompatibility, 400
Desirably, it is set to ~ 600 ° C.

Table 1 shows an example of the measurement results of the above-mentioned scratching strength.
Shown in When the temperature during the heat treatment (firing temperature) is 300 ° C., the scratching strength is 5 gf or less. When the temperature at the time of the heat treatment is 600 ° C., the scratch strength is more than 20 gf and less than 30 gf. When the scratching strength is lower than 10 gf, there is a possibility that the alkali titanate layer may be peeled off due to handling at the time of implantation into a living body. Therefore, the temperature during the heat treatment is set to 600 ℃
, The scratching strength was sufficiently high, but at 300 ° C., the scratching strength was insufficient.

[0055] In order to examine the form of calcium in the alkali titanate layer, the titanium or titanium alloy was subjected to alkali treatment and then calcium introduction treatment.
Analysis by line diffraction was attempted. As a result, what is detected
Only Ti, no calcium compound crystals were detected. From this, it can be said that calcium in the alkali titanate layer exists as amorphous.

The bone substitute material according to the present invention quickly forms an HAP layer in a living body and bonds to a living bone via the HAP layer.

In the present invention, titanium refers to pure titanium. The titanium alloy is not particularly limited, and for example, a titanium alloy containing Al, V, Mo, Zr, Nb, Ta, or the like as an alloy element can be used.

[0058]

[Example 1] A pure titanium plate having a thickness of 1 mm, a width of 10 mm and a length of 10 mm was polished using # 400 abrasive paper, washed with acetone, washed with pure water, dried, and dried. The substrate was immersed in a 5 M aqueous solution of sodium hydroxide at 24 ° C. for 24 hours for alkali treatment, and then washed in pure water using an ultrasonic cleaner. Observation of the pure titanium plate after this treatment with a scanning electron microscope revealed that the surface had a three-dimensional network structure as shown in FIG.

The pure titanium plate after the alkali treatment and the washing is washed.
It was immersed in a 10 mM calcium hydroxide aqueous solution at 60 ° C. for 24 hours to perform a calcium introduction treatment, then washed in pure water and dried at room temperature. Thus, a test material according to Example a (hereinafter also referred to as a test material obtained by an alkali treatment / calcium introduction treatment method) was obtained.

Further, the pure titanium plate after the alkali treatment and the washing as described above is heated at 600 ° C. for 1 hour in a firing furnace before the calcium introduction treatment, and thereafter,
Perform the same calcium introduction treatment, washing and drying as above,
As a result, a test material according to Example b (hereinafter, also referred to as a test material obtained by an alkali treatment / heating treatment / calcium introduction treatment method) was obtained.

On the other hand, by subjecting the pure titanium plate after the alkali treatment and washing as described above to a heating treatment at 600 ° C. for 1 hour in a firing furnace, the test material according to the comparative example (hereinafter referred to as a conventional alkali treatment and Test material obtained by a heat treatment method) was obtained.

Each of the test materials was immersed in a simulated body fluid having an inorganic ion composition substantially equal to that of a human body fluid, and the ability to form a HAP layer on the surface of the test material (the number of days required for HAP layer formation) was examined. The pH of the simulated body fluid was 7.40, and the temperature during immersion was 37 ° C.

Table 2 shows the results. If no HAP was formed, × indicates the HAP formation area (HA
The ratio of the area where P is formed is about 30% or less, Δ, the ratio of the HAP formation area is 30 to 60%, and the ratio of the HAP formation area is 60 to 100%. %
Is indicated by ◎ (the same applies to Tables 3 to 5 described later).

As can be seen from Table 2, in the case of the comparative example (test material obtained by the conventional alkali treatment / heat treatment method), HAP started to form on day 14 of immersion in the simulated body fluid. In the case of Example a (test material obtained by the alkali treatment / calcium introduction treatment method), the HAP layer was already formed on the entire surface on the second day of immersion in the simulated body fluid. In the case of Example b (a test material obtained by an alkali treatment, a heat treatment, and a calcium introduction treatment method), HAP was applied on the third day of immersion.
Formation started, and on the fifth day of immersion, the HAP layer was formed on the entire surface.

FIG. 2 shows the results of elemental analysis in the depth direction by AES (Auger electron spectroscopy) of the pure titanium plate after the alkali treatment and washing. FIG. 3 shows the results of the same analysis on the test material obtained by the alkali treatment / calcium introduction treatment method (Example a). FIG. 4 shows the results of the same analysis on the test material obtained by the alkali treatment, the heat treatment, and the calcium introduction treatment method (Example b).

As shown in FIG. 2, in the case of the pure titanium plate after the alkali treatment and the washing, titanium, oxygen and sodium were confirmed. It can be seen that the alkali titanate layer has a thickness of about 1000 nm. Sodium is contained in the outermost surface of the alkali titanate layer at about 8 atomic% (AC%), and about 8 atomic% of sodium exists up to a depth of about 300 nm.

As shown in FIG. 3, in the case of the test material obtained by the alkali treatment / calcium introduction treatment method (Example a), titanium, oxygen, sodium and calcium were confirmed. An alkali titanate layer is formed from the surface to a depth of about 1000 nm. The sodium content was lower than in the case of FIG. 2, and a high concentration of calcium was confirmed. Although the calcium concentration was about 18 atomic% at the outermost surface of the alkali titanate layer and decreased in the depth direction, the presence of calcium was confirmed throughout the entire alkali titanate layer.

As shown in FIG. 4, in the case of the test material (Example b) obtained by the alkali treatment, heat treatment and calcium introduction treatment, titanium, oxygen,
Although sodium and calcium are confirmed, the thickness of the alkali titanate layer is about 1000 nm, but the calcium concentration is about 10 atomic% at the outermost surface of the alkali titanate layer, which is lower than that in FIG. This is because the heat treatment reduced the calcium introduction efficiency.

Example 2 A pure titanium plate after the same alkali treatment and washing as in Example 1 was subjected to calcium introduction treatment by changing the type of the calcium introduction treatment solution. That is, 10 mM calcium hydroxide aqueous solution, 10 mM calcium phosphate aqueous solution, 10 mM calcium nitrate aqueous solution, or 10 mM calcium chloride aqueous solution, respectively,
It was immersed at 60 ° C. for 24 hours to perform a calcium introduction treatment. Thereafter, washing and drying were performed in the same manner as in Example 1 to obtain a test material according to Example 2.

The test material was immersed in the same simulated body fluid as in Example 1 to examine the ability to form a HAP layer. Table 3 shows the results. HAP depending on the type of solution for calcium introduction
The ability to form a layer is different, and the use of an aqueous solution of calcium hydroxide is most excellent in the ability to form a HAP layer, then the use of an aqueous solution of calcium phosphate, followed by the use of an aqueous solution of calcium nitrate. When used, the ability to form a HAP layer was the lowest.

Example 3 The same pure titanium plate as in Example 1 was polished, washed and dried in the same manner, and then alkali-treated using various concentrations of aqueous sodium hydroxide.
That is, a 0.1 M aqueous sodium hydroxide solution, a 0.5 M aqueous sodium hydroxide solution, a 2 M aqueous sodium hydroxide solution, or
It was immersed in a 5M aqueous solution of sodium hydroxide at 60 ° C. for 24 hours to carry out alkali treatment. Next, the substrate was washed in pure water using an ultrasonic cleaner.

After drying the pure titanium plate after the alkali treatment and washing, the plate is heated at 600 ° C. for 1 hour, and then immersed in a 10 mM calcium hydroxide aqueous solution at 60 ° C. for 24 hours to introduce calcium. did. Thereafter, washing and drying were performed in the same manner as in Example 1 to obtain a test material according to Example 3.

The test material was subjected to elemental analysis in the depth direction by AES, and the thickness of the alkali titanate layer was determined from the distribution of oxygen atoms. Further, it was immersed in the same simulated body fluid as in Example 1, and the ability to form a HAP layer was examined. Table 4 shows the results.

As can be seen from Table 4, the higher the concentration of the aqueous sodium hydroxide solution during the alkali treatment, the greater the thickness of the alkali titanate layer. When the thickness of the alkali titanate layer is 0.3 μm or less, the HAP forming ability is poor.
Exhibits HAP-forming ability over 0.3 μm.

Example 4 The same alkali treatment and washing as in Example 1 were performed, and the pure titanium plate was dried, dried, and heated at 600 ° C. for 1 hour.
The calcium introduction treatment was performed by changing the concentration of the calcium hydroxide aqueous solution and the treatment temperature as shown in Table 5. The immersion time in the aqueous calcium hydroxide solution is 24 hours. After the calcium introduction treatment, washing and drying were performed in the same manner as in Example 1 to obtain a test material according to Example 4.

The calcium concentration on the surface of the test material was measured by AES elemental analysis. Further, it was immersed in the same simulated body fluid as in Example 1, and the ability to form a HAP layer was examined.
Table 5 shows the results.

As can be seen from Table 5, the efficiency of calcium introduction into the alkali titanate layer could be increased by increasing the concentration of the aqueous solution of calcium hydroxide during the calcium introduction treatment and increasing the treatment temperature. . A correlation was found between the calcium concentration at the outermost surface of the alkali titanate layer and the ability to form a HAP layer in the simulated body fluid, and the calcium concentration at the outermost surface of the alkali titanate layer was 4.2 atomic%. Has poor HAP-forming ability and HAP
It was confirmed that the HAP-forming ability was remarkably excellent when the content was 10 atomic% or more.

[0078]

[Table 1]

[0079]

[Table 2]

[0080]

[Table 3]

[0081]

[Table 4]

[0082]

[Table 5]

[0083]

The bone substitute material according to the present invention has the above-mentioned structure and functions, and is described in, for example, Japanese Patent Application Laid-Open No. 7-813100. A method of treating the surface of a substrate made of titanium or a titanium alloy with an aqueous alkali solution, followed by heat treatment), and the alkali treatment / heat treatment method described above. The HAP forming ability (hydroxyapatite forming ability) on the surface is remarkably higher than that of the bone substitute material obtained in the above, and it is extremely excellent in biocompatibility. Therefore, the time required for bonding with the living bone is greatly reduced. It has a remarkable effect that it can be shortened. Further, the method for producing a bone substitute material according to the present invention can have a remarkable effect that a bone substitute material having such excellent properties can be easily obtained. That is, according to the present invention, as easily as the case of the alkali treatment and heat treatment method, a biocompatibility extremely superior to that of the case of the alkali treatment and heat treatment method is applied to a substrate made of titanium or a titanium alloy. Can be granted.

[Brief description of the drawings]

FIG. 1 is a view showing a measurement state of a scratch strength of an alkali titanate layer on a titanium surface.

FIG. 2 shows the results of elemental analysis by AES (Auger electron spectroscopy) of a surface layer formed by alkali treatment of a pure titanium plate according to Example 1, and shows the depth of the surface layer (from the outermost surface). FIG. 5 is a diagram showing a relationship between a distance in a thickness direction of a surface layer) and an element concentration [AC% (atomic%)].

FIG. 3 shows an alkali treatment of a pure titanium plate according to Example 1.
FIG. 4 is a diagram showing the results of elemental analysis by AES of a surface layer of a test material obtained by a calcium introduction treatment method, and showing the relationship between the depth of the surface layer and the element concentration [AC%].

FIG. 4 shows an alkali treatment of a pure titanium plate according to Example 1.
FIG. 4 is a diagram showing the results of elemental analysis by AES of a surface layer of a test material obtained by a heat treatment / calcium introduction treatment method, showing the relationship between the depth of the surface layer and the element concentration [AC%].

FIG. 5 is a photograph substituted for a drawing, showing a metal structure of a titanium surface alkali-treated with a 5M alkaline solution.

FIG. 6 is a drawing substitute photograph showing a metallographic structure of a titanium surface alkali-treated with a 10M alkaline solution.

FIG. 7 is a photograph substituted for a drawing showing a metallographic structure of a titanium surface alkali-treated with a 15M alkaline solution.

Continued on the front page (72) Inventor Yoshio Sasaki 1-3-18 Wakihama-cho, Chuo-ku, Kobe-shi, Hyogo Kobe Steel, Ltd. Kobe Main Office (72) Inventor Tomiharu Matsushita 1 Wakihama-cho, Chuo-ku, Kobe-shi, Hyogo 3-18 Chome Kobe Steel, Ltd. Kobe headquarters (72) Inventor Tadashi Kokubo 50F term of Umegaoka 2, Nagaokakyo-shi, Kyoto 4F081 AB02 AB04 BA13 BA17 BB04 BB08 CF012 CF142 CF26 CG02 CG03 DC03 DC04 DC05 DC06 DC14 EA04 EA05 EA06

Claims (5)

[Claims] 1. A substrate made of titanium or a titanium alloy,
A bone substitute material comprising an amorphous alkali titanate layer formed on the surface of the substrate, wherein the alkali titanate layer contains calcium, and the concentration of calcium is the alkali titanate. 5 to 20 atomic% at the outermost surface of the layer
And said alkali titanate layer has a thickness of 0.3
A bone substitute material having a three-dimensional network structure of more than 5 μm and less than 5 μm. 2. The bone substitute material according to claim 1, wherein the scratch strength of the alkali titanate layer is 10 gf or more. 3. A substrate made of titanium or a titanium alloy,
A method for producing a bone substitute material, comprising immersing in a sodium hydroxide aqueous solution or potassium hydroxide aqueous solution, and then immersing in one kind of aqueous solution selected from a calcium hydroxide aqueous solution, a calcium phosphate aqueous solution, and a calcium nitrate aqueous solution. 4. The method for producing a bone substitute material according to claim 3, wherein the one selected aqueous solution is a calcium hydroxide aqueous solution. 5. After immersing the substrate in an aqueous sodium hydroxide solution or an aqueous potassium hydroxide solution, the selected 1
5. The method for producing a bone substitute material according to claim 3, wherein the substrate is heated at 400 to 800 [deg.] C. before dipping in the aqueous solution of the seed or after dipping in the aqueous solution of the selected one.