JP2002248163A - Bioactive titanium oxide coating material formed with titanium oxide layer directly on surface by aqueous solution synthesis - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a bioactive material in which a titanium oxide layer (or a film) is formed at room temperature independently of the material type of a material to be coated (substrate), the substrate shape and complexity of a surface structure, and which has a bioactivity of the titanium oxide layer left as it is. SOLUTION: The bioactive material is manufactured by soaking the material to be coated (substrate) in an aqueous solution containing a water soluble compound containing titanium and a reagent producing titanium oxide from the compound, in particular an aqueous solution containing a titanium fluorocomplex compound as the water soluble compound containing titanium, and a fluoride ion trapping agent, and by forming a titanium oxide thin film on the surface of the material to be coated (substrate). Furthermore, bioactivity of the bioactive material is improved by processing the titanium oxide thin film formed by the above-mentioned method in lukewarm water or in a solution containing calcium salt.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a bioactive material in which a titanium oxide layer having bioactivity as it is is formed on a surface of a material to be coated (hereinafter sometimes referred to as a substrate) in various shapes. In particular, a bioactive titanium oxide layer is directly formed at a low temperature of 100 ° C. or less on the surface of a material to be coated made of an electrically insulating material, a small heat-resistant organic plastic material, or the like without an intermediate layer. The present invention relates to a bioactive material having a surface formed with a bioactive titanium oxide layer useful as an implant material having high bioactivity as it is. As it is means that after forming the titanium oxide layer, there is no need for heat treatment, chemical treatment, or the like for bioactivation.

[0002]

2. Description of the Related Art To date, alloy materials such as titanium and titanium alloys have been used as constituents of bioactive materials such as artificial bones, implant materials, cell culture vessels, etc., but the surface of the material remains unaffected by body fluids. In the case of contact with, for example, no apatite film is formed because of no biological activity or extremely low biological activity. Therefore, in order to impart practicality as a biomaterial,
It is used after a treatment to form an apatite film on the surface. The reason is that a bonding form called osseointegration that directly bonds to bone is desired. Osseointegration refers to a state in which living bone and an implant body are directly bonded to each other. This is not realized with a material having no biological activity, and fibrous connective tissue is interposed.

[0003] Also, hydroxyapatite (HA) is formed on the surface of Ti.
Implants coated with P) are also commercially available. Conventionally, as a method of coating a bioactive titanium oxide layer on such a substrate surface, a method of coating a liquid titania gel or sol on the substrate surface, drying and heating treatment to bond the titania gel to the substrate ( Sol-
Gel method) (゛ Apatite-Forming)
Ability Of Titania Gels W
is Different Structure S, B
ioceramics, Volume 12, p. 149
(1999)). However, in this method, in order to form a bioactive titanium oxide layer on the surface, it is necessary to heat at a temperature of 500 ° C. or more, and the material constituting the base material is required to have heat resistance, and the heat resistance is low. However, there is a disadvantage that an organic plastic material cannot be used as a base material. Further, even when a substrate having high heat resistance such as metal or ceramics is used, a crack is easily generated in the coating layer in the heating and cooling process of the bioactivation due to a difference in thermal expansion coefficient between the substrate and the titanium oxide film. There was also a problem.

The present inventors have proposed a method for forming a titanium oxide layer having photocatalytic activity on a substrate surface at a low temperature of less than 100 ° C. and a heat-resistant material as a material constituting the substrate (material to be coated). Irrespective of the thermal and electrical properties such as insulation and insulation, and irrespective of the complexity of the surface shape,
A method by which the layer can be formed has been proposed [US Pat.
066,359 (patented on May 23, 2000), International Application Publication No. WO98 / 11020 (republished patent) (March 19, 1998)]. However, the surface property having sufficient bioactivity as an implant material or the like without the surface treatment such as coating the hydroxyapatite (HAP) or the like with the titanium oxide layer as it is, in other words, I have no idea about having

Japanese Patent Application Laid-Open No. 12-271206 discloses that in order to improve the bioactivity of an implant material having titanium or a titanium alloy on the surface, a bioactive surface layer such as the apatite film is formed at room temperature by an electrolytic method. Alternatively, it is described that the titanium oxide layer is formed on the surface of a titanium alloy, but does not mention that a biocompatible titanium oxide layer itself is formed at room temperature.

[0006]

SUMMARY OF THE INVENTION The present invention provides a titanium oxide layer (or coating) on a surface of a substrate at room temperature, regardless of the material of the substrate and the complexity of the shape and surface structure of the substrate.
It is an object of the present invention to provide a bioactive material on which a titanium oxide layer is formed, in which a titanium oxide layer is formed and a bioactivity is expressed as it is. To this end, while examining the methods of forming various titanium oxide layers and the bioactive properties of the layers, the inventors proposed a low temperature (100 ° C. or lower).
It has been surprisingly found that a titanium oxide film formed by applying the method of forming a titanium oxide film exhibits bioactivity without requiring a conventional bioactivation treatment,
Furthermore, they have found that a titanium oxide layer having the same biological activity as described above can be formed even by using a water-soluble compound containing titanium that can form a titanium oxide layer by hydrolysis or the like, thereby solving the problem of the present invention.

[0007]

Means for Solving the Problems The present invention basically comprises:
A material to be coated (substrate) was placed in an aqueous solution containing a water-soluble compound containing titanium and a reagent for generating titanium oxide from the compound, and a titanium oxide layer having bioactivity was formed on the surface of the material to be coated. A bioactive material having a bioactive titanium oxide layer formed thereon. Preferably, the titanium-containing water-soluble compound is a fluorotitanium complex compound, the reagent for generating titanium oxide is a fluoride ion scavenger, and the titanium-containing water-soluble compound is titanium tetrafluoride, which forms titanium oxide. The bioactive titanium oxide layer, wherein the reagent to be adjusted is one that adjusts the pH of the solution, or the water-soluble compound containing titanium is titanium oxosulfate and generates titanium oxide by hydrolysis. Is a bioactive material. More preferably, it is a bioactive material having a bioactive titanium oxide layer formed on the surface of the base material, wherein the concentration of the fluorotitanium complex compound is 1 × 10 ⁻⁵ to 1 mol / L. 1x fluoride ion supplement
It is a bioactive material having a bioactive titanium oxide layer formed on the surface of each of the base materials, characterized in that it is added in an amount of 10 ⁻² mol / L or more. Or forming a titanium oxide layer (or a thin film) and then immersing the substrate in warm water at 40 to 100 ° C. or in a solution containing a calcium salt. It is a bioactive material on which a titanium oxide layer is formed. Even more preferably, the aqueous solution forming the titanium oxide layer has a particle size of 0.001 to 10 μm
In particular, the aqueous solution containing the fluorotitanium complex compound contains 0.001 to 1
The present invention relates to a bioactive material comprising a titanium oxide seed crystal in a range of 0 μm, wherein a bioactive titanium oxide layer is formed on the surface of each base material. According to the method for producing a bioactive material of the present invention, a material suitable for various uses can be appropriately selected as a base material. In particular, as a biomaterial, depending on the site to be used, and a material that improves biocompatibility,
For example, porous (may be non-woven fabric, paper, binding fiber, etc.)
Are preferred. In the present invention, the fact that the organic polymer (polymer) material can be used as a constituent material of the base material can be said to be a remarkable effect in that the uses can be diversified.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in more detail. A, As the water-soluble compound containing titanium used in the production of the bioactive material of the present invention, the above-mentioned fluorotitanium complex compound, titanium tetrafluoride, titanium oxysulfate and the like can be mentioned as preferable ones. The aqueous solution containing the fluorotitanium complex compound can be prepared by dissolving titanium oxide in hydrofluoric acid. In addition, the fluorotitanium complex compound is synthesized by dissolving a hydroxide or oxyhydroxide of titanium in an aqueous solution of an alkali metal hydrogen difluoride such as ammonium hydrogen difluoride or sodium hydrogen difluoride. You can also.

B. The aqueous solution containing a fluorotitanium complex compound used for forming the titanium oxide layer is an aqueous solution having a metal content of usually 10 ^{-9 to} 10 mol / L, preferably 10 ^{-5 to 1} mol / L. It is prepared and used as If the concentration of the fluorotitanium complex compound is higher than 10 mol / L, it is not preferable in terms of economy. Here, the aqueous solution may be an aqueous solution containing excess hydrogen fluoride used for synthesizing the complex compound.

C. In the present invention, the titanium oxide constituting the titanium oxide layer can be obtained as a stable phase by allowing the seed crystal to be present in the aqueous solution containing the fluorotitanium complex compound. The seed crystal is in the range of 0.001 to 10 μm, preferably as small as 0.001 to 1 μm, and the amount of the seed crystal can be appropriately determined in consideration of the amount of titanium oxide to be precipitated. The precipitation rate can be controlled by selecting the particle size and the amount of the seed crystal to be added. If necessary, seed crystals can be replenished during the precipitation. When a seed crystal is added, ultrasonic dispersion is effective in forming a uniform film.

D. The fluoride ion scavenger used in the present invention may be any as long as it can scavenge fluorine ions from an aqueous solution containing a fluorotitanium complex compound to deposit a titanium oxide coating layer. Generally, a fluoride ion scavenger includes a homogeneous system used by being dissolved in a liquid phase and a heterogeneous system which is a solid. Depending on the purpose, either one of these two may be used or both may be used. Various acids and alkali compounds can be used as the pH adjusting material.

E, 1, a homogeneous fluoride ion scavenger,
By reacting with hydrogen fluoride to form a stable fluorotitanium complex compound and / or fluoride, the equilibrium of fluorine ions is shifted so as to precipitate titanium oxide. Besides boric acid such as orthoboric acid and metaboric acid, examples thereof include aluminum chloride, sodium hydroxide, and aqueous ammonia. Such a capture agent is usually used in the form of an aqueous solution, but may be added in the form of a powder and dissolved in the system. Such addition of the scavenger may be performed once or several times intermittently, or may be performed continuously at a controlled feed rate, for example, at a constant rate. The homogeneous fluoride ion scavenger is 1 × 10 ⁻³ mo
1 / L ^-1 or more, preferably 1 × 10 ^-2 mol / L ^-1 or more. 2. Heterogeneous fluoride ion scavengers include metals such as aluminum, titanium, iron, nickel, magnesium, copper, zinc, ceramics such as glass,
And compounds such as silicon, calcium oxide, boron oxide, aluminum oxide, silicon dioxide, and magnesium oxide. When such solid matter is added or inserted into the solution, F near solids ^- are consumed, because its concentration decreases, the chemical equilibrium of the portion is shifted, titanium oxide is precipitated. When such a solid is used, depending on the method of addition or insertion and the reaction conditions, titanium oxide can be deposited on the entire surface of the substrate immersed in the aqueous solution, or the deposition can be locally performed, that is, the solid can be selected. It is also possible to limit to the vicinity where. Alternatively, by using a combination of a homogeneous and a heterogeneous fluoride ion scavenger, the thickness of the deposit thin film on the substrate surface can be partially increased.

F. The bioactive titanium oxide layer obtained according to the present invention is mainly composed of oxygen and titanium, but may contain some fluorine.

G. As the base material, any material such as metal, glass, ceramics, and organic polymer can be used. Further, the shape may be any shape including a complicated shape such as a plate shape, a rod shape, a fiber shape (including a wet or dry nonwoven fabric, a fiber bundle, etc.), and a granular shape. 1, Coating bioactive titanium oxide layer on a material that shows high mechanical strength such as stainless steel, cobalt-chromium alloy, titanium metal or titanium alloy, alumina, zirconia, carbon, etc., and is chemically stable in the living body This is useful as an artificial bone that can bear a large load and is firmly fixed to the bone. 2. Organic polymers are useful as lightweight implants. Organic polymers include silicone, polyvinyl chloride (PVC), polyethylene terephthalate (PET),
Polycarbonate, polyether sulfone (PE
S), polypropylene (PP), polyethylene (P
E), nylon 6, polymethyl methacrylate (PMM
A), polyurethane (PUR) and the like are used. 3. The material of the base material may be a single material or a composite material in which a plurality of materials are combined.

H, The substrate may be immersed in the aqueous solution of the fluorotitanium complex compound before, during, or after the addition or insertion of the fluoride ion scavenger. However, when using a substrate that may be affected by the system, attention must be paid to the composition of the solution, the reaction conditions, and the timing of immersion. The reaction temperature can be arbitrarily set as long as the system maintains an aqueous solution, but is preferably in the range of 10 to 80 ° C. The reaction time is preferably 1 hour or more, and more preferably 4 hours or more from the viewpoint of imparting uniform bioactivity to the entire substrate. After immersing the substrate in an aqueous solution of a fluorotitanium complex compound and forming a titanium oxide thin film, the substrate was heated at 40 ° C.
When the titanium oxide is immersed in warm water at １００100 ° C., the crystallinity of the titanium oxide is increased, and the biological activity is improved. Furthermore,
After forming the titanium oxide thin film, if the titanium oxide film is immersed in a solution containing a calcium salt, the biological activity of the titanium oxide layer is improved. Preferred calcium salts include calcium salts of inorganic acids such as calcium nitrate and calcium chloride and calcium salts of organic acids such as calcium acetate. Before the formation of the bioactive titanium oxide layer by using the present invention, a resist film can be formed on the base material by a method such as photolithography to limit the portion where the titanium oxide layer is formed. In addition, a treatment for cleaning the surface, for example, a chemical treatment with an acid or the like, a physical treatment with an ultrasonic wave, a jet stream, or the like, a mechanical treatment such as sand blast, or a combination thereof can be performed.

G. Thus, a bioactive titanium oxide layer can be formed on the substrate surface at a low temperature of 100 ° C. or less. However, a heating step may be provided as necessary under conditions that do not cause thermal deterioration of the base material. After coating titanium oxide on the surface of an artificial bone, a bioimplant treatment material, a bioimplant medical device, an instrument, or the like using the present invention, when implanting in a body, it is immersed in a supersaturated solution to apatite in advance. Alternatively, an apatite layer can be formed on the surface.

[0017]

The present invention will be described in more detail with reference to the following examples. It goes without saying that the present invention is not limited only to this embodiment. Example 1 A plate-shaped titanium metal of 10 mm × 10 mm × 1 mm was used as a base material. Ammonium hexafluorotitanate (NH ₄ ) ₂ TiF ₆ was dissolved in distilled water, and then boron oxide was added and stirred quickly. The above-mentioned base material is added to this treatment solution for 40 minutes.
C. for 24 hours. After the treatment, the substrate was taken out of the treatment liquid, washed and dried to obtain a substrate having a titanium oxide film. The concentration of ammonium hexafluorotitanate in the treatment solution is 1 × 10 ⁻¹⁰ , 1 × 10 ⁻⁸ , 1 × 10 ⁻⁶ , 1
× 10 ⁻⁴ , 1 × 10 ⁻² , 1 mol / L, concentration of boron oxide is 1 × 10 ⁻³ , 1 × 10 ⁻² , 1 × 10 ⁻¹ , 3 × 10 ⁻¹
And After immersing the base material in a solution having substantially the same ion concentration as the human body fluid shown in Table 1 (hereinafter abbreviated as pseudo body fluid) for two weeks, the formation of apatite was examined by thin-film X-ray diffraction measurement. Table 2 shows the results.

[0018]

[Table 1]

[0019]

[Table 2]

Comparative Example 1 A plate-shaped titanium metal of 10 mm × 10 mm × 1 mm was used as a substrate. After spraying a liquid in which fine particles of anatase type titanium oxide were suspended in water, the mixture was calcined at 850 ° C. for 3 hours. After the substrate coated with titanium oxide was immersed in the simulated body fluid for 2 weeks, the formation of apatite was examined by thin film X-ray diffraction measurement, but no peak attributed to apatite was confirmed.

Example 2 A plate-shaped titanium metal of 10 mm × 10 mm × 1 mm was used as a substrate. Ammonium hexafluorotitanate was dissolved in distilled water to a concentration of 1 × 10 ^-1 mol / L, and then boron oxide was added to a concentration of 3 × 10 ^-1 mol / L, followed by rapid stirring. The above substrate was immersed in this treatment solution at 40 ° C. for 24 hours. After treatment, 30
℃, 80 ℃ immersed in hot water for 9 hours, then dried,
A substrate having a titanium oxide film was obtained. After immersing the substrate coated with titanium oxide in the simulated body fluid for 1-2 weeks,
The formation of apatite was examined by thin film X-ray diffraction measurement.
Table 3 shows the results.

[0022]

[Table 3]

Example 3 As substrates, stainless steel (SUS316L) of 10 mm × 10 mm × 1 mm, cobalt-chromium alloy (vitalium), titanium alloy (Ti—Al—V alloy), silicone, polyvinyl chloride, polyethylene Terephthalate, polypropylene, polyethylene, polymethyl methacrylate, polyurethane, alumina, and zirconia were used. Ammonium hexafluorotitanate was dissolved in distilled water to a concentration of 1 × 10 ^-1 mol / L,
Next, boron oxide was added so that the concentration became 3 × 10 ⁻¹ mol / L, and the mixture was rapidly stirred. The above-mentioned base material is added to this treatment solution for 40 minutes.
C. for 24 hours. After the treatment, the substrate was taken out of the treatment liquid, washed and dried to obtain a substrate having a titanium oxide film. Substrate coated with titanium oxide in simulated body fluid 2
After immersion for a week, the formation of apatite was examined by thin film X-ray diffraction measurement. In each case, an X-ray peak attributed to apatite was observed.

Example 4 A plate-shaped titanium metal of 10 mm × 10 mm × 1 mm was used as a substrate. Ammonium hexafluorotitanate was dissolved in distilled water to a concentration of 1 × 10 ^-1 mol / L, and then boron oxide was added to a concentration of 3 × 10 ^-1 mol / L, followed by rapid stirring. The above substrate was immersed in this treatment solution at 40 ° C. for 24 hours. After treatment, the substrate
After being immersed in a mol / L calcium chloride aqueous solution for 6 hours, the substrate was washed and dried to obtain a substrate having a titanium oxide film. Titanium oxide-coated substrate in simulated body fluid 3
After immersion for a day, the formation of apatite was examined by thin film X-ray diffraction measurement, and a peak attributed to apatite was observed. From this, it was found that the biological activity of the titanium oxide film was improved by treating the titanium oxide film with a solution containing a calcium salt after forming the titanium oxide film.

[0025]

According to the present invention, regardless of the material of the material to be coated (substrate) and the complexity of the shape and surface structure of the material to be coated (substrate), the titanium oxide layer (or coating) can be formed at room temperature. The formed titanium oxide layer has an excellent function and effect that a bioactive material having bioactivity can be provided as it is. In addition, the bioactive material is expected to be useful as a member for handling biomaterials, for example, the bioactive material of the present invention may be useful as a material constituting a cell culture container for handling biomaterials.

 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4C081 AB03 AB31 BA12 CA021 CA041 CA091 CA191 CA211 CA231 CA271 CA281 CF121 CF142 CF151 CF161 DB03 DB07 DC03 EA06 4G047 CA02 CB05 CC03 CD02

Claims (17)

[Claims] 1. A material to be coated is placed in an aqueous solution containing a water-soluble compound containing titanium and a reagent for generating titanium oxide from the compound, and a titanium oxide layer having bioactivity is formed on the surface of the material to be coated. A bioactive material having a bioactive titanium oxide layer formed thereon. 2. The bioactive titanium oxide layer according to claim 1, wherein the water-soluble compound containing titanium is a fluorotitanium complex compound, and the reagent for generating titanium oxide is at least a fluoride ion scavenger. Bioactive material formed. 3. The method according to claim 1, wherein the concentration of the fluorotitanium complex compound is 1 × 1.
The bioactive material according to claim 2, wherein the bioactive titanium oxide layer is formed on the surface of the material to be coated, from 0 ^{-5 to 1} mol / L. 4. A fluoride ion scavenger of 1 × 10 ^-2 mol
The bioactive material according to claim 4, wherein a bioactive titanium oxide layer is formed on the surface of the material to be coated. 5. The titanium-containing water-soluble compound is titanium tetrafluoride, and the reagent for producing titanium oxide is p-solution of the solution.
The bioactive material according to claim 1, wherein H is adjusted. 6. The bioactive material having a bioactive titanium oxide layer according to claim 1, wherein the water-soluble compound containing titanium is titanium oxosulfate and generates titanium oxide by hydrolysis. 7. The reaction for producing titanium oxide is carried out by 10 to 80.
The bioactive material having a bioactive titanium oxide layer according to any one of claims 1 to 6, wherein the bioactive material is formed at a temperature of 0 ° C. 8. After the formation of the titanium oxide thin film, 40 to 100
The bioactive material according to any one of claims 1 to 7, wherein the bioactive titanium oxide layer is formed on the surface of the material to be coated, wherein the bioactive titanium oxide layer is immersed in warm water at ℃. 9. The method according to claim 1, wherein after forming the titanium oxide thin film, the thin film is immersed in a solution containing calcium ions.
8. A bioactive material having a bioactive titanium oxide layer formed on the surface of the material to be coated according to any one of items 1 to 7. 10. An aqueous solution for forming a titanium oxide layer has a particle diameter.
The bioactive material according to any one of claims 1 to 9, wherein a titanium oxide seed crystal is contained in a range of 0.001 to 10 µm. 11. The bioactive material having a bioactive titanium oxide layer formed on the surface of the material to be coated according to claim 1, wherein the material to be coated is made of a metal. 12. The bioactive titanium oxide layer on the surface of the material to be coated according to claim 11, wherein the metal is selected from the group consisting of titanium metal, titanium alloy, stainless steel, and cobalt chromium alloy. Bioactive material formed. 13. The bioactive material according to claim 1, wherein the material to be coated is made of an organic polymer. 14. The organic polymer is silicone, polyvinyl chloride (PVC), polyethylene terephthalate (PE).
T), polyethersulfone (PES), polypropylene (PP), polyethylene (PE), nylon 6, polymethyl methacrylate (PMMA), polyurethane, selected from the group consisting of: A bioactive material having a bioactive titanium oxide layer formed on the surface of a coating material. 15. The bioactive material according to claim 1, wherein the material to be coated is made of ceramics or glass. 16. The bioactive material according to claim 15, wherein the ceramic is made of alumina, zirconia or carbon. 17. The bioactive material according to claim 1, wherein the surface of the material to be coated has a porous structure.