JPH0999054A - Bio-compatible material - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a bio-compatible material having dynamical properties necessary as a medical material and high bio-compatibility or bioactivity in combination. SOLUTION: This bio-compatible material has both of an org. chain (-C-C-) and a silanol group (-Si-OH) in its structure. Further, the material has calcium and vinyl group (-C=C-) in the structure. This bio-compatible material is effective as well even if a base body surface is coated with this material.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an implant having excellent biocompatibility used in the fields of plastic surgery, dentistry and orthopedics. More specifically, the present invention relates to a material exhibiting high biocompatibility or bioactivity by containing both an organic chain and a silanol group in the structure.

[0002]

2. Description of the Related Art In the field of plastic surgery, organic polymer materials such as polyvinyl chloride and silicone polyurethane are used as materials for artificial breasts, facial prostheses and the like. However, these materials often have the problem of causing inflammation due to foreign body reaction after implantation. Furthermore, since it has no property of binding to a living tissue and does not integrate with a tissue, there is a problem that a shift or a looseness occurs during implantation in a living body for a long time.

On the other hand, in the field of orthopedic surgery, metal materials such as titanium and titanium alloys are used as materials for medical materials such as artificial hip joints, artificial knee joints, and bone cements that come into contact with living bones. These materials have a problem in that, in addition to not being able to bond to bone tissue, their elastic modulus is largely different from that of natural bone, so that large stress is generated at the joint surface with bone, resulting in loosening and peeling.

[0004] As a material showing a small inflammatory reaction after implantation and also showing a tissue-binding property, there are known materials having an inorganic substance such as bioactive glass and hydroxyapatite. Among these, bioactive glass has the property of forming an apatite layer on its surface in a simulated body fluid containing calcium and phosphate ions or in vivo, and binds to bone or soft tissue through such an apatite layer. Therefore, it is suitable for a medical material that needs to be bonded to a living tissue because it is integrated with the living tissue. However, these bioactive glasses have problems of insufficient mechanical strength, toughness, and flexibility required as medical materials.

Therefore, there is also provided titanium or titanium alloy in which a coating layer of calcium phosphate ceramics such as bioactive glass or hydroxyapatite having excellent biocompatibility is formed on the surface of the implant body made of titanium or titanium alloy by thermal spraying or sintering. There is. However, the coating layer of the bioactive substance has poor adhesion to the surface of the implant made of titanium or titanium alloy. Further, although the improvement method requires a complicated manufacturing process, the problem that the elastic modulus is significantly different from that of natural bone has not been solved.

As a method of imparting bioactivity to a polymer material, a method of mixing hydroxyapatite or crystallized glass with polymethylmethacrylate cement has been proposed. Since it is necessary to increase the proportion of hydroxyapatite, crystallized glass, etc., the mechanical properties such as toughness and strength of the organic polymer may be impaired.

These physical properties are rather the physical properties of the above metal materials and organic polymer materials. Therefore, it has been desired to develop a material having both mechanical properties of metallic materials and organic polymer materials and bioactivity of inorganic materials.

[0008]

It is an object of the present invention to provide the mechanical properties required for bioactive materials, such as bioremediation materials,
It is to provide a material that also exhibits high biocompatibility or bioactivity.

[0009]

Means for Solving the Problems As a result of intensive studies on the solution of the above problems, the present inventors have found that after polymerizing a vinyl group of an organosiloxane compound having a vinyl group, a siloxane group (Si-OR, R: A polymer material obtained by hydrolyzing an alkyl group or a group containing an unsaturated bond or an ether bond) to generate an organic chain and a silanol group in the structure has high biocompatibility. It was confirmed.

Further, it was confirmed that when calcium is introduced into the structure during hydrolysis of the siloxane group, the obtained polymer material also exhibits bioactivity.

That is, the present invention is a biocompatible material containing both an organic chain and a silanol group. The organic chain is basically a saturated hydrocarbon chain (-CC-) obtained by polymerizing a vinyl compound, but a vinyl group (-C = C-), that is, an unsaturated hydrocarbon is included in the structure. Good.

The organosiloxane compound used as the starting material here may be any one as long as it contains a vinyl group and a siloxane group, and the siloxane group is hydrolyzed after the polymerization of the vinyl group. For example, vinyltrimethoxysilane, methacryloxymethyltriethoxysilane, methacryloxymethyltrimethoxysilane, 3-butenyltriethoxysilane, allyltrimethoxysilane, triethoxysilylethylene, vinyltriethoxysilane, vinyltriisopropoxysilane, Vinyltrimethoxysilane, vinyltriphenoxysilane, vinyltri-t-butoxysilane, vinylmethyldiethoxysilane and the like.

Polymerization of the vinyl group of the organosiloxane compound may be radical polymerization, anionic polymerization or cationic polymerization.

The siloxane group is hydrolyzed by heating at room temperature to 90 ° C. in a solvent in which both the organosiloxane compound after polymerization and water are dissolved. Any solvent may be used as long as it can dissolve both the organosiloxane compound after polymerization and water, but methanol, ethanol, tetrahydrofuran or the like is preferable.

When hydrolyzing the siloxane group, it is possible to adjust the concentration of the silanol group by adding tetraethoxysilane. A material containing calcium can also be obtained by adding a calcium compound soluble in the solvent. Calcium chloride, calcium nitrate, calcium acetate and the like are suitable as the calcium compound added at this time.

When the solution obtained under the above conditions is kept sealed at room temperature to 80 ° C., a gel substance is produced. When the gel-like substance is further dried at room temperature to 80 ° C, a bulk material is obtained.

After coating this solution on various substrates, 20 to 80
When heat-treated at ℃, various materials coated with the above materials are obtained. A wide range of materials such as metals, plastics, and ceramics can be used for the substrate, and examples include titanium, titanium alloys, cobalt-chromium alloys, stainless steel,
Polymethyl methacrylate, alumina, zirconia, calcium phosphate-based, crystallized glass and the like may be used as long as they are not biotoxic and are not particularly limited.

The obtained bulk material and coating material are
Si—OH groups are confirmed on the surface, or an apatite layer is formed on the surface in a simulated body fluid containing calcium ions and phosphate ions or in the body. Therefore, the biocompatible material obtained by these methods exhibits biocompatibility in the living body, or adheres or integrates with the biological tissue via the apatite layer formed on the surface.

[0019]

BEST MODE FOR CARRYING OUT THE INVENTION According to the method of the present invention, it is possible to obtain a biocompatible material exhibiting both mechanical strength, toughness, flexibility and biocompatibility or bioactivity required as a medical material. Even for parts that require even more severe mechanical conditions, the surface of metal materials and organic polymer materials with excellent physical properties can be given high biocompatibility or bioactivity at a low temperature of 100 ° C or less, In particular, it is preferably used as a tissue replacement material that requires bondability with bone or soft tissue.

Particularly in the bone-joint part of the stem material for artificial hip joints, it is desired to change the mechanical properties from the surface of the artificial bone material in a stepwise and inclined manner. Such requirements can be met by thickly coating the surface of the artificial bone material having the methyl methacrylate polymer on the surface. FIG. 5 is a conceptual diagram of the artificial bone surface. FIG. 6 is a diagram showing an example in which the biocompatible polymer material of the present invention is applied to an artificial hip joint having a tilted mechanical function.

The shape of the biocompatible material referred to in the present invention may be any shape such as columnar shape, plate shape, block shape, sheet shape, fiber shape and pellet shape. For example, it can be used for a stem material for artificial hip joints, a bone filling material, an artificial vertebral body, an artificial intervertebral disc, a bone plate, a bone screw, an artificial facial prosthesis material, an artificial breast and the like.

[0022]

The present invention will be described below in detail with reference to examples. FIG. 1 shows a schematic diagram of the synthesis procedure of Examples 1 to 4. The present invention is not limited to the embodiments.

Example 1 Vinyltrimethoxysilane (H ₂ C = CHSi (OC
Using H ₃ ) ₃ ), di-t-butyl peroxide was added as a polymerization initiator, and the vinyl group was radically polymerized at 120 ° C. for 4 hours. Vinyltrimethoxysilane: ethanol: distilled water was added to this solution at a molar ratio of 1: 8: 3, and hydrolyzed under reflux at 80 ° C. for 1 hour. The resulting solution was placed in a styrene case (30 × 30 × 10 mm) and kept at 40 ° C. for 3 days,
A gel was obtained. The obtained gel body was dried at 40 ° C. for 7 days to obtain a polymer bulk body.

Aqueous solutions containing the various ions shown in Table 1 at the concentrations shown in Table 1 were used as a reference [Otsuki et al., Journal of.
Journal of Non-Crystal
lineSolids), Vol. 143, pp. 84-92 (1992)], and tris (hydroxymethyl).
The pH was adjusted to 7.25 using an aqueous solution of aminomethane and hydrochloric acid (hereinafter, this is abbreviated as simulated body fluid). The above-mentioned bulk polymer body was immersed in a simulated body fluid to observe its affinity with a living body. The results are listed in Table 2 along with other examples. The result is that Si—OH groups are confirmed on the surface of the polymer bulk body and biocompatibility is recognized.

[0025]

[Table 1]

Example 2 Vinyltrimethoxysilane (H ₂ C = CHSi (OC
Using H ₃ ) ₃ ), di-t-butyl peroxide was added as a polymerization initiator, and the vinyl group was radically polymerized at 120 ° C. for 4 hours. Vinyltrimethoxysilane: ethanol: distilled water: calcium acetate was added to this solution at a molar ratio of 1: 8: 3: 0.05 and hydrolyzed under reflux at 80 ° C. for 1 hour. The obtained solution was put in a styrene case (30 × 30 × 10 mm) and kept at 40 ° C. for 3 days to obtain a gel body. The obtained gel body was dried at 40 ° C. for 7 days to obtain a polymer bulk body.

Aqueous solutions containing various ions shown in Table 1 at the concentrations shown in Table 1 were used as a reference [Otsuki et al., 143, above].
Vol., Pp. 84-92 (1992)] and adjusted the pH to 7.25 using an aqueous solution of tris (hydroxymethyl) aminomethane and hydrochloric acid (hereinafter, this is abbreviated as simulated body fluid). Yes).

From the polymer bulk body obtained above (15 × 10 ×
1 mm) test pieces were cut out and immersed in 40 ml of simulated body fluid at 36.5 ° C. The test piece was taken out at regular intervals and the Fourier transform infrared (FT-IR) reflection spectrum and the thin film X-ray diffraction pattern were measured. Fig. 2 shows the FT-IR reflection spectrum, and Fig. 3 shows the thin film X-ray diffraction pattern. 1-3 days after immersion,
Peaks corresponding to hydroxyapatite (1130cm- ¹ , 1040cm- ¹ , 610cm- ¹ , 570cm- ¹ ) on the FT-IR reflection spectrum
Was recognized. In addition, 2θ = 2 in the X-ray diffraction pattern
The crystal structure of hydroxyapatite was confirmed from the 6 ° and 32 ° peaks. From the above, it was confirmed that the hydroxyapatite layer was formed on the surface of the polymer synthesized by this method. The thickness of the hydroxyapatite layer was about 10 μm. FIG. 4 shows scanning electron micrographs of the polymer bulk body before immersion in the simulated body fluid and when immersed for 3 days. It can be clearly seen that the hydroxyapatite crystals cover the surface 3 days after the immersion.

Example 3 In Example 2, tetraethoxysilane was added at the time of hydrolysis, and vinyltrimethoxysilane: ethanol: distilled water: calcium acetate: tetraethoxysilane was added in a molar ratio of 1: 8: 3: 0.05: 0.5. A polymer bulk body was obtained by the same operation as in Example 2 except that the compounding ratio was used. The bulk polymer obtained was added to 40 ml of simulated body fluid at 36.5 ° C.
And soaked for 7 days. FT-IR reflection spectrum and thin film X
By the measurement of the line diffraction pattern, it was confirmed that the hydroxyapatite layer was formed on the surface of the polymer bulk body.

Example 4 The solution obtained by hydrolysis in the same manner as in Example 2 was applied to a polymethylmethacrylate plate (15 × 10 × 1 mm), and this was kept at 40 ° C. for 7 days for gelation. Polymerization and drying gave a polymer-coated polymethylmethacrylate plate. The obtained polymer-coated polymethylmethacrylate plate was immersed in 40 ml of simulated body fluid at 36.5 ° C for 7 days. By measuring the FT-IR reflection spectrum and the thin film X-ray diffraction pattern,
It was confirmed that a hydroxyapatite layer was formed on the surface of the polymethylmethacrylate plate.

The biocompatibility of the polymer bulk bodies described in Examples 1 to 3 and the polymer coated bodies described in Example 4 were compared by the evaluation method shown in Table 3. The results are shown in Table 2. In Example 1, biocompatibility was confirmed by the presence of silanol groups in the structure. As a comparative example, performance comparison was performed using uncoated silicone or PMMA.

[0032]

[Table 2]

[0033]

[Table 3]

Embodiment 5 FIG. 5 is a conceptual diagram of an artificial hip joint as a representative example of the artificial joint. Thus, the surface-treated titanium or titanium alloy implant alloy 2 is used for the fracture of the femur 1,
The metal surface was further coated with the solution obtained in Example 2,
In the same manner as in Example 4, when the polymer coating film 3 having an appropriate thickness (which can be arbitrarily set to be thick or thin between 1 μm and 10 mm) was used, the mechanical characteristics at the bone boundary were used. Has an elasticity value closer to that of bone or bone marrow than that of metal in direct contact, and it has become possible to provide a material having less stress on bone.

Example 6 FIG. 6 shows a polymer obtained by coating the surface of metal 2 of the example shown in FIG. 5 with polymethylmethacrylate (PMMA) 4 and applying the solution obtained in Example 3 to the surface. FIG. 4 is a cross-sectional view of the vicinity of the metal surface on which a coating film 3 is formed. When the polymer coating film 3 having an appropriate thickness is used, the mechanical properties at the bone boundary exhibit an elasticity value close to that of the bone, and it is possible to obtain the effect of inclining the mechanical function and giving it to the bone. We can now provide materials with less stress.

[0036]

EFFECTS OF THE INVENTION According to the present invention, a biocompatible material having a combination of mechanical strength, toughness, flexibility and biocompatibility or bioactivity can be obtained. It is preferably used as a tissue replacement material. Even for sites that require more severe mechanical conditions, various organic polymers and metal materials with different mechanical properties can be given a high biocompatibility or bioactivity at a low temperature of 100 ° C or less by a very simple method. Therefore, it has an excellent effect in the medical industry, which is preferably used as a material for artificial bones, which is particularly required to have high bondability with a tissue.

[Brief description of drawings]

FIG. 1 is a schematic diagram of a synthetic procedure of a biocompatible material of the present invention.

FIG. 2 shows the polymer bulk body of Example 2 after immersion in simulated body fluid.
FT-IR reflection spectrum (time is simulated body fluid immersion time, ◆ indicates the presence of apatite).

FIG. 3 is a thin film X-ray diffraction pattern of a polymer bulk body of Example 1 after immersion in a simulated body fluid (time indicates simulated body fluid immersion time, o indicates presence of apatite).

FIG. 4 Scanning electron micrographs of the polymer bulk body of Example 1 before and after the immersion in the simulated body fluid (0h: before immersion in the simulated body fluid,
3day: Immersion of simulated body fluid for 3 days).

FIG. 5 is a conceptual diagram of an artificial bone surface.

FIG. 6 is a cross-sectional view of essential parts showing an example in which the biocompatible material of the present invention is applied to an artificial hip joint having a tilted mechanical function.

[Explanation of symbols]

 1 Femur 2 Implant alloy 3 Polymer coating 4 Polymethylmethacrylate

Claims (4)

[Claims] 1. A biocompatible material having an organic chain (-CC-) and a silanol group (-Si-OH) in its structure. 2. The biocompatible material according to claim 1, wherein the structure contains calcium. 3. The material according to claim 1 or 2, wherein
A biocompatible material having a vinyl group (-C = C-) in its structure. 4. A biocompatible material obtained by coating the surface of a substrate with the material according to claim 1, 2 or 3.