WO2022138924A1

WO2022138924A1 - Surface treatment method for titanium or titanium alloy

Info

Publication number: WO2022138924A1
Application number: PCT/JP2021/048219
Authority: WO
Inventors: 眞裕岡島; 智宣松野; 貴仁三木
Original assignee: 株式会社エー・アイ・システムプロダクト
Priority date: 2020-12-25
Filing date: 2021-12-24
Publication date: 2022-06-30

Abstract

The purpose of the present invention is to provide a surface treatment method that enables, easily at a low cost, property modification of the surface of titanium or a titanium alloy. The present invention pertains to a surface treatment method for titanium or a titanium alloy, the method comprising immersing titanium or a titanium alloy in an alkaline ionized water obtained through electrolysis of an aqueous solution containing a mineral salt including silicon and phosphorus.

Description

Surface treatment method for titanium or titanium alloy

The present invention relates to a surface treatment method for titanium or a titanium alloy.

In the field of dental implants, titanium or titanium alloy has been mainly used as a material. The reason is that the surface of titanium or titanium alloy is coated with an oxide film mainly composed of titanium oxide, and this film becomes a passivation film against corrosion in body fluid and suppresses corrosion of titanium or titanium alloy. , And this capsule has a high affinity for bone.

Especially for dental implants, it is necessary to place the implant in the jawbone once and wait for sufficient connection between the implant and the bone before attaching the prosthesis to the upper part of the implant body. The time it takes to attach the implant depends on the time it takes for the implant to bond to the bone. The time required for bone connection is 3 to 4 months for the lower jaw and 6 months for the upper jaw. At present, as the momentum for implant treatment that focuses on patients is increasing, it is an issue to shorten the period of 3 to 6 months required to obtain bone connection.

For that purpose, it is extremely important to achieve bone connection at an early stage, and for that purpose, the development of a technique for modifying the surface of the implant material is underway. As one of such surface modification methods, a method for treating a medical implant including a step of irradiating the medical implant with high-energy radiation (ultraviolet rays) has been proposed (for example, Patent Document 1).

Japanese Patent Publication No. 2008-532640

However, in order to modify the surface of the implant material using the method of Patent Document 1, it is necessary to irradiate high-energy radiation (ultraviolet rays) for a long time using expensive equipment, and therefore the implant treated by this method. Has problems such as high cost.
Under such circumstances, it is an object of the present invention to provide a surface treatment method capable of modifying the surface properties of titanium or a titanium alloy easily and inexpensively.

As a result of diligent studies to develop a surface treatment method capable of modifying the surface properties of titanium or a titanium alloy easily and inexpensively by the present inventors, alkaline ionized water produced on a titanium surface by a specific production method. It was found that the titanium surface became hydrophilic and the amount of protein adsorbed and the cell adhesion rate were improved by the treatment with. The present invention has been completed based on such findings.

That is, the present invention is as follows.
Item 1.
A method for surface treating titanium or a titanium alloy, which comprises a step of immersing titanium or a titanium alloy in alkaline ionized water obtained by electrolyzing an aqueous solution containing a mineral salt containing silicon and phosphorus.
Item 2.
Item 2. The surface treatment method according to Item 1, wherein the alkaline ionized water contains 0.4 to 400 mass ppm of silicon and 400 to 800 mass ppm of phosphorus.
Item 3.
Item 2. The surface treatment method according to

Item

1 or 2, wherein the alkaline ionized water further contains at least one mineral selected from the group consisting of calcium, potassium, sodium, and magnesium.
Item 4.
The surface treatment method according to any one of Items 1 to 3, wherein chlorine is further contained in the alkaline ionized water.
Item 5.
The surface treatment method according to any one of Items 1 to 4, wherein the pH of the alkaline ionized water is 10 to 12.5.
Item 6.
The surface treatment method according to any one of Items 1 to 5, wherein the surface tension of the alkaline ionized water is 55 to 68 mN / m.
Item 7.
An electrolysis step in which the alkaline ionized water electrolyzes an aqueous solution containing a mineral salt containing silicon and phosphorus and water, and the alkaline water on the cathode side obtained in the step and a mineral containing silicon and phosphorus. The surface treatment method according to any one of Items 1 to 6, which is obtained by an electron supply step of mixing with a salt to obtain a mixed solution and supplying electrons to the mixed solution.
Item 8.
An implant made of titanium or a titanium alloy whose surface is treated with alkaline ionized water obtained by electrolyzing an aqueous solution containing a mineral salt containing silicon and phosphorus.
Item 9.
A step of electrolyzing an aqueous solution containing a mineral salt containing silicon and phosphorus to obtain alkaline ionized water, and
A method for manufacturing an implant made of titanium or a titanium alloy, comprising a step of treating the surface of titanium or a titanium alloy with the alkaline ionized water.

At present, the above implants are so difficult that it is impossible or almost impractical to completely identify the structure of the object, so the invention of the object is described by the product-by-process claim.

According to the surface treatment method of the present invention, the surface properties of titanium or a titanium alloy can be easily and inexpensively modified.

FIG. 1 is a schematic diagram illustrating an apparatus for producing alkaline ionized water. The results of trace element analysis by X-ray photoelectron spectroscopy (XPS) on the alkaline ionized water treatment group immediately after the pretreatment and after 4 weeks, and the control group immediately after the pretreatment and after 4 weeks are shown in FIG. 2A. It is the result of wide scan analysis, and FIG. 2B is the result of narrow scan analysis. FIG. 3 is a photograph at the time of contact angle measurement. A (upper row) shows the control group, B (middle row) shows the alkaline ionized water treatment group, and C (lower row) shows the UV group. 1 (left column) indicates immediately after pretreatment, 2 (center column) indicates 1 week later, and 3 (right column) indicates 4 weeks later. FIG. 4 is a diagram showing the measurement results of the contact angle. FIG. 5 is a diagram showing the results of a protein adsorption test. FIG. 6 is a diagram showing the results of the cell adhesion test. FIG. 7 is a diagram showing the results of the cell proliferation test. FIG. 8 is a photograph of the rabbit femur at the time of implanting the titanium disc, FIG. 8A shows the groove formation for implanting the titanium disc, and FIG. 2B shows the state after implanting the titanium disc. FIG. 9 is a micro CT image of a rabbit femur. FIG. 10 is a Villanueva bone-stained image of a rabbit femur. FIG. 11 is a schematic diagram illustrating a BIC measurement range. a: Length of titanium disk surface (dotted line), b: Length of bone bonded to titanium disk surface (arrow), c: New bone FIG. 12 is a diagram showing the measurement results of BIC.

The present invention relates to a surface treatment method for titanium or a titanium alloy. The titanium or titanium alloy is titanium or a titanium alloy for implants to be implanted in a living body.
In the surface treatment method for titanium or a titanium alloy of the present invention, alkaline ionized water (hereinafter, simply referred to as "alkaline ionized water") obtained by electrolyzing an aqueous solution containing a mineral salt containing silicon and phosphorus may be used. ) Is used to immerse a titanium or titanium alloy implant in alkaline ionized water obtained by electrolyzing an aqueous solution containing a mineral salt containing silicon and phosphorus. The surface treatment method of the present invention simply immerses titanium or a titanium alloy in alkaline ionized water obtained by electrolyzing an aqueous solution containing a mineral salt containing silicon and phosphorus, and the surface properties of titanium or the titanium alloy. Can be modified, so that surface modification can be performed inexpensively and easily as compared with conventional ultraviolet irradiation that requires expensive equipment. Here, alkaline ionized water can be paraphrased as alkaline electrolyzed water.

The target of surface treatment is titanium or titanium alloy. As titanium alloys, for example, an alloy of titanium (Ti), aluminum (Al) and vanadium (V), an alloy of titanium (Ti), aluminum (Al) and niobium (Nb), titanium (Ti) and nickel (Ni). ), An alloy of titanium (Ti) and platinum (Pt), and the like. It is preferable to use Ti, Ti-6Al-4V alloy, Ti-6Al-7Nb alloy or the like as the target of surface modification.

For the surface treatment, alkaline ionized water obtained by electrolyzing an aqueous solution containing a mineral salt containing silicon and phosphorus is used.
The alkaline ionized water obtained by electrolyzing an aqueous solution containing a mineral salt containing silicon and phosphorus contains silicon and phosphorus. Specifically, silicon (Si) is about 0.4 to 400 mass ppm (mg / L), preferably about 0.8 to 390 mass ppm, and more preferably about 1.0 to 380 mass ppm in the alkaline ionized water. And phosphorus (P) is contained in an amount of about 2 to 800 mass ppm, preferably about 4 to 780 mass ppm, and more preferably about 10 to 770 mass ppm. Elemental analysis was performed by inductively coupled plasma (ICP) emission spectroscopy (SPECTRO ACROSII manufactured by Hitachi High-Tech Science Co., Ltd.).

The alkaline ionized water obtained by electrolyzing an aqueous solution containing silicon and a mineral salt containing phosphorus may contain phosphorus and other elements other than silicon, and for example, calcium (Ca) may be 0.0001 to 900 mass ppb. About 0.001 to 800 mass ppm, more preferably about 0.01 to 700 mass ppm, potassium (K) about 0.0005 to 3000 mass ppm, preferably about 1 to 2900 mass ppm, more preferably about 5 to 2800 mass. About ppm, magnesium (Mg) about 0.0001 to 300 mass ppb, preferably about 0.001 to 250 mass ppm, more preferably about 0.01 to 200 mass ppm, sodium (Na) about 34 to 8000 mass ppm, preferably about 34 to 8000 mass ppm. It may contain about 40 to 7900 mass ppm, more preferably about 50 to 7800 mass ppm. Further, chlorine (Cl) may be contained in the alkaline ionized water obtained by electrolyzing an aqueous solution containing a mineral salt containing silicon and phosphorus, and for example, chlorine (Cl) is 1.5 to 1.5 to. It may be contained in an amount of about 450 mg / kg, preferably about 1.5 to 440 mg / kg, and more preferably about 1.5 to 430 mg / kg.

The silicon contained in the alkaline ionized water can be present in a state of silicate ions such as H ₃ SiO ₄ ⁻ , H ₅ Si ₂ O ₇ ⁻ , H ₅ Si ₃ O ₉ ^{− and} the like.

Phosphorus contained in the alkaline ionized water can be present in the state of phosphate ions, for example, H ₂ PO _4- ^, H ₃ P ₂ O _7- ^, H ₄ P ₃ O _10- , ^and the like.

The pH of alkaline ionized water obtained by electrolyzing an aqueous solution containing a mineral salt containing silicon and phosphorus is usually about 10 to 12.5. The surface tension is usually 70 mN / m or less, preferably about 50 to 69 mN / m, and more preferably about 55 to 68 mN / m. Further, the alkaline ionized water physically contains an excessive amount of electrons.

The alkaline ionized water used in the present invention includes an electrolysis step of electrolyzing an aqueous solution containing a mineral salt containing silicon and phosphorus and water, and the alkaline water on the cathode side obtained in the above step, silicon and phosphorus. It can be obtained by an electron supply step of mixing with a mineral salt containing the above water to obtain a mixed solution and supplying electrons to the mixed solution. As the mineral salt containing silicon and phosphorus, for example, an electrolyte containing silicon and phosphorus obtained from seawater can be used. Seawater can be used without particular limitation, and for example, Japanese seawater can be used. Mineral salts containing silicon and phosphorus may be added in an amount of about 0.001 to 3% by mass of the amount of water used.

In addition to the above steps, the method for producing alkaline ionized water includes a deoxidizing step of deoxidizing an aqueous solution containing a mineral salt containing silicon and phosphorus and water to reduce the dissolved oxygen concentration to 1 ppm or less, and the above-mentioned method. It is preferable to include a stabilizing step of applying a pressure of 1 kg / cm ² to 12 kg / cm ² to a mixed solution of alkaline water on the cathode side and a mineral salt containing silicon and phosphorus. Here, as the mineral salt containing silicon and phosphorus mixed with the alkaline water on the cathode side, the same mineral salt containing silicon and phosphorus used in the electrolysis step can be used, for example, Japan. It is possible to use the one collected from the seawater of.

Hereinafter, a method for producing alkaline ionized water will be described.
The first step is an electrolysis step of electrolyzing an aqueous solution containing water and a mineral salt containing silicon and phosphorus.

Pure water, ion-exchanged water, etc. can be used as the raw material water. In water, a mineral salt containing silicon and phosphorus obtained from seawater as a supporting electrolyte is dissolved. It is preferable to use water in which the concentration of dissolved oxygen in the water is reduced to 1 ppm or less by deoxidizing treatment. As the deoxidizing treatment, there are a physical treatment method and a chemical treatment method, and conventionally, a method of using the chemical treatment method alone or a method of using the physical treatment method and the chemical treatment method in combination is adopted. Examples of the physical treatment method include degassing treatment using a heating degassing device, a membrane degassing device, and the like. Examples of the chemical treatment method include a method of adding hydrazine, sodium sulfite, a saccharide (glycose, etc.) as a deoxidizing agent. As a deoxidizing treatment, for example, the oxygen removing agent can be added to water.

It is preferable that the electrolysis is performed in a closed space such as an electrolytic cell. The inside of the electrolytic cell is preferably an inert atmosphere such as nitrogen and carbon dioxide. Further, instead of using water whose dissolved oxygen concentration has been reduced to 1 ppm or less by pre-deoxidizing treatment, or in addition to using pre-deoxidized water, electrolysis is carried out in the electrolytic tank. It is also possible to put an oxygen scavenger into the electrolytic bath when performing in. The electric energy applied by electrolysis is preferably 1000 W to 3000 W.

The second step is an electron supply step of mixing the alkaline water on the cathode side obtained in the first step with a mineral salt containing silicon and phosphorus to obtain a mixed solution, and supplying electrons to the mixed solution. be.

It is preferable that the alkaline water on the cathode side obtained by electrolysis is taken out from the electrolytic cell and supplied to the mixing tank. It is preferable that the mixing tank is provided with a means for supplying a mineral salt containing silicon and phosphorus obtained from seawater and an electron supply means for supplying electricity to alkaline water.

Examples of the silicon-containing raw material (or silicon-containing mineral salt) include alkali metal silicates such as sodium silicate and potassium silicate; alkaline earth metal silicates such as calcium silicate; magnesium silicate and the like. Can be mentioned. The content of silicon contained in the mixed solution is preferably about 0.005 to 5% by mass, more preferably 0.01 to 1% by mass, when the total amount of the mixed solution is 100% by mass. ..

Examples of the phosphorus-containing raw material (or phosphorus-containing mineral salt) include alkali metal phosphates such as sodium phosphate and potassium phosphate; alkaline earth metal phosphates such as calcium phosphate; magnesium phosphate and the like. .. The content of phosphorus contained in the mixed solution is preferably about 0.005 to 5% by mass, more preferably 0.01 to 1% by mass, when the total amount of the mixed solution is 100% by mass. ..

The mass ratio of the silicon-containing mineral salt added to the alkaline water to the phosphorus-containing mineral salt is preferably 1: 0.5 to 1.5.

As an electron supply means, for example, a cathode terminal can be mentioned. Electrons can be supplied by contacting the cathode terminal with alkaline water on the cathode side obtained by electrolysis. Electrons are discharged from the cathode electrons, and many electrons are supplied to alkaline water.

It is preferable that a direct current is applied to the cathode terminal. The voltage of the direct current applied to the cathode terminal is, for example, 10 to 1000 V, preferably 50 to 300 V, and more preferably 100 to 300 V. It is considered that the produced alkaline ionized water can effectively modify the surface properties of titanium or a titanium alloy by supplying electrons to the mixed solution.

It is preferable that a direct current having a voltage of 100 to 300 V is applied to the mixing tank and the amount of electricity emitted from the cathode electrons is 1000 to 3000 W.

It is preferable to apply a pressure of 1 kg / cm ² to 12 kg / cm ² (98 to 1177 kPa) to the mixing tank, and more preferably 2 kg / cm ² to 6 kg / cm ² (196 to 588 kPa). Applying pressure improves the stability of alkaline ionized water.

The inside of the mixing tank is preferably an inert atmosphere such as nitrogen and carbon dioxide. It is also possible to put an oxygen scavenger into the mixing tank. It is preferable that the mixing tank is insulated from the ambient temperature by a heat insulating means so as not to be affected by the ambient temperature, and the inside of the mixing tank is adjusted to the range of -5 ° C to 25 ° C by the temperature adjusting means. .. The temperature of the mixed solution is preferably 0 ° C to 10 ° C.

The mixing tank is preferably arranged in an isolation tank isolated from the outside air atmosphere, and the isolation tank is preferably filled with nitrogen or carbon dioxide. As a result, deterioration of alkaline ionized water can be prevented, so that the performance can be maintained for a long period of time.

By stabilizing the alkaline ionized water in the above mixing tank for 24 to 36 hours, the final product, alkaline ionized water, can be obtained. The obtained alkaline ionized water can be taken out directly from the alkaline ionized water outlet. Alternatively, alcohol can be mixed with alkaline ionized water and taken out from the outlet of the mixed alkaline ionized water. As the alcohol, it is preferable to use an alcohol having a high compatibility with water, and examples thereof include methanol, ethanol, and isopropyl alcohol.

Hereinafter, a manufacturing apparatus that can be used for producing alkaline ionized water will be described.
FIG. 1 shows a schematic diagram illustrating an apparatus for producing alkaline ionized water. The alkaline ionized water producing apparatus 101 includes an electrolytic cell 1 and a mixing tank 11, and the electrolytic cell 1 and the mixing tank 11 are connected by an alkaline water outlet pipe 9. A water pipe 2 is connected to the electrolytic cell 1, and raw water (an aqueous solution containing a mineral salt containing silicon and phosphorus and water) is supplied by the water pipe 2. The electrolytic cell 1 has an anode chamber 4 and a cathode chamber 5 partitioned by a diaphragm 3. The anode chamber 4 is provided with an anode 6, and the cathode chamber 5 is provided with a cathode 7. Electrolytic current is applied to both electrodes, acidic water is taken out from the acidic water discharge pipe 8 connected to the anode chamber 4, and alkaline water is taken out from the alkaline water outlet pipe 9 connected to the cathode chamber 5. The alkaline water is cooled by a cooling device 10 provided with a cooling pipe in which a refrigerant is circulated while passing through the alkaline water outlet pipe 9, and is introduced into the mixing tank 11.

The mixing tank 11 is connected to the alkaline water outlet pipe 9, the raw material liquid storage tank 12, and the outlet pipe 16. The raw material liquid is supplied to the mixing tank 11 from the raw material liquid storage tank 12 via the inflow amount adjusting device 13. The amount of raw material liquid supplied is adjusted by the amount of electricity that is energized. As the raw material liquid, a mineral salt containing silicon and phosphorus collected from Japanese seawater is used. A stirring device 14 is provided in the mixing tank 11 so that the alkaline ionized water and the raw material liquid are uniformly mixed.

The cathode terminal 100 is arranged in the mixing tank 11. A direct current of 200 V is applied to the cathode terminal 100. The amount of electricity emitted from the cathode terminal 100 is preferably 1000 W to 3000 W.

The mixing tank 11 is insulated by the heat insulating means 15 so as not to be affected by the ambient temperature, and the internal temperature is adjusted to about 15 ° C to 25 ° C by the temperature adjusting means (not shown). The temperature of the mixing tank 11 is preferably about 0 ° C to 10 ° C.

The pH of the alkaline ionized water derived from the mixing tank 11 is measured by the pH measuring means 17 provided in the outlet pipe 16. The pH of the alkaline ionized water taken out from the mixing tank 11 is preferably about 10 to 12.5.

The outlet pipe 16 connected to the mixing tank 11 is branched into an alkaline ionized water outlet pipe 18 and a mixed alkaline ionized water outlet pipe 21. The alkaline ionized water in the mixing tank 11 is directly taken out from the alkaline ionized water outlet pipe 18. The alkaline ionized water can also be mixed with alcohol to obtain mixed alkaline ionized water. In this case, alkaline ionized water and alcohol may be mixed in the alcohol mixing tank 20 in which alcohol is injected from the alcohol storage tank 19 and taken out as mixed alkaline ionized water from the mixed alkaline ionized water outlet pipe 21. As the alcohol to be mixed with alkaline ionized water, alcohol having a high compatibility with water, for example, methanol, ethanol, isopropyl alcohol and the like can be used.

The above-mentioned alkaline ionized water production apparatus 101 is isolated from the outside air by being housed in the isolation chamber 22. The isolation chamber 22 is replaced with nitrogen or is coupled to the outside air atmosphere by a ventilation device filled with carbon dioxide, an oxygen scavenger, or the like. By providing the alkaline ionized water production device 101 in the isolation chamber 22, it is possible to prevent the deterioration of the alkaline ionized water and maintain the performance for a long period of time.

Commercially available products can be used as the alkaline ionized water obtained by electrolyzing an aqueous solution containing a mineral salt containing silicon and phosphorus. Examples of commercially available products include trade names S-100 and S-100G (both manufactured by AI System Products Co., Ltd.).

The surface treatment method of the present invention is characterized in that titanium or a titanium alloy is immersed in alkaline ionized water obtained by electrolyzing an aqueous solution containing a mineral salt containing silicon and phosphorus.

The temperature of the alkaline ionized water is usually about 0 to 40 ° C, preferably 10 to 30 ° C. Titanium or a titanium alloy may be immersed in alkaline ionized water at room temperature (normal temperature).

The processing time is not particularly limited. It is usually 1 minute or more, preferably 3 minutes or more and 10 minutes or less.

The surface treatment method of the present invention simply immerses titanium or a titanium alloy in alkaline ionized water obtained by electrolyzing an aqueous solution containing a mineral salt containing silicon and phosphorus, and the surface properties of titanium or the titanium alloy. Can be modified, so that surface modification can be performed inexpensively and easily as compared with conventional ultraviolet irradiation that requires expensive equipment.

The present invention also includes an implant made of titanium or a titanium alloy surface-treated by the above-mentioned surface treatment method. Therefore, the implant of the present invention is an implant made of titanium or a titanium alloy whose surface is treated with alkaline ionized water obtained by electrolyzing an aqueous solution containing a mineral salt containing silicon and phosphorus.

In the present specification, the implant made of titanium or a titanium alloy means a molded body formed of titanium or a titanium alloy for use in a living body. The shape, usage form, and the like of the titanium or titanium alloy implant are not particularly limited as long as they have the physical properties and safety necessary for use in a living body. For example, as the artificial bone metal material, any shape such as a columnar shape, a plate shape, a block shape, a sheet shape, a fibrous shape, and a pellet shape can be used. Further, it may be in the form of a product such as a stem material for an artificial hip joint, a bone filling material, an artificial vertebral body, an artificial tooth root, an artificial intervertebral disc, a bone plate, and a bone screw.

Hereinafter, the present invention will be described in more detail by way of examples, but the technical scope of the present invention is not limited to these examples.

(Production Example 1) Production of alkaline ionized water Alkaline ionized water was produced as follows using the above-mentioned alkaline ionized water production apparatus 101.
Ion-exchanged water was prepared as the raw material water. Ion-exchanged water was produced by removing impurities from tap water using an ion-exchange resin (manufactured by Samsung). An aqueous solution prepared by adding 1% by mass of a mineral salt containing silicon and phosphorus collected from Japanese seawater to ion-exchanged water was introduced into an electrolytic cell 1 through a water guide tube 2, and electricity was passed through the anode 6 and the cathode 7. The conditions for electrolysis were a voltage of 200 V and an electric energy of 2500 W. The ion-exchanged water was electrolyzed, acidic water was generated in the anode chamber 4, and alkaline water was generated in the cathode chamber 5. The acidic water generated in the anode chamber 4 was discharged from the acidic water discharge pipe 8. The alkaline water generated in the cathode chamber 5 was led out to the alkaline water outlet pipe 9, and the alkaline water passing through the alkaline water outlet pipe 9 was cooled by the cooling device 10 and introduced into the mixing tank 11.

In the mixing tank 11, the cooled alkaline water and the silicon and phosphorus-containing mineral salts collected from the Japanese seawater supplied from the raw material liquid storage tank 12 were mixed by the stirring device 14. The mineral salt containing silicon and phosphorus collected from Japanese seawater in the raw material liquid storage tank 12 contains the silicon and phosphorus-containing mineral salt collected from Japanese seawater in the mixed liquid in the mixing tank 11. However, it was adjusted and supplied by the inflow amount adjusting device 13 so as to be 0.3% by mass. The mixed solution was stored at a pressure of 294 kPa and a temperature of 4 ± 3 ° C. for 24 hours. During storage, electrons were emitted from the cathode terminal 100 into the mixed solution.
After that, the alkaline ionized water was taken out from the outlet pipe 16, the pH of the alkaline ionized water was measured by the pH measuring means 17, and then the alkaline ionized water was taken out from the alkaline ionized water outlet pipe 18.

<Elemental analysis>
The alkaline ionized water of Production Example 1 taken out from the alkaline ionized water outlet tube was subjected to elemental analysis using ICP emission spectroscopy (manufacturing company: Hitachi High-Tech Science Co., Ltd., product name: SPECTRO ARCOSII).
As a result, it was found that silicon was contained in 100 mass ppm and phosphorus was contained in 760 mass ppm. Further, in detail, it was found that sodium was contained in an amount of 7500 mass ppm, potassium was contained in an amount of 2700 mass ppm, calcium was contained in an amount of 0.2 mass ppm, and magnesium was contained in an amount of 0.1 mass ppm or less.

In addition, since gas such as chlorine cannot be detected by the above ICP emission spectroscopy, the alkaline ionized water (Sample 1) of Production Example 1 taken out from the alkaline ionized water outlet tube is separately used by the Japan Food Research Laboratories Center. Was measured using the following combustion-coulometric titration method.
As a combustion-coulometric titration method, about 10 mg of the above sample 1 was burned using a chlorine / sulfur analyzer TSX-10 manufactured by Nittoseiko Analytech Co., Ltd., and the chloride ion concentration was calculated by optimizing the coulometric amount. .. By this measurement, the amount of chlorine in the sample can be obtained regardless of whether it is organic chlorine or inorganic chlorine. For the amount of organic chlorine, the value obtained by subtracting the amount of inorganic chlorine from the total amount of chlorine was used. The amount of inorganic chlorine was determined by extracting 5 g of a sample with hot water and measuring chlorine ions in the extract by an ion chromatograph method.
As a result, it was found that the alkaline ionized water of Production Example 1 contained 410 mg / kg of chlorine.

<Measurement of pH>
When the pH of the alkaline ionized water obtained in Production Example 1 was measured using a pH meter (HORIBA F-74SP manufactured by HORIBA, Ltd.), the pH value was 12.

<Measurement of surface tension>
The surface tension of the alkaline ionized water obtained in Production Example 1 was measured by using the Wilhelmy method.
As a result, the surface tension of the alkaline ionized water obtained in Production Example 1 was about 65.41 mN / m (20 ° C.). When the surface tension of purified water was measured by the same method, it was about 72.96 mN / m (20 ° C.). Therefore, the alkaline ionized water containing a mineral salt containing silicon and phosphorus used in the present invention. The surface tension was about 7.55 mN / m lower than the surface tension of purified water.

(Manufacturing Example 2)
Alkaline ionized water was produced in the same manner as in Example 1 except that the raw material of the mineral salt containing silicon and phosphorus was changed from seawater in Japan to seawater in Okinawa Prefecture.
As a result of elemental analysis of the obtained alkaline ionized water using ICP emission spectroscopy in the same manner as in Example 1, it was found that silicon was contained in 370 mass ppm and phosphorus was contained in 450 mass ppm. Further, in detail, it was found that sodium was contained in an amount of 6900 mass ppm, potassium was contained in an amount of 1 mass ppm or less, calcium was contained in an amount of 0.9 mass ppm or less, and magnesium was contained in an amount of 0.3 mass ppm or less.
Further, as a result of measuring chlorine contained in the alkaline ionized water obtained in Example 2 at the Japan Food Research Laboratories using the combustion-coulometric titration method in the same manner as in Example 1, Example 2 It was found that 410 mg / kg of chlorine was contained in the alkaline ionized water.

(Manufacturing Example 3) Treatment of Titanium Disc As the titanium disc, a mirror-polished Ti-6Al-4V disc (manufactured by Osaka Yakken) having a diameter of 9.5 mm and a thickness of 1.0 mm was used. As a pretreatment, the titanium disc was immersed in ethanol, acetone, and two-stage distilled water (DDW), and ultrasonic treatment was performed for 10 minutes. The pretreated titanium disc was subjected to the following treatment immediately after the pretreatment, after standing in a clean bench for 1 week, or after standing for 4 weeks.
(1) The product was immersed in the alkaline ionized water produced in Production Example 1 for 3 minutes. Hereinafter, the treated group is referred to as an alkaline ionized water treatment group.
(2) Immersed in DDW for 3 minutes. Hereinafter, those subjected to the treatment are referred to as a control group.
(3) A 15 W germicidal lamp (λ = 253.7 nm, manufactured by Panasonic Corporation) in a clean bench was irradiated for 48 hours. Hereinafter, those subjected to the treatment are referred to as UV groups.
The following tests were performed on the titanium discs (alkaline ionized water treatment group, control group, or UV group) that had been subjected to the above treatment immediately after the pretreatment, 1 week later, or 4 weeks later.

(Example 1) Scanning X-ray photoelectrons by X-ray photoelectron spectroscopy (XPS) for the alkaline ionized water treatment group immediately after pretreatment and 4 weeks after the trace element analysis , and the control group immediately after pretreatment and after 4 weeks. Wide scan analysis (1300.00-0.00 eV, 20.000 s) and narrow scan analysis (C1s: 298.00-278.00 eV, N1s: 411.00-391.00 eV) using the spectrophotometer PHI X-tool (manufactured by ULVAC Phi Co., Ltd.) , O1s: 543.00-523.00 eV, Ti2p: 469.00-449.00 eV, 20.000 s) to measure trace elements (n = 4). The results of the wide scan analysis are shown in FIG. 2A, and the results of the narrow scan analysis are shown in FIG. 2B.

From FIG. 2A, the presence of carbon (C), oxygen (O), and titanium (Ti) was confirmed in the control group and the alkaline ionized water treatment group in the wide scan analysis. It was observed that carbon (C) decreased and oxygen (O) increased in the alkaline ionized water treatment group as compared with the control group. From FIG. 2B, it was also confirmed in the narrow scan analysis that carbon (C) decreased and oxygen (O) increased in the alkaline ionized water-treated group as compared with the control group.
Titanium aging is related to the decrease in surface polarity due to the adhesion of trace elements (carbon, etc.) in the air to the titanium surface over time, and the change to hydrophobicity due to the decrease in surface energy. It is known. From the results of the above trace element analysis, it is considered that the acquisition of hydrophilicity in the alkaline ionized water treatment group is related to the removal of carbon (C) from the difference in the percentage of carbon between the control group and the alkaline ionized water treatment group. .. Further, it is considered that the increase in oxygen (O) is due to the fact that the titanium oxide layer on the surface of the titanium disk became apparent due to the removal of carbon (C).

(Example 2) Measurement of contact angle (evaluation of hydrophilicity)
Immediately after the pretreatment, 0.5 μL of DDW was dropped onto the surface of the titanium disk after 1 week and 4 weeks, and the contact angle was measured using a contact angle meter LSE-ME3 (manufactured by Nick Co., Ltd.) to determine the hydrophilicity. Evaluated (n = 5).

Figure 3 shows a photograph when measuring the contact angle. In FIG. 3, A (upper row) shows a control group, B (middle row) shows an alkaline ionized water treatment group, and C (lower row) shows a UV group. Further, 1 (left column) indicates immediately after the pretreatment, 2 (center column) indicates 1 week later, and 3 (right column) indicates 4 weeks later.

From FIG. 3, in the control group (A), the DDW dropped on the titanium disk had a dome shape, whereas in the alkaline ionized water treatment group (B) and the UV group (C), the DDW had the entire surface of the titanium disk. It was found that it spreads thinly and shows good hydrophilicity (wetting property).

Figure 4 shows the measurement results of the contact angle. The measurement results were tested by the Tukey method after performing one-way ANOVA. In FIG. 4, * indicates p <0.01.

From FIG. 4, it was found that the contact angle tended to increase with time in all the groups. A significant difference was observed in the contact angle values between immediately after the pretreatment and 1 week after the pretreatment of the control group, and between immediately after the pretreatment and 4 weeks after the pretreatment. Moreover, at all the measurement points, the values of the contact angles of the alkaline ionized water treatment group and the UV group were significantly lower than those of the control group. Comparing the alkaline ionized water treatment group and the UV group, the value of the contact angle of the UV group was significantly lower immediately after the pretreatment and after 1 week and 4 weeks.
From these results, it can be seen that the surface energy of titanium was increased by treatment with alkaline ionized water, and it was possible to modify the surface from a hydrophobic surface to a hydrophilic surface. This time, the contact angle in the alkaline ionized water treatment group was about 10 °, and the reason why it did not become super-hydrophilic (less than 5 °) was that the titanium disc used was mirror-polished, and the original surface energy was reduced. Probably because it was very small.

(Example 3) Titanium disk surface of each of the alkali ionized water treatment group immediately after the protein adsorption test and 4 weeks after the pretreatment, the control group immediately after the pretreatment and 4 weeks, and the UV group immediately after the pretreatment and 4 weeks after the pretreatment. 200 μL of bovine serum fibronectin was added dropwise to the drug, and after 24 hours, the amount of protein adsorbed was measured by the Bradford method using a protein assay kit (Bio-Rad Protein Assay Kit, manufactured by Bio-Radra Volunteers Co., Ltd.). (N = 5). The results are shown in FIG. The measurement results were tested by the Tukey method after performing one-way ANOVA. In FIG. 5, * indicates p <0.05 and ** indicates p <0.01.

From FIG. 5, immediately after the pretreatment, the UV group showed a significantly higher value than the control group, but no significant difference was observed between the control group and the alkaline ionized water treatment group. After 4 weeks, the values in the alkaline ionized water treatment group and the UV group were significantly higher than those in the control group.
Since a significant difference was observed between the control group after pretreatment and after 4 weeks, the surface changed to hydrophobic after 4 weeks due to aging, and the amount of protein adsorbed compared to immediately after pretreatment. Is thought to have decreased. Furthermore, no significant difference was observed between the control group and the alkaline ionized water treatment group immediately after the pretreatment, but 4 weeks after the aging progressed, the titanium surface of the control group changed to hydrophobic and alkaline ions. Since the titanium surfaces of the water-treated group and the UV group became hydrophilic, it is considered that the alkaline ionized water-treated group and the UV group showed higher protein adsorption amounts.

(Example 4) Cell adhesion test Osteoblast-like cell line MC3T3E-1 (RIKEN cell bank) was used as a medium α-MEM (manufactured by Nakarai Tesk Co., Ltd., Eagle's minimum essential medium α modified type), 10% FBS (fetal bovine serum). ), 1% penicillin-streptomycin (manufactured by Gibco) was cultured at 37 ° C. and under 5% CO ₂ . The culture solution was changed every 3 days.

MC3T3E was placed on the titanium discs of the alkaline ionized water treatment group immediately after the pretreatment and after 4 weeks, the control group immediately after the pretreatment and 4 weeks, and the UV group immediately after the pretreatment and after 4 weeks, which were placed in the 24-well plate. -1 cells were seeded at 500 μL (4.0 × 10 ⁴ cells / well) and incubated for 24 hours. Then, those stained with rhodamine phalloidin and 4', 6-diamidino-2-phenylindole (DAPI) were observed with a confocal laser scanning microscope (LSM700, manufactured by Carl Zeiss). The contact area of the stained cells was quantified using image analysis software (ImageJ, NIH, Bethesda, ML) (n = 5). The results are shown in FIG. The measurement results were tested by the Tukey method after performing one-way ANOVA. In FIG. 6, * indicates p <0.01.

From FIG. 6, the cell adhesion area immediately after the pretreatment showed a significantly larger value in the UV group than in the control group and the alkaline ionized water treatment group. After 4 weeks, the alkaline ionized water treatment group and the UV group showed significantly larger values than the control group.
It is known that cell adhesion is reduced on the surface that has become hydrophobic due to aging, which also affects the subsequent cellular response and contributes to the proliferation and differentiation of osteoblasts. From the above results, it is considered that in the control group, cells are less likely to adhere to the titanium surface due to a decrease in surface energy due to adhesion of carbon or the like, a change in surface potential, and the like. On the other hand, in the alkaline ionized water treatment group and the UV group, it is considered that more cells were attached due to an increase in surface energy due to carbon removal, a change in surface potential, and the like.

(Example 5) Cell proliferation test The cell proliferation ability was measured after seeding the cells on the surface of the titanium disk immediately after the pretreatment under the same conditions as the cell contact test and incubating for 24 hours or 72 hours. The proliferation ability was 24. Celltiter 96 (registered trademark) (manufactured by Promega Co., Ltd.) is added to the well plate, and the cells are incubated at 37 ° C. for 15 minutes for colorimetric color development. Microplate reader (Bio-Rad Model 680, manufactured by Bio-Rad Laboratories Co., Ltd.) ) Was used to measure the absorbance at a wavelength of 490 nm (n = 5). The results are shown in FIG. The measurement results were tested by the Tukey method after performing one-way ANOVA. In FIG. 7, * indicates p <0.05 and ** indicates p <0.01.

From FIG. 7, at 24 hours, the proliferative ability of the alkaline ionized water-treated group and the UV group was significantly higher than that of the control group. At 72 hours, the proliferation ability of the UV group was significantly higher than that of the control group and the alkaline ionized water treatment group.
From this result, since the hydrophilicity of the titanium surface contributes to the initial adhesion of cells, the alkaline ionized water-treated group and the UV group to which the hydrophilicity was imparted showed high values in 24 hours, and UV having higher hydrophilicity. It is considered that the group showed a high value at 72 hours.

(Example 6) Animal experiment Six New Zealand white rabbits were given a general anesthesia by intramuscularly injecting a three-kind mixed anesthetic (butorphanol tartrate, medetomidin hydrochloride, and midazolam) into the thigh. After disinfecting the left and right femurs with povidone iodine, local anesthesia was performed with 2% xylocaine, the skin was incised with a # 15 scalpel, the muscle layer was peeled off, the periosteum was incised, and the femur was excised. Then, the femur was formed into a groove having a length of 10.0 mm, a width of 1.0 mm, and a depth of 10.0 mm using an ultrasonic bone cutting tool (PIEZOSURGERY (registered trademark)) (see FIG. 8A). Titanium discs immersed in alkaline ionized water or saline for 3 minutes were embedded in the groove (see FIG. 8B). For the wound, the periosteum was sutured with 5-0 VICRYL suture and the skin was sutured with 5-0 nylon thread. Four weeks after implantation, sodium pantobarbital was overdose from the auricular vein for euthanasia, and the femur was collected. A micro CT was taken of the collected femur. The micro CT image is shown in FIG. In FIG. 9, A (upper row) shows a control group, and B (lower row) shows an alkaline ionized water treatment group. Further, 1 (left column) is the XY plane, 2 (center row) is the YY plane, and 3 (right column) is the ZZ plane.

Then, a non-decalcified polished specimen was prepared and stained with Villanueva bone. The Villanueva bone-stained image is shown in FIG. A indicates a control group, and B indicates an alkaline ionized water treatment group. The scale bar in FIG. 10 is 100 μm.
Then, the BIC (bone-implant contact rate) in the range of 5 mm from the center of the disc to the bone marrow side was measured (n = 5). BIC was calculated from the following equation 1 using ImageJ.

The length of the bone bonded to the surface of the titanium disk in BIC and the length of the surface of the titanium disk were measured based on the schematic diagram of the BIC measurement range shown in FIG. In FIG. 11, a indicates the length of the titanium disk surface (dotted line), b indicates the length of the bone bonded to the titanium disk surface (arrow), and c indicates new bone. The result of BIC is shown in FIG. The measurement results were subjected to t-test. In FIG. 12, * indicates p <0.05.

From FIG. 9, compared with the control group, active formation of new bone was observed around the titanium disc on the bone marrow side of the alkaline ionized water treatment group. From FIG. 10, as compared with the control group, more osteoids stained in reddish purple were observed around the titanium disk on the bone marrow side of the alkaline ionized water treatment group. From FIG. 12, the BIC of the alkaline ionized water treatment group showed a significantly higher value than that of the control group.
It is known that the hydrophilicity of the titanium surface is involved in the adsorption or cell adhesion of various proteins or cytokines that affect osseointegration and lowers BIC. From this, it is considered that the BIC was higher in the hydrophilic alkaline ionized water treatment group than in the control group having a hydrophobic surface.

From the above, by immersing the titanium disc in alkaline ionized water obtained by electrolyzing an aqueous solution containing a mineral salt containing silicon and phosphorus for a short time, the surface is almost the same as that of conventional ultraviolet irradiation. It was found that a reforming effect was obtained. Currently, for the surface treatment of implants, it is necessary to install special equipment in a disinfection room or the like, but if the surface treatment method of the present invention is used, it is possible to modify the surface of the implant easily and at low cost in a space-saving manner. It will be possible.

1 Electrolyzer 2 Water guide tube 3 Diaphragm 4 Anodium 5 Cathode room 6 Cathode 7 Cathode 8 Acidic water discharge tube 9 Alkaline water outlet tube 10 Cooling device 11 Mixing tank 12 Raw material liquid storage tank 13 Inflow amount adjusting device 14 Stirring device 15 Insulation means 16 Outlet pipe 17 pH measuring means 18 Alkaline ionized water outlet pipe 19 Alcohol storage tank 20 Alcohol mixing tank 21 Mixed alkaline ionized water outlet pipe 22 Isolation chamber 100 Cathode electron 101 Alkaline ionized water production equipment

Claims

A method for surface treating titanium or a titanium alloy, which comprises a step of immersing titanium or a titanium alloy in alkaline ionized water obtained by electrolyzing an aqueous solution containing a mineral salt containing silicon and phosphorus.
The surface treatment method according to claim 1, wherein the alkaline ionized water contains 0.4 to 400 mass ppm of silicon and 400 to 800 mass ppm of phosphorus.
The surface treatment method according to claim 1 or 2, wherein the alkaline ionized water further contains at least one mineral selected from the group consisting of calcium, potassium, sodium, and magnesium.
The surface treatment method according to any one of claims 1 to 3, wherein chlorine is further contained in the alkaline ionized water.
The surface treatment method according to any one of claims 1 to 4, wherein the pH of the alkaline ionized water is 10 to 12.5.
The surface treatment method according to any one of claims 1 to 5, wherein the surface tension of the alkaline ionized water is 55 to 68 mN / m.
An electrolysis step in which the alkaline ionized water electrolyzes an aqueous solution containing a mineral salt containing silicon and phosphorus and water, and the alkaline water on the cathode side obtained in the step and a mineral containing silicon and phosphorus. The surface treatment method according to any one of claims 1 to 6, which is obtained by an electron supply step of mixing with a salt to obtain a mixed solution and supplying electrons to the mixed solution.
An implant made of titanium or a titanium alloy whose surface is treated with alkaline ionized water obtained by electrolyzing an aqueous solution containing a mineral salt containing silicon and phosphorus.
A step of electrolyzing an aqueous solution containing a mineral salt containing silicon and phosphorus to obtain alkaline ionized water, and
A method for manufacturing an implant made of titanium or a titanium alloy, comprising a step of treating the surface of titanium or a titanium alloy with the alkaline ionized water.