JPH11164880A - Manufacture of titania containing inorganic/organic hybrid bioactive material - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a material with excellent bioactivity usable for a bone substitutional material, by adding a hydrolytic titanium compound to an aqueous solution containing an organoalkoxysilane and end silanol type dialkylsiloxane, mixing them, and then adding a calcium salt to it and mixing and heating it. SOLUTION: The bioactive material manufactured by adding a hydrolytic titanium compound to an aqueous solution containing an organoalkoxysilane SiR'n (OR)4-n and end silanol type dialkylsiloxane (HO(Si(R)2 O)n )H and mixing and then adding a calcium salt of inorganic acid and mixing and heating, is used as a bone substitutional material or bone reparative material. Tetraethoxysilane is preferably used as organoalkoxysilane SiR'n (OR)4-n and end silanol type polydimethylsiloxane preferably used as end silanol type dialkylsiloxane. Tetraisopropyltintanate is suitable as the titanium compound.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing an inorganic / organic hybrid bioactive material containing titania.
This bioactive material can be suitably used as a bone substitute material or a bone repair material.

[0002]

2. Description of the Related Art Conventionally, ceramics such as apatite, metals such as titanium, and polymers such as polyethylene have been used as bone substitute materials and bone repair materials. Not all of the affinity and mechanical properties are satisfied. That is, apatite is brittle and easily broken. Titanium has too high an elastic modulus, so that a load is not applied to the surrounding living bone, thereby making the living bone thin. Polyethylene has no natural osteointegration, has a low Young's modulus, and has a 50-500M that of cancellous bone.
It is far below Pa.

Recently, Tsuru et al. Have synthesized a bioactive material containing calcium ions, which is a silicate modified with an organic substance called Omosil (ORMOSILS) (Journal of Materials Science). ： Materials in Medicine 8th 1997
157-161). Omosyl is an organic-inorganic hybrid material obtained by the reaction of tetraethoxysilane with polydimethylsiloxane terminated with silanol, and has been published by Schmidt before its synthesis (Non-Crystallin Solids, 1985, 73rd) 681). Omosil uses its inorganic components (Si, C
It is an excellent material in that the elasticity can be adjusted by changing the ratio between a) and the organic component (CH ₃ ). Tsuru and colleagues introduced calcium nitrate into the omosyl reaction process to impart osteointegration to the product.

[0004]

However, the conventionally synthesized Omosil has a Young's modulus of 45 to 80 MPa,
Still too low compared to that of living bone. In addition, Omosyl synthesized by Tsuru et al. Takes a long time for osseointegration in a living body, and there is a possibility that a foreign body reaction may occur in the body before osseointegration. Therefore, one object of the present invention is to provide a material having mechanical properties similar to those of a living bone and having excellent bioactivity. Another object of the present invention is to provide a manufacturing method capable of freely adjusting the mechanical properties of the obtained bioactive material.

[0005]

In order to achieve the object, a method for producing a bioactive material according to the present invention comprises an organoalkoxysilane SiR ′ _n (OR) _4-n and a silanol-terminated dialkylsiloxane (HO (Si A hydrolyzable titanium compound is added to and mixed with an aqueous solution containing (R) ₂ O) _n H, and then a calcium salt of an inorganic acid is added and mixed, followed by heating.

[0006] With this feature, the obtained material exhibits elasticity close to that of living bone and has excellent apatite forming ability. Then, it is quickly bonded to the living bone via the formed apatite. Moreover, the Young's modulus of the obtained material can be adjusted by changing any of the relative amount of water in the aqueous solution, the amount of the titanium compound, and the heating temperature. The reason is probably as follows.

The steps before adding the titanium compound are as follows:
It is similar to the conventional synthesis process of omosyl. Therefore, a long molecular chain serving as the basic skeleton of omosyl is formed before the addition of the titanium compound. Then, to react with immediately Omoshiru the titanium compound is added, to shorten the molecular chain Si-O ^- simultaneously forming a large number of cleavage points negatively charged as. Since the cleavage point attracts positively charged calcium ions, the ability to form apatite is improved. Omosyl having a long molecular chain is flexible as described above, but titania having a stronger bonding force than silica is bonded to the molecular chain shortened by the addition of the titanium compound to increase the Young's modulus.

[0008]

DETAILED DESCRIPTION OF THE INVENTION Organoalkoxysilane Si
R ' _n (OR) _4-n is preferably tetraethoxysilane (hereinafter referred to as "TEOS"). This is because the liquid is stable at normal temperature and hydrolyzes at an appropriate rate. The terminal silanol-type dialkylsiloxane is preferably a terminal silanol-type polydimethylsiloxane (hereinafter, referred to as "didimethylsiloxane").
"PDMS"). This is because the higher alkyl group becomes a steric hindrance to the bending motion of the molecular chain, making it difficult to adjust the Young's modulus. However, the thermal stability of the obtained material is improved by substituting a part or all of the methyl group with an ethyl group. Preferred as the titanium compound is tetraisopropyl titanate (hereinafter referred to as “TiP
T ”). This is because it is a stable liquid at normal temperature and hydrolyzes at an appropriate rate.

[0009]

EXAMPLES Example 1 As starting materials, TEOS manufactured by Nacalai Tesque, TiPT, Ca (NO ₃ ) ₂ , and hydrochloric acid (35) were also used as starting materials.
%). PDMS (10 cm stock solution; average molecular weight 1100 measured by gel permeation chromatography using polystyrene as a standard sample) manufactured by Aldrich Chemical Co. was used as an organic component.

FIG. 1 shows a process sequence of an embodiment of the manufacturing method of the present invention. The composition of the raw materials is as shown in Table 1. First TE
OS was placed in a mixed solvent of isopropyl alcohol (IPA) and tetrahydrofuran (THF), and distilled water was added with vigorous stirring using hydrochloric acid as a catalyst. After a 2 hour hydrolysis reaction, PDMS was added. Stirring was continued for as long as 15 hours or more, and then TiPT was added dropwise. Subsequently, the mixture was mixed for 1.5 hours, and then a mixed solution of Ca (NO ₃ ) ₂ , distilled water and IPA was added and stirred for 1 hour. At this time, the pH of the reaction solution was 3.0 to 4.0. Put the reaction solution in a plastic container with a lid and put it in air at 40 ° C.
And aged for one day. A part of the solvent was evaporated and the reaction solution became a gel. By heating this gel at 60 ° C. for 3 days, a disk having a diameter of 70 mm and a thickness of 7 mm was obtained.

[0011]

[Table 1] [Immersion in simulated body fluid] Separately, a simulated body fluid having a composition similar to human plasma and having a pH of 7.25 and 36.5 ° C (inorganic ion concentration [mM]: Na ⁺ 142, K ⁺ 5.0, Mg ^{2 +} 1.5,
^{Ca 2+ 2.5, Cl - 148,} HCO 3 - 4.2, HPO 4
² 1.0, were prepared SO ₄ ^2- 0.5). 10 from the disk
A sample having a size of × 10 × 2 mm ³ was cut out and had a roughness of 40 mm.
Polish with a No. 0 grinder, wash and dry, then 30ml
Immersed in simulated body fluid.

[Analysis and Measurement] A sample was taken out of the simulated body fluid, washed with ion-exchanged water, dried, and analyzed by a thin film X-ray diffractometer (TF-XRD) and a Fourier transform infrared reflection spectrometer (FT-IRRS). . The surface structure of the sample was observed with a scanning electron microscope (SEM) equipped with an energy dispersive X-ray spectrum (EDX). Eight samples each having a size of 3 × 4 × 30 mm ³ were cut out from each of the disks, and the three-point bending strength was measured using an Instron type testing machine. The Young's modulus was calculated from the stress-deformation curve at the time of this measurement.

[Results] TF-XRD and FT-IRRS
According to the results, apatite was formed on the surface of each sample within 4 weeks. However, as shown in Table 2, when the apatite generation rates of Samples AD were compared, A <B <C <D, that is, the content increased with the titanium content. For example, in the case of sample A containing no titanium, no apatite peak was observed within 14 days, whereas in the case of sample D obtained by dripping a large amount of TiPT, apatite was formed in only 0.5 days. did. Also, apatite particles such as large leaves had grown on the surface of Sample C immersed in the simulated body fluid for 14 days. It was similar to apatite formed on the surface of bioactive glass (AW glass manufactured by NEC Corporation).

Table 2 also shows the Young's modulus and strain of the sample. As shown in Table 2, the drop of TiPT during the synthesis process significantly increased the Young's modulus. In addition, the Young's modulus could be adjusted to be similar to that of living bone by the amount of TiPT dropped.

[0015]

[Table 2]

Example 2 Finally, instead of heating at 60 ° C. for 3 days, 12
After producing disks in the same procedure as in Example 1 except for heating for 8 hours, eight samples for measuring three-point bending strength were cut out from each disk. The composition of the raw materials is as shown in Table 3. The composition of Sample CH, Sample BH and Sample DH is
Samples C, B and D of Example 1 are the same.

[0017]

[Table 3]

As shown in Table 3, the Young's modulus changed remarkably only by increasing the heating temperature. From this, T
It is apparent that the Young's modulus can be freely adjusted not only by the amount of iPT dropped but also by the heating temperature. It is considered that the bending strength is further increased by hot pressing at a temperature at which the organic components do not decompose (usually 300 ° C. or lower).

Example 3 A disk was manufactured in the same procedure as in Example 1 except that heating was performed at 150 ° C. for 1 day instead of heating at 60 ° C. for 3 days. 8 samples were cut out. The composition of the raw materials is as shown in Table 4. The composition of sample Ti0R2 is the same as that of sample A of Example 1.

[0020]

[Table 4]

As can be seen from Table 4, even when the amount of TiPT dropped and the heating temperature were the same, the Young's modulus changed significantly only by changing the amount of water in the reaction solution. From this, TiPT
It is clear that the Young's modulus can be freely adjusted not only by the amount of water added and the heating temperature but also by the amount of water during the hydrolysis.

[0022]

The material obtained according to the present invention has mechanical properties close to that of living bone and is excellent in biological activity, so that apatite is formed on the surface in a short time and is bonded to living bone through this. be able to. According to the production method of the present invention,
Since the mechanical properties of the obtained bioactive material can be freely adjusted, it can be applied to various living bones.

[Brief description of the drawings]

FIG. 1 is a process chart of a manufacturing method according to an embodiment.

Claims (4)

[Claims] 1. An organoalkoxysilane SiR ' _n (O
R) _4-n and silanol-terminated dialkylsiloxane (H
A bioactive material characterized by adding a hydrolyzable titanium compound to an aqueous solution containing O (Si (R) ₂ O) _n H and mixing, then adding a calcium salt of an inorganic acid, mixing and heating. Manufacturing method. 2. An organoalkoxysilane SiR ' _n (O
The method according to claim 1, wherein R) _4-n is tetraethoxysilane. 3. The method according to claim 1, wherein the silanol-terminated dialkylsiloxane is a silanol-terminated polydimethylsiloxane. 4. The method according to claim 1, wherein the titanium compound is tetraisopropyl titanate.