JP3069921B2 - Manufacturing method of implant material - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an implant material which can be safely implanted in a living body as a prosthetic restoration for bone and teeth and which can be combined with living tissue.

[0002]

2. Description of the Related Art In recent years, there has been an aspiration to develop an implant material that can be safely implanted in a living body as a prosthetic restoration of a bone or a tooth lost due to a disease such as a traffic accident, a bone tumor, and a tooth decay, and that can be combined with a living tissue. Have been.

Although metallic implants have sufficient mechanical properties for these prostheses, their biocompatibility is poor. On the other hand, ceramic-based implants have insufficient mechanical properties, but have high biological safety and compatibility. Therefore, various composite materials in which a metal and a ceramic are composited have been developed as implant materials.

[0004] For example, a product obtained by coating lhydroxyapatite on titanium by plasma spray coating is already commercially available. Also, a method of applying and baking a nitric acid aqueous solution of hydroxyapatite on a metal substrate (JP-A-63-2)
No. 4952), a slurry of fine powder of the phosphate glass material is coated on the substrate surface, to form a binder layer and a heat treatment,
A production method comprising a step of coating and heat treating a slurry of calcium phosphate fine powder, a deflocculant and water on a binder layer (JP-A-63-134672), and further mixing and sintering hydroxyapatite and bioactive glass powder. Ceramics have also been proposed (JP-A-60-186455).
issue).

The present inventors have previously developed the following biocompatible complex and a method for producing the same. That is, on a metal substrate, having a glass layer in which hydroxyapatite is dispersed,
A biocompatible composite, wherein a surface layer of a glass layer has countless holes and apatite is exposed.
As a production method, a method of producing a composite in which glass powder and hydroxyapatite are mixed and dispersed, coated on a metal substrate, fired, and then the glass layer on the surface is dissolved and etched with acid to expose a myriad of pores and apatite. (JP-A-63-102762).

[0006]

SUMMARY OF THE INVENTION In view of such circumstances, the present invention provides an excellent biocompatibility by forming active hydroxyapatite on the surface of a base material ,
Implant that regenerates bone early and bonds with bone early
An object of the present invention is to provide a method for producing an implant material, which can easily produce the material .

[0007]

That is, according to the present invention , calcium phosphate is dispersed as a base material on a metal substrate.
Glass layer, and the surface layer of the glass layer has countless holes
Biocompatible with exposed calcium phosphate
Using a complex , the base material is immersed in an artificial body fluid simulating the inorganic salt concentration of the extracellular fluid, and needle-like crystals of hydroxyapatite are formed on the surface of the base material, thereby producing an implant material. It provides a method.

Hereinafter, the present invention will be described in detail.

[0009]-based Material of the implant material of the present invention,
A glass layer with calcium phosphate dispersed on a metal substrate
The surface layer of the glass layer has numerous holes and
Biocompatible, characterized by exposure of calcium phosphate
It is a complex.

[0010] As the base material, metals, among them titanium or a titanium alloy.

Examples of the calcium phosphate include hydroxyapatite [Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ], α-tricalcium phosphate [α-TCP: Ca ₃ (PO ₄ ) ₂ ], β-
Tricalcium phosphate [β-TCP: Ca ₃ (P
O ₄ ) ₂ ], octacalcium phosphate [OCP: Ca ₈ H ₂ (P
O _{4) 6} · 5H ₂ O], Bull site [Brushite:
CaHPO ₄ · 2H ₂ O] and the like are used, hydroxyapatite is particularly preferable.

Among these base materials , those particularly preferred when used in the present invention have a glass layer in which hydroxyapatite is dispersed on a metal substrate, and the surface layer of the glass layer has countless vacancies. And a biocompatible composite characterized in that apatite is exposed (Japanese Patent Application Laid-Open No. 63-10 / 63).
2762).

In the present invention, the base material is immersed in an artificial body fluid simulating the inorganic salt concentration of the extracellular fluid. The composition of the artificial body fluid is apparent to those skilled in the art. Of composition. Of course, each component may be varied as long as the object of the present invention is not impaired.

[0014]

[Table 1]

The base material is immersed in such an artificial body fluid.
Then, the calcium phosphate on the surface of the base material once becomes an artificial body
It is considered that calcium ions, phosphate ions and the like are eluted in the liquid and precipitate and grow as hydroxyapatite on the remaining dispersed particles.

The phase change of calcium phosphate in a living body is as follows:
It is said that:

That is, it has been reported that α-TCP and β-TCP are unstable in the presence of water and react as shown in Chemical formula 1.

[0018]

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It is said that octacalcium phosphate, hydroxyapatite, brucite and the like undergo a phase change in a living body as shown in the following chemical formula 2.

[0020]

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That is, it is presumed that hydroxyapatite is ultimately likely to be produced in any of the calcium phosphates in the living body. However, hydroxyapatite in a living body can be converted to C by other metals such as Mg and Fe.
a is partially substituted, so that the Ca / P ratio becomes 1.5 to 1.6.

In the present invention, calcium phosphate is newly generated on the surface of the base material because C is generated near the surface.
The concentration of a and P becomes high, and calcium phosphate is precipitated and formed as crystal nuclei in accordance with the chemical equilibrium.
As a supply source of Ca and P at this time, it is considered that calcium phosphate on the surface of the base material is once dissolved and deposited. In order to promote the increase in the concentration of Ca and P, a substance having a higher solubility than hydroxyapatite, for example,
α-tricalcium phosphate [α-TCP], β-tricalcium phosphate [β-TCP], octacalcium phosphate [OC
P], brucite [Brushite] or the like is preferably coated on the surface of the base material . The coating base by dispersing these powders in gelatin solution
It may be applied to the surface of the material .

The immersion time and temperature are not particularly limited, and may be several hours to about ten months, 0 ° C. to 50 ° C., etc., as long as calcium phosphate is dissolved once and deposited crystals grow.

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

Japanese Patent Application Laid-Open No. 63-10, which was previously proposed by the present inventors.
According to No. 2762 , a biocompatible composite (hereinafter referred to as biocompatible composite) having a glass layer on which a hydroxyapatite is dispersed on a metal substrate, wherein the surface layer of the glass layer has a myriad of pores and the apatite is exposed . A composite was called) , two of them were superimposed, and left immersed in an artificial body fluid. The overlapped portion was firmly joined by hydroxyapatite. On the other hand, the two sheets are not superposed, and needle-like crystals are observed in both of the gaps (see FIGS. 4 and 5). The crystal is hydroxyapatite newly generated in the artificial body fluid as a result of X-ray analysis.

On the other hand, a hole was made in the femur of the dog, and the same biocompatible composite was implanted. After about three months, the joined state was similarly observed. The biocompatible composite is integrally bonded to the bone as a whole and is firmly joined, and the part where the biocompatible composite and the bone are not yet joined, the bone is starting to grow in the biocompatible composite There are some parts. Needle-like hydroxyapatite crystals are newly formed in the part where the bone has not yet joined and the part where the bone has begun to grow in the biocompatible composite, which greatly contributes to the growth of new bone. Is asked. In addition, since a hydroxyapatite needle-like crystal is newly formed in the living body, the biocompatible complex is immersed in an artificial body fluid, and the same crystal morphology as that generated in vitro and in vitro By forming needle-like crystals of hydroxyapatite having the following formula, it becomes easier to bond with bone when the biocompatible composite is implanted in a living body.

(Production Example 1) First, a biocompatible composite was prepared as a base material,
The state of hydroxyapatite formation in the body was confirmed.

The alumina borosilicate glass was quenched from 1400 ° C. into water to produce a frit. By the wet method,
High purity calcium hydroxide aqueous solution (pH12 ~ 13)
₃ PO ₄ aqueous solution was added dropwise to obtain a precipitate, which was calcined and calcined.
Hydroxyapatite (hereinafter, referred to as HA) was synthesized. Both frit and HA were mixed at various ratios (0 to 90%) with powder passing through 200 mesh to prepare an HA / glass mixture for coating.

The titanium rod was degreased, blasted and heat-treated to form an oxide film on its surface. Glass or an HA / glass mixture (slip) having a small content of HA was baked on the titanium rod in an electric furnace at 900 ° C. for 3 minutes. HA having an HA content of 30%, 50%, or 70%
/ Layered glass mixture (slip) in the above procedure
Was. Next, etching treatment with a mixed solution of HF and HNO ₃
I do. Thus, a biocompatible complex was obtained.

The resulting embedded biocompatible complex femur of a dog, after 3 months, removed from the bone was observed at the surface electrolytic <br/> emission scanning electron micrograph (FE-SEM) . Where the gap between the bone and the biocompatible composite is small,
The bone has grown into the biocompatible composite, which provides a strong bond between the bone and the biocompatible composite. In the vicinity, a portion where bone has grown into the biocompatible complex and a new needle-like crystal of HA coexist, and in a portion where the gap between the bone and the biocompatible complex is large, ,
Needle-like crystals of HA are formed both on the surface of the biocompatible complex (FIG. 1) and on the opposite bone surface (FIG. 2).

Example 1 A Kamaboko-shaped biocompatible composite was obtained in the same manner as in Production Example 1 using a Kamaboko-shaped titanium substrate. The two pieces were placed back to back and immersed in an artificial body fluid composed of the components shown in Table 1 for 3 months. The two superimposed back-to-back are peeled off, and the HA crystal having the same shape as the HA crystal generated in the living body (FIGS. 1 and 2) is generated in the part that is firmly joined to each other (FIG. 3). In the part where the two were not overlapped and were separated from each other, HA needle crystals in the initial growth stage were observed from both sides (FIGS. 4 and 5).

When the immersion was extended for six months, the number of joints by HA increased, and the needle-like crystals of HA grew greatly.

[0033]

According to the present invention, as described above,
Crystal forms similar to those produced in vivo in vitro
Of needle-like hydroxyapatite crystals
Therefore, when implanted in the living body,
An implant material that facilitates can be easily manufactured.

[Brief description of the drawings]

1 is a <br/> morphism scanning electron micrograph discharge electric field that represents the growth of the crystal structure when embedded biocompatible complex as the base material to the femur of a dog.

2 is a <br/> morphism scanning electron micrograph discharge electric field that represents the growth of the crystal structure when embedded biocompatible complex as the base material to the femur of a dog.

3 is a electric field emission scanning electron microscope photograph representative of the crystal structure of the implant material obtained by the present invention.

4 is a electric field emission scanning electron microscope photograph representative of the crystal structure of the implant material obtained by the present invention.

5 is a electric field emission scanning electron microscope photograph representative of the crystal structure of the implant material obtained by the present invention.

────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Satoshi Ishikawa 39-1 Yakucho, Shinjuku-ku, Tokyo Tokyo Health and Welfare Pension Hospital Dormitory 103 (56) References JP-A-3-97466 (JP, A) (58) ) Surveyed fields (Int. Cl. ⁷ , DB name) A61L 27/00 A61K 6/00-6/10

Claims (2)

(57) [Claims] As claimed in claim 1 the base material, on a metal substrate, phosphorus
It has a glass layer in which calcium acid is dispersed.
The layer has a myriad of holes and the calcium phosphate
An implant material, characterized in that the base material is immersed in an artificial body fluid similar to the inorganic salt concentration of the extracellular solution using the biocompatible composite that has been put out , and hydroxyapatite is precipitated on the surface of the base material. Recipe. 2. The method according to claim 1, wherein the calcium phosphate is hydroxyapatite.
Preparation of the implant material according to claim 1, characterized in that the bets.