JP4737925B2 - Titanium oxide-organic polymer composite suitable for artificial bone - Google Patents

Description

The present invention is a polyolefin, polyester or polyamide used as the supporting bearing member material is treated immersed in room temperature to 95 ° C. The solution was added to hot water or acid followed directly titania solution treatment and to the support surface, apatite The present invention relates to a titanium oxide-organic polymer composite material for artificial bone formed with a titanium oxide film that forms apatite having the same Ca / P atomic ratio as apatite of mammalian bone from a supersaturated aqueous solution or mammalian body fluid.

An organic polymer containing an ester group and / or a hydroxyl group having strength as a bone and having a high ability to form apatite in a simulated body fluid (SBF), in other words, familiar to the formation of a highly bioactive layer; For example, for an artificial bone in which an ethylene-vinyl alcohol copolymer (hereinafter referred to as EVOH) is used as a base material, and an inorganic material layer capable of forming an apatite layer from SBF is formed on the surface of the base material made of the polymer. Research on composite materials is actively conducted.
Under such circumstances, research has been conducted to facilitate the formation of a highly bioactive layer on the surface of the substrate material. In particular, when an organic polymer having no functional group advantageous for the formation of the bioactive layer is used, the formation of such an intermediate layer has been considered essential. In addition, a substrate material modified by reacting 3-isocyanatopropyltriethoxysilane [OCN (CH ₂ ) ₃ Si (OC ₂ H ₅ ) ₃ ] (hereinafter IPTS) and a silica solution for the formation of the intermediate layer has been proposed. Furthermore, it has been proposed to treat the surface with a calcium silicate solution.

M.M. Uchida, H .; -M. Kim, T .; Kokubo, S .; Fujibayashi, T .; Nakamura J. et al. Biomed. Mater. Res. 64A (2003) 164-170. JP-A-2002-325834, claims, [0012], [0013]

In contrast to the above technique, Non-Patent Document 1 reports that Ti—OH groups in a titania gel having a specific structure such as anatase cause the formation of apatite nuclei in SBF within a short period of time. The sample treated with IPTS on the surface of the base material and further treated with a calcium silicate solution forms apatite on the surface even within 2 days in SBF, but the calcium silicate gel layer rapidly in SBF. Since it was difficult to control the formation of apatite on the surface of the sample because it dissolves in Ti, the solubility of titania gel in SBF is much smaller than that of the calcium silicate gel layer. The titania gel layer possessed is excellent as a bioactive layer.

In Patent Document 1, a titania gel is formed on the surface of a substrate substantially composed of an organic polymer, and then the titania glu is treated with warm water or an aqueous acid solution, so that the same Ca / An invention of a titanium oxide-organic polymer composite material for artificial bone obtained by modifying to a titanium oxide film capable of forming an apatite having a P atomic ratio has been reported, but a titanium oxide film forming apatite is formed as an intermediate layer. It is reported that it is essential to use a polymer containing a hydroxyl group and / or a derivative thereof, a thiol group, an aldehyde group, or an amino group as a polymer constituting a base material that can be formed [ 0013].
Therefore, the composite material of the artificial bone uses a material having an active group as a polymer constituting the base material, or requires an intermediate treatment that enables formation of a bioactive layer.

An object of the present invention is to use a polymer having no active group as a base material of an artificial bone as a material constituting the base material, and titanium oxide for artificial bone without requiring the formation of the intermediate layer. An organic polymer composite is provided.
In order to solve the above-mentioned problems, the intermediate is used by using a polyolefin, particularly polyethylene, particularly low-density polyethylene, polyester, particularly polyethylene terephthalate, or nylon, particularly 6-nylon, which is a widely used or advantageous material as a base polymer. A titanium oxide-organic polymer composite material for artificial bone cannot be obtained without forming a layer, or a sample obtained from the base material constituting material, a bioactive titanium oxide layer forming material, and a titanium oxide-organic polymer composite material The combination of formation conditions was examined by many trials and errors. As can be seen from the later examples and comparative examples using EVOH, surprising results were obtained. That is, the temperature of 0 to 50 ° C. obtained by adding a solution composed of an acidic alcohol and water to an alcohol solution of titanium tetraalkoxide described in Patent Document 1 reported by the inventors of the present invention. A titania solution treatment is performed by immersing the solution in a solution for several seconds to one week to form a titania gel on the surface of the substrate, and the substrate on which the titania gel is formed is added to a room temperature to 95 ° C solution to which 50 ° C to 95 ° C warm water or acid is added. It is confirmed that the titanium oxide layer formed on the surface of the substrate after immersion treatment has high bioactivity and that the apatite formed thereon has high peel resistance in the peel test using adhesive tape. And the above-mentioned problem could be solved.

The first aspect of the present invention is (1) a base material consisting of low density polyethylene, polyethylene terephthalate and 6-nylon selected from the group consisting of polyolefin, polyester and nylon, and an acidic alcohol and water directly in an alcohol solution of titanium tetraalkoxide. A titania solution treatment is performed by immersing in a solution at a temperature of 0 ° C. to 50 ° C. obtained by adding a solution comprising a titania solution treatment for several seconds to 1 week to form a titania gel on the surface of the substrate, and the substrate on which the titania gel is formed is treated at 50 ° C. It is immersed in a solution at room temperature to 95 ° C. to which warm water or acid at ˜95 ° C. is added, and the same Ca / P atomic ratio as that of apatite of mammalian bone is obtained from an aqueous solution supersaturated with apatite or from a mammalian body fluid. Titanium oxide-organic polymer composite for artificial bone obtained by modification to titanium oxide film forming apatite It is a method of manufacture. Preferably, (2) the titanium tetraalkoxide is tetraisopropyl titanate, the alcohol is ethanol, and the acid is an inorganic acid, the titanium oxide-organic polymer composite material for artificial bones according to (1) above, Preferably, (3) the titanium oxide-organic polymer composite material for artificial bone according to (1) or (2) above, wherein the polyolefin is low density polyethylene, the polyester is polyethylene terephthalate, and the nylon is 6-nylon. More preferably, (4) the titania-treated solution is a solution comprising an acidic alcohol and water while maintaining a solution of titanium alkoxy and alcohol at a temperature of 0 ° C. to 10 ° C., particularly while maintaining the temperature with ice-cold water. The artificial bone according to (1), (2) or (3), which is prepared by dripping Titanium oxide - a method for producing an organic polymer composites.

The second of the present invention is (5) a base material consisting of low density polyethylene, polyethylene terephthalate and 6-nylon selected from the group consisting of polyolefin, polyester and nylon, and an acidic alcohol directly in an alcohol solution of titanium tetraalkoxide. A titania solution treatment is performed by immersing in a solution at a temperature of 0 ° C. to 50 ° C. obtained by adding a solution made of water for several seconds to 1 week to form a titania gel on the surface of the substrate, and the substrate on which the titania gel is formed is heated to 50 ° C. It is immersed in a solution at room temperature to 95 ° C. to which warm water or acid at ˜95 ° C. is added, and the same Ca / P atomic ratio as that of apatite of mammalian bone is obtained from an aqueous solution supersaturated with apatite or from a mammalian body fluid. Modified with titanium oxide film forming apatite to obtain titanium oxide-organic polymer composite material for artificial bone, the composite material A method for producing supersaturated dipping to form apatite in aqueous artificial bone for complex relative apatite, preferably, (6) artificial bone titanium oxide - titanate organic polymer composite as a titanium tetraalkoxide tetra The method for producing a composite for artificial bone according to the above (5), which is obtained using isopropyl, ethanol as alcohol, and inorganic acid as acid, more preferably (7) The apatite according to (5) or (6) above, wherein the titanium oxide-organic polymer composite material for artificial bone is obtained by using low density polyethylene as the polyolefin, polyethylene terephthalate as the polyester, and 6-nylon as the nylon. a form the process for producing an artificial bone for the complex, more preferably, 8) Using a titania-treated solution prepared by dropping a solution composed of acidic alcohol and water while maintaining a solution of titanium tetraalkoxide and alcohol at a temperature of 0 ° C to 10 ° C. This is a method for producing a composite for artificial bone formed with the apatite according to the above (5), (6) or (7).

As an effect of the invention, it was possible to provide a titanium oxide-organic polymer composite material for artificial bone in which the formed apatite layer and the titanium oxide-organic polymer composite material are firmly bonded.

The present invention will be described in more detail.
A. As the substrate material, a polymer compound selected from the group consisting of polyolefin, polyester and nylon can be used. Particularly preferred are low density polyethylene (Sumitomo Chemical Co., Ltd.), polyethylene terephthalate (PET, Toyo Kasei Co., Ltd.) and 6-nylon (Scientific Polymer Products, Co. Ltd.). As a sample (S) for confirming the usefulness as an artificial bone, a 10 × 10 × 1 mm ³ substrate was manufactured and used.
The substrate may be of various structures such as blocks, sheets, fibers, tapes, filaments, threads, and the like, and further processed from the above materials, such as woven fabrics (including three-dimensional woven fabrics), non-woven fabrics, and slivers. as such, characteristics of the reinforcing artificial bone can improve shape and to Rukoto a.

B. FIG. 1 shows a process of titania treatment titania treatment for forming a titania film.
A. A platinum wire (Pt) was fused to one corner of the sample substrate (S) prepared in (1).
The titania solution (TS) is a solution kept at 0 to 10 ° C. containing Ti (OiC ₃ H ₇ ) ₄ (= TiPT) and a half amount of C ₂ H ₅ OH. It was prepared by slowly dropping a solution containing the remaining half amount of C ₂ H ₅ OH, HNO ₃ and H ₂ O under the condition of holding. The raw material ratio is Ti (OiC ₃ H ₇ ) ₄ : H ₂ O: C ₂ H ₅ OH: HNO ₃ = 1.0: 0.1 to 10: 1 to 100: 0.01 to 10 (molar ratio) is there.
The sample was immersed in the prepared titania solution at 0 to 50 ° C., for example, 25 ° C. for several seconds to 1 week, for example, 24 hours. Thereafter, the sample was pulled up at a speed of 0.1 to 10 cm, for example, 2 cm / min (PU), and a titania solution treated sample (TS) was obtained. It was dried for 24 hours at a constant temperature dryer (in the air, manufactured by Yamato, DK-600) at a heating temperature of 30 to 150 ° C.

C. B. Treatment for imparting apatite-forming ability to the titania gel layer prepared in (1).
This treatment is to form a titania film having a Ti-OH group in anatase microcrystals by warm water or acid aqueous solution (WWT) treatment of titania gel, and has an acid concentration of pH 7 or less and / or a period of 1 hour to 1 The conditions of immersion treatment can be preferably employed in a room temperature to 95 ° C solution to which warm water or acid at a temperature of 30 ° C to 120 ° C, particularly 50 ° C to 95 ° C, and particularly an acid is added.
Here, the case where it processed using HCl aqueous solution as an inorganic acid solution was shown (FIG. 2). For example, the B.I. The treated sample was subjected to warm water treatment in which the sample was immersed in a 0.1 M aqueous hydrochloric acid solution at 80 ° C. for 8 days.

D. Changes in the surface structure of various polymers treated with titania solution and further with hot water were analyzed using the following measuring instruments.
1, field emission scanning electron microscope (FE-SEM); manufactured by Hitachi, Ltd., product name S-4700.
2, energy dispersive X-ray spectroscopic analysis (EDX); manufactured by Horiba Ltd., product name EMAX-7000.
3, X-ray photoelectron spectrometer (XPS: MT-5500, manufactured by ULVAC-PHI Co. Ltd.)
4, Thin film X-ray diffractometer (TF-XRD: RINT2500, manufactured by Rigaku Corporation)
5, Measurement of peel strength of titania thin film; Measurement of adhesive strength of apatite formed on the substrate surface by the product name Scotch Tape (registered trademark) manufactured by Sumitomo 3M

E. A test sample of apatite-forming ability by immersion in simulated body fluid (SBF) is immersed in 30 mL of SBF adjusted to pH 7.40 and temperature 36.5 ° C. for various periods up to a maximum of 7. The sample is taken out from the solution, gently washed with ultrapure water, and dried at room temperature.
An example of an aqueous solution supersaturated with apatite (simulated body fluid: SBF, having an inorganic ion concentration almost equal to that of human plasma. Table 1 shows ble to reproduct in vivo surface-structural changes in bioactive glass-ceramic A-W ”, J. Biomed, Mater. Res. 24, 721.734 (1996)].

Example 1 of the present invention will be described.
Sample preparation.
Pressure 90 kgf / Cm ² , time 10 minutes, temperature of each resin, polyethylene (PE) 180 ° C., polyethylene terephthalate (PT) 270 ° C., nylon 6 (N-6) 230 ° C., comparative ethylene- A vinyl alcohol copolymer (EVOH) was pressed under pressure at 210 ° C. to prepare an organic polymer substrate.

The raw materials shown in Table 2 below were used for preparing the titania solution. A solution containing TiPT (3.8687 g) and half amount of C ₂ H ₅ OH (2.9 g) was prepared, and the solution was ice-cooled to 0 to 10 ° C. while the remaining half amount of ethanol (2. 9 g), water (0.2450 g) and nitric acid (0.0858 g) were added and hydrolyzed to prepare a titania gel solution.
Each press-molded sample was immersed in 10 g of the titania gel solution held at 25 ° C. for 24 hours, and treated with a titania solution. After the immersion, the sample was pulled up at a rate of 2 cm / min, and press-molded in a drier at 80 ° C. for 1 day to prepare a titania solution treated sample (S).

In order to provide the titania gel layer of the titania solution-treated sample (S) with an apatite forming ability, the titania solution-treated sample (S) was immersed in 10 mL of 0.1 M hydrochloric acid aqueous solution at 80 ° C. for 8 days, and was supersaturated with respect to the apatite. Was modified to a titanium oxide layer having the ability to form an apatite layer by contact with an aqueous solution.

FIG. 3 shows a thin film X-ray of PE, PET, nylon-6 and EVOH in which a sample subjected to the titania gel solution treatment and subsequent hot water treatment without silane coupling agent (SC) treatment was immersed in the SBF for 7 days. The diffraction pattern is shown. In the case of PE, a peak attributed to anatase and / or brookite was observed by titania-warm water treatment. After 7 days of SBF immersion, a peak attributed to apatite was observed in any sample.

FIG. 4 shows FE-SEM photographs of PE, PET, Nylon 6 and EVOH immersed in SBF for 2 days or 7 days after performing titania solution and subsequent hot water treatment without SC treatment. A thin layer was formed by the titania-warm aqueous solution treatment. According to EDX measurements, this layer contained titanium. From this, it can be seen that a titania layer can be formed on the surface of the sample by direct titania-warm water treatment without SC treatment. After 2 days of SBF immersion, it was found that a substantially uniform apatite layer was formed on the surfaces of PE, PET and Nylon 6, but no apatite was formed on the surface of EVOH. After 7 days of SBF immersion, apatite was also formed on the EVOH surface, but the amount was very small.

In FIG. 5, the FE-SEM photograph of the sample surface after the peeling test by a Scotch tape (trademark) is shown. In the case of PE, PET, and Nylon 6, the apatite was not peeled by the peeling test, but in the case of EVOH, the apatite was peeled from the substrate.

From the above, a titania solution that forms a titania gel on the surface of a base material developed by the present inventors without using a pretreatment such as SC treatment by using a specific base material, and the titania gel Is immersed in warm water of 50 ° C. to 95 ° C. or a solution of room temperature to 95 ° C. to which an acid is added, and the same Ca / P atom as apatite of mammalian bone is obtained from an aqueous solution supersaturated with apatite or from a body fluid of a mammal. Titanium oxide-organic polymer composite for artificial bones, which has apatite with excellent bond strength with titanium oxide film and is bioactive by combining with treatment to modify titanium oxide film to form a specific ratio of apatite Could provide material.

Explanation of process of titania solution treatment of sample Explanation of hot water treatment process of sample Example 1 titania solution treated-warm water treated sample and TF-XRD (thin film X-ray diffraction) pattern after SBF immersion Example 1 titania solution treated-warm water treated sample, and FE-SEM (field emission scanning electron microscope) photograph showing apatite formation characteristics after immersion in SBF FE-SEM (Field Emission Scanning Electron Microscope) photograph after the peel test of the apatite-formed sample obtained in Example 1 with Scotch tape (registered trademark)

Claims (7)

A base material made of a polymer compound selected from the group consisting of low-density polyethylene, polyethylene terephthalate and 6-nylon , without forming an intermediate layer, an alcohol solution of titanium tetraalkoxide with an acid alcohol and water solution. In addition, a titania solution treatment was performed by immersing the obtained solution in a temperature of 0 ° C. to 50 ° C. for several seconds to 1 week to form a titania gel directly on the surface of the substrate, and the base material on which the titania gel was formed was 50 ° C. to 95 ° C. Apatite with the same Ca / P atomic ratio as that of mammalian bone apatite in aqueous solution supersaturated with apatite or from bodily fluids of mammals by immersion in a solution of room temperature to 95 ° C. with the addition of warm water or acid A method for producing a titanium oxide-organic polymer composite material for artificial bone, characterized by being modified into a titanium oxide film. The method for producing a titanium oxide-organic polymer composite material for artificial bone according to claim 1, wherein the titanium tetraalkoxide is tetraisopropyl titanate, the alcohol is ethanol, and the acid is an inorganic acid. Artificial according to Der Ru請 Motomeko 1 or 2 as titania treatment solution was prepared by dropping a solution composed of alcohol and acid water while maintaining the solution of titanium tetraalkoxide and an alcohol at a temperature 0 ° C. to 10 ° C. A method for producing a titanium oxide-organic polymer composite material for bone.
To a base material made of a polymer compound selected from the group consisting of low-density polyethylene, polyethylene terephthalate and 6-nylon , an acid alcohol and water solution is added to an alcohol solution of titanium tetraalkoxide without providing an intermediate layer. The obtained solution having a temperature of 0 ° C. to 50 ° C. is treated with a titania solution soaked for several seconds to one week to form a titania gel directly on the surface of the substrate, and the substrate on which the titania gel is formed is heated to 50 ° C. to 95 ° C. Alternatively, it is immersed in a solution at room temperature to 95 ° C. to which an acid is added to form an apatite having the same Ca / P atomic ratio as that of mammalian bone apatite in an aqueous solution supersaturated with apatite or from a body fluid of a mammal. Titanium membrane is modified to obtain titanium oxide-organic polymer composite material for artificial bone, and the composite material is supersaturated with apatite. Process for producing an artificial bone for the complex formed apatite by dipping into the solution. The artificial bone-formed artificial apatite according to claim 4 , wherein the titanium oxide-organic polymer composite material for artificial bone is obtained by using tetraisopropyl titanate as titanium tetraalkoxide, ethanol as alcohol and inorganic acid as acid. A method for producing a bone composite. The apatite according to claim 4 or 5, wherein the titanium oxide-organic polymer composite material for artificial bone is obtained using a polymer compound selected from the group consisting of low density polyethylene, polyethylene terephthalate and 6-nylon. A method for producing the formed composite for artificial bone. A titanium oxide-organic polymer composite material for artificial bone is obtained by using a titania-treated solution prepared by dropping a solution comprising an acidic alcohol and water while maintaining a solution of titanium tetraalkoxide and alcohol at a temperature of 0 ° C to 10 ° C. A method for producing a composite for artificial bone having apatite formed thereon according to claim 4, 5 or 6.

Images