KR20030039763A - Ti-BASED ALLOY BIOMATERIALS WITH ULTRA FINE BIOACTIVE POROUS SURFACE AND MANUFACTURING METHOD THEREOF - Google Patents

Abstract

PURPOSE: Provided are a titanium base alloy for biomaterial having the ultramicro bioactive porous surface and a preparation method thereof to enhance the bone binding strength and the bone binding ability and have good biocompatibility. CONSTITUTION: The preparation method of a titanium base alloy for biomaterial having the ultramicro bioactive porous surface comprises adding 5 to 20 wt.% of indium, 2 to 5 wt.% of niobium and 3 to 5 wt.% of tantalum on the basis of total alloy weight to the balance of titanium and mixing, alkali treating with an alkali aqueous solution, and then heat treating in a vacuum heat treating furnace to form a ultramicro bioactive porous layer of sponge structure and a micro network structure on all the alloy surface.

Description

Titanium-based alloy for a biomaterial having an ultra-fine bioactive porous surface and a method of manufacturing the same {Ti-BASED ALLOY BIOMATERIALS WITH ULTRA FINE BIOACTIVE POROUS SURFACE AND MANUFACTURING METHOD THEREOF}

The present invention relates to a titanium-based alloy for a biomaterial having an ultra-fine bioactive porous surface for a living body, and a method of manufacturing the same, and to a titanium-based alloy for biomaterials such as artificial bones, artificial joints, and artificial teeth. (Nb) and a tantalum (Ta), such as a predetermined amount of a composite compound, and the surface modification by alkali treatment and heat treatment to form a nano-sized ultra-fine bioactive porous structure on the alloy surface It relates to a titanium-based alloy and a method of manufacturing the same.

As the aging society and the desire to extend human life and welfare are amplified, researches to understand life phenomena such as medicine and biotechnology are rapidly developing, and human damage caused by natural or acquired thinking There is widespread research to artificially replace organs or tissues.

According to Ratner et al., 11,000,000 Americans have at least one medical-device implant, and more than 500,000 implant surgeries are performed every year (Lettner et al., Biomaterial Science, Academic Press, (1996)). Moreover, the age of those who need such implants is gradually decreasing and the number is increasing day by day.

The basic problem in implant implantation to date has been the biocompatibility of the artificial biomaterials used. In other words, biomaterials should maintain safety without toxicity in vivo with functionality. To meet these requirements, artificial biomaterials have appropriate physical properties and are free from chemical reactions such as cytotoxicity and allergic reactions. The suitability for living tissue should be good. Therefore, the selection of good biomaterials has a great influence on the success and prognosis of artificial teeth, artificial joints, etc., and therefore, the selection of the right biomaterials is very important.

As the biological metal material, stainless steel, Co-Cr alloy, pure titanium (Ti) and the like have been mainly used (castleman et al., J. Biomes. Mat. Res., 10, 695 (1979); lemons, JADA 121, 716 (1990); and Linder et al., Acta Orthopaedica Scandinavica 60, 135 (1989)). In particular, titanium has very excellent corrosion characteristics and biocompatibility, but its use has been limited due to the difficulty in processing due to high melting point, but recently, the application range has been expanded with the development of processing technology. It is widely used as a material for implantation of teeth (Far et al., J. Prosth. Dent. 54, 410 (1985); and Solar et al., J. Biomes. Mat. Res., 13, 217 (1970)). In addition, titanium alloys in which other elements are added to pure titanium in order to obtain more excellent mechanical and physical properties are known to satisfy both biocompatibility, mechanical properties and physical properties. have.

As such a titanium alloy, Ti-6Al-4V Extra Low Interstitials (ELI) to which aluminum (Al) and vanadium (V) are added has been most used as a biomaterial because of its excellent strength and corrosion resistance. The Ti-6Al-4V ELI has been found to have about 60% better mechanical strength than pure titanium, but it is toxic when aluminum and vanadium, the alloying elements of titanium, are eluted. It is controversial. In other words, aluminum is suspected to combine with inorganic phosphorus to deplete phosphorus in blood or bone and cause Alzheimer's dementia, and vanadium has been pointed to cytotoxicity [Lukovsky et al., Journal of Biomedical Materials Research, 25 (1991); Yoshimitsu et al., Journal of the Metal Society of Japan, Vol. 61, No. 5 462 (1997).

In this regard, the present inventors have added titanium with alloying elements such as zirconium (Zr), niobium (Nb), tantalum (Ta), palladium (Pd), and indium (In), which are not cytotoxic alloys. Invented the alloy, the cytotoxicity test using cell culture and animal experiments of white rabbits proved that the biocompatibility of the alloying element is very excellent, the biocompatible titanium-based alloy with excellent biocompatibility. Patent application has been filed (Korean Patent No. 211097 (1999.4.29)). However, the patent No. 211097 has a problem that a small amount of indium is added, the mechanical properties and corrosion resistance is still insufficient. Patent application for a titanium alloy for biomaterials having a low elastic modulus and excellent corrosion resistance by adding a large amount of indium (3-20 wt%), similar to that of Patent No. 211097 (Korean Patent Application No. 10-1999-00742467) There is.

In addition, when the implant metal is inserted into the human body, a direct bond is not formed between the human tissue such as bone and the implant metal, and a problem that the fibrous tissue is formed due to a biological foreign body reaction results in isolation of the inserted metal and tissue. Will occur. Therefore, in order to fix the implant to human tissues such as bone, conventionally, the surface of the implant is roughened to pres-fit, or the bone tissue and the implant are bonded using bone cement (PMMA) or the like, A method of inducing bone growth using a porous surface implant obtained by sintering a bead or fiber type metal has been used. Such porous surfaces are known to increase bone bonding strength and bone bonding speed (Matthew, Advanced Material & Process, 7 (1998)). However, the conventional physical bonding methods as described above not only damage bone tissue and shorten the life of the implant, but also the implant is easily detached from the bone and bone cement is separated from the joint because the bond with the bone is not stable. There was a problem that secondary tissue damage could be caused by sintered metal fragments.

In addition, in recent years, the surface area of the implant by applying a bio-ceramic (hydroxyapatite, Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ) having a chemical composition similar to that of bone to the surface of the implant by plasma spraying coating Methods to increase bond strength and bond speed by widening and inducing chemical bonds with bone have been used (Cook et al., Journal of Material Processing & Technology, 89-90 (1999)). However, the apatite hydroxide layer coated in this way easily falls under low external stress, the composition of the laminated apatite hydroxide layer is uneven due to rapid solidification, and the crystal is unstable and easily absorbed into the bone in a short time when inserted into the body. There is a problem in that it does not provide a stable bond in the long term.

In recent years, as a best way to solve the above problems, by chemically surface-modifying the biological metal, it prevents the sequestration by the fibrous cells when inserted into the living body, and without the coating of bioactive ceramics such as apatite hydroxide Methods to enable direct chemical bonding are being studied.

In this study, bioactivity on TiO2 produced by the sol-gel method was reported [Lee et al., Journal of Biomedical Materials Research, 27 (1993)], and bioactivity on pure titanium surfaces was treated by H2O2 solution treatment [Otsu Ski et al., Journal of Biomedical Materials Research, 35 (1997)], or through alkali treatment and heat treatment [Kokubo et al., Journal of Biomedical Materials Research, 32 (1996)], or acid (HCl + H ₂ SO ₄ ). It has been reported that alkalis can be derived through two-step chemical treatment [Wen et al., Biomaterials, 18 (1997)].

In addition, the clock kebold and the like is related to bone bonding force and bone bonding rate, which is one of the important requirements in the biomaterial for implants, the greater the surface roughness, the faster the bone formation and growth, the greater the bone bonding force, but the smooth surface It has been found that in titanium alloys, bone growth does not occur and fibrous tissue covers the surface (Clokkebold et al., Clin. Oral. Implant Research, 8-6 (1997). At this time, the marginal section of the surface roughness is about 1 ~ 100 nm microscopic grade and about 0.11 ~ 100 ㎛ macroscopic grade, only bone marrow cells (bone marrow cells) are reported to generate and grow on the surface only in this section. Rough surface in this zone increases the nucleation of bone marrow cells and accelerates the growth of bone marrow cells (Del. Anri et al., Biomaterials, 22 (2001)), and when the surface forms a sponge structure, As the bonding area with bone is greatly increased, bone bonding force is greatly increased.

In this regard, the present inventors have intensively studied, and as a result of complex addition of alloying elements such as indium, niobium, and tantalum alloy elements to the titanium (Ti) alloy system, the internal structure of the alloy is changed, and during chemical treatment and heat treatment It has been found that an ultrafine bioactive porous layer with a dense cavernous structure of less than 100 nm is formed on the alloy surface. The surface area of the alloy is greatly increased by the method for producing an ultra-fine bioactive porous surface, thereby improving bone bonding ability such as bone bonding strength and bone bonding speed, and titanium alloy for biomaterial having excellent biocompatibility. It was found that can be obtained and came to complete the present invention.

Accordingly, an object of the present invention is to add an alloying element such as indium, niobium and tantalum, which is harmless to the living body, to a biological titanium having a low modulus of elasticity and excellent corrosion resistance, and then chemically treated and heat treated to provide ultra-porous surface to the surface. By forming a structure, there is provided a titanium-based alloy for biomaterials having improved bone bonding ability and biocompatibility and a method of manufacturing the same.

1 is a scanning electron microscopy (SEM) photograph showing the surface microstructure generated by surface modification through alkali treatment and heat treatment, (a) is a Ti-6Al-4V ELI alloy of a conventional biomaterial Surface microstructure, (b) shows the surface microstructure of the Ti-In-Nb-Ta alloy of the surface nanoporous structure according to the present invention.

2 shows the plasma and ion concentrations of humans with respect to surface modification through alkali treatment and heat treatment of a conventional biomaterial Ti-6Al-4V ELI alloy and Ti-In-Nb-Ta alloy having a surface nanoporous structure of the present invention. Scanning electron micrographs showing the surface microstructure obtained after in vitro testing with similar simulated biological solutions. (a) 10 day test tube test of conventional Ti-6Al-4V ELI alloy, (b) 10 day test tube test of Ti-In-Nb-Ta alloy according to the present invention, (c) conventional Ti-6Al 20 day test tube test of -4V ELI alloy, (d) 20 day test tube test of Ti-In-Nb-Ta alloy according to the present invention, (e) 30 day test tube test of conventional Ti-6Al-4V ELI alloy , (f) shows the surface microstructure obtained after a 30 day test tube test of the Ti-In-Nb-Ta alloy according to the present invention.

The present invention relates to a titanium-based alloy for a biomaterial having an ultra-fine bioactive porous surface and having excellent bone bonding ability and biocompatibility, and a method of manufacturing the same, and having proven excellent mechanical properties and corrosion resistance, such as artificial bone, artificial joint, artificial tooth, and the like. A certain amount of non-toxic non-toxic alloying elements such as indium (In), niobium (Nb), and tantalum (Ta) are added to titanium, which is used as a biomaterial for nanomaterials, and surface-modified by alkali treatment and heat treatment to nano-size the alloy surface. The present invention relates to a titanium-based alloy for bio-incorporation and to a method of manufacturing the ultra-microbial porous structure.

First, the present invention is a method of manufacturing a titanium-based alloy, by adding a compound in a predetermined amount in accordance with the present invention to the pure titanium to the biologically harmless alloy element by changing the internal structure of the alloy, the nano-size on the surface of the alloy during chemical treatment and heat treatment It is characterized by the formation of ultra fine bioactive porous structure and network structure (network structure) of the, increase the surface roughness of the titanium alloy for biotechnology, heterogeneous nucleation site due to the high surface energy of the ultra fine bioactive porous structure By increasing the bone binding ability, such as bone bonding strength and bone bonding speed (improved) provides a method for producing a titanium alloy for biomaterials having excellent biocompatibility (biocompatibility).

According to the present invention, a method for preparing a bio-based titanium alloy having an ultra-fine bioactive porous surface includes 5 to 20% by weight of indium, 2 to 5% by weight of niobium, 3 to 5% by weight of tantalum, and The remaining amount of titanium is added to change the internal structure of the alloy, to form an ultra-fine bioactive porous surface of the spongy structure consisting of nano-sized pores during alkali treatment, the sodium-titanium hydrogel layer produced during the alkali treatment ( forming a fine network structure produced by shrinkage when the sodium titanate hydrogel layer is crystallized into sodium titanate (Na ₂ Ti ₅ O ₁₁ or Na ₂ Ti ₆ O ₁₃ ) due to heat treatment. It is composed.

This will be described in more detail as follows.

First, 5 to 20% by weight of indium, 2 to 5% by weight of niobium, 3 to 5% by weight of tantalum and the balance of titanium were dissolved in a vacuum arc melting furnace and then at 1100 ° C. (1373 K). After holding for 1 hour and rolling β, reheat at 950 ° C. (1223 K) to roll α / β. At this time, in order to remove the internal defects that may occur after rolling, to prepare a mother alloy by annealing at 700 ℃ (973 K) for 2 hours in a vacuum atmosphere, and then the mother alloy is alkali-treated in an aqueous alkali solution, 10 Heat treatment is carried out in a vacuum heat treatment furnace of ^-5 to 10 ^-6 torr vacuum degree.

There is no restriction | limiting in the alkali aqueous solution used at the time of the said alkali treatment, NaOH was used in the specific example of this invention. At this time, the concentration of the NaOH aqueous solution used is preferably 5 to 10 molar concentration, and the treatment time is preferably 12 to 24 hours. If the concentration of the NaOH aqueous solution is higher than 10 molar concentration, a porous layer having a pore size of 200 nm or more during alkali treatment is not generated, the bone bonding capacity is lowered, and less than 5 molar concentration, the alkali treatment time increases rapidly. In addition, if the alkali treatment time in the 10 molar NaOH solution is more than 24 hours, the depth of the corrosion layer is increased, and the bone bonding ability is lowered, and if it is less than 12 hours, the bioactive porous layer having a size of about 200 nm is not formed. Do not. In addition, temperature and corrosion time are inversely related to alkali treatment. As the temperature increases, the anode reaction becomes active, and the corrosion reaction becomes active, and the corrosion time is shortened. Therefore, in order to complete the alkali treatment in a titration time (12-24 hours), it is preferable to use NaOH solution at 60 ° C.

The heat treatment temperature is preferably 550 ~ 650 ℃, the heat treatment time is preferably 30 ~ 120 minutes. If the heat treatment temperature is higher than 650 ℃, titanium oxide (rutile, TiO ₂ ) is formed on the surface to inhibit the stability of sodium-titanate to reduce the surface modification effect, when lower than 550 ℃ sodium-titanium hydrogel layer Failure to fully crystallize results in lowering the hardness of the alloy. In addition, when the heat treatment time is less than 30 minutes, the sodium-titanium hydrogel layer does not completely crystallize into sodium titanate, and if it exceeds 120 minutes, sodium-titanate is evaporated by sodium on the surface in a high vacuum atmosphere. Inhibits stability.

When the Ti-In-Nb-Ta alloy according to the present invention is alkali treated with a NaOH solution, a passivated TiO ₂ natural oxide film formed on the surface is locally corroded to the OH ^- group so that a part of the film is dissolved into the alkaline solution.

TiO ₂ + OH ^- → HTiO ₃

Ti directly exposed to the alkaline solution due to the reaction is subjected to the following hydration (hydration).

^{Ti + 3 OH - → Ti (} OH) 3 + + 4e -

^{_{Ti (OH) 3 + + e}} - → TiO 2 · H 2 O + 0.5 H 2 ↑

Ti (OH) ₃ ⁺ + OH ^- ↔ Ti (OH) ₄

When the hydrated TiO ₂ further reacts with the OH ^- group, a negatively charged hydroxide is formed on the surface as shown below.

TiO ₂ nH ₂ O + OH ^- ↔ HTiO ₃ ^- nH ₂ O

The negatively charged hydroxide thus reacts with Na ⁺ ions in the alkaline solution and forms a porous sodium-titanium hydrogel layer.

When the alkali-treated Ti-In-Nb-Ta alloy is heat-treated as a surface modification process, water is removed from the sodium-titanium hydrogel layer and crystallization is made into a stable sodium-titanate layer, thereby improving the strength of the porous layer.

In addition, the present invention contains 5 to 20 weight percent of indium, 2 to 5 weight percent of niobium, 3 to 5 weight percent of tantalum and the balance of titanium, based on the total alloy weight, and the surface by alkali treatment and heat treatment. Provided is a titanium alloy for a biomaterial having an ultrafine bioactive porous layer having a spongy body structure formed therein and a fine network structure. Titanium alloy for biomaterials according to the present invention by the ultra-fine porous surface and the surface of the network structure, the bone bonding ability such as bone bonding strength and bone bonding speed is improved, and has excellent biocompatibility. The biological titanium alloy according to the present invention can be produced by the above production method.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, the scope of the present invention is not limited to these embodiments.

<Example>

In the following examples, the surface was observed by an alkali treatment and heat treatment in comparison with the Ti-6Al-4V ELI alloy, which is currently commercially available titanium alloy, to investigate the surface modification of the biomaterial prepared by the manufacturing method according to the present invention.

In addition, in vitro tests were performed in simulated body fluids with similar plasma and ion concentrations to simulate bioactive behavior, and the surface changes of the specimens with the loading time in the simulated biological solution were investigated. Observed and analyzed the product.

Example 1

16.3% by weight of indium, 3.29% by weight of niobium, 3.96% by weight of tantalum and the balance of titanium were dissolved in a vacuum arc melting furnace, then held at 1100 ° C. (1373 K) for 1 hour and β-rolled, Reheat at 950 ° C. (1223 K) and roll α / β. At this time, in order to remove internal defects that may occur after rolling, the mother alloy prepared by annealing at 700 ° C. (973 K) for 2 hours under vacuum atmosphere was alkali treated in a 5 molar concentration of 60 ° C. NaOH aqueous solution for 24 hours, Titanium alloys were prepared by heat treatment at 600 ° C. for 1 hour in a vacuum heat treatment furnace of 10-5 torr vacuum degree.

In order to investigate the surface modification of the biomaterial prepared by the manufacturing method of the present invention, the surface structure was observed through a scanning electron microscope (SEM).

As shown in FIG. 1A, a porous sponge body having a size of about 150 nm or more is generated during alkali and heat treatment of the Ti-6Al-4V-ELI alloy. However, at the time of alkali and heat treatment of the biomaterial prepared by the manufacturing method according to the present invention, a nano-sized, ultra-fine porous surface is formed, and as shown in FIG. 1B, prepared by the embodiment of the present invention. At about 50-100 nm, porous cavernous structures were produced.

Referring to the results of FIG. 1, the biomaterial prepared by the manufacturing method according to the present invention is Ti-6Al- due to the change in the internal structure of the alloy due to the complex addition of alloying elements such as indium, niobium and tantalum. Dense porous cavernous structures than 4V ELI alloys are produced, resulting in network structures about 5-10 μm in size.

Example 2

In order to simulate the bioactivity behavior of the alloy prepared according to the method of Example 1, in vitro tests were performed in simulated biological solutions with similar plasma and ion concentrations in humans. Indicated. In addition, the surface change of the specimen with the loading time in the simulated biological solution was observed and shown in FIG. 2. At this time, XRD (X-ray diffractometry) and EDS (energy dispersive spectroscope) were used to analyze the compound produced during the in vitro test.

Inorganic ion concentrations in simulated biological solutions and human plasma Ion concentration (mM) Na ⁺ K ⁺ Mg ²⁺ Ca ²⁺ Cl ^- HCO ₃ ^- HPO ₄ ^2- SO ₄ ^2- SBF 142.0 5.0 1.5 2.5 147.8 4.2 1.0 0.5 Human plasma 142.0 5.0 1.5 2.5 103.0 27.0 1.0 0.5

Referring to the results of FIG. 2, the surface of the specimen prepared by the test method of the biological material prepared by the method of the present invention and the conventional Ti-6Al-4V ELI alloy in a simulated biological solution for 10 days can be seen in FIGS. 2A and 2B. Hemispherical particles were observed to be produced as shown. The hemispherical particles were found to be apatite hydroxide, which is one of the main constituents of human bone, as a result of EDS and XRD.

As can be seen in Figure 2, the generation and growth rate of the apatite hydroxide nucleus in the biomaterial prepared by the manufacturing method of the present invention appeared faster than the Ti-6Al-4V ELI alloy. As a result, the heterogeneous nucleation sites of the hydroxide apatite are larger than the heterogeneous nucleation sites of the Ti-6Al-4V ELI alloy due to the dense structure of the porous sponge body having a compact structure of about 50 to 100 nm or less as shown in FIG. It can be seen that the creation and growth was fast. In addition, it can be seen that the bone bonding ability, such as the bone bonding rate of the biological material produced by the production method of the present invention is superior to the Ti-6Al-4V ELI alloy currently used.

As indicated in our prior patent No. 211097 ("Biocompatible Titanium-Based Alloys with Good Biocompatibility"), cytotoxicity experiments and animal experiments have revealed excellent biological stability of titanium alloys. In addition, in the present invention, an alloy prepared by complex addition of 5 to 20% by weight of indium, 2 to 5% by weight of niobium and 3 to 5% by weight of tantalum to pure titanium is disclosed in Korean Patent Application No. 10-199-00742467 ( Titanium alloys with excellent mechanical properties and corrosion resistance), have a higher tensile strength than pure titanium, have similar tensile strength values as Ti-6Al-4V ELI alloys, and commercially available titanium It has a very low modulus of elasticity compared to artificial biomaterials (pure titanium, Ti-6Al-4V alloy). In addition, in terms of corrosion resistance, the alloys produced according to the invention are known to exhibit low corrosion rates approaching pure titanium, which is considered to be the most ideal.

According to the titanium-based biocompatible alloy having a super-fine bioactive porous surface of the present invention and a method for producing the same, the biocompatibility is superior to that of the current commercial alloy by using an alloy element that is not cytotoxic, and by using the alloy element in a predetermined amount By changing the alloy structure, the ultrafine bioactive porous structure and the network structure are formed on the surface of the alloy during chemical treatment and heat treatment to improve bone bonding ability such as bone bonding strength and bone bonding speed. It is possible to provide a biomaterial that does not require any other materials. Therefore, the titanium-based biocompatible alloy and the method of manufacturing the ultrafine bioactive porous surface according to the present invention artificially repair the damaged organs or tissues of humans caused by the aging of society, the prolongation of human life, and congenital or acquired accidents. This could be in line with the increased demand for biological materials and their biological stability.

Claims (8)

Based on the total alloy weight, 5 to 20 weight percent indium, 2 to 5 weight percent niobium and 3 to 5 weight percent tantalum are added to the remaining amount of titanium, mixed, alkali treated with an aqueous alkali solution, and then vacuum heat treated. Including the heat treatment in the furnace, the method of producing a titanium alloy for biomaterials, characterized in that to form an ultrafine bioactive porous layer and a fine network structure of the spongy structure throughout the alloy surface. The method of producing a titanium alloy for biomaterials according to claim 1, wherein an aqueous NaOH solution is used as the aqueous alkali solution. The method of claim 2, wherein the concentration of NaOH solution is 5 to 10 molar concentration. The method of claim 2, wherein the alkali treatment time using the NaOH solution is 12 to 24 hours. The method for producing a titanium alloy for biological material according to any one of claims 2 to 4, wherein the temperature of the NaOH solution is 60 ° C. The method of claim 1, wherein the heat treatment temperature is 550 ~ 650 ° C. The method of claim 1, wherein the heat treatment time is 30 to 120 minutes. A cavernous structure formed on the entire surface by alkali treatment and heat treatment, containing 5 to 20 weight percent of indium, 2 to 5 weight percent of niobium, 3 to 5 weight percent of tantalum, and a balance of titanium based on the total weight of the alloy. Titanium alloy for biomaterials having an ultrafine bioactive porous layer and a fine network structure.