WO2013165051A1

WO2013165051A1 - Ultra-hydrophilic titanium implant, and surface treatment and storage methods thereof

Info

Publication number: WO2013165051A1
Application number: PCT/KR2012/005490
Authority: WO
Inventors: 김수경; 장일석; 박기태; 강은정; 송주동; 엄태관; 최규옥
Original assignee: 오스템임플란트주식회사
Priority date: 2012-04-30
Filing date: 2012-07-11
Publication date: 2013-11-07
Also published as: KR101248785B1

Abstract

The present invention relates to a method for modifying a titanium surface into an ultra-hydrophilic surface by precise dry surface cleaning without changing the physical shape of the titanium surface without additional surface treatments such as RBM and SLA, and a storage method for maintaining the ultra-hydrophilicity thereof for a long period of time. Body fluid and blood affinity is improved by securing the ultra-hydrophilicity of the surface of an implant for a long period of time, thereby ultimately enabling excellent initial osteogenesis and a short osseointegration time after implantation. In addition, an implant ultra-hydrophilized thereby is provided.

Description

[Specifications

[Name of invention]

Superhydrophilic titanium implant, surface treatment and storage method

Technical Field

The present invention is a superoleophilic titanium or titanium alloy material (hereinafter,

The present invention relates to a surface treatment method that gives such superhydrophilicity and a storage method capable of preserving the superhydrophilicity imparted by the surface treatment method for a long time. After surface treatment with RBM or SLA, which is widely used as a method, it provides superhydrophilicity to the surface of titanium implants through dry cleaning method using room temperature plasma or ultraviolet rays, and immediately transfers titanium implants to organic zwitterionic buffer. The present invention relates to a titanium implant having a superhydrophilic property to preserve superhydrophilic properties for a long time by supporting the same, and a surface treatment and storage method thereof.

Background Art

In the medical field dealing with the bones of the human body, such as orthodontics and dentistry, there is a great interest in the prosthesis, or implants that can replace damaged or missing bones. The excellent biocompatibility of titanium as an implant material has been known for a long time and has been actively used to date. The success of the implant procedure is how firm and fast Osseointegration of artificial implants can be incorporated into bone tissue. It depends on the completion.

As an important determinant in bone fusion, the surface treatment method of the implant has been pointed out. In this connection, the smooth surface treatment method by lathe processing has the longest history and the long term history due to the excellent biocompatibility and tissue stability with bone. Has been used. However, efforts have been made to improve the surface in order to improve the success rate in bones with low bone density. Predecki et al. Reported that irregularly-imposed implants were able to observe rapid bone growth and good mechanical bonding. In addition, Buser et al. Reported that implants with irregular and rough surfaces showed more bone contact rates than those with smooth surfaces in animal experiments.

In the evolution of the implant surface, first-generation implants have smooth surfaces, second-generation implants are coated surfaces, and the blasting technique is used as an absorbent medium. It is divided into RBMC Resorbable Blasted Media blasting, which increases the roughness of the implant, Titanium Plasma Spray (TPS), and sandblast large grit acid etch (SLA) with high biocompatibility. can see. Implants with a hydroxyapatite (HA) coating surface belong to the third generation.The surface area is increased by the effect of particles and coatings sprayed on the surface, which increases the interfacial bond strength of the implant and activates the reaction of cells on the rough surface. Has the advantage of being.

-By the way, RBM (Resorbable Blasted Media blasting)

In the case of an implant surface treatment method such as SLACSandblast Large grit Acid etch, an oxide layer grows on the surface of the product when the product is exposed to air vapor after the surface treatment process, as shown in FIG. Adsorption of contaminants occurs and hydrophobizes while changing to a chemically stable state. Since the surface of the hydrophobized implant has low wettability to body fluids and blood, it has a disadvantage of prolonging the period of stabilization of the implant by preventing the overall process of fusion with bone after implant implantation.

Prior art according to EP 1,150,620 describes an implant having a hydrophilic surface after SLA surface treatment. The manufacturing method in this document shows that i) mechanically roughening the titanium surface through various methods. Ii) cleaning the surface with pure water, which may contain additives, and iii) packaging the titanium surface in a container containing inert gas without further processing. In addition, the wettability of the titanium surface is described as maintaining a hydrophilic surface exhibiting a contact angle of 20 to 50 ° with respect to water. In addition, water containing salts is mentioned as an alternative to an inert gas, and in the case of salt concentration, 100 to 200 mEq / Mg for monovalent salts such as Na and K and 1 to 1 for divalent salts such as Ca. A concentration range of 20 mEq / is described.

However, EP1, 150 _. In the case of the prior art according to No. 620, a method of cleaning titanium surface using pure water is applied, and when applying such a wet method such as ultrasonic method in surface cleaning, it is possible to remove 1 or less fine surface contaminants present on the surface. Not only is it difficult to remove, but there are disadvantages in that it is difficult to clean the minute irregularities that ultrasonic waves cannot reach.

As a method of determining the degree of cleaning, Handbook of Physical Vapor Deposition (PVD) Processing, Donald M. Mattox, Noyes Publications (1998) The degree of cleaning of the surface can be judged by measuring the contact angle, and it is assumed that the surface with the contact angle for ultrapure water is 20 ° or more because contamination remains. It is described as having. In addition, in order to maintain the surface hydrophilicity, a method of storing in an aqueous solution containing salt was applied. At this time, the concentration of the applied salt is sufficient at a concentration of 100 200 mEq / i for the monovalent salt, whereas for the divalent salt, 1-20 mEq When the concentration is too low in the / i range when applied to the actual dental implant abutment there is a problem that the amount is too small to cover the entire surface of the abutment.

The prior art of EP 2,121,058, on the other hand, uses a sulfuric acid surface treatment to form a nanopore structure of 50-100 nm on the surface of titanium to overcome the hydrophilic limitations of the technique according to EP 1,150,620. It is described that a hydrophilic surface can be secured and that it should be stored in a salt-containing aqueous solution having a high total ion concentration of at least 0.5 mo \ / i and preferably at least 1 mol / «as a method for maintaining hydrophilicity after drying.

However, in order to obtain a superhydrophilic surface with a contact angle of 10 or less, it is possible only by a complicated process of forming nanopores by the surface treatment of sulfuric acid, and the concentration of the salt in the aqueous solution to maintain the superhydrophilicity of the titanium surface is also high. Therefore, when implant implants are implanted in the human body, there is a possibility that safety problems such as toxicity expression due to high concentrations of salts occur.

[Detailed Description of the Invention]

[Technical problem]

It is an object of the present invention to provide a method of modifying a surface with superhydrophilicity through a precise dry surface cleaning method and a method of storing the hydrophilicity for a long time.

In addition, the present invention is to improve the body fluid and blood affinity through the super-hydrophilicity secured by the above method to finally provide an implant having an excellent initial bone formation effect and a short bone fusion period after the implant procedure The purpose.

【Esoteric Solution】

In addition to surface treatments such as RBM and SLA, the present invention provides ultra-hydrophilic properties through precise dry surface cleaning, without changing the physical shape of the titanium surface. It is related to the method of modifying the surface and the method of storing it to maintain its superhydrophilicity for a long time. By securing the superhydrophilicity of the implant surface for a long time, it improves the fluid and blood affinity, and finally the excellent initial bone formation effect after the implant procedure. And a short bone fusion period, and to provide such superhydrophilized implants.

The present invention comprises the steps of modifying the macro-micromorphology to a superhydrophilic surface having a contact angle of 10 ^ο or less through dry cleaning of room temperature full-lasma or ultraviolet irradiation in a timed manner to sufficiently remove the microcontamination present on the structured titanium surface. And, after the contaminant cleaning, the implant surface is immersed in a concentration of organic amphoteric bilayer complete solution so that the surface of the implant is not hydrophobized and the superhydrophilicity of 10 ° or less is continuously maintained.

The first step of the present invention is a dry cleaning method that decomposes a fine contaminant layer on the surface of an implant by reaction of an ionized component by room temperature plasma or ultraviolet light in a vacuum or atmosphere without using a solvent. It is the step of changing the surface contact angle to less than 10 ^ο superhydrophilicity without changing the physical shape.

In addition, the second step of the present invention, in order to maintain the superhydrophilic for a long time is to support in a buffer containing a salt based on organic amphoteric material, the salt concentration of the titanium surface even if stored for a long period of about 3 years It is characterized by being protected by an aqueous solution containing a salt in a layered amount capable of maintaining hydrophilicity of 10 ° or less without being hydrophobized. Examples of the organic zwitterionic material include, for example, ACE, BES, CHES, HEPES, MOPS, PIPES, TES, etc., and it was confirmed that the salt concentration is preferably in the range of 0.1M to 1M.

Advantageous Effects

According to the surface treatment and storage method of the implant of the present invention, organic zwitterionic buffer having a sulfonic acid group and removing contaminants adsorbed on the metal surface by pretreatment such as plasma or light irradiation. It is possible to maintain superhydrophilicity for a long period of time by being supported on the base material so that hydrophobicity as in conventional titanium surfaces does not occur.

In addition, the superhydrophilic titanium implant of the present invention has a surface that not only effectively prevents the adsorption and stabilization of pollutants in the air, but also uniformly surrounds the surface. Superhydrophilicity of the surface is maintained by the solution; Excellent blood affinity, excellent bone formation effect and has an effect of shortening the bone fusion period.

[Brief Description of Drawings]

1 is a view schematically showing the surface treatment and storage method of the super-hydrophilic titanium implant of the present invention.

2 is dry cleaned. Figure showing the results of SEM and EDS analysis of the surface shape and components before and after the titanium disk is supported in the organic zwitterionic buffer solution having a sulfonic acid group.

Figure 3 is a photograph showing the contact angle of the titanium disk stored on the organic zwitterionic complete layer liquid having a titanium disk and sulfonic acid group hydrophobized by surface contamination.

4 is a view showing a change in contact angle with a change in the irradiation time of ultraviolet rays during dry cleaning.

FIG. 5 shows changes in implant-bone interface binding force at 4 months accelerated aging conditions. FIG.

Figure 6 shows the change in implant-bone interface binding force under three-year accelerated aging conditions.

FIG. 7 shows the change in implant-bone interface binding force with concentration of organic zwitterionic buffer at 3 years accelerated aging conditions.

Best Mode for Implementation of the Invention

Hereinafter, the present invention will be described in detail through examples.

Example 1

Removal of contaminants on the surface of titanium discs and supporting of organic amphoteric ions with sulfonic acid groups

Machined titanium disks are blasted for 1 to 60 seconds with blast pressure of 1 to 10 atm using A1 ₂ Q ₃ powder with particle size of 1mm or less, and then macro acid is applied to titanium disk surface by acid treatment with mixed acid aqueous solution. Micromorphology was assigned (hereinafter referred to as 'SA treatment' or 'SA'). The acid-treated titanium disc was ultrasonically cleaned for 30 minutes with ethanol and for 30 minutes with distilled water and then dried.

1 minute by room temperature plasma or 2 minutes by UV light on the titanium disk The dry cleaning process was performed to remove contaminants adsorbed and stabilized on the surface, and was supported on an organic zwitterionic buffer having 0.2M sulfonic acid group on the surface. HEPES (4- (2-hydroxyethyl) -l-piperazineethanesulfonic acid) was used as the ionic material.

Another method that can be used for dry cleaning is RFGD (Radio-Frequency Glow Discharge). Organic zwitterionic materials with sulfonic acid groups that can be used in addition to HEPES include ACES, BES, CHES, MOPS, PIPES, TES, etc.

Titanium discs prepared through the above process were used in Examples 2 and 3 below.

Example 2

Surface shape and component observation of accelerated aging titanium disc

SEM and EDS were analyzed in order to observe the surface shape and components of the titanium disk loaded on the organic amphoteric ion complete solution having the sulfonic acid group prepared in Example 1. At this time, a titanium disc not supported in the organic zwitterionic buffer was used as the negative control group.

As shown in Figure 2, the surface of the negative control group (SA) is the same as the SA-treated basic shape, but the surface component is present only titanium, in the case of the experimental group has a shape that the SA surface is covered with the supporting solution and the surface component of the supporting solution Ingredients S, 0, and C were detected with titanium.

Therefore, even if the SA-treated titanium disk is extracted after being supported on the organic amphoteric complete layer solution having a sulfonic acid group, it can be confirmed that the organic amphoteric buffer component remains on the surface thereof. Example 3

Measurement of Contact Angle of Titanium Disk Supported on Organic Amphoteric Complete Solution with Sulfonic Acid Group

In order to measure the contact angle of the organic zwitterionic buffer-carrying titanium disc having the sulfonic acid group prepared in Example 1, the sample was washed three times or more with distilled water for 10 minutes, and then dried by spraying with nitrogen. From the side after The contact angle was measured by close-up photography. At this time, the negative control group used a titanium disk in which the pollutant was adsorbed on the surface by exposure to the air after the SA treatment and dry cleaning using plasma or ultraviolet light at room temperature.

As shown in the photograph of FIG. 3, the negative control group was hydrophobized, and the contact angle showed a large value of 107 °, while the contact angle of the experimental group was 0 ° and it was confirmed that superhydrophilicity was maintained.

On the other hand, Figure 4 is a graph showing the change in contact angle with the time change of the dry cleaning process using ultraviolet light. As shown, it can be seen that when irradiated with ultraviolet rays for a time of 2 minutes or more, it is possible to secure a superhydrophilic surface having a contact angle of 0 °.

Therefore, the SA surface is treated with SA, wet cleaning, and drying, followed by dry cleaning for 1 minute with room temperature plasma or at least 2 minutes with ultraviolet light to remove pollutants adsorbed and stabilized on the surface. It was confirmed in this example that the superhydrophilic titanium surface having a contact angle of 0 ° may be maintained when supported on the complete layer solution.

Example 4

Removal of contaminants on the surface of dental titanium implants and supporting of organic amphoteric buffers with sulfonic acid groups

The machined dental titanium implant is blasted for 1 to 60 seconds with a blast pressure of 1 to 10 atm using A1 ₂ 0 ₃ powder with a particle size of 1 mm or less. Macro-micromorphology was imparted to the titanium disc surface by acid treatment with aqueous solution (SA treatment). In addition, the acid-treated titanium disc was ultrasonically washed with ethanol for 30 minutes and distilled water for 30 minutes and then dried.

The implant was removed by a dry cleaning treatment of at least one minute of plasma at room temperature or at least two minutes of ultraviolet light to remove contaminants adsorbed and stabilized on the surface, and was supported in an organic amphoteric buffer (HEPES) having 0.02M sulfonic acid group on the surface.

The titanium implant prepared as above was used in Examples 5, 6 and 7 below. Example 5 Animal Experiment for Measurement of Bone Interfacial Adhesion of Organic Amphiphilic Complete Serum with Dental Accelerated Sulfonate Group (1)

After placing the HEPES-supported dental titanium implant prepared in Example 4 for 2 weeks under accelerated aging conditions (about 55 ° C.) for 4 months, the micro-pig (to check the implant-bone interface strength) was established. micropig) The implant was placed in the tibia and after 16 days of bone formation, the removal torque was measured.

At this time, a titanium implant without a contaminant was removed as a negative control, and a titanium implant (pretreatment) without undergoing accelerated aging conditions was used as a positive control after dry removal of the contaminant.

As shown in Figure 5, compared to the negative control group in the positive control group about 50% increase in the removal power, the experimental group also confirmed that the removal of the removal of the forest control about 55% compared to the negative control group.

In addition, in the case of an implant carried out in a distilled water rather than a HEPES complete solution after dry removal of the contaminant as a comparative control group, the bond-bone interface coupling force decreased by about 20% due to accelerated aging conditions. It was also confirmed that the removal ability of the skid was improved by about 5%.

Therefore, the support of dental implants in organic zwitterionic buffers with sulfonic acid groups still maintains the improvement of bone interface binding force even after the accelerated aging condition of 4 months of storage period. It can be seen that this effect is superior to the case of supporting in distilled water.

Example 6

Animal Experiment for the Measurement of Bone Interfacial Adhesion of Dental Acupuncture Supported Dental Acupuncture with Accelerated Aging Sulfonate Group (2)

The HEPES-supported dental titanium implant prepared in Example 4 was left for 18 weeks under accelerated aging conditions (about 55 ° C) to create a three-year storage period, followed by micro-implantation to check the implant-bone interface. The implant was placed in the pig tibia and measured for removal torque after 16 days of bone formation. At this time, a titanium implant that did not remove the contaminant was used as a negative control group, and a titanium implant that was subjected to a pretreatment process to remove the contaminant as a negative control group was not supported in the HEPES solution and was not subjected to accelerated aging conditions.

As shown in Figure 6, compared to the negative control group compared to the negative control group about 50% increase in the removal of the Birlin, the experimental group also confirmed that the removal of the Birlin removal force about 50% compared to the negative control group.

Therefore, the implant-bone interface binding force of the experimental group that underwent the accelerated aging condition of 3 years of storage period was maintained at the same level as the implant-bone interface binding force of the positive control group which did not undergo any accelerated aging condition. It is confirmed that the storage of implant in ionic complete layer solution is very effective in maintaining superhydrophilicity of implant surface.

Example 7

Animal Experiments for the Measurement of Bone Interfacial Adhesion of Dental Implants Supported in Organic Amphoteric Compartments with Various Sulfonate Groups

The HEPES-supported dental titanium implant described in Example 4 was varied in the concentration of HEPES and left for 18 weeks under accelerated aging conditions (approximately 55 ⁰ C) to create a condition for one year of storage, and then implants— The implant was placed in the micropig tibia to check the bone interface binding force, and the removal torque was measured after 16 days of bone formation period.

At this time, the negative control group was used as a titanium implant that did not remove the contaminant, and the positive control group was subjected to a pretreatment process but not carried out in the HEPES solution and subjected to accelerated aging conditions.

As the control group, the source was dry-removed and used as an implant supported in distilled water instead of HEPES buffer. .

As shown in FIG. 7, the removal ability of Birlin was increased by about 50% in the positive control group compared to the negative control group.

And, compared with the control group which carried out the pretreatment process to remove the contaminants but not the HEPES solution, but distilled water, compared to the control group which was loaded in the HEPES solution of 0.1M or more, the removal ability of the soil was improved by more than 10%. Confirmed. Also, 0.1M In the experimental group carried in the above HEPES solution, the higher the concentration of HEPES buffer solution, it can be seen that maintaining the improvement of bone interface binding force equal to or more than the positive control. ^'

However, if the concentration of HEPES buffer exceeds 1M, the HEPES buffer itself is toxic, but considering that the actual amount of HEPES buffer remaining on the implant surface is not too high, the concentration of HEPES buffer is set to 1M or less. It can also be evaluated that the level of safety is secured.

Therefore, when the concentration of the HEPES buffer supporting the implant is set in the range of 0.1M ~ 1M it was confirmed that the effect of the impingement bone interface binding strength is clearly maintained. On the other hand, the embodiment is intended to help the description of the present invention is not limited by the embodiment, the person skilled in the art of the present invention within the scope of the technical idea of the present invention Various modifications and equivalent other embodiments are possible based on the claims and the content of the invention.

Industrial Applicability

The ^first invention can be applied widely throughout the first half of the implant of titanium or titanium alloy material which lip expression in human bone tissue in the field of medicine dealing with the human bone, such as orthopedic medicine or dentistry.

Claims

[Claims]-

[Claim 1]

Preparing a titanium impurant having a surface structure of macro-micromorphology;

Modifying the surface of the titanium implant to a superhydrophilic surface having a contact angle of 10 ° or less through dry cleaning of room temperature plasma or ultraviolet irradiation; And

Storing the titanium implant modified with the superhydrophilic surface by supporting the implant in a complete solution containing a salt based on an organic zwitterionic material;

Surface treatment and storage method of the titanium implant comprising a.

[Claim 2]

The method of claim 1,

The surface modification step of the surface treatment and storage method of the titanium implant, characterized in that the dry cleaning is carried out by at least one minute phase is plasma or ultraviolet irradiation at least two minutes.

[Claim 3]

The method of claim 1,

The complete solution is a surface treatment and storage method of the titanium implant, characterized in that it comprises an organic amphoteric material based salt having a concentration in the range of 0.1M ~ 1M.

[Claim 4]

The method of claim 3,

The organic amphoteric material is a surface treatment and storage method of a titanium implant, characterized in that it has a sulfonic acid group.

[Claim 5]

The method of claim 4,

The organic zwitterionic material is at least one material selected from the group consisting of ACE, BES, CHES, HEPES, MOPS, PIPES, TES, surface treatment and storage method of a titanium implant.

[Claim 6]

A titanium implant prepared by the method for surface treatment and storage of the titanium implant according to any one of claims 1 to 5. [Claim 7]

The method of claim 6,

The titanium implant is a titanium implant, characterized in that for dental.