JPH0747116A - Implant manufacturing method - Google Patents

Abstract

(57) [Summary] [Object] To provide a method for producing an implant that is stable in vivo for a long period of time and has excellent affinity with bone tissue. [Composition] An implant core body in which all or only the surface of the core body is made of titanium or a titanium alloy is anodized in an electrolyte solution containing glycerophosphate and calcium salt to form an anodized film on the core body. Next, a method for producing an implant, characterized by hydrothermally treating in high-pressure steam to deposit a calcium phosphate compound on the anodized film so as not to cover the entire film.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention relates to an artificial tooth root, an artificial bone,
Artificial joints, bone substitutes, bone screws, bone plates
The present invention relates to a method for manufacturing an implant used in the fields of dentistry, bone frame and other dentistry and orthopedics.

[0002]

2. Description of the Related Art There have been remarkable advances in medical technology in recent years, and great expectations are placed on the development of that technology as the aging society advances. As one of such techniques, there is a technique of a bone substitute material or a bone reinforcing material such as an artificial tooth root, an artificial bone and an artificial joint, and the use thereof is rapidly spreading. These materials are so-called "implants" or "implant materials", and most of them are composed of metal, ceramics or the like.

Of these, the materials for the in-vivo implant that have been put to practical use include stainless steel, Ni-Cr alloys, and Co-Cr.
There are alloys, titanium, titanium alloys, noble metals and their alloys, etc., each of which is used according to the application. Among them, titanium and titanium alloys are corrosion resistant, biocompatible,
These metals are used in most implants because of their excellent mechanical properties.

However, the use of a metal having a high biocompatibility is not sufficient for the implant to function stably in a living body for a long period of time. Therefore, a method has been used in which a bioactive material such as hydroxyapatite is coated on the surface of the implant to directly bond it to bone. Hydroxyapatite is a material having a very high affinity for bone tissue and has a property of directly chemically bonding to bone. But,
Since the sintered body has low strength, it is mainly used by coating on the surface of metal.

[0005]

Therefore, a method of obtaining a coating film (a film of a bioactive material such as hydroxyapatite) which has a large adhesive strength and is stable in the living body for a long period of time has been attempted. At present, coating by the plasma spraying method is most commonly used, and other thermal decomposition method,
Although the sputtering method and the like have been tried, these have not yet been technically established.

[0006] When a coating is formed by coating hydroxyapatite on the surface of an implant core body (hereinafter sometimes abbreviated as a core body), the most important point among the conditions required for the film is The strength of adhesion to the core and the stability in vivo. In other words, since the coating made of hydroxyapatite and the bone are very strongly bonded, if the bond strength with the core that exceeds the bonding strength is not maintained for a long period of time, the coating will peel from the core and stabilize the implant. I can't get it to work.

When coating hydroxyapatite on the surface of titanium (implant core) by the plasma spraying method, the difference in the coefficient of thermal expansion and the difference in crystal structure between the two causes
There is a problem that it is basically difficult to form a film having high adhesion strength. In addition, the alkaline component such as oxidized apatite, which is formed by thermal decomposition of the hydroxyapatite powder when passing through a high-temperature plasma flame, remains in the film, and the film is easily dissolved in the living body ( Stability).

The present invention has been made in view of the above problems, and it is an implant that solves the problems of the prior art, is stable in vivo for a long period of time, and has excellent affinity with bone tissue. It is intended to provide a manufacturing method.

[0009]

Therefore, in the first aspect of the present invention, an "implant core body in which all or only the surface of the core body is made of titanium or titanium alloy is anodized in an electrolyte solution containing glycerophosphate and calcium salt. An implant characterized by being oxidized to form an anodic oxide film on the core, and then hydrothermally treated in high-pressure steam to precipitate a calcium phosphate compound so as not to cover the entire film on the anodic oxide film. Manufacturing method (claim 1) ".

Further, the present invention secondly provides the "production method (claim 2) according to claim 1, wherein the calcium phosphate compound is hydroxyapatite."

[0011]

[Function] Anodic oxidation uses an object (which is anodized) in an electrolyte solution as an anode to apply a voltage between it and a cathode such as stainless steel to electrolyze the surface of the object of the anode electrochemically. It is a method of forming an oxide film by oxidation. According to this method, an oxide film can be formed uniformly on the surface of the object, and the adhesion between the film and the object is good. Moreover, there is also an advantage that processing can be performed in a short time without requiring a special device.

For example, the implant core can be used as an anode for anodic oxidation, but the anodic oxide film formed on the implant core has irregularities due to minute projections formed by spark discharge during anodic oxidation, A micro anchoring effect occurs between the bone tissue and the bone tissue. That is, the concavity and convexity on the surface and the bone tissue are entangled with each other, so that the retaining force for the rotation and the pulling force applied to the implant is obtained.

Furthermore, when the bioactive calcium phosphate compound is formed on the anodic oxide film by, for example, hydrothermal treatment in high-pressure steam, the calcium phosphate compound directly binds to the bone, so that the implant is more firmly bonded to the bone. It is preferable because it binds. In the present invention, titanium or titanium alloy is used for the base material as the core. The shape thereof may be any shape, and may be rod-shaped or plate-shaped, and may be perforated or threaded. Further, the whole core does not have to be titanium or titanium alloy, and only the surface of the core may be coated with titanium or titanium alloy by plasma spraying or the like.

In order to increase the adhesion strength of the anodized film formed on the core body, the surface of the core body is sandblasted in advance,
It is preferable to increase the surface area of the core by roughening the titanium powder by a method such as plasma spraying or acid etching. In the case of anodizing, it is preferable that the core body is previously polished by a normal polishing method and the surface thereof is cleaned by alcohol cleaning, water cleaning or the like. For those that cannot be polished, it is preferable to clean the surface by pickling or the like. Further, by etching the core surface with an acid to remove the oxide film formed on the core surface naturally or through various heat treatments in the atmosphere, the active metal surface is exposed. It is preferable because the adhesion strength of the formed anodic oxide film increases. A masking agent may be previously applied to the surface portion of the core body that does not need to be anodized, and the whole may be treated and then removed. It is preferable to perform anodic oxidation after performing the above pretreatment. As the glycerophosphate contained in the electrolyte solution used when performing anodization, α-sodium glycerophosphate, β-sodium glycerophosphate, calcium glycerophosphate and the like are preferable. Particularly preferred is sodium β-glycerophosphate, which has high solubility in water.

Similarly, as the calcium salt contained in the electrolyte solution, calcium chloride, calcium nitrate, calcium carbonate, calcium hydroxide, calcium acetate, calcium lactate, calcium gluconate, calcium citrate, calcium propionate and the like are preferable. Calcium acetate is particularly preferable because it has a high solubility in water and does not contain ions harmful to the living body. Even if glycerophosphate and calcium salt are dissolved at the same time, they do not react to cause precipitation, and an electrolyte solution containing Ca and P at a high concentration can be prepared, and further stable anodic oxidation can be performed up to a high voltage. . The solvent of the electrolyte solution is not limited to water, and an organic solvent or molten salt may be used. An implant core made of titanium or a titanium alloy can be dipped in such an electrolyte solution, and anodization can be performed, for example, as follows. Important conditions for anodic oxidation include voltage, current density, concentration of electrolyte, temperature of electrolyte and the like.

Since the voltage affects the composition of the anodized film, the fine structure of the surface, the film thickness, the adhesion strength, etc., these conditions should be set to be optimum. Preferably 100 to 50
It is in the range of 0 V, particularly preferably in the range of 200 to 400 V, but is not limited to this range. The higher the current density, the faster the voltage rises, and the anodic oxidation is completed in a short time. However, if the anodic oxidation is too rapid, the adhesion strength of the coating may be reduced, and the fine structure of the coating may be disturbed. Further, if the current density is too low, it takes too much time, so it may be adjusted according to the surface area of the core. For example, the range of 5 to ²⁰⁰ mA / cm ² is preferable, but the range is not limited to this range.

Under a constant voltage, the setting of the electrolyte concentration determines the composition of the anodized film formed, and as a result, the composition of the calcium phosphate compound deposited on the anodized film by hydrothermal treatment. That is, by setting the concentration of each electrolyte (glycerophosphate, calcium salt), it is possible to form an anodized film or a calcium phosphate compound having a desired composition.

For example, in order to precipitate hydroxyapatite (an example of a calcium phosphate compound) crystal having a theoretical Ca / P ratio, the calcium salt concentration may be adjusted by keeping the glycerophosphate concentration constant, or vice versa. Good. Further, the higher the concentration of the electrolyte, the more Ca and P are taken into the anodized film, so that the amount of the calcium phosphate compound deposited on the anodized film also increases and the anodized film can be covered without any gap.

However, when such a large amount of calcium phosphate compound is deposited, since a large amount of Ca and P are contained in the anodic oxide film, after the hydrothermal treatment, the crystal structure of the interface between the oxide film and the core is changed. The consistency is reduced as compared with the case where Ca and P are contained in small amounts. Therefore, the adhesion strength at this interface decreases. Alternatively, a large amount of Ca and P are diffused toward the surface by the hydrothermal treatment, and the strength of the anodic oxide film left behind is reduced.

As described above, the higher the concentration of the electrolyte or the higher the temperature of the hydrothermal treatment, the more the calcium phosphate compound is deposited on the anodized film, so that the adhesion strength of the film tends to decrease. Therefore, in order to increase the adhesion strength of the film, the amount of the calcium phosphate compound deposited may be reduced. To do so, lower the electrolyte concentration (for example, the concentration of sodium β-glycerophosphate is 0.05 mol / l
Below, the concentration of calcium acetate is preferably 0.5 mol / l or less), the temperature of the electrolyte solution is lowered (for example, 30 ° C. or less is preferable), a calcium phosphate compound having a nonstoichiometric composition such as Ca-deficient water. Adjust the electrolyte concentration so as to precipitate oxide apatite crystals and adjust the composition of Ca and P contained in the anodic oxide film, and mild hydrothermal treatment conditions (for example, make the temperature 250 ° C or lower). Is preferable), and the addition of a trace amount of a metal compound (particularly preferably a compound of an alkaline earth metal other than Ca) to the electrolyte solution suppresses the precipitation of hydroxyapatite crystals or the like on the anodized film. Should be used.

However, if the precipitation amount of the calcium phosphate compound is too small, the effect of bioactivity will be lost, so that the minimum precipitation is necessary. That is, it is advisable to deposit the calcium phosphate compound to the extent that it does not cover the entire anodized film. When the electrolyte concentration is constant, the composition of the anodic oxide film changes depending on the voltage. Therefore, in order to precipitate a hydroxyapatite crystal having a theoretical composition ratio, the electrolyte concentration may be adjusted according to the voltage.

The temperature of the electrolyte rises due to the heat generated by the anodic oxidation, but depending on the concentration of the electrolyte, the adhesion strength of the coating film is affected by the temperature and the deposition amount of the calcium phosphate compound is affected, so that the control is accurately performed. Is preferred. If the temperature range for hydrothermal treatment is lower than 100 ° C, it will be difficult for calcium phosphate compounds to form,
If it is higher than 0 ° C, the adhesion strength of the coating tends to decrease, so 100 to 500 ° C is preferable. The hydrothermal treatment is preferably carried out mainly in high pressure steam using an autoclave, but it may be carried out in water or in water containing Ca and P.

The calcium phosphate compound to be precipitated is α
Alternatively, β-tricalcium phosphate, octacalcium phosphate, hydroxyapatite, amorphous calcium phosphate and the like are preferable. Particularly preferred is hydroxyapatite having a theoretical composition ratio or a composition ratio close thereto. This is because it has a high affinity for living organisms and has many excellent points such as direct binding to bone and promotion of new bone formation on the material.
In the present invention, Ca / P of precipitated hydroxyapatite crystals
The ratio can be adjusted by adjusting the concentration of the electrolyte, which is very easy. Since the hydroxyapatite crystal is a single crystal or has a very high crystallinity, it is difficult to be absorbed by the living body, and the effect of bioactivity lasts for a long time.

As described above, according to the present invention, first, Ca
An anodized film containing P and P is formed on the surface of titanium or a titanium alloy (core). Since this film is formed by oxidizing the surface of the metal, the crystal structures of both films are highly compatible and the adhesion strength is high. Further, since the individual crystals of the calcium phosphate compound deposited on the anodized film by the hydrothermal treatment and the crystal structure of the oxide film have a high degree of conformity, the bond strength between the two is also high. Therefore, an implant in which the anodized film and the calcium phosphate compound are firmly attached to the core body can be obtained. In addition, the adhesive strength does not decrease with time in the living body.

The present invention is basically different from the coating method in which a ceramic material is adhered to the metal surface from the outside such as the plasma spraying method (there is no need for a special apparatus such as a plasma spraying apparatus, and it can be easily performed. A film can be formed with good reproducibility), and the adhesion strength of the film can be greatly increased. Furthermore, by reducing the precipitation amount of the calcium phosphate compound, it is possible to achieve the effects of extremely high adhesion strength and durability and bioactivity at the same time.

The implant produced by the method of the present invention has a grayish white surface and is made of titanium (or titanium alloy).
Compared to the metallic color of the core, it gives a greater cleanliness to the patient. Hereinafter, the present invention will be described in more detail by way of examples, but the present invention is not limited to the examples.

[0027]

Example: β-sodium glycerophosphate (molecular weight: 306) and calcium acetate (molecular weight:
176), the voltage was kept constant at 350 V and the current density was kept constant at 50 mA / cm ^2, and each condition (No. 1 to 10) shown in Table 1 and Table 2
After anodizing each pure titanium (implant core: No. 1 to 14) under each condition (No. 11 to 14) shown in (1), all were hydrothermally treated in high-pressure steam for 2 hours.

The film obtained was subjected to a tensile test to measure the average adhesive strength. By X-ray diffraction analysis,
It was confirmed that all the calcium phosphate crystals deposited on the anodized film were hydroxyapatite. The surface of the film was observed with an electron microscope to examine the state of precipitation of hydroxyapatite crystals. The above results are summarized in Tables 1 and 2.

Under conditions 1 and 2, when the electrolyte concentration was made extremely low, a small amount of hydroxyapatite crystals were deposited and scattered on the anodized film. Under conditions 3 to 5, when the anodization was performed with the temperature of the electrolyte at 3 ° C, the amount of hydroxyapatite crystals deposited decreased compared to the case of anodizing at 30 ° C, and everything on the anodized film (entire surface) Did not cover.

Under the conditions 6 to 8, when the calcium acetate concentration was made lower than the concentration of sodium β-glycerophosphate in the electrolyte to precipitate the hydroxyapatite crystals in which Ca was much less than the stoichiometric composition, the stoichiometric composition was found. Alternatively, compared with the case where a little Ca was precipitated in hydroxyapatite, the amount of precipitation was reduced and scattered on the anodized film. Condition 9-1
At 0, when the hydrothermal treatment temperature was 200 ° C., the precipitation amount of hydroxyapatite crystals decreased and the bond strength increased as compared with the hydrothermal treatment at 300 ° C.

Conditions 11 to 14 are formed when anodizing is performed by adding a small amount (0.005 mol / l) of magnesium acetate to the electrolyte solution containing sodium β-glycerophosphate and calcium acetate, and when it is not added. The adhesion strength of the different coatings was compared. The temperature of the electrolyte solution during anodization is
The hydrothermal treatment temperature of the anodic oxide film was kept constant at 30 ° C and 300 ° C.

As a result, under the conditions 11 and 13 in which magnesium acetate was not added, HAp crystals were deposited on the anodized film without gaps, but under the conditions 12 and 14 in which magnesium acetate was added, HAp crystals were not deposited. Suppressed and sparsely precipitated. The adhesive strength of the coating was significantly increased by adding magnesium acetate. The HAp crystal of bone contains a small amount of Mg, but the HAp crystal containing a small amount of Mg synthesized under the conditions 12 and 14 has an effect of further excellent affinity for bone.

Histologically, the affinity for bone tissue was good under all conditions. The adhesive strength of the coating did not decrease at all, and the durability was very high. It was confirmed that the precipitated hydroxyapatite crystals were either single crystals or had extremely high crystallinity, and thus were difficult to be absorbed in vivo and remained on the anodized film even after 8 weeks.

[0034]

[Table 1]

[0035]

[Table 2]

[0036]

According to the present invention, it is possible to manufacture an implant which is stable in a living body for a long period of time and has an excellent affinity with bone tissue. In addition, the surface of the implant manufactured by the method of the present invention is grayish white, and compared to the metallic color of the titanium (or titanium alloy) core, the implant has a greater sense of cleanliness.

[0037]

Claims (2)

[Claims] 1. An anodic oxide film is formed on the core body by anodizing an implant core body in which all or only the surface of the core body is made of titanium or titanium alloy in an electrolyte solution containing glycerophosphate and calcium salt. And then hydrothermally treating in high-pressure steam to deposit a calcium phosphate compound on the anodized film so as not to cover the entire film, a method for producing an implant. 2. The method according to claim 1, wherein the calcium phosphate compound is hydroxyapatite.