JP2775523B2 - Bone substitute material and its manufacturing method - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a bone substitute material and a method for producing the same. This bone substitute material can be suitably used as a repair material for a portion to which a large load is applied such as a femur, a hip joint, a tooth root, and the like.

BACKGROUND ART It is considered that a condition for an artificial material to exhibit bioactivity of binding to bone in a living body is to form a phase of apatite of the same kind as the inorganic substance of bone on the surface thereof in a living body.

Conventionally, Na ₂ O-
CaO-SiO ₂ and -P ₂ O ₅ based glass, sintered hydroxyapatite _{(Ca 10 (PO 4) 6} (OH) 2), or MgO-CaO-SiO ₂
-P like ₂ O ₅ based crystallized glass is used. These are excellent materials having the property of forming a layer of apatite of the same type as the inorganic substance of bone on the surface thereof in a living body and directly binding to bone, and having bioactivity. However, their fracture toughness (1-2M
Pam ^1/2 ) is less than that of human cortical bone (2-6 MPam ^1/2 ) and cannot be used as a substitute for a hip or femur under heavy load.

Therefore, at present, titanium and its alloys, which have the highest biocompatibility among metallic materials, are used as substitute materials. However, these metallic materials have high fracture toughness, but require a long period of about 10 years to directly bond with bone.

Therefore, it has been practiced to apply bioactivity by plasma coating molten metal apatite on the surface of these metallic materials. The material obtained by this method has both the fracture toughness of titanium and the bioactivity of apatite.

However, in the manufacturing method using the plasma coat, (1)
Expensive plasma spraying equipment is required. (2) Since the hydroxyapatite powder, which is a thermal spray material, is temporarily exposed to a high temperature of about 30,000 ° C., it is difficult to control the composition and crystallinity of the hydroxyapatite formed on the metal substrate surface. .
(3) It is difficult to form a dense apatite layer because the semi-molten hydroxyapatite powder is simply deposited on the substrate by free fall. (4) For the same reason, the apatite layer is strongly adhered to the substrate. There is a problem that it is difficult and easy to leave.

An object of the present invention is to solve such a conventional problem and to provide, at low cost, a bone repair material having both the fracture toughness of titanium and the biological activity of apatite, and further having titanium and apatite firmly adhered to each other. .

DISCLOSURE OF THE INVENTION In order to achieve the object, a bone repair material of the present invention comprises a substrate made of titanium Ti or a titanium titanium alloy, and a titanium oxide phase and an amorphous phase of an alkali titanate formed on the surface of the substrate. Including a coating (first coating). As a substrate, pure Ti is good in terms of biocompatibility,
In terms of formability, Ti-6Al-4V, Ti-5Al-2.5Sn, Ti-3Al
-13V-11Cr, Ti-15Mo-5Nb-3Ta, Ti-6Al-2Mo-Ta
An alloy like is good.

Further, a second coating mainly composed of apatite may be further formed on the first coating.

It is preferable that the first coating has a concentration of the titanium oxide phase gradually decreasing toward the outer surface and a total concentration of alkali ions gradually increasing toward the outer surface.

The thickness of the first coating is preferably about 0.1 to 10 μm, and the thickness of the second coating is preferably 1 μm or more. In particular, the thickness of the first coating is 1μ
m, the thickness of the second coating is preferably 10 μm.

A preferred manufacturing method for manufacturing the bone substitute material as described above is to immerse a substrate made of titanium Ti or a titanium Ti alloy in an alkaline solution, and then heat the substrate to a temperature equal to or lower than the transition temperature of titanium Ti or a titanium Ti alloy. It is characterized by doing. In order to make immersion and heating progress simultaneously, you may heat under pressure during immersion. Further, following the heat treatment, it may be immersed in an aqueous solution containing calcium Ca and phosphorus P having a solubility equal to or higher than the apatite solubility, for example, in a simulated body fluid.

Here, the alkaline solution is desirably sodium Na ⁺
It is an aqueous solution containing one or more of ions, potassium K ⁺ ions and calcium Ca ²⁺ ions. The preferred concentration, temperature and reaction time of the alkaline solution are 2 to 10 mol and 40, respectively.
7070 ° C. and 1 to 24 hours.

The heating temperature is preferably from 300 to 800 ° C, particularly preferably from 550 to 650 ° C.

On the surface of titanium Ti or titanium titanium alloy, there is an extremely thin film made of an oxide originally close to TiO ₂ . TiO ₂ is an amphoteric substance that reacts with both strong acids and strong bases. Therefore, when a substrate made of titanium Ti or a titanium Ti alloy is immersed in an alkaline solution, an amorphous alkali titanate is formed on the surface of the substrate with a concentration gradient gradually increasing from the inside having a small reaction amount to the outside having a large reaction amount. Is generated. Thereafter, the substrate is heated to a temperature equal to or lower than the transition temperature of titanium Ti or titanium titanium alloy for 1 to 24 hours, whereby oxygen is diffused and the thickness of the generated phase is increased.

In this way, a film composed of the titanium oxide phase and the amorphous alkali titanate phase is formed on the surface of the substrate. Moreover, since the alkali titanate produced in the intermediate step as described above has a gradual concentration gradient that gradually increases outward in the thickness direction of the coating film, the titanium oxide phase as a starting material of this compound is: Tapering outwards,
The total concentration of alkali ions (Na ⁺ , K ⁺ , Ca ^2+, etc.) contained in the amorphous alkali titanate phase, which is the product,
It gradually increases toward the outside. Since the concentration changes with such a gentle gradient, the interface between the substrate and the coating film and the interface between each phase in the coating film are firmly adhered to each other. In this regard, when the substrate is immersed in a separately prepared titania gel, Ti
A gel is formed on the surface that is easily bonded to the bone, but is different from that in which the bonding force between the Ti and the gel layer is weak and easily peeled off. In addition, since the outermost surface is rich in alkali ions, the alkali ions are exchanged for hydrogen ions in the simulated body fluid or body fluid, and a titanium hydroxide phase that easily reacts with calcium Ca or phosphorus P is generated.

On the other hand, aqueous solutions and body fluids containing calcium Ca and phosphorus P at or above the solubility of apatite contain components that generate apatite at or above the solubility of apatite, and therefore have the ability to grow apatite crystals. Due to the high activation energy for formation, it lacks the ability to form an apatite nucleus by itself as a barrier. On the other hand, the amorphous titanium hydroxide phase formed by hydration of titanium oxide is highly reactive because it is amorphous. Thus, it reacts with osteogenic components in body fluids to form apatite nuclei. After the heat treatment, the apatite nucleus may be formed in advance by immersion in an aqueous solution containing calcium Ca or phosphorus P having a solubility equal to or higher than the apatite solubility, preferably in a simulated body fluid.
In particular, those treated with a simulated body fluid having an ion concentration close to the body fluid, because the composition and structure of the apatite formed on the surface is similar to the composition and structure of the apatite of the bone, it is easy to combine with the bone is there.

However, if the temperature of the heat treatment is lower than 300 ° C., the air does not diffuse and the supply of oxygen is insufficient, the thickness of the first coating does not increase, and the ability to form apatite on the surface in the body is inferior. On the other hand, if the temperature exceeds 800 ° C., the transition temperature of Ti is reached, which is not preferable. This is because the mechanical strength of the base is deteriorated when the Ti or titanium Ti alloy of the base is transferred.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a view showing the results of thin-film X-ray diffraction when a specimen which has been immersed in a NaOH solution and then heat-treated at 600 ° C. is immersed in a simulated body fluid.

BEST MODE FOR CARRYING OUT THE INVENTION A titanium Ti alloy plate of 15 × 10 × 1 mm ³ is polished with ♯400, washed with acetone and distilled water in this order, and placed in a 10 M NaOH or KOH aqueous solution at 60 ° C. for 24 hours. Dipped. The specimen was washed with distilled water using an ultrasonic cleaner for at least 20 minutes, and the surface was observed.Those immersed in an NaOH aqueous solution were uniform pale yellow, and those immersed in a KOH aqueous solution were uniform yellow. And it was found that alkali titanate was generated.

After that, place the Ti metal plate in a furnace at a rate of 5 ° C / min.
The temperature was raised to 0, 500, 600, or 800 ° C. and maintained at each temperature for 1 hour. The structural change of the titanium metal surface after each of the above treatments was examined by thin film X-ray diffraction and scanning electron microscope-energy dispersive X-ray analysis (SEM-EDX).

In the thin film X-ray diffraction pattern of the test piece after immersion in the alkaline aqueous solution, a broad peak due to the amorphous phase was observed when 2θ was 23 to 30 ° C. It is considered that this phase was formed by the reaction of titanium oxide with alkali ions. The intensity of the X-ray diffraction peak of the titanium oxide crystal phase increased with an increase in the heat treatment temperature of the test piece. However, when the heating temperature was 600 ° C. or lower, a peak due to the amorphous phase was also observed. On the other hand, when the heat treatment was performed at 800 ° C., the peak of the amorphous phase disappeared, and instead, many peaks of titanium oxide and alkali titanate began to be observed. 600 ℃
The thickness of the amorphous layer on the specimen heat-treated at
Thus, the surface of the titanium metal was uniformly covered. Also, KOH
After immersion in the solution, SEM-
According to EDX, it was observed that the concentration of potassium gradually decreased from the surface to the inside in the amorphous layer.

 Table 1 shows the results.

As shown in Table 1, a titanium oxide phase (rutile type, anatase type) and an amorphous phase of alkali titanate were formed on the surface of the Ti metal plate heated at 400 to 600 ° C. The amorphous phase of the alkali titanate disappeared on the surface of the Ti metal plate heated at 800 ° C., and instead, a Na ₂ Ti ₅ O ₁₁ crystal phase was confirmed.

Next, the obtained specimen was immersed in a simulated body fluid having an inorganic ion concentration substantially equal to that of a human body fluid, and the presence or absence of the formation of an apatite layer was examined. The simulated body fluid, each of the ion concentration ^{K + 5.0, Na + 142,} Mg 2+ 1.5, Ca 2+ 2.5, Cl - 148, HCO 3 - 4.2, HPO
₄ ² 1.0, has a composition such SO ₄ ^2- 0.5 [mM], tri -
(Hydroxymethyl) -aminomethane and hydrochloric acid at 37 ° C
PH adjusted to 7.4 was used.

FIG. 1 shows the results of thin-film X-ray diffraction when a test piece immersed in a NaOH solution and then heat-treated at 600 ° C. was immersed in a simulated body fluid. Within two weeks after immersion, apatite began to form on the surface, and three weeks later, the apatite layer grew and covered the surface, and almost no titanium metal peak was observed. After immersion for 3 weeks, the apatite layer having a thickness of 5 to 10 μm was uniformly formed on the surface of the titanium metal. 400
Specimens heat-treated at 500C and 500C also had the same tendency.

INDUSTRIAL APPLICABILITY The bone repair material and the method for producing the same according to the present invention have the above-described configuration, and therefore have the following remarkable effects. That is, since only heating is required after immersing the Ti metal in the alkaline solution, an expensive device is unnecessary. When implanted in the body as it is, apatite of the same quality as the bone mineral is naturally formed on the surface thereof, through which it is firmly bound to the bone. Also, when this is immersed in an aqueous solution containing calcium ions and phosphorus ions exceeding the saturated concentration of apatite, desirably a simulated body fluid, apatite of the same quality as bone mineral is formed on the surface, and through this, apatite is further strengthened with the bone. To join. Excellent in biological freshness.

Moreover, since the substrate made of Ti metal and the second film made of apatite are chemically bonded via the first film made of titanium oxide or the like with a gradient concentration gradient, the adhesive strength of apatite to the substrate is high. .

Claims (10)

(57) [Claims] 1. A bone repair material comprising a substrate made of titanium Ti or a titanium Ti alloy, and a film containing a titanium oxide phase and an amorphous phase of alkali titanate formed on the surface of the substrate. 2. The bone repair material according to claim 1, wherein a second coating mainly composed of apatite is further formed on the coating. 3. The method according to claim 1, wherein the concentration of the titanium oxide phase in the coating gradually decreases toward the outer surface, and the total concentration of alkali ions in the coating gradually increases toward the outer surface.
Item 3. The bone repair material according to any one of Items 2. 4. The bone repair material according to claim 1, wherein the thickness of the first coating is 0.1 to 10 μm. 5. The bone repair material according to claim 1, wherein the thickness of the second coating is 1 μm or more. 6. A method for producing a bone repair material, comprising immersing a substrate made of titanium Ti or a titanium Ti alloy in an alkaline solution, and then heating the substrate to a temperature lower than the transition temperature of titanium Ti. 7. A substrate made of titanium Ti or a titanium Ti alloy is immersed in an alkaline solution, and then heated to a temperature lower than the transition temperature of titanium Ti, and then contains calcium Ca and phosphorus P at or above the solubility of apatite. A method for producing a bone repair material, characterized by being immersed in an aqueous solution. 8. The bone repair material according to claim 6, wherein the alkaline solution is an aqueous solution containing at least one of sodium Na ⁺ ion, potassium K ⁺ ion and calcium Ca ²⁺ ion. Manufacturing method. 9. The method for producing a bone repair material according to claim 6, wherein the heating temperature is 300 to 800 ° C. 10. The method for producing a bone repair material according to claim 6, wherein the heating temperature is 550 to 650 ° C.