WO1986001725A1

WO1986001725A1 - Bone cement and process for its manufacture

Info

Publication number: WO1986001725A1
Application number: PCT/EP1984/000275
Authority: WO
Inventors: Klaus Draenert
Original assignee: Klaus Draenert
Priority date: 1984-09-10
Filing date: 1984-09-10
Publication date: 1986-03-27

Abstract

A bone cement which is made of a mixture of polyacrylic acid-ester- and/or polymethacrylic acid-ester "prepolymers", monomeric acrylic acid- and/or methacrylic-acid derivatives, a polymerization catalyst and if necessary a stabilizer and an accelerator, as well as a process for its production and use. In the bone cement, the prepolymer is a mixture of 5 - 50% by weight of polyacrylate- and/or polymethacrylate fibres having a length of from 2 mm up to 15 mm and a thickness of 50 - 750 mum, and 50 - 95% by weight polyacrylic acid ester- and/or polymethacrylic acid ester perlpolymerisate from polymer spheres measuring 1 - 140 %g(m)m.

Description

Bone cement and process for its production The invention relates to a bone cement based on polymeric acrylic and methacrylic acid esters, which can be used in particular as bone replacement, bone composite and prosthesis anchoring material.

Known bone cements consist of a polymeric component (acrylic acid ester or methacrylic acid ester "prepolymer", which is in the form of beads and is referred to as "spherical polymer" or "bead polymer"), a monomeric acrylic or eth-acrylic acid derivative, e.g. Methyl methacrylate, a polymerization catalyst and, if necessary. a stabilizer and an accelerator. For use, the components are mixed homogeneously and in a suitable manner, e.g. brought to the application site by means of a cement syringe. The monomeric component hardens by polymerization and thereby encloses the prepolymer / so that a homogeneous polymer structure is formed.

Bone cements based on polyacrylic acid esters are not resorbable, but are built into the tissue by ingrowth of the body's own tissue and firmly enclosed. A stable connection between the implant and the implant bearing is only possible with a kind of blocking. A connection at the molecular level has so far not been proven or shown. Under biomechanically favorable conditions, ie, avoiding overloading of the border zone between implant and bone _r , however, there is closed bony contact and thus the implant is blocked in the patient's bony implant bed.

Very often, however, it occurs due to biomechanical overloading of the implant, i.e. , due to bending and shear forces acting on the implant to form surface displacements between implant and implant bearing

OMPI - 1 - 1 (bone surface), which leads to bone resorption, the rapid bone remodeling of lamellae into a lower quality braided bone and finally to the formation of a tight connective tissue sheath. Due to the

5 Overloading of the interface due to shear and bending stresses can be observed at all stages of loosening up to the complete loosening of the entire implant.

0 ^{There was} no lack of attempts at the interface

Enlarging implant bones through improved implantation methods (impactors). In particular, attempts have also been made to considerably enlarge the adjoining surface to the implant site by adding resorbable material; see. DE-B-29 05 878. If the addition of such fillers or filling substances is an impressive way of realizing the increase in surface area and if bone ingrowth deep into the implant has been possible and proven, then the addition means. _Q quantity of filling substances on the other hand

The weakening of the mechanical strength of these bone cements with regard to the bending and curling of the prosthesis cement sheath.

This weakening of the mechanical strength of the bone cements is particularly pronounced in the case of the cements which add aqueous gels or soluble fillers to the cement; see. DE-A-25 18 153 and J. Biomed. Mater. Res. Vol. 11 (1977), pp. 373-394. 0

Ultimately, all of these bone cements lack the stability required to form a stable cement sheath around a prosthetic component.

5 This disadvantage was different with the creation tried to solve by fiber cement. In DE-A-2724814, for example, the bending strength of the bone cements was increased considerably by adding glass fibers of different lengths. However, it was found that the addition of these fibers led to so-called "lattice phenomena ¹¹ " in that the fibers lay as a lattice against the bone bed and followed the cement matrix into the transverse anchoring pores of the bony bed. This led to a considerable weakening of the cement in On the other hand, the miscibility and processability of the bone cements decreased drastically, so that ultimately the pouring of the bone cavities with these fiber cements was equivalent to the primary application of ceramic prostheses.

The plastic cross anchoring of the bone cements was insufficient. The fiber reinforcement with carbon fibers described in EP-A-6414 • also showed the same results and was from this. Reason not to be used for clinical use.

The invention is based on the object of providing a bone cement of the type mentioned at the outset, which both creates a large surface area for the implant bearing and, on the other hand, forms sufficient mechanical strength around a closed cement sheath around the prosthesis component. __ _

This problem was solved by the surprising finding that by replacing part of the spherical polymer with acrylic ester and / or M≥t-acrylic ester fibers of a certain length and thickness, without significantly changing the miscibility of the cement, a significantly higher mechanical one Can achieve stability. - -

1 The behavior of the bead polymer during the polymerization of the commercially available bone cements has shown that the ball is a morphologically valuable component as a form-forming element for

5 is the bone-forming cell, but that for the

Matrix composite of the bone cement has an extremely unfavorable configuration.

The invention thus relates to a bone cement consisting of a mixture of polyacrylic acid esters and / or polymethacrylic acid ester prepolymers, monomeric acrylic acid and or methacrylic acid derivatives, a polymerization catalyst and possibly. a stabilizer and an accelerator, which is characterized in that the prepolymer 5 is a mixture of 5-50% by weight of polyacrylic acid ester and / or polymethacrylic acid ester fibers with a length of more than 2 mm up to 15 mm and a thickness of 50 - 750 microns, and 50 to 95 wt .-% polyacrylic ester and / or polymethacrylic acid ester spherical polymer from polymer spheres of size 1 - 140 microns represents. 0

The amount and size of the fiber replacement of the bead polymer determine the mixing and implantation behavior of the bone cements. With a precisely defined particle size, all requirements regarding short-term and long-term stability can be met.

These bone cements furthermore have the advantage that they material characteristics by the strongly improved mechanical Ma¬ are preferably suitable for the stage ⁰ by the addition of resorbable fillers, as described in DE-B-29 05878 to considerable increase in surface area in the border zone .

The invention also relates to the use of -poly- 5 acrylic acid ester and / or poly ethacrylic acid ester in the form of fibers with. a length of more than 2 mm to 15 mm and a thickness of

_ OMPI 50 - 750 μm monofilament or cross-linked to tissues in bone cements based on polyacrylic acid esters and the use of this bone cement in the treatment of bone defects.

The invention further relates to a method for producing the bone cement according to claim 1, characterized in that 5-50% by weight of polyacrylic acid ester and / or polymethacrylic acid ester fiber with a length of more than 2 mm to 15 mm and a thickness of 50 - 750 μm are monofilament or as crosslinked to form fabrics, together with 50-95% by weight of polyacrylic acid ester and / or poly-methacrylic acid ester ball polymer made from polymer balls of size 1 - 140 μm, add the onomeric acrylic acid and / or methacrylic acid derivatives and the mass together with a polymerization catalyst and if necessary, a stabilizer and an accelerator mixed evenly.

In a preferred embodiment of the method, the mixing of the components is accelerated and improved by coaxial rotation and the occurrence of monomer bubbles by pre-compression of the bone cement during the first time of the polymerization with pressures of about 1 to 20 bar, preferably 5 to 6 bar. as a function of the viscosity of the bone cement.

The particular advantage of the implantation materials according to the invention is that the material as such is not changed by replacing the spherical polymer, so that only an improvement in the mechanical properties results.

In the present invention, fibrous polymers of acrylic and / or methacrylic acid esters are used, such as - t - they are used in the light guide industry.

Copolymers of acrylic and methacrylic acid esters can also be used. Ethyl methacrylate polymers are preferred. These materials are known per se and can be produced by known processes. These are essentially extrusion processes, the threads being spun in precipitation baths and being rolled up on bobbins. The threads are made in all thicknesses with various polymers and copolymers and are commercially available. These threads are delivered on rolls as kilometer goods. They can then be chopped to the desired length in chopping machines and mixed with the polymer powder in infrasonic vibrators.

The addition of fibers to the spherical polymer, which consist of the same "material, has the particular advantage that it has been shown that there is an optimal wetting of the prepolymer components, as could not be observed with foreign fibers, carbon fibers or glass fibers. Because of the approximately same chemical structure of all Bestand¬ parts there will be a lasting and permanent materialbe¬ composite that is neither self-destructs, still incoherent and anisotropic behavior _r as was demonstrated in foreign fiber composites.

The negative properties of foreign fiber admixtures could not be observed with these isogenic materials.

An important advantage of the present invention is that a material reinforcement is achieved with a composite material which is nevertheless homogeneous and which reacts in the same way in its mechanical behavior. This too could

'O PI

surprisingly be solved advantageously by the present invention. The mixing of the bead polymer with fibrous polyacrylic acid ester or - ethacrylic acid ester leads to complete wetting of these components by the liquid monomer. Filling defects and air pockets occur to a far lesser extent than was observed with the foreign fiber admixtures.

It is now mentioned in DE-B-29 05 878 that prepolymers are preferred in the bone cement described there, which are present in irregular granulate form or as scales or as a thread-like cylinder. These filiform cylinders should not exceed a length of 1 * - 2 mm. The use of a mixture of prepolymers ^"with verschiede¬ ner outer shape, for example, from Kugelpolymerisat and faserförmi- according polymer is not .gelehrt in DE-B-2,905,878th

It has now been shown that a thread length of 2 mm does not increase the bending strength and the torsional strength of the bone cements. Compared to these short, thread-like cylinders, polymer balls lead to a denser ball packing, so that, on the contrary, a decrease in the mechanical strength, in particular the bending strength, was found. It has also been found in experiments that a pure thread polymer leads to a drastic deterioration in the miscibility and applicability of the bone cements, and in biological studies it was found that the bead polymer compared to the thread polymer has the better shape-forming properties compared to the osteoblasts, the bone-forming cells. shows. The success sought with the invention occurs only when a mixture of spherical polymer and fiber additives is used, the effectiveness of the fiber admixtures only - β ^~ begins mm a minimum length of about 2 and an optimal material property 3-8 mm, particularly about 3-4 mm fiber length, at a thickness of 100 to 300, especially approximately 200 ^μ m, is achieved. By varying the mixture, all possible miscibilities and types of application of bone cement can be narrow

Connection with their strength properties are determined and put together. The polymer spheres of the spherical polymer have a size of 1 to 140 μm, preferably 10 to 100 μm.

This variability in the production of bone cements has great advantages, in particular in current practice, in which various anchoring principles of the prosthetic components are followed.

In the conventional joint replacement components, the prosthetic components are anchored in the bone with the bone cement, i.e. the joint components are completely surrounded by bone cement and this anchors them over a large surface in the bony bearing. In recent years, prosthetic components have also been developed that can be used on their own, without the addition of bone cement. block the implant bearing. However, these so-called self-locking or straight-stem prostheses cannot do without the use of bone cements, because blocking in a physiologically curved area, for example, is only possible at two or three points, so that rotational instability or an instability in the sagittal direction remains. In order to prevent this, all self-locking straight stem prostheses are advantageously blocked with bone cement in the bony bearing. Due to the very thin cement sheath in at least three places, these bone cements have to meet very high material requirements. The cements which have a high addition of acrylic acid fiber are preferably suitable for this, so that they have a high resistance to bending and torsion.

O PI ^' The prepolymer used according to the invention consists of 5-50, preferably 15-45 and in particular 20-40 wt .-% fibrous

Components. The weight ratio of prepolymer to onomeric components in the bone cement of the invention is 50:50 to 80:20, preferably 60:40 to 70:30. The substances normally used for this purpose in bone cements are used as the polymerization catalyst, stabilizer and accelerator. A specific example of a suitable catalyst is dibenzoyl peroxide, hydroquinone for a stabilizer and N, N'-dimethyl-p-toluidine for an accelerator.

5 to 35% by weight, based on the mass of the prepolymer and the monomers, of resorbable tricalcium phosphate with a particle size between 50 and 300 μm and an available pore volume of less than 0.1 ml / g can be added to the bone cement of the invention. The type of tricalcium phosphate that can be used and the resultant effect are described in DE-B-29 05 878.

For rapid wetting of the prepolymer, which consists of fibers and beads, the coaxial rotation in the compressed air-powered turbine of the bone cement syringe, as described in patent application ^p 3425566.4, has preferably proven itself.

In order to avoid infections of the implant and the implant site, which cannot always be prevented even by careful aseptic work, which usually take place even by hematogenous spread, since the implant removes the germs from the body's own defense, an antibiotic can also be added to the implant material according to the invention. In particular, an admixture of gentamycin is preferred, with which very good results could be achieved. The use of gentamycin in bone cement is per se known from DE-A-2o 22 117. Nevertheless, it was not obvious to use the aster-reinforced bone

OMPI cement gentamycin, as each addition further. Fillers, as can be seen from the literature, must lead to a mechanical weakening of the cements and it was precisely the mechanical strength that was the objective of these fiber cements. However, it was found that the addition of gentamycins up to 6 g to 40 g of cement powder does not lead to any significant changes in the material properties of the wedding duck of the invention. This can be explained by the high elastic properties of these substances. In particular, gentamycin admixtures between 1 - 4 percent by weight did not result in any change in the mechanical parameters.

Other substances, such as "bone morphogenetic protein", which can be obtained from the basic substance of animal bones, can also be added to the bone cement according to the invention. This enables bioactivation of the bone cements in such a way that even small additions, homogeneously distributed in the cement, lead to a considerable acceleration of the bone ingrowth. Additions between 0.01 and 2% by weight do not lead to a change in the mechanical properties of the bone cement.

Further possible additives are all possible chemotherapeutically active substances, such as cytostatics and also other antibiotics and antiseptics, and for example the hormone calcitonin. From the large number of antibiotics in question, mention should be made of those which are not damaged at the temperatures occurring during the polymerization: erythromycin, lyncomycin, clyndamycin, novobiocin, vancomycin, fusidic acid, rifampicin, polymycine, neomycin, kanamycin or also tobramycin.

Air pockets and polymerisation bubbles can be largely avoided by pre-compressing the cement. The mixing of the bone cements can be improved by using coaxial rotation to improve the

O PI - II - Serious wetting of the prepolymer is achieved. If this rotation is carried out before the pre-compression, the enclosed air in the cement mixture can be completely removed through suitable ventilation holes in the syringe cartridge, as described in patent application P 3425566.4. The mixing is then precompressed with pressures of 1 to 20, preferably 5 to 6, bar. After the 4th minute after the start of mixing, the cements become slow after releasing the pressure

¹ increasing piston pressure applied to the implant site. The bone cements prepared in this way not only show significantly better material properties, but also have far fewer morphological blister inclusions. In suitable cases they can be used in industrial applications

- ~ ° be similar to plexiglass.

By the present invention it could be shown that only a mixture of perϊpolymers with fiber polymers can be biologically active, since the morphological

²⁰ equivalent of the osteoblast, the bone-forming cell, represents a 20 - 40 μm ball. By partially cross-linking the polymer fibers to pieces of tissue with a fiber length between 2 and 15 mm, the shear strength and torsional strength of the bone cements can be completely

² ° are significantly improved, a material property which is of crucial importance for the stress on the cement quiver. This is evident from the results of the bending test described below.

30

35

- II - To carry out the bending test, the bone. Cement of the invention standardized test specimen in the form of a cylinder. The test specimens are produced under clinical conditions, with a short mixing phase being followed by a compression phase of approximately 1-2 minutes. The production of test specimens is described in detail below using three examples.

Example 1 :

6 g of a commercially available polymethacrylic acid methyl ester bead polymer are mixed with 4 g chopped polymethacrylic acid methyl ester fibers with a thickness of 125 μm and an average fiber length of 4 mm and mixed with a wooden spatula in a plastic dish with 4 ml of monomeric methacrylic acid methyl ester. If the mixture is homogeneous, it is poured into a 5 ml disposable syringe, the pressure ram is pressed in with moderately strong pressure and placed in a pressure chamber. After closing the chamber, a pressure of 5 bar is applied for 2 minutes using a compressed gas. After dismantling ^• the pressure allowing the cement sample in the syringe cure at room temperature.

Example 2:

8 g of a commercially available polymethacrylic acid methyl ester bead polymer are mixed with 2 g of polyπrethacrylic acid methyl ester fibers (thickness 125 μm, length 30-40 mm) and then added to 5 ml of monomeric methyl methacrylic acid. The mixture is then stirred in a plastic bowl with a wooden spatula until sufficient homogeneity is achieved. The mixture is then poured into a 5 ml disposable syringe, the pressure ram is pressed in and the syringe is pressurized to 5 bar in a pressure chamber for 2 minutes.

^{~ "} - II - After the compression phase has ended, the cement sample is allowed to harden at room temperature.

Example 3;

7 g of a commercially available polymethacrylic acid methyl ester

Bead polymers are mixed with 3 g of chopped polymethacrylic acid methyl ester fibers with a thickness of 125 μm and a length of 5-15 mm and added to 4 ml of monomeric methyl methacrylic acid. This mixture is stirred in a 20 ml disposable syringe until homogeneous (approx. 1 min.) And the contents are then pressed into a 5 ml disposable syringe after the syringe opening has been widened. The 5 ml disposable syringe is then placed in a pressure chamber and a pressure of 5 bar is applied. The compression phase is approximately 2 minutes. After the pressure has been released, the cement sample is allowed to harden in the syringe.

The methods described by the above-manufactured ^'bekörper process are analyzed using a Unversalprüfmaschine on BLegebeanspruchung, taking care that the test conditions were exactly the same for all measurements.

The results of the bending tests show strength values for the bone cement described in claim 1 which are far above those of the bone cements available on the market. A strength value of 1187 kg / cm ^{2 is} achieved in the bending test with the bone cement produced in Example 3. This value is shown graphically in FIG. 1 in comparison with the bending strengths of known bone cements. The peak values achieved with the bone cements of the invention come close to the flexural strength of pure Plexiglas.

In contrast, the mixing behavior of the cement described does not differ from the commercially available bone cement. The processing and curing phases are also comparable.

Claims

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10

15

Claims:

20th

. Bone cement consisting of a mixture of polyacrylate and / or polyethacrylate prepolymers, monomeric acrylic and / or methacrylic acid derivatives, a polymerization catalyst and possibly a stabilizer

25 lizer and an accelerator, characterized in that the prepolymer is a mixture of 5-50% by weight of polyacrylate and / or polyethacrylate fibers with a length of more than 2 mm up to 15 mm and a thickness of 50-750 μm, and 50 to 95% by weight of polyacrylic acid ester and / or polymeth 30 acrylic acid ester spherical polymer from polymer spheres

Represents size 1 - 140 μm.

2. Bone cement according to claim 1, characterized in that the polyacrylic esters and / or polymethacrylic esters are used for fibers monofilament or crosslinked to form tissues.

- £ - 3. Bone cement according to claim 1 and 2, characterized gekenn¬ characterized in that a pharmaceutical active ingredient is additionally contained.

4. Bone cement according to claim 3, characterized in that gentamycin is contained as the active ingredient.

5. Bone cement according to claim 3, characterized in that ^" only or additionally a" bone morphogenetic protein "is contained as the active ingredient.

6. Bone cement according to claim 1 to 5, characterized gekenn¬ characterized in that it additionally 5 to 35 wt .-%, based on the mass of the prepolymer and the monomers, absorbable tricalcium phosphate with a particle size between 50 and 300 microns and an available Contains pore volume of less than 0.1 ml / g.

7. A method for producing the bone cement according to claim 1, characterized in that 5-50 wt .-%

Polyacrylic ester and / or polymethacrylic acid fibers with a length of more than 2 mm to 15 μm and a thickness of 50-750 μm monofilament or as crosslinked to form fabrics together with 50-95% by weight of polyacrylic and / or polymethacrylic acid ester spherical polymer Adds polymer balls of size 1 - 140 μm to the monomeric acrylic acid and / or methacrylic acid derivatives and uniformly mixes the mass together with a polymerization catalyst and possibly a stabilizer and an accelerator.

8. The method according to claim 7, characterized in that the mixture is compressed and / or coaxially flung before curing.

9. The method according to claim 8, characterized in that the mixture under a pressure of about 1 - 20 bar - compressed.

o. Use of polyacrylic acid ester and / or poly ethacrylic acid ester in the form of fibers with a length of more than 2 mm to 15 mm and. a thickness of 50 - 750 μm monofilament or cross-linked to tissue in bone cements based on polyacrylates.

1 . Use of the bone cement according to claims 1 to 6 in the treatment of bone defects.