KR100453289B1 - Electrolyte solution for implant surface treatment and method of implant surface treatment using the same - Google Patents

Abstract

PURPOSE: To provide an electrolyte for implant surface treatment, with which surface-treated implant has a porous film on the surface thereof to have large specific area, and educes a large amount of hydroxy apatite crystals when being treated with hot water, a method for implant surface treating by using the electrolyte and an implant prepared by the method. CONSTITUTION: The electrolyte comprises 0.01-0.08 mol/liter of glycerol phosphate, 0.1-0.4 mol/liter of calcium acetate hydrate and 0.001-0.01 mol/liter of buffer. The method comprises the steps of (a) oxidizing anode made of titanium or titanium alloy with the electrolyte; and (b) hot water treating the film-formed anode at the step (c).

Description

ELECTROLYTE SOLUTION FOR IMPLANT SURFACE TREATMENT AND METHOD OF IMPLANT SURFACE TREATMENT USING THE SAME}

[Industrial use]

The present invention relates to an electrolyte solution for implant surface treatment and an implant surface treatment method using the electrolyte solution, and more particularly, a porous film is formed on the surface to have a large surface area advantageous for stress dispersion and a large amount of water on the surface when hydrothermal treatment is performed. Since hydroxyapatite (HA) crystals are deposited, the present invention relates to an electrolyte solution for implant surface treatment having excellent biocompatibility and an implant surface treatment method using the electrolyte solution.

[Prior art]

Implants are biomedical medical devices that are implanted in vivo and exert their desired functions. Therefore, implants should be manufactured using biocompatible materials that are very stable against biological tissues so that they do not have side effects and do not cause chemical and biochemical reactions. They are filled with complete bones without any soft tissues between bones and implants after being implanted in vivo. As the bone bonding force to be combined with the bone should be high. In addition, the implant must be made of a material having a very high mechanical strength since it must not be deformed or destroyed even under repeated loading and imposing pressure.

In order to satisfy the above conditions, various metals and alloys have been developed as suitable materials for implants. However, when a metal implant is implanted in a living body and placed in the body for a long time, the metal ion of the metal implant is eluted by the tissue fluid or body fluid in the body, and the metal implant is in contact with or rubbed against the tissue in the body, thereby eluting the metal ion of the metal implant. Due to the elution of these metal ions, the implant is corroded and macrophage of the living body reacts to induce inflammatory cells or giant cells.

For the same reason, the problem that the metal implant cannot satisfy biocompatibility, chemical compatibility, and mechanical compatibility, which are conditions to be provided as a biomaterial, has emerged. In order to solve the above problems, various types of bio-ceramic and the like have been developed, but most of the ceramics have a problem in that they cannot be used alone to manufacture implants because they are weak to impact and difficult to process.

Currently, the most widely used implant materials include titanium and titanium alloys, which are highly biocompatible. Titanium is not only easy to process, but also relatively lighter than other metals and can be made of alloys of other metals or subjected to proper treatment to increase strength, and is very dense and highly reformable in air or water. It forms an oxide film and has a very large corrosion resistance, and when it is embedded in bone, it has the great advantage of having a close bond of bone and osteointegration and is currently widely used as an implant material.

However, the oxide film on the surface of titanium produced naturally is non-uniform, and has a disadvantage of not dense. For this reason, various surface treatment methods have been introduced in order to form a dense passivation film on the surface of the titanium implant and to promote bonding with bone and stress distribution.

In order to improve the mechanical holding force, screw formation, sand blasting treatment, electrochemical oxidation, etc. are performed, and anodization, plasma spraying, alkali treatment, Ion implantation and the like (McQueen 1982; Kasemo and Lausmaa, 1985; Lee et al., 1993; Schroeder et al., 1996; Kokubo et al., 1996; Yan et al., 1997).

Recently, the surface of titanium implant is coated with hydroxyapatite (hereinafter referred to as 'HA'), which is a biocompatible calcium phosphate ceramic, to prevent the implantation of metal ions and to prevent biocompatibility. Implants with mechanical strength have been developed and widely applied as biomedical medical devices for dental, orthopedic, maxillofacial and mandibular surgery.

Plasma spraying is most commonly used as a method of coating HA on implants. The plasma spraying method is mainly used for coating ceramic materials having a relatively high melting point, so that a large amount of coating can be easily performed at one time. It is a method of forming HA film by dissolving HA powder in a flame) and spraying it onto an implant.

Plasma spraying, however, provides a porous film with a high free energy, but suffers from problems such as crack formation and fused particles falling off at the interface with the substrate (Lemons, 1998; Wang et al., 1993). In addition, during the HA spraying using the plasma spray method, HA powder is exposed to high temperature during the coating process, thereby forming an HA coating layer that is not chemically uniform, and having a long period of time, decomposition or resorption occurs. .

In addition, the HA coating layer of the existing implant coated with HA is only about 6.7 ± 1.5 Mpa adhesion to the implant and is not suitable for use as an implant having a strong and dense coating layer required by orthopedic or dental.

As described above, conventional implants coated with HA have been reported to have problems such as low crystal uniformity of the coating layer, weak adhesion with metal implants, and degradation or absorption in vivo. That is, the adhesion between the HA coating layer and the bone of the existing implant is good, but there is a problem that the HA coating layer is dissolved in vivo and the HA coating layer is separated from the metal implant surface to be separated. Since the HA coating layer is not absorbed by osteoclasts in vivo, it can not induce bone remodeling, so that the implant is isolated from the new bone. Therefore, the existing HA implant has excellent initial reactivity, but it can be seen that it is not desirable for clinical applications for a long time.

Recently, researches on the film formation method by anodization and flame discharge treatment have been actively conducted. As a method of forming a dense oxide film on the surface of titanium by electrochemically treating titanium in an electrolyte solution, It has the advantage of excellent biocompatibility.

In particular, in recent years, in the electrochemical implant surface treatment method using anodization and flame discharge treatment, a study on the type and concentration of an optimal electrolyte solution containing calcium and phosphorus in order to improve the corrosion resistance and biocompatibility of the implant surface Are actively underway (Hitoshi Ishizawa and Makoto Orgino, 1995).

The present invention is to solve the above-mentioned problems, an object of the present invention is to form a porous film on the surface has a large surface area advantageous for stress dispersion and also a large amount of hydroxyapatite (HA) crystals are deposited on the surface when the hydrothermal treatment It is to provide an electrolyte solution for implant surface treatment excellent in biocompatibility.

It is also an object of the present invention to provide an implant surface treatment method using the electrolyte solution.

It is also an object of the present invention to provide an implant made by the method.

1A to 1C are scanning electron micrographs of the specimens of Example 1 and Comparative Examples 1 to 2. FIG.

2a to 2b are the results of X-ray diffraction analysis for the specimens of Example 1 and Comparative Example 1.

Figures 3a to 3b is a scanning electron micrograph of the surface of the specimen prepared in Example 1 was immersed in the analog solution (Hanks solution) for 15 days and 30 days.

Figure 4 is a graph comparing the tensile bond strength of Example 1, Comparative Example 1 and the control specimens.

5A and 5B are scanning electron micrographs of the wavefront of Example 1 in the tensile bond strength measurement test.

6a to 6d are scanning electron micrographs of the specimens after anodization in Example 1 and Comparative Example 3. FIG.

7a to 7d are scanning electron micrographs of the specimens after hydrothermal treatment in Example 1 and Comparative Example 3.

8a to 8d are scanning electron micrographs of the specimens after the immersion test in the analogous fluid in Example 1 and Comparative Example 3.

In order to achieve the above object, the present invention (a) Glycerol phosphate (Glycerolphosphate); (b) Calcium acetate hydrate; And (c) provides an electrolyte solution for implant surface treatment comprising a buffer (Buffer).

The present invention also provides an anode oxidation step of oxidizing the anode using (a) titanium or a titanium alloy as an anode, platinum or silver as a cathode, and the solution as an electrolyte; and (b) forming a cathode in the anodization step. It provides an implant surface treatment method using an electrolyte solution comprising a hot water treatment step of hot water treatment.

The present invention also provides an implant prepared by the above method.

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

The electrolyte solution for implant surface treatment of the present invention includes (a) Glycerol phosphate, (b) Calcium acetate hydrate, and (c) Buffer as essential components.

The (a) glycerol phosphate and (b) calcium acetate hydrate contain phosphate and calcium, so that when adsorbed on the implant surface and embedded in the body, the bone and its components are similar, so that the biocompatibility is excellent.

At this time, the molar concentration of the (a) glycerol phosphate in the electrolyte solution is preferably 0.01 to 0.08 mol / L. If the molar concentration of (a) glycerol phosphate is less than 0.01 mol / l, the concentration of phosphoric acid adsorbed on the implant surface is low, and thus the biocompatibility of the implant is poor. In contrast, the molar concentration of (a) glycerol phosphate is 0.08. If the mol / L exceeds, the oxide film is too thick, which is not preferred because the bond strength of the film and the lower substrate is lowered.

Specific examples of such (a) glycerol phosphate include β-glycerol phosphate disodium salt hydrate, glycerin phosphate calcium salt, glycerol phosphate disodium salt hydrate, and DL- Glycerolphosphate disodium salt, or mixtures thereof, and the like, and in particular, acicular hydroxapatite during hot water treatment in a film treated with DL-α-glycerolphosphate disodium salt It is more preferable because a large amount of (HA) crystals are precipitated.

In addition, the concentration of (b) Calcium acetate hydrate in the electrolyte solution of the present invention is preferably 0.1 to 0.4 mol / l, more preferably 0.2 mol / l. In this case, when the concentration of (b) calcium acetate hydrate is less than 0.1 mol / L, the concentration of calcium adsorbed on the implant surface is small, and thus the amount of precipitation of hydroxyapatite (HA) is lowered. On the contrary, the (b) calcium acetate When the concentration of hydrate exceeds 0.4 mol / l, the concentration of phosphorus adsorbed on the coating decreases, which adversely affects the formation of hydroxyapatite (HA), and the thickness of the coating increases, which may cause peeling at the interface when an external force is applied. Not desirable

In addition, the electrolyte solution of the present invention contains a buffer solution, more preferably HEPES as the buffer solution. This is because the use of HEPES as a buffer increases the amount of hydroxyapatite (HA) due to the increased phosphorus content in the anodized layer.

At this time, the concentration of the buffer (C) is preferably 0.001 to 0.01 mol / L.

In addition, the electrolyte solution of the present invention may further include (d) solute, and the solute is preferably a compound containing phosphate ions, or the electrolyte solution is preferably a solution containing sulfate and phosphate. Moreover, distilled water is preferable as a solvent.

The present invention also provides a method of implant surface treatment using the electrolyte solution. The method will be described in detail below.

The implant surface treatment method of the present invention is used as the material of the implant by using an electrolyte solution containing calcium and phosphorus, unlike the conventional plasma spraying method, electrochemical oxidation method and the like to form a coating film as an anode, platinum as a cathode Or a method of forming a film on the surface of the positive electrode material using an electrochemical reaction using silver or the like.

First, when a constant current is applied with titanium or a titanium alloy as an anode, platinum, tungsten or silver as a cathode, and the electrolyte solution is used as an electrolyte, the anode is oxidized and calcium and phosphorus components in the electrolyte are adsorbed onto the anodizing film ( (A) step).

The reaction condition of this anodization step is carried out in a constant voltage constant current mode, and reaches a final voltage of 280 to 350 V at a constant current density of 5 to 50 mA / cm 2, and is maintained for 5 to 10 minutes at the final voltage conditions. In the process, the spark discharge phenomenon occurs due to dielectric breakdown, and the surface of the anode specimen becomes porous due to the spark discharge.

The dielectric breakdown usually starts around 210 to 230V, and it is preferable to maintain the final voltage of 280 to 350V in order to proceed with the breakdown efficiently. The higher the voltage, the greater the intensity of the spark discharge, and if it is above 350 V, cracks are formed in the coating layer.

The reason for maintaining the voltage causing insulation breakdown in the present invention is to induce spark discharge in the film of the positive electrode specimen, and thereby to destroy the film to make the film surface porous. Since the surface layer of the porous oxide film is mechanically bonded by bone structure and uneven structure, a strong bonding force can be obtained.

In this case, titanium or a titanium alloy is used as the anode on which the coating layer is formed, and as the titanium alloy, Ti-6Al-4V, Ti-6Al-7Nb, Ti-13Nb-13Zr, Ti-15Mo, Ti-35.3Nb-5.1Ta- 7.1Zr, Ti-29Nb-13Ta-4.6Zr, and the like.

Titanium is not only easy to process, but also relatively lighter than other metals, and can be made of alloys of other metals or subjected to appropriate treatments to improve strength, and also very dense and reformable in air or water. It forms an excellent passivation oxide film and has a very large corrosion resistance, and it is preferable because it has a great advantage of having a close bond of bone and osteointegration when embedded in bone.

The hydrothermal treatment of the titanium or titanium alloy of the anode prepared through the first anodization and flame discharge treatment is carried out by steam (step (b)). The purpose of such hydrothermal treatment is to induce the precipitation of hydroxyapatite (HA) on the surface of the coating to impart activity to the implant surface, thereby improving bone adhesion with bone and inducing plate crystals on the anatase. .

The hydroxyapatite (HA), which is the biocompatible calcium phosphate-based ceramic, functions to prevent metal ions from eluting the implant and improve biocompatibility.

Conventionally, the method used for coating HA is plasma spraying method. When the plasma spraying method is used, a porous film having a high free energy can be obtained, but problems such as crack formation or fused particles are dropped at the interface with the substrate. In addition, during the coating process, the HA powder is exposed to high temperature to form a chemically non-uniform HA coating layer, and there is a vulnerability in that decomposition or resorption occurs over a long period of time. However, the present invention was able to improve the problem of the conventional plasma spray method by introducing a hot water treatment method.

This hot water treatment step is carried out in an autoclave, preferably a hot water treatment temperature of 250 to 350 ° C., a hot water pressure of 1200 to 1400 psi, and a hot water treatment time of 2 to 4 hours.

The implant prepared by the hydrothermal treatment method is similar to the similar condition of 37 ° C. and pH 7.4 in order to investigate the surface activity after embedding hydroxyapatite crystals on the surface as a biocompatible and excellent biocompatibility material. Reactivity was investigated by maintaining it in the body fluid (simulated body fluid, Hanks solution) for a certain time.

Analog solution can be prepared by mixing 1.5 mM MgCl ₂ · 6H ₂ O, 2.5 mM Na ₂ SO ₄ , 1 mM K ₂ HPO ₄ · 3H ₂ O, 4,2 mM NaHCO ₃ , 136.8 mM NaCl and 3 mM KCl. have. In addition, the ion concentration of the prepared analog solution can be measured through ICP-AES.

The implants surface-treated using the electrolyte solution of the present invention described above have a large surface area which is advantageous for stress dispersion due to the formation of a porous film on the surface, and when hydrothermally treated, a large amount of hydroxyapatite (HA) crystals are deposited on the surface, thereby making it compatible with biocompatibility. This has an excellent effect.

Hereinafter, preferred examples and comparative examples of the present invention are described. The following examples and comparative examples are described for the purpose of more clearly expressing the present invention, but the contents of the present invention are not limited to the following examples and comparative examples.

(Example 1)

A commercially pure titanium plate with a thickness of 1 mm was cut to a size of 20 mm x 0 mm, and the surface was sequentially polished with SiC abrasive papers of # 220 to # 600, and then ultrasonically cleaned for 5 minutes each with distilled water, alcohol, and acetone solution. The prepared specimens were stored for at least 24 hours in a dryer at 50 ° C. until the surface treatment was performed.

The prepared specimen and platinum plate were connected to the anode and cathode of the DC electrostatic source device, and the voltage was raised to 300 V at a current density of 30 mA / cm 2 and maintained for 5 minutes under constant voltage conditions. Stored. As the electrolyte solution, a solution containing calcium ions and phosphate ions was used. As an electrolyte solution, a sigma-made DL-α-glycerol phosphate 0.05 M, calcium acetate hydrate 0.3 M, and HEPES 0.005 M dissolved in distilled water were used.

After anodization and flame discharge treatment, hydrothermal treatment was performed in an autoclave to induce precipitation of hydroxyapatite crystals by crystallization of calcium and phosphorus adsorbed on the coating layer. In order to evaluate the surface activity of the specimens after the surface treatment, pH and ionic concentrations were deposited in the analogous fluid adjusted to human plasma.

(Comparative Example 1)

A specimen was prepared in the same manner as in Example 1 except that the hydrothermal treatment was not performed.

(Comparative Example 2)

The specimen was prepared by polishing only without performing anodization, flame discharge treatment, and hot water treatment.

(Comparative Example 3)

The same procedure as in Example 1 was conducted except that no HEPES buffer was used.

Morphological Microstructure of Specimen Surface Layer

Morphological microstructure of the specimen surface layer was observed by scanning electron microscopy (SEM), and the results are shown in FIGS. 1A to 1C. Figure 1a is a scanning electron micrograph of the specimen of Example 1, Figure 1b is a scanning electron micrograph of the specimen of Comparative Example 1, Figure 1c is a scanning electron micrograph of the specimen of Comparative Example 2.

As shown in FIGS. 1A to 1C, in Example 1 specimens, a plurality of needle-shaped precipitates were observed on the porous oxide film, and in Comparative Example 1 specimens, a dense porous oxide film having a diameter of 1 to 5 μm was observed. Abrasion marks were observed on the surface.

X-ray diffraction analysis of the specimen

X-ray diffraction analysis of the specimen is shown in Figures 2a to 2b. FIG. 2A is an X-ray diffraction analysis result of Example 1 specimen, and FIG. 2B is an X-ray diffraction analysis result (XRD pattern) of Comparative Example 1 specimen. The crystal structure of the elements present in the coating layer was analyzed with an X-ray diffraction device equipped with a thin-film analyzer.

As shown in Figure 2a to 2b, the Ti component and TiO ₂ of the base material was observed in the specimen (Comparative Example 1) that was not subjected to the hot water treatment, but the Ti component of the base material in the base material of the specimen (Example 1) subjected to the hydrothermal treatment, Peaks of TiO ₂ and HA on anatase were observed.

Therefore, when the hydrothermal treatment was further performed on the specimen subjected to anodization and flame discharge, it was confirmed that hydroxyapatite phase crystals were deposited on the specimen surface.

Analog fluid deposition test result

The specimen prepared in Example 1 was immersed in the analog solution (Hanks solution) for 15 days and 30 days, and then photographs taken with a scanning electron microscope are shown in FIGS. 3A and 3B.

As shown in Figure 3a and Figure 3b, it can be seen that as the deposition time elapses, the HA crystal densified into a protrusion.

Tensile Bond Strength Comparison

In FIG. 4, tensile bond strengths of the specimens sprayed with alumina having a mean particle diameter of 125 μm in Ti round bars having a diameter of 10 mm as Example 1, Comparative Example 1 and a control group are shown. Toughness was measured based on ASTM standard C633-79.

As shown in FIG. 4, the specimen of Example 1 treated with hydrothermal treatment showed a significant decrease in bonding strength compared to Comparative Example 1 specimen not treated with hydrothermal treatment.

Nevertheless, it was found that the anodized, flame discharged, and hydrothermally treated implants exhibit sufficient bonding strength for use as implants.

Scanning electron micrograph of wavefront

Scanning electron micrographs of the specimen wavefront of Example 1 in the tensile bond strength measurement test are shown in FIGS. 5A and 5B. FIG. 5B is an enlarged view of FIG. 5A. In the tensile bond strength measurement test, epoxy resin was used as the adhesive.

As shown in FIGS. 5A and 5B, the interfacial fracture between the Ti base material and the oxide film was partially, but the interfacial fracture between the acid lime film and the epoxy resin and the cohesive fracture between the epoxy resin were shown.

Therefore, the tensile bond strength test results showed that the Example 1 specimen showed excellent bond strength, and that the bond strength of the film was found to be mainly observed at the interface between the epoxy and the oxide film and the epoxy itself, not the base material and the oxide film. It is assumed to be larger than.

Apatite precipitation pictures

6A to 6D are scanning electron micrographs and enlarged views of specimens after anodization in Example 1 and Comparative Example 3, respectively. 6A is a photograph of a specimen of Example 1, FIG. 6B is an enlarged view of FIG. 6A, FIG. 6C is a photograph of a specimen of Comparative Example 3, and FIG. 6D is an enlarged view of FIG. 6C.

7a to 7d are scanning electron micrographs of the specimens after hydrothermal treatment in Example 1 and Comparative Example 3. 7A is a photograph of the specimen of Example 1, FIG. 7B is an enlarged view of FIG. 7A, FIG. 7C is a photograph of the specimen of Comparative Example 3, and FIG. 7D is an enlarged view of FIG. 7C.

8a to 8d are scanning electron micrographs of the specimens after the immersion test in the analogous fluid in Example 1 and Comparative Example 3. FIG. 8A is a photograph of the specimen of Example 1, FIG. 8B is an enlarged view of FIG. 8A, FIG. 8C is a photograph of the specimen of Comparative Example 3, and FIG. 8D is an enlarged view of FIG. 8C.

As shown in FIGS. 6A to 8D, when HEPES solution was used as a buffer, needle-like apatite precipitated on the surface of the specimen.

(A) Glycerol phosphate of the present invention; (b) Calcium acetate hydrate; And (c) implants prepared through oxidation, flame discharge, and hot water treatment processes using an electrolyte solution for implant surface treatment containing buffer as an essential component, having a porous surface formed on the surface, which is advantageous for stress dispersion. In addition, it is excellent in biocompatibility because a large amount of hydroxyapatite (HA) crystals are deposited on the surface when the hydrothermal treatment is carried out.

Claims (11)

(a) 0.01 to 0.08 mol / l glycerol phosphate; (b) 0.1 to 0.4 mol / l Calcium acetate hydrate; And (c) Buffer 0.001 to 0.01 mol / l Electrolyte solution for implant surface treatment comprising a. The method of claim 1, The (a) glycerol phosphate is β-glycerol phosphate disodium salt hydrate (Glycerolphosphate disodium salt hydrate), glycerol phosphate calcium salt (Glycerolphosphate calcium salt), glycerol phosphate disodium salt hydrate (Glycerolphosphate disodium salt hydrate), and DL-α- Glycerol phosphate disodium salt (Glycerolphosphate disodium salt) electrolyte solution for implant surface treatment, characterized in that selected from the group consisting of. The method of claim 1, (C) the buffer solution is an electrolyte solution for implant surface treatment, characterized in that HEPES. The method of claim 1, The electrolyte solution is an electrolyte solution for implant surface treatment, characterized in that it further comprises (d) solute. The method of claim 4, wherein (D) the solute is an electrolyte solution for implant surface treatment, characterized in that the compound containing phosphate ions. delete (A) anodizing step of oxidizing the anode by using titanium or titanium alloy as an anode, platinum, tungsten or silver as a cathode, the solution of any one of the preceding claims as an electrolyte; And (B) a hydrothermal treatment step of hydrothermally treating the anode in which the film is formed in the anodization step Implant surface treatment method using an electrolyte solution comprising a. The method of claim 7, wherein The anodic oxidation step (a) is an electrolyte characterized in that a constant current density of 5 to 50 mA / cm 2 at a constant current constant current mode to reach a final voltage of 280 to 350 V and maintained for 5 to 10 minutes at a final voltage condition. Implant surface treatment method using a solution. The method of claim 7. The (b) hot water treatment step is an implant surface treatment method using an electrolyte solution, characterized in that for 2 to 4 hours at 250 to 350 ℃, 1200 to 1400 psi in an autoclave. The method of claim 7. The titanium alloy used in the (a) hydrothermal treatment step is Ti-6Al-4V, Ti-6Al-7Nb, Ti-13Nb-13Zr, Ti-15Mo, Ti-35.3Nb-5.1Ta-7.1Zr or Ti-29Nb- Implant surface treatment method using an electrolyte solution, characterized in that 13Ta-4.6Zr. (A) anodizing the titanium or titanium alloy as an anode, and oxidizing the anode by using platinum, tungsten or silver as a cathode; And (B) a hydrothermal treatment step of hydrothermally treating the anode in which the film is formed in the anodization step Implants prepared according to the implant surface treatment method using an electrolyte solution comprising a.