JPH05502603A - Bioactive glassy compositions for bone implants, filaments made therefrom and methods - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] Bioactive glassy compositions for bone implants, filaments made therefrom and Method The present invention relates to a so-called bioactive gas for bone grafting according to the preamble of claim 1. This invention relates to a lath-like composition or glass.

This type of glass has been the subject of research since the 1970s, and advanced ceramics Materials Vol. 1, No. 4, 1986, pp. 306-310 and 324. He wrote a paper titled ``Ceramic Implants for Humans.'' Written by Lee L. Bench.

Examples of such known glasses are the following patent document FR-A-2243915, US- A-4159358, US-A-4171544, US-A-4234972, CB-A-2080281, El)-A-3248649, EP-A-0145 210, vine seen in EF'-A-0154513.

In addition to being biocompatible, these known glasses also have the ability to interact with each other as described below. Due to its structure, it is biodegradable.

When the type of glass in question comes into contact with human or animal interstitial fluid, natural bone remodels. create a gel with an ionic composition similar to that of the osteogenic surface found in the . The formed gel is recognized by osteoblasts as a substrate for bone matrix precipitation. be recognized. Interaction between collagen fibrils, matrix mucopolysaccharides and gels is a stable bond that should be formed between the glass and the newly added bone matrix. characterized by the precipitation of hydroxyapatite crystals that allow

Often for glass implants, the bone gradually disappears until it completely disappears. It is desirable to reshape and/or recreate to make room for the latter.

From the experiments carried out, it appears that this completely occurs with the known bioactive glasses identified above. It was discovered that there was no such thing. These glasses are made of dust emanating from a bath of molten glass. cannot be turned into filaments by pulling them through a If you try to pull them, they will become ceramic at the exit of the die and their properties will be The requirements for biodegradable glass filaments or fibers are very different. produces a fragile product.

For this reason, the only way to use these known glasses in prosthetic implants is to is to crush these to produce powder. In most applications, bone defects The cavity is made into a binder paste and filled with this powder. The size of powder particles is Not uniform (uneven in the range of several microns to several hundred microns. Non-uniformity of particles) Due to their size, most of the smallest particles are completely reabsorbed during the previous construction process. , - Large force particles are not resorbed or reduced and constitute a discontinuity, and the corresponding desired reconstruction bone Produces undesirable glassy inclusions. Random array of particles of different sizes are bone fibers Facilitates a similar random arrangement of bones for the purpose of mechanical force It is desirable for the fibers to reorganize into an array.

In some applications, the use of powder in prosthetic implants is difficult because on the one hand blood is mixed with a kind of powder; form a mixture, which constitutes an obstacle to bone growth, while the powder particles form a blood It can even be dangerous because it can be carried around and form blood clots.

The problem that follows the present invention is that it can be used initially to produce bone implants that do not have the aforementioned drawbacks. It provides glass that can be

According to the invention, this problem is solved as defined in the characterizing part of claim 1. The solution is a glassy composition.

The present invention also provides filaments or fibers obtained by drawing the glass composition. fibers, products obtained from the filaments, and methods for producing the filaments. .

Both K, O and A 1203 are amorphous strips when drawn into filaments. properties that prevent glassy compositions from ceramifying by keeping them at a constant temperature. have

Amorphous conditions then repeat during the life of the filament.

The presence of 20 in bioactive glassy compositions is beneficial with respect to bioactivity. this Regarding the point, K, O also applies to patients who have or are prone to hypertension. It constitutes the profit that replaces Na2O in the in-brand.

However, increasing the amount of 20% makes the glassy composition more soluble in water. have This is a very high percentage of the vitreous composition, which contains 20% of the normal When placed under ambient conditions, by hydrolysis of 20% by interaction with atmospheric moisture. , means to soften or turn into a gel. i.e. 20% too high Filaments of glassy composition with , can be processed and knitted, for example. However, this is very unrealistic from an industrial point of view. be.

The undesirable effects of K, O! on glassy compositions include A1□O! By adding can be successfully reduced. However, increasing the amount of Al2O3 It has the disadvantage of reducing the reactivity of the product, ie its affinity for bone tissue.

Glassy compositions containing proportions of 20 and Al2O3 within the claimed range are The filament is fully prevented from ceramising and the bone tissue is It has been found to be implemented from the standpoint of maintaining sufficient affinity for .

FR-A-2243915, GB-A-2080281, DE-A-32486 49 and EP-A-0145210, all from scratch (FR-A-224391 5 is 0. (from 4%) to 20%, including 20 Bioactive glassy compositions are disclosed. Such literature describes the use of anticeramic agents. It does not teach the use of 20. GB-A-2080281 and US-A-4 708652 is both A1103 + ZrO2 + Nb20B zero to 8% uncertainty Disclosed is a bioactive glassy composition comprising an amount of The percentage of A1□Os is specific It has not been. On the other hand, A1tOs, Zr0z and Nb2O3 are The biological activity is disclosed in the literature as a reaction modifier. On the other hand, A1□ 03, ZrO2 and Nb,05 are known as inhibitors for biological activity.

Further disclosed by CB-A-2080281 and US-A-4708652 , compositions containing indeterminate amounts of A1□0° are primarily of the ceramic type.

In other words, these documents teach the use of Al2O3 as an anti-ceramizing agent. Not shown.

According to the invention, a filament having a diameter of the order of 10-50 microns or It is possible to produce fibers. products from such filaments or fibers, For example, fiber bundles, textiles, especially gauze and nets, felt and wool from the powder made by crushing the filament and the filament scraps. Special manufactured products can be obtained.

The filaments or fiber bundles of the claimed glassy composition are considered to be bone fibrous. Implants are created by inserting a filament into the bone defect with the filament oriented in the direction that They can be used as promotes normal development.

The small diameter of the filaments or fibers means that they are completely collapsed, i.e. ensure that the bone is completely replaced by bone tissue and is gradually reconstructed and remodeled Make it.

Fabrics, especially nets and gauze and fabrics produced from the glass filaments of the invention Felt and ``cotton wool'' are produced in the same way as bundles of fibers with respect to degradation. use, but allow bone growth in several planned and preferred directions. In other words, the net gauze promotes bone tissue and creates a network similar to that of the original bone tissue do.

Netting and gauze can be used in the form of bandages to bind broken parts of bone. can.

The filaments of the glassy composition of the present invention have lengths of the same size as their diameters. Can be cut into pieces or small cylinders that are on the same scale. For example, the cylinder Can be produced in diameters and lengths as large as 20 microns.

The particulate product thus obtained, made into a paste with a binder, is produced using the same technology. According to the prior art, the glass powder was imbued with uniformly sized particles that lacked bone. Can be implanted with the difference that it is filled with a child, the decline of the implant and the time promoting its complete replacement by bone tissue over time. Naturally, this application Justified if there is no risk of clot formation with blood and/or transport of powder particles by blood. be done.

Preferably, however, the particulate material of the glassy composition according to the invention is e.g. Lasma spray technology allows for example permanent titanium prostheses to be sprayed with a small amount of particles. It tends to be applied as a coating, with progressive coverage by bone tissue and eventually Complete replacement improves its means of fixation to the surrounding bone. In this application The uniform size of the glass particles produces a constant and uniform coverage. They are “ If applied by spraying at high temperatures in the "plasma spray" process, some Because of their non-uniform particle size, especially since these known glasses become ceramics. However, this is not possible with known biocompatible glass powders.

Glass filaments or fibers and fabrics produced from these fibers are described in the document FR- A-2548658, containing calcium phosphate as main components and 80% by weight Contains less CaO+P2O5, plus alumina, silica, and sodium oxide , iron oxide, magnesium oxide, kaolin and mixtures thereof. This is possible by adding .

They are all biocompatible and 'recognized as hydroxyapatite by osteoblasts. However, these glass fibers are not biodegradable and therefore these The fibers made from the fibers of the bone remain permanently attached within the re-formed bone tissue. .

Below are two currently preferred glassy compositions according to the present invention.

composition engineering The composition is essentially characterized as having the following composition in weight percentages:

5i0250%, P2O26%, Ca016%, Na2020%, K2O3%, Mg01%, A12032%.

Composition■ The composition is essentially characterized as having the following composition in weight percentages:

5iOz50%, P2O56%, Ca016%, Na2O15%, K2O3%, Mg01%, A12032%, B2O33%.

A tolerance of ±7% in weight percent of each component was allowed for both compositions. Ru.

From a biological point of view, the action of both compositions is the same.

The compositions have a die at the bottom and if the molten composition is drawn through the die they will It is transformed into a filament by melting it in a crucible. Preferably, the bath and the To avoid contaminating the filament, the crucible is made of virtually pure titanium. It is.

Composition I was prepared at moderately narrow temperatures of about 900°C and 1050°C, where the glassy mass turned into a flow. can be drawn into filaments very easily only within a high temperature range. Therefore the problem The problem is that the temperature of the melt bath must be regulated very precisely.

In composition H, due to the presence of B2O3, the cellar temperature between 800°C and 1050°C Spread over a temperature range where the composition can be drawn into filaments without becoming Ru. However, within this temperature range the glassy mass is more fluid than Composition I. Therefore, the pulling speed must be precisely adjusted.

Minor traces of calcium fluoride and/or calcium fluoride phosphate in the composition In addition, it catalyzes biological processes. These fluoride-containing compositions are used for dental surgery. Tests are particularly suitable for creating implants in vivo in rats and rabbits, Compositions I and II were applied in fiber and powder form to the medullary indentation of the tibia of each animal. The experimental protocol for inserting the powder was followed.

After a period varying from 10 days to 7 months, the part of the bone involved in the test is killed and exposed under a light microscope. removed from animals prepared for experiments with mirror or scanning electron microscopy and for X-ray microanalysis did.

Upon examination after 10 days, optical microscopic examination of the samples obtained showed that they were composed of fibers and particles. cells with basophilic cytoplasm that adhere to the surface and begin to produce bone matrix announced that it would. Among other things, this ensured that there would be no rejection.

In subsequent investigations at 20 and 30 days, the fiber and particulate materials were found to have a glassy composition. by the bone matrix without the intervention of a connective membrane or capsule between the object and the biological matrix. It appeared to be completely surrounded. Certain cells further resemble primary bone cells in appearance appeared to be incorporated into the matrix near the glassy composition. this is, No barrier capable of arresting bone growth between the glassy composition and the bioactive matrix I confirmed that.

In 30 days, the cortical bone defect was completely filled with newly formed bone.

Fibers of glassy composition incorporated into the bone matrix retain their properties and become fibrous. circularly in the histological section taken in a plane perpendicular to the major axis of the fibers, and Appears rectangular in histological sections taken in a plane parallel to the major axis of the fibers. Ta.

Also, in 30 days, the particles of the glassy composition nevertheless form bone marrow without the intervention of connective membranes. The non-uniform contours incorporated into the matrix and the subsequent time interval (2 to 7 months) ) were incorporated and maintained in their bone matrix. However, no change was observed in the glassy composition. As a result of bone remodeling Therefore, the examination at 4.5.6 and 7 months extended to the bone surrounding the implanted material. It showed resorption depressions exposing its surface. These depressions are preferably vascularized. It consisted of a similar number of parts that are easy to feel raw. Surveys done at the same time interval are The collection of fibers released from the skeletal composition and bone matrix appears unevenly torn. , and was gradually taken up by multinucleated giant cells. That is, they gradually become matric Glassy material that did not come into contact with osteogenic bone cells removed from the bone, e.g. moved from the periosteum The resulting material is due to an inflammatory infiltrate composed mainly of neutrophilic polymorphonuclear and multinucleated giant cells. It looked like I was surrounded. The presence of inflammatory infiltrates is evidence of a promising strengthening of blood circulation. Ta.

In addition to demonstrating the surface characteristics of the glassy compositions according to the invention, the experiments also demonstrate that they was carried out to demonstrate osteoconductivity, and the material has a differentiated tensile strength for osteogenic activity. Connective tissue intervenes provided a sufficient number of cells were present at the implant location. Histologically evidenced by the fact that it was incorporated into your matrix without did. Both fibers and particles of the glassy composition inserted into cortical bone defects exhibit this property. showed that. In the case of fibers, when these are soaked in blood, they fill the empty spaces between the fibers. form a three-dimensional network or “felt” that defines the provided an expensive surface for attachment of osteogenic cells. However, the glass of the present invention The particles of the composition form a tight agglomeration in contact with the blood, with only the outer surface participating in the binding. Available.

That is, the chemical surface characteristics of the two forms of the composition, i.e., fibers and particles, are identical, but Their biological responses may vary depending on their physical properties, such as shape and size. I can do it. In general, fibers are easier to handle than particles in experiments and are more susceptible to bone defects. distributed evenly.

In the experiments carried out, when they are incorporated into the bone matrix, the present invention The agglomeration of fibers or particles of the glassy composition did not show any change in the investigation for up to 7 months. No cellular reaction occurred. This means that the incorporated material is no longer an interstitial solution. or in any case, the interstitial circulation within the bone undergoes a significant deterioration process. This can be attributed to the fact that there was not enough to

The presence of quartzite residue within the bone matrix did not appear to interfere with the previous modeling process. However, an investigation carried out at 4 months revealed that the resorption (the swelling had completely recovered by that time) Already observed in areas of cortical defects. Osteoclasts cause matrix resorption It does not appear to attack the fibers of the ingested particles, but rather to surround them. When all of the containing matrix has been reabsorbed, the glassy composition Contact with ducts and cellular components. The histological appearance of the fibers at this stage shows a fragmented shape; The dissolution process of the glassy composition has progressed and the fragments have been absorbed by multinucleated giant cells. This suggests that the

Since bone remodeling consists of subsequent resorption and addition, the newly added The dissolution of the glassy composition or its reincorporation in the matrix depends on two factors. appears to be influenced by

1) Number of osteogenic cells present in the depression 2) Shape and size of the glassy material, In fact, while fibers exhibit generalized dissolution, some particle aggregations are also a newly added material. has a surface with

These results are not only influenced by the chemical characteristics of the materials, but also by biological responses. Properties are also influenced by the shape and size of the fibers and particles, especially the uniformity of their dimensions. Uniformity appears to prove beneficial.

Summary book The present invention provides a bone graft bioactive material containing the following approximate weight percentages of the following oxides: The present invention relates to a lath composition. Si○s40 to 55%, P2O55 to 8%, ( : aO (MgO) 20 to 40%, N a 2 (K 20) 20 to 3 0%. The composition contains no more than 9% by weight of 20 and Al2O3, A1 □The percentage of 03 is 0. By adding an amount of 5% to 2.5%, Cera It can be turned into filament without becoming a mic. The file obtained in this way The filament may be a bundle of filaments, gauze, net or other fabric, felt, It can be used to prepare bone graft products in the form of cotton wool etc. . The filament is used, inter alia, for application in permanent material prostheses of coating layers of glassy compositions. It can be turned into powder particles for this purpose.

Submission of translation of written amendment (Article 184-8 of the Patent Act) August 7, 1992

Claims (17)

[Claims] 1. The following approximate weight percentages of the following oxides: SiO24O to 55%; P2O54 to 8%, CaO (MgO) 20 to 40%, Na2O and/or is a bioactive glassy composition for bone grafting containing up to 30% K2O, which The overall weight of K2O and A12O3 is between 2% and 9% as stabilizing compounds. The percentage of Al2O3 is from 0.5% to 0.5%. At 2.5% this allows the composition to be drawn into filaments or fibers from the molten bath. Can be done. 2. The glass-like material of claim 1, characterized in that it has the following components in weight percent: Composition: SiO250%, P2O56%, CaO16%, Na2O20%, K2 O5%, MgO1%, Al2O32%, tolerance of ±7% in percentage of each component has. 3. Claim 1 characterized in that it has, in weight percent, essentially the following ingredients: Glassy composition. SiO250%, P2O56%, CaO16%, Na2O15 %, K2O5%, MgO1%, Al2Oa2%, B2O55% Percentage of each component It has a tolerance of ±7%. 4. Contains at least traces of calcium fluoride and/or calcium fluoride phosphate. The glassy composition according to any one of claims 1 to 3, characterized in that it contains: 5. Any one of claims 1 to 4 for forming a bone implant or a part thereof. Uses of the glassy composition. 6. Produced by stretching the glassy composition according to any one of claims 1 to 4. filament. 7. Claim 5 characterized in that their diameter is between 10 and 50 microns. filament. 8. By the multiple filaments of claim 7 or claim 8 for implantation in bone defects. A bundle made up of. 9. Formed from the filament of claim 6 or claim 7 for repairing bone defects. textiles, especially nets or gauze. 10. Formed from the filament of claim 6 or claim 7 for repairing bone defects. felt or "cotton-wool". 11. Claims for use in preparing products for grafting or bone implants in bone defects A particulate product produced from the filament of claim 6 or claim 7. 12. Fragments or small cylinders produced by cutting the filament 12. The particulate product of claim 11 consisting of. 13. 12. Particle production according to claim 11 in the form of a powder produced by crushing filaments. thing. 14. Any one of claims 11 to 13 at least partially from the surface of the body. an organism characterized in that it is coated with a layer produced by the application of a particulate product of Permanent bone prosthesis constructed with a solid body of compatible material. 15. The coating layer is produced by the application of particles produced by "plasma spray" technology. 15. The prosthesis of claim 14. 16. The use is made of a glassy composition according to any one of claims 1 to 3. Bone graft preparation by pulling the molten composition through a die from a molten bath featuring A method for producing filaments of a bioactive glassy composition. 17. characterized by using a crucible of substantially pure platinum to contain the molten bath 17. The method of claim 16.