JPH0373157A - Composite product for medical treatment exhibiting bioactivity - Google Patents

Abstract

PURPOSE:To obtain the bioactive composite product having a coating layer which has the excellent adhesive property to a base body and naturally forms an apatite layer in the body by constituting the above product of the glassy or crystallized glassy coating layer which is provided on the surface of the base body and exhibits bioactivity and incorporating the oxide component of the element constituting the above-mentioned base body into the glassy or crystallized glassy coating layer. CONSTITUTION:The metallic body 10 which is previously molded to a prescribed shape is provided with the glassy coating layer 20 by, for example, means for coating or baking. The glassy coating layer 20 dispersedly contains the metals or metal oxides 22 integrated by the heat treatment at the time of baking and a small quantity of the remaining metal ions 24. The composite product is integrated and combined with the in-vivo structure, such as bone, via the spontaneously generated apatite layer 30. The glassy or crystallized glassy coating layer 20 may be any if the apatite layer is formed thereon and is more specifically obtd. by using CaO and SiO2 as its essential component and adding a small amt. of the simple metal or oxide of the same metal components as the components of the metal to constitute the metal body 10 thereto and further adding B2O3, etc., thereto, and, for example, coating the mixture onto the metal body and baking the coating.

Description

Detailed Description of the Invention (Field of Industrial Application) The present invention relates to a bioactive medical composite product and a method for producing the same, particularly a coating on the surface of various metal products and alloy products useful as artificial bones and artificial tooth roots. The present invention relates to a medical composite product provided with a coating layer of material and a method for manufacturing the same.

(Prior technology) Conventionally, materials for artificial bones and artificial tooth roots have been made of corrosion-resistant alloys such as cobalt chromium alloys, stainless steel, and titanium alloys, as well as high-density materials that are relatively stable in vivo, such as polymethyl methacrylate, silicone, and high-density polyethylene. Molecular materials have been used.

Among these materials, although metal materials have excellent mechanical properties, they have poor affinity with living organisms and tissue, and metal ions eluted from the material body may have a negative effect on the human body. It has drawbacks such as:

Furthermore, it has been pointed out that monomers generated from polymeric materials due to wear and the like have a negative effect on the human body.

On the other hand, ceramic materials generally have excellent biocompatibility, and there is little risk that the components eluted from them will have a negative effect on the human body. It is becoming.

However, for example, Al-Nasera Soft, which has traditionally been used as a material for bones and artificial tooth roots, has excellent mechanical strength but cannot be directly chemically bonded to bone. Therefore, some type of fixation is required between the tube and the surrounding tubes, and in the long term, there is also the problem of loosening of such mechanical fixation.

0) In a reasonable situation, today, we will make a direct chemical bond with ``4''
Materials for spacing are being actively searched for.

The best L) material to date is M2O-CaO-310°11Os-based crystallized glass (Japanese Patent Publication No. 6210939). It is a so-called insect-activated ceramic material.

The unique feature of this bioactive material is that it naturally forms a bioactive apatite layer within the body.

In fact, this crystallized glass has high mechanical strength and is easy to manufacture, so it has begun to be used for a considerable amount of bone substitute materials. ,
on the surface of the material! Research is continuing to create 1 somatopathic ``mebatalytic'' materials, which are extremely superior.

In addition, one of the achievements of this research is the property of "directly chemically bonding bones in the living body" (in the book of the present invention, I' 71 Physical activity, not written in C h). As a material with extremely high mechanical strength, fused glass6.
A composite material ([,] Book-1 Remix Association, X988th Annual Symposium J7f Paperback, p. 393) has been obtained by reinforcing ZrO with dispersed ZrO.

However, since this method is manufactured using the pot press sintering method, it is difficult to manufacture large products such as artificial hip joints.

On the other hand, since the technology of forming a 7° batite layer within the surface of the material has been realized, it has become possible to chemically integrate it with the surrounding bone, and it has become possible to create a layer of batite with greater stress (... There has been a growing demand for materials that can withstand the forces that are exerted over time.In order to solve this problem, metal materials 1 (stainless steel, stainless steel,
Titanium alloys, etc.) have been under review, and many attempts have been made to coat their surfaces with bioactive apatite ceramics (including glass).

For example, I (eneh et al. 316L thread stainless steel 7,

) Meme Spray Co., Ltd. and Tobuzuke propose materials coated with hioglass, that is, insect-active apatite-based ceramics. According to it, first 1. The spray coating easily peeled off between the residual droplets and the glass layer. At Moko, Dobusuke made a femur bone for a monkey according to the law, and placed it inside his body to see how it progressed. However, it was found that the adhesion between the gold and glass layers was the weakest, and there was a concern that they would eventually peel off.

(Problems that cannot be solved by the invention) Herein, an object of the present invention is to provide a material that has excellent adhesion to the base body,
What's more, it is a coating active composite product with an IUI that naturally generates an apatite layer in the body.The manufacturing method is V! This is a kota to serve.

(Step 8 for Solving the Problems) First, in order to achieve the above-mentioned object, the present inventors developed a four-step method that increases the adhesion between the metal substrate and the glassy coating layer, which is different from the conventional method.・) We focused on the method, which is mostly used in wax technology, to form a glassy or crystallized glassy layer with ions that have the same total bending as the metal material.

J.? taL, Sci, 22 (1987) 1228-
Refer to No. 1234. However, if this lj method is used, the metal oxide (FelOz) is contained in the glassy layer in an amount of 3%. The adhesion of the residual droplet to the substrate was satisfactory, and the resulting coating layer was not bioactive.

Therefore, the present inventors have repeatedly studied these points, and as a result, have obtained the following knowledge.

In other words, Cab-3in! In the case of a vitreous material, biological activity is thought to be achieved through appropriate N-dissolution IHi of Ca and Si ions from the material surface. In other words, Ca ions increase the degree of supersaturation of the surrounding body fluid, while Si ions have one rib that serves as a site for batite vegetation. Then, bioactive apatite (ICa) is deposited on the surface of the material.
+o(PO4)a(011)z) It is thought that it also affects Wl and connects to bone via it.

However, when a small amount of metal oxide is added to it, the elution of appropriate amounts of Ca and Si ions is inhibited, making it difficult to form an apatite layer.

However, even if metal oxides are contained, by adding and adjusting trace components, it is possible to ensure the elution of an appropriate amount of Ca and 54 ions that can chemically bond with bone, and to prevent the elution of excessive amounts of Ca and 54 ions. It was also found that the metal oxide component could be prevented from being eluted. In other words, even if it contains the metal oxide mentioned above, N
By containing either or a suitable combination of each component of azO2Btus and P2O, or by crystallizing the oxide by heat treatment, an appropriate amount of Ca and Si ions can be eluted, and living organisms can be deposited on the surface. We have discovered that it is possible to generate an active apatite layer and create a medical composite product with extremely excellent biocompatibility, leading to the present invention. Note that this principle is not limited to the combination of metal substrate and metal oxide;
The same can be said of the combination of constituent elements with oxides when a ceramic substrate is used.

Therefore, the gist of the present invention is to consist of a biologically inert substrate body and a bioactive vitreous coating layer provided on the surface of the substrate body, and to form the substrate body in the vitreous coating layer. This is a medical composite product that exhibits biological activity, and is characterized by containing an oxide component of an element.

In addition, from another aspect, the gist of the present invention is to prepare a substrate body, and to prepare a vitreous substance exhibiting bioactivity containing an oxide component of an element constituting the substrate body on the surface of the substrate body. By baking the coating layer and changing the heat treatment temperature during baking, a concentration gradient of the oxide component in the vitreous coating layer is realized, and the degree of bioactivity of the vitreous coating layer is adjusted. This is a method for producing a medical composite product that exhibits bioactivity.

Here, the "medical composite products" referred to in the present invention include artificial bones, artificial joints, artificial tooth roots, heating elements for implantation in the body, fixation rods for fractures, plates, etc., but all of them have a base material. Any product that has a main body that has a predetermined shape and is further provided with a bioactive coating layer containing components of the base body as a surface coating layer is included in the medical composite product according to the present invention.

In addition, for the "base body", a metal base made of a corrosion-resistant alloy such as a cobalt chromium alloy, stainless steel, or a titanium alloy is usually preferable due to its excellent strength, but if necessary, a metal base made of a ceramic base such as aluminum ceramics or zirconia ceramics is preferable. A substrate can also be used.

(Function) FIG. 1 is a schematic explanatory diagram of the covering structure of the medical composite product according to the present invention. In the illustrated example, a metal body is used as the base body.

In the figure, a metal body 10 previously formed into a predetermined shape is provided with a glassy coating layer 20 by, for example, coating or baking. The glassy coating layer 20 contains a dispersed metal or metal oxide 22 accumulated by the heat treatment during the baking process and a small amount of remaining metal ions 24. In addition,
This glassy coating layer 20 may have a multilayer structure as described later.

Apatite 1i30 is formed on the vitreous coating layer 20, and this is naturally formed in the body, and the composite product according to the present invention can absorb bone through this naturally generated apatite layer 30. It integrates and bonds with in-vivo tissues such as.

The vitreous or crystallized vitreous coating layer 20 may be of any material as long as it exhibits bioactivity, that is, as long as an apatite layer is formed thereon, but more specifically, it may be made of CaO and StO□ is the main component, and a small amount of an elemental metal or oxide of the same composition as the metal constituting the metal body 10 is blended therein, generally about 1 to 60% by weight, and further B2O3, P2O3, Na, It is obtained by, for example, applying and baking a composition containing at least one of the following.

Note that "1 crystallization" here refers to the crystallization of glass that occurs during the baking of the glassy coating layer or due to the heat treatment performed after baking. The advantage is that active crystal combos can be easily obtained (b).The temperature conditions for crystallization are *rJ, = the same, ζ, - You may perform the crystallization process again after baking at 11. However, it is usually grilled.
Crystallization is achieved by applying heat treatment to the surface.Of course, crystallization progresses partially due to baking treatment.

Next, the reason why the composition of the glass cover 1'W layer 20 is limited as described above in the clever embodiment of the present invention will be explained in detail.

When the metal body of the vitreous V-layer 20 according to the present invention is made of an iron alloy (e.g. stainless steel), specifically, the vitreous V-layer 20 contains CaO-5i0 containing 1 to 60% Pe103.
2 series glassy substance -ζ, and the fil combination fireflies are 3
=30mli% B2O2, P, 01, and Nano
Add at least wormwood seeds. In addition, Li1O1K and O may be added, but 1. It is preferable to limit the content to 1% or less, with sufficient consideration given to its influence on the living body and activity.

In this way, the glass coating layer is CaO-5if! is the main component, and at least one of 8□01, P, 05, and Nano is added thereto to ensure biological activity.

Here, NazO18,0, or P,0. The reason for choosing it is that a small amount of elution will not cause any problems to the body, and it also has the effect of promoting the formation of a 7-batite layer on the material surface. be.

However, from a practical standpoint, a glass containing a larger amount of metal oxide component is more desirable. For example, when using this as a coating material, it is known that if about 20% of gold decomposition oxide is included, the adhesion between the base metal and the glassy layer will be improved.

Alternatively, when used as a heating element for hyperthermia, it is necessary to contain about 40% or more of a metal oxide. However, when such a relatively large number of annihilated oxides are blended, NazOl [1,0° or P2O, as mentioned above] is blended, and ζ also has sufficient bioactivity! There are times when it is not red due to reservation.

Therefore, in order to solve this problem, we followed the conventional method of producing crystallized glass and produced 40% Fc40. .

After baking, CaO-5i02 glass (containing a small amount of RJx, PxOs) was heated at room temperature to 10°C under oxidizing atmosphere condition F.
By heating at 50°C for 30 to 300 minutes,
Metal ions aggregate through thermal diffusion to produce fine C, magnetite (FezO4) particles, and metal oxide particles are dispersed in an active glass matrix containing a small amount of remaining Fe ions to form a composite. According to this heat-treated horn method, the rate of biological activity (for example, the rate of bonding with bone) is determined by the amount of F ion in the glass matrix.
can be controlled.

The purpose of blending ions of the same type of metal as the metal body, for example in the form of an oxide, is to enhance the adhesion with the base metal. If it is added to the vitreous layer itself, the biological activity of the vitreous underlayer itself will be lost. - Generally, in the present invention, gold X oxide and 1
Limited to ~60%.

Such combinations of metal bodies and metal ions include titanium alloys and titanium oxides (Tie), stainless steels and iron oxides (pesoa, FezO3), and Iff
Aluminum oxide (ccrzoa), aluminum and lead oxide (PbO), etc., are already generally known.

When the base body is made of ceramic such as alumina or zirconia, the combination of the base body and the elements is, for example, alumina-aluminum J~ or zirconia-zirconia.

Here, the method for manufacturing a medical composite product according to the present invention will be described in further detail.

Well, 1 human bone or 11 human bones! ■ Medical products such as roots, and 4 base pieces in the shape of a piece 4. The bottom shape may be formed in the same manner as in the conventional method, and the present invention is not limited to specific means or forms.

The base body prepared in this way may be degreased and
After performing preliminary treatments such as washing and drying, a coating acid compound adjusted in the proportions described above is applied to the surface. In that case, the means for forming the coating layer is not particularly limited, and for example, spray coating or dipping may be used depending on the method.
．． The above formulation may be applied and then baked (=1).

The baking temperature at this time is preferably 950 to 1100°C.

At temperatures below this range, Na, B.

Another reason is that ions such as P and metal ions are not thermally diffused sufficiently, and biological activity cannot be obtained. On the other hand, 1
If the temperature exceeds 100°C, the oxide layer formed between the base body and the glassy layer becomes thick and easily peels off. Regarding the thermal diffusion state of metal ions, in the case of iron, it is sufficient to check the optimum baking temperature in advance by checking the Mössbauer spectrum, VSM, etc.

As mentioned above, when baking this coating layer, crystallization is achieved by further heat treatment during or after baking, and a concentration gradient of the oxide component in the glassy coating layer is realized, so that the concentration gradient of the oxide component within the glass matrix is achieved. By adjusting the content of the element or its oxide, the adhesion to the substrate and the degree of bioactivity of the vitreous coating layer can be adjusted.

Specifically, it utilizes the phenomenon of phase separation caused by thermal diffusion.

Furthermore, the coating of the glassy layer on the surface of the substrate body may be carried out in several parts. It is easier to obtain biological activity by reducing the content of Nan.
Although the biological activity of the glassy surface can be ensured without the need to incorporate o, Btus, or P 205, the elution of Ca and sl ions becomes excessive, and the apatite layer formed is likely to peel off.

In addition, when the glassy coating layer has a multilayer structure as described above, the baking temperature is preferably in the range of 950 to 1100''C.

In the bioactive medical composite product thus obtained according to the present invention, the formation of an apatite layer in vivo occurs extremely rapidly. For example, when a glassy coating layer is formed on a stainless steel metal body, the main component is CaO5lOz and 3% by weight of Fe1.
03, and a total amount of 3 to 30% by weight of N.
It was found that when a-myo was added, an apatite layer could be formed on the surface of the glassy coating layer obtained after baking in just two days under an environment similar to that in vivo. B,
(Compared to h and P!0., an apatite layer can be formed fastest when Na, 0 is added.

The composite product according to the present invention can be used not only as an artificial tooth root and an artificial bone as described above, but also as a heating element for thermotherapy. That is, the metal or metal oxide generates heat due to electromagnetic induction, and the surrounding apatite layer has excellent biocompatibility, so long-term implantation in the body is possible.

Next, the present invention will be explained in more detail with reference to examples thereof.

Example 1 A vitreous ceramic material having the composition shown in Table 1 was applied to the surface of a stainless steel plate and baked at 1000°C for 60 minutes. Crystallization was observed in some parts of the glassy coating layer.

The thus obtained composite product was immersed in a simulated body fluid to observe whether an apatite layer was formed on the surface.

The adhesion between the metal surface and the vitreous or crystallized glass coating layer thereon was evaluated by a pull-off test, and the results are also shown in Table 1.

! Table 111 (% by weight) Example 2 In this example, Example 1 was then repeated, but with a weight ratio of 1:1.
The iron oxide (F
The amount of addition of vitreous (ears) was varied, and the changes in the adhesion of the glassy or crystallized glass coating layer and the presence or absence of the formation of an apatite layer were investigated. The results are summarized in Table 2.

Table 2 Table 3 Example g43 Next, in this example, Example 2 was repeated, but NazO was replaced with B□Os+PJs at a total content of 4 ml and 1 it%.

The amount of iron oxide (PezO) added, changes in the adhesion of the vitreous or crystallized glass a'4!1 covering layer, and the effects of the apatite layer were investigated. The results are summarized in Table 3.

Implementation VA4 Titanium-based alloy (Ti-68Q-, l V
Example 1 was repeated, except that titanium oxide was used instead of iron oxide.

Obtained similar results.

Example 5 This example shows the correlation between the baking temperature of the glassy coating layer and the metal oxide concentration gradient.

A vitreous coating layer was provided in accordance with Example 2, and the baking temperature was varied. For each baking temperature! The variation in metal oxide concentration within the matrix is qualitatively illustrated graphically in FIG.

At first, the uniform composition is covered by y! ! However, after baking (=1), there is a tendency for the metal oxide concentration in the matrix to decrease depending on the baking temperature.

(Effects of the Invention) As described above, according to the present invention, it is possible to obtain a medical composite product that has excellent adhesion to the base body and has excellent bioactivity, and the base has sufficient mechanical strength. Not only does it have excellent biocompatibility, but it is especially suitable for use as a heating element for electric induction. is a manifestation.

[Brief explanation of drawings]

Fig. 1 is a schematic explanatory diagram of the melting and covering structure of the next-therapeutic product according to the present invention; and Fig. 2 is a schematic illustration of the melting structure of the vitreous sintering product (1) and Fig. 2 shows the changes in the concentration of gold-i oxide in the matrix. It is a graph qualitatively showing the correlation between: Metal substrate 20; Glassy coating layer Metal oxide Metal ion avatar/fl/layer

Claims (2)

[Claims] (1) Consisting of a biologically inert substrate body and a bioactive vitreous or crystallized glass coating layer provided on the surface of the substrate body, the glassy or crystallized glass coating layer is coated with the substrate body. A medical composite product exhibiting biological activity, characterized by containing an oxide component of the elements that constitute the. (2) Prepare a substrate body, bake a biologically active vitreous or crystallized glass coating layer containing an oxide component of the element constituting the substrate body on the surface of the substrate body, and heat treatment during baking. A biological method characterized by realizing a concentration gradient of the oxide component in the vitreous coating layer by changing the temperature and adjusting the adhesion with the substrate and the degree of bioactivity of the vitreous coating layer. A method for producing an active medical composite product.