Improved bone cement

Abstract: An acrylate based bone cement with well balanced low exotherm, low residual monomer, and high strength properties formulated from (1) a liquid component containing at least three different monomeric (meth)acrylates, e.g. a C₁-C₂ alkyl methacrylate, a straight or branched long chain (meth)acrylate having a molecular weight of at least 168, and a cyclic (meth)acrylate having a molecular weight of at least 168, and (2) a polymer powder component containing (meth)acrylate polymers or copolymers. The final bone cement may also contain conventional additives such as polymerization inhibitors, activators, crosslinkers, X-ray contrast material, polymerization initiators, antibiotics, antiseptics, and the like.

Description: The present invention relates to an improved bone cement or adhesive composition. More particularly, the invention pertains to an improved acrylic bone cement, which is especially useful for orthopedic implants. BACKGROUND OF THE INVENTION The introduction of bone cement in the 1960s was a major breakthrough in orthopedic surgery. It was possible thereafter for the surgeon to replace nearly any damaged joint with implants attached to the bone with cement that fills irregularities of the bone/implant interface and furthermore acts as a filler of larger spaces or voids. Recent estimates indicate that each year in industrialized countries there are 1,000 implants per one million inhabitants. These have mainly involved the implantation of artificial hip joints. Although the initial results of such implants have been excellent, long term clinical studies have shown loosening of the implant with time. This occurs either at the interface between implant and cement or more commonly at the interface between cement and bone. After about 10 years of service, at least 20% of hip joint implants require revision, which generally involves the insertion of new components. Such high replacement statistics have led to considerable work to improve implant designs and to improve the bone cements. The latter generally have been formulated from methylmethacrylate (MMA) monomer and polymethylmethacrylate (PMMA) powder. Commercially available bone cements have differed from each other in particle size and composition of the PMMA powder, concentrations of accelerators such as N,N-dimethyl-p-toluidine, or the use of special additives such as radiopaque or X-ray contrast agents, antibiotics, dyes and the like. As is well documented in numerous medical studies as well as in the patent literature, the cement, which cures in vivo after insertion of the implant, gives rise to problems; the major problem is bone necrosis, often as much as 0.5 cm, caused by the high exotherm at the interface between cement and bone and release of monomeric methylmethacrylate. High exotherm, exceeding 70°C, results from the polymerization or curing taking place in the bone cement following admixing of the ingredients immediately preceeding its use with the implant. Unreacted methylmethacrylate is the source of the released monomeric methacrylate, which is highly toxic to bone cells. Moreover, the literature indicated that monomeric methacrylate may deleteriously affect local blood circulation as well as the blood pressure of the patient. It also has been observed that with time a membrane is formed at the cement/bone interface. As the membrane increases in thickness the bone becomes thinner and loosening of the implant and secondary dysfunction is observed. Ultimately, revision surgery is required. Although the reasons for this membrane formation are not fully understood at this time, histologic examinations show unspecified inflammatory tissue and it is supposed that the long term release of monomeric methylmethacrylate as well as an accelerator such as N,N-dimethyl-p-toluidine stimulates the development and growth of the undesirable inflammatory membrane. Set forth below are prior patents that reveal the development of acrylate bone cements, the disadvantages of such bone cement, and recent efforts to overcome these problems; a discussion of the most relevant patents follows: U.S. PATENTS 3,468,977 Bruckmann et al. 4,093,576 deWijn 4,268,639 Seidel et al. 4,341,691 Anuta 4,404,327 Crugnola et al. 4,490,497 Evrard et al. 4,552,906 Podszun et al. 4,588,583 Pietsch et al. OTHER PATENTS 1,431,211 United Kingdom 1,532,318 United Kingdom 0,218,471 EPA US.Pat.No. 4,093,576 (de Wijn) discloses acrylic bone cements made from polymer powder (PMMA) and liquid monomer mixed with an incompatible high viscosity aqueous gel. The gel is soluble in the body fluids and dissolves out after implanting. This leaves a porous structure in the cured cement and reduces the exotherm. In order to control porosity the liquid monomer should preferably contain up to 5% of a tertiary amine, 10-45% by weight of ethyl-, propyl-, butyl-, isopropyl-, isobutyl-, isopentyl- or pentylmethacrylate, the remaining monomer being MMA. U.S. Pat.No. 4,404,327 (Crugnola et al) discloses orthopaedic acrylic based cements with increased toughness and resistance to fracture due to the rubbery nature of the included polyacrylate phase. The polymer powder component has a glass transition temperature (Tg) below the body temperature (37°C) and is embedded in the rigid glassy matrix of the polymerized liquid MMA monomer. The preferred rubbery polymer is poly-n-butylmethacrylate. The modulus of these cements is significantly reduced (3-5 times) compared with conventional cements based on PMMA powder. U.S.Pat.No. 4,490,497 (Evrard et al) discloses compositions for acrylic based surgical cements with the aim of reducing exotherm temperature. The polymer powder comprises PMMA with particle size from 20 to 150 microns. The liquid contains at least 65% by weight of an acrylic monomer, preferably MMA, up to 35% by weight of an acrylic polymer and from 0.01 to 1% by weight of a chain-stopping agent such as diunsaturated monocyclic terpenes and monosaturated bicyclic terpenes. U.S.Pat.No. 4,588,583 (Pietsch et al) discloses acrylic based surgical cements with reduced exotherm and residual monomer obtained by adding 1-15% by weight of a non-toxic, liquid, non-reactive plasticizer. Suggested plasticizers are saturated aliphatic esters with boiling points above 100°C; preferred esters contain one or more free hydroxyl-groups like triethylcitrate. U.K. Pat.No. BP 1,431,211 (Sulzer Bros.) discloses acrylic bone cements with reduced exotherm obtained by mixing the PMMA powder with a liquid comprising at least 50% MMA and between 10 and 45% of at least one C₂-C₆-alkyl methacrylate, preferably isobutylmethacrylate. European Patent Application No. 0,218,471 (Bonar Cole) discloses an acrylic composition for forming a bone cement. The powder component comprising polyethylmethacrylate incorporating opacifier therein, and the monomer comprising n-butylmethacrylate (BMA). The use of BMA as liquid monomer instead of MMA reduces the loss of liquid monomer to an aqueous medium during polymerization, reduces the exotherm and reduces the modulus of elasticity (softer polymer). It has been argued that some reduction in mechanical strength would be beneficial (Bonar Cole and Crugnola), but a reduction of more than 50% in comparison with the commercially available cements is considered risky as the major portion (about 80%) of the commercially available PMMA/MMA based cements function satisfactorily. It is noteworthy that no low strength cements have become commercially accepted so far, and despite the other numerous attempts to overcome the problems associated with conventional bone cement there has been little, if any, commercial acceptance of new proposals. It would be advantageous therefore to have available a bone cement that would not only overcome the known problems but would also, because of its outstanding properties, be commercially acceptable and consequently reduce substantially the number of revisions and replacements of implants that are so prevalent in this field after finite periods of time. These are the objects of the present invention. SUMMARY OF THE INVENTION In accordance with the present invention it has been found advantageous to use a combination of a poly(meth)acrylate powder component and a liquid monomeric acrylate component comprising at least three different monomeric (meth)acrylates. More particularly, the liquid component contains at least a C₁-C₂ alkyl methacrylate, a straight or branched chain (meth)acrylate having a molecular weight of at least 168, and a cyclic (meth)acrylate having a molecular weight of at least 168. One of the preferred liquid monomeric components comprises a mixture of methylmethacrylate, n-decylmethacrylate, and iso-bornylmethacrylate. The powder component may comprise acrylic polymers or copolymers with a glass transition temperature in the range of 37 to 90°C such as poly(butylmethacrylate-co-methylmethacrylate). Mixtures of polymers and copolymers may also be utilized. When these components are employed the exotherm is substantially reduced along with a much lower residual monomer content, when compared with commercially available bone cements. The compressive strength and modulus are still close to (50%-95%) that of commercially available bone cements. Furthermore by using certain accelerators or special combination of accelerators the amount needed to give the specified cure time can be low, which lead to minimized long term release of toxic toluidine derivatives. It is these characteristics that lead to the superior bone cement composition of the present invention upon mixing the powder components with the liquid component. It will be further understood that both the liquid and powder components may contain the conventional additives in this field. Thus, for example, the powder component may contain minor amounts of an X-ray contrast material, polymerization initiators, antibiotics, antiseptics, and the like. Additionally, the liquid component may contain minor amounts of polymerization inhibitors, activators, color agents, and the like. Also, cross-linking agents may be present (and will often be present in commercially available monofunctional monomers), provided, however, that the amounts thereof are so small that the bone cement does not become too brittle; this normally means that any cross-linking agents should be present in amounts of at the most 10% by weight, calculated on Component A, preferably at the most 4% by weight, and more preferably at the most 1% by weight. DETAILED DESCRIPTION OF THE INVENTION AND THE PREFERRED EMBODIMENT As discussed above, the bone cement of the invention is prepared by admixing particles of a polymeric powder component, namely polymers or copolymers of (meth)acrylate as well as mixtures thereof with a mixture of at least three liquid (meth)acrylate monomers, more specifically the bone cement composition is prepared from a liquid monomeric (meth)acrylate component A and a polymer powder component B comprising (meth)acrylate polymers or copolymers or a mixture thereof, characterized in that component A comprises a mixture of 20-75% by weight of C₁-C₂ alkyl methacrylate, 5-40% by weight of a straight or branched monofunctional long chain (meth)acrylate having a molecular weight of at least 168 and 6-18 carbon atoms in the straight or branched chain substituents, and 5-60% by weight of a cyclic (meth)acrylate having a molecular weight of at least 168 and 6-18 carbon atoms in the cyclic substituents, said mixture having a glass transition temperature, when polymerized, in the range of 23 °C to 70 °C; and that the component B polymer has a glass transition temperature in the range of 37 °C to 90 °C; whereby, when the liquid monomeric component A is admixed with the polymer component B in a weight ratio from 1:1.5 to 1:2.5, the resulting bone cement composition has a glass transition temperature in the range of 37 °C to 70 °C. One of the most important aspects of the present invention is the composition of the liquid monomeric component. More specifically, it will contain at least three distinct (meth)acrylate monomers. The three groups are listed below along with certain of the preferred materials: 1) C₁-C₂ Alkyl methacrylates: Methylmethacrylate Ethylmethacrylate 2) Straight or branched monofunctional long chain (meth)acrylates having a molecular weight of at least 168 and 6 to 18 carbon atoms in the straight or branched chain substituents: n-hexylmethacrylate n-heptylmethacrylate ethylhexylmethacrylate n-decylmethacrylate isodecylmethacrylate lauric methacrylate stearic methacrylate polyethyleneglycolmethacrylate polypopyleneglycolmethacrylate ethyltriglycolmethacrylate 3) Cyclic preferably monofunctional (meth)acrylates having a molecular weight of at least 168 and 6 to 18 carbon atoms in the cyclic substituents: cyclohexylmethacrylate benzylmethacrylate iso-bornylmethacrylate adamantylmethacrylate dicyclopentenyloxyethylmethacrylate dicyclopentenylmethacrylate dicyclopentenylacrylate 3,3,5-trimethylcyclohexylmethacrylate 4-tert-butylcyclohexylmethacrylate Thus, the straight or branched long chain substituent of the long chain monofunctional (meth)acrylate of component A is preferably an alkyl radical or a polyalkylen glycol radical which contains 6 to 18 carbon atoms. In particular, the long chain (meth)acrylate of component A is selected from the group consisting of ethylhexyl methacrylate, isodecylmethacrylate, n-decylmethacrylate, and laurylmethacrylate. As will appreciated, the cyclic substituent of the cyclic methacrylate of Component A is cycloalkyl, arylalkyl, cycloalkenyl, cycloalkenyloxyalkyl, or cycloalkyloxyalkyl, which groups may optionally be substituted, where appropriate, with from one to four lower alkyl groups. In particular, the cyclic methacrylate of component A is selected from the group consisting of iso-bornylmethacrylate, dicyclopentenyloxyethylmethacrylate, 4-tert. butylcyclohexylmethacrylate, and 3,3,5-trimethylcyclohexylmethacrylate. As noted above, the liquid component or phase may contain crosslinking agents and minor amounts of additives such as polymerization inhibitors, activators, and the like. The polymerization inhibitors may be hydroquinone, hydroquinonemonomethylether, ascorbic acid, mixtures thereof, and the like in amounts ranging from about 10 to 500 ppm, preferably 20 to 100 ppm w/w. The activator is employed in amounts ranging from 0.2 to 3.0% w/w, preferably 0.4 to 1.0%, and may be N,N-dimethyl-p-toluidine, N,N-hydroxypropyl-p-toluidine, N,N-dimethyl-p-aminophen ethanol, N,N,-diethyl-p-aminophenyl acetic acid, and the like. In accordance with a further feature of the present invention, it has been found helpful to use a combination of N,N-dimethyl-p-toluidine and N,N-hydroxypropyl-p-toluidine. Most preferably, the latter compound is used in greater proportions, e.g. 2 parts by weight for each part of N,N-dimethyl-p-toluidine. As mentioned above, crosslinking agents may be present in small amounts. Examples of crosslinking agents include: Ethyleneglycol dimethacrylate 1,4-butanediol dimethacrylate 1,3-butanediol dimethacrylate Triethyleneglycol dimethacrylate Tetraethyleneglycol dimethacrylate Polyethyleneglycol-400 dimethacrylate Neopentylglycol dimethacrylate Bisphenol A dimethacrylate Ethoxylated Bisphenol A dimethacrylate Trimethylolpropane trimethacrylate Tripropyleneglycol diacrylate The powder component or phase comprises a (meth)acrylate polymer, copolymer or a mixture of both. Illustrative material include: polyethylmethacrylate polyisopropylmethacrylate poly-sec-butylmethacrylate poly-iso-butylmethacrylate polycyclohexylmethacrylate poly(butylmethacrylate-co-methylmethacrylate) poly(ethylmethacrylate-co-methylmethacrylate) poly(styrene-co-butylacrylate) poly(ethylacrylate-co-methylmethacrylate) The polymer of component B is preferably poly(butylmethacrylate-co-methylacrylate). The content of butylmethacrylate in the poly(butylmethacrylate-co-methylmethacrylate) copolymer is preferably in the range of 30-60% by weight, preferably in the range of 35-50% by weight, in particular about 40% by weight. Another preferred polymer is polyethylmethacrylate. The polymer powder may be utilized in finely divided form such as, for example, 20 to 400 microns, in particular 20 to 250 microns, preferably from 20 to 120 microns. Admixed with the solid material is normally a polymerization initiator. X-ray contrast additives, antibiotics, antiseptic additives, and the like may also be present. Conventional X-ray contrast additives such as barium sulphate, zirconium dioxide, zinc oxide, and the like are used in amounts ranging from 5 to 15% w/w. Typical polymerization initiators can be used in amounts ranging from about 0.5 to 3.0% w/w. Examples of such initiators are benzoyl peroxide, lauroyl peroxide, methyl ethyl peroxide, diisopropyl peroxy carbonate. As noted above, the powder component may also contain an antibiotic or antiseptic additive such as aminoglycosides, cephalosporins, macrolides, polymyxin-peptides, tetracyclines, fusidic acid, bacitracin/neomycin. Typically the amount of such additive will be less than 1% based on the weight of the solid polymer or copolymer. Such additives are employed in conventional amounts that range from 0.1 to 2% w/w. It will be understood that neither the use of most of the aforementioned additives nor the amounts thereof constitute essential features of the present invention. Moreover, the final composition may also contain filler materials such as carbon fibers, glass fibers, silica, alumina, boron fibers, and the like. The weight ratios of the liquid monomer component and the polymer powder component will range from 1 : 1.5 to 1 : 2.5, and will preferably be about 1 : 2. As is well known in the art the final bone cement composition is obtained by mixing the liquid monomeric component with the free-flowing, polymeric powder component. The materials may be admixed and dispensed in the conventional manner using known equipment. In this connection, one of the advantages of the composition is that during the mixing operations, the concentration of acrylate vapour in the surroundings will be reduced compared to the use of known commercial bone cements, e.g. to as low as about one third. This is believed to be due to the fact that the C₁-C₂ alkyl methacrylate has a relatively high solubility in the two other acrylate constituents of Component A. Preferably, the constituents of Components A, including additives, are mixed in advance and sterilized, either by sterilization, such as sterile filtration, of each component, or, preferably, by sterilization, such as sterile filtration, of the liquid mixture. The constituents of Component B are also preferably mixed in advance, including optional additives as mentioned above. It is highly preferred that a polymerization initiator be included in Component B, and, if it is not present in the polymer powder, it will thus preferably be admixed to the polymer powder. Also, it is normally preferred to include an X-ray contrast additive in the mixture, or the polymer powder may be one in which in X-ray contrast additive is included in the particles of the powder. Component B and/or the constituents from which it is made may be sterilized by irradiation and/or with ethylene oxide. Components A and B are preferably each packed aseptically or with additional sterilization and are thus preferably presented as a two-component kit ready for use and provided with instructions for use of the kit to make the bone cement. In practice, the mixing of Component A and Component B is preferably performed by adding the liquid Component A to the powdery Component B and stirring to obtain a homogeneous mix, which is then normally transferred to an application device, e.g. of any commercial type, and applied within between about 0.5 to 5 minutes after mixing. If it is desired to secure a longer open time, the mix may be cooled. It may be advantageous to apply vacuum to the mix to minimize the amount of entrapped air. The invention also relates to an acrylate bone cement surgery kit comprising a package A containing a measured amount of a mixture of C₁-C₂ alkyl methacrylate, a straight or branched monofunctional long chain (meth)acrylate having a molecular weight of at least 168, and a cyclic (meth)acrylate having a molecular weight of at least 168, said mixture having a glass transition temperature, when polymerized, in the range of 23°C to 70°C; and a package B containing a measured amount of a polymer powder component comprising (meth)acrylate polymers or copolymers or a mixture thereof having a glass transition temperature in the range of 37°C to 90°C, whereby, when the liquid monomeric component of package A is admixed with the polymer component of package B, the resulting bone cement composition has a glass transition temperature in the range of 37°C to 70°C. It is a feature of this invention that the polymer powder component has a glass transition temperature in the range of 37 to 90°C; while the liquid monomer component, when polymerized, has a glass transition temperature of 23 to 70°C, and where the final bone cement composition has a glass transition temperature in the range of 37 to 70°C. The glass transition temperatures (Tg) are known from literature for all the acrylic homopolymers, see Polymer Handbook, J. Brandrup editor, 2nd Edition, John Wiley & Sons N.Y. (1975). For (random) copolymers the Tg can be calculated from the equation: where the W's are the weight fractions of the monomers in the copolymers and Tg is measured in Kelvin. See for example S. L. Rosen, Fundamental Principles of Polymeric Materials, John Wiley & Sons, N.Y. (1982), p. 95. The glass transition temperatures listed here are all cited values or calculated in this way. Experimentally, glass transition temperatures can be determined by DSC, Differentiel Scanning Calorimetri, as well as by other methods. The invention wil be more fully understood by reference to the following examples: EXAMPLE 1 A series of comparative runs were carried out utilizing a composition falling within the scope of the present invention (Runs 1 and 8), similar compositions with only two of the three monomeric acrylics present (Runs 2, 3 and 4), three compositions using n-butylmethacrylate as the only monomer (corresponds to EPA 0,218,471), (Runs 5, 6 and 7), and a presently available commercial bone cement, CMW-1 from CMW Laboratories, (Run 9). The formulations are specified in Tables A and B. Before mixing, all the cement compounds and molds were conditioned at 23°C plus/minus 2°C at least 2 hours prior to testing. Liquid monomer component was admixed with polymer powder component by stirring with a spatula for 1 minute. The polymer powder component was added to liquid monomer component and stirred with a spatula for 1 minute. The cement was then transferred to the molds. Molds, samples and tests were made in accordance with ASTM F451. The final bone cement compositions were evaluated and the results are also set forth in Tables A and B. Underlined values indicate undesirable results. The tests as well as the significance of the results are discussed in detail below. The above data demonstrate that Runs 1 and 8, which are within the scope of the present invention, not only show excellent exotherm and residual monomer characteristics but also have excellent modulus of elasticity and compression strength properties. As will be noted, the high exotherm that occurs with many presently available bone cements and a number of bone cements which do not utilize the three separate liquid monomeric acrylates of the present invention, can be avoided. More particularly, the exotherm should be less than about 60°C, and preferably less than about 56°C which is the denaturation point of proteins. Furthermore, a low monomer residual content of about 1% or lower, generally from about 0.5 to 1%, is attained. At the same time, Runs 1 and 8 reveal elasticity modulus and compressive strength characteristics in the desired range. It follows that the bone cement of the invention have a unique balance of highly desirable properties. In contrast, the comparative bone cements, as enumerated in Tables A and B, fail to meet the desirable standards in one or more respects. As noted above, the specific points of failure are shown by underlining in the tables. In carrying out the foregoing examples 5, 6, and 7 it was found that the use of n-butylmethacrylate had the further disadvantage of having a very bad, unpleasant smell. The elasticity modulus (Young's modulus) was determined from the compressive stress/strain data. Compressive strength, on the other hand, was measured by following the procedure outlined in ASTM F451 using a Nene M5 test equipment and running at a crosshead speed of 20 mm/min. The tests were conducted both at ASTM F451 standart temperature (23°C plus/minus 2°C) and at body temperature (37°C plus/minus 1°C). The samples were conditioned 2 hours before testing. Residual monomer content was determined by conditioning samples in a 37°C Ringer-lactate solution for 24 hours. Then the samples are removed and extracted with methanol over a 24 hours period before analyzing the methanol-phase for acrylic monomers on a Perkin-Elmer High Performance Liquid Chromatograph. EXAMPLE 2 A further series of illustrative runs was carried out as in Example 1, but where powder content was varied. Results follow: It is also important to recognize that the foregoing data demonstrate the importance for the bone cement to have the specified glass transition temperatures. Although the present invention has been described and exemplified with respect to its preferred embodiment, it will be understood that the invention may be subject to variations and modifications without departing from its broader aspects. Moreover, it should be understood that known procedures for mixing the liquid and the free-flowing powder components and for dispersing the resulting admixture into the bone cavity may be employed in the practice of the present invention. EXAMPLE 3 A typical commercial bone cement (Palacos R (Palacos is a trade mark)) comprising a liquid monomer consisting of methyl methacrylate and a powder component comprising poly(methylmethacrylate-co-methylacrylate) was compared with the bone cement of Example 1-1. Beeswax was used as "blank". 16 dogs were used. The hip joint was laid open and a hole 8 mm diameter and approx. 100 mm long was drilled down through the femur. In 7 dogs, the hole in one femur was filled with Palacos R; the hole in the other femur was filled with beeswax. In 8 dogs, one hole was filled with Palacos R; the hole in the other femur was filled with bone cement according to Example 1-1. One dog was used to compare Example 1-1 with beeswax. Blood samples were taken 30 and 60 seconds after each filling, and the concentration of methacrylates was measured by head-space gas chromatography. The analysis gave the following average concentrations in ppm: Palacos R vs beeswax: 192 ppm Example 1-1 vs. beeswax: 55 ppm Palacos vs. Example 1-1: 32 ppm vs 8 ppm. In none of the sample using Example 1-1 could any other acrylate than methylmethacrylate be detected. The examples thus show that the use of the bone cement according to the invention reduces the concentration of toxic acrylate in the bloodstream during surgery to about 1/4, compared to the conventional cement. EXAMPLE 4 Canine investigations (one the dogs from Example 3) on the bone cement of Example 1-1 in comparison with Palacos R has shown the following after 4 weeks: 1. Increased blood flow of the tibia containing the bone cement of Example 1-1 as compared to Palacos (Sc microspheres, qualitative Tc-99-MDP isotopes, desulphine). The relative difference was equivalent to observations in dogs with Palacos in one leg and beeswax in the contralateral. 2. Increased bone remodelling (fluorochromes) throughout the entire cortical and higher number of Haversian systems than at the Palacos side, where the bone remodelling is limited to the outer one third of the cortex. 3. Highly reduced membrane formation at interface, increased bone apposition, osteoid bone formation throughout entire cortex. At Palacos side scattered osteoid bone, totally enclosing fibrous membrane. (Bone histology) 4. No physiological adverse effects on central blood pressure, heart frequency, blood oxygen saturation intraoperatively or at blood chemistry (exemplifying hematopoetic system liver and kidney) at up to 3 weeks. 5. A 3 fold decrease of monomer evaporation when the cement according to the invention is mixed in an open bowl as compared to 5 commercially available bone cements.

Claims: An acrylate bone cement composition prepared from a liquid monomeric (meth)acrylate component A and a polymer powder component B comprising (meth)acrylate polymers or copolymers or a mixture thereof, characterized in that component A comprises a mixture of 20-75% by weight of C₁-C₂ alkyl methacrylate, 5-40% by weight of a straight or branched monofunctional long chain (meth)acrylate having a molecular weight of at least 168 and 6-18 carbon atoms in the straight or branched chain substituents, and 5-60% by weight of a cyclic (meth)acrylate having a molecular weight of at least 168 and 6-18 carbon atoms in the cyclic substituents, said mixture having a glass transition temperature, when polymerized, in the range of 23 °C to 70 °C; and that the component B polymer has a glass transition temperature in the range of 37 °C to 90 °C; whereby, when the liquid monomeric component A is admixed with the polymer component B in a weight ratio from 1:1.5 to 1:2.5, the resulting bone cement composition has a glass transition temperature in the range of 37 °C to 70 °C. The acrylate bone cement composition of claim 1, wherein component A comprises 35 to 55% by weight of C₁-C₂ alkyl methacrylate, 20 to 40% by weight of the straight or branched monofunctional long chain (meth)acrylate having a molecular weight of at least 168, and 20 to 60% by weight of the cyclic (meth)acrylate having a molecular weight of at least 168, said mixture having a glass transition temperature, when polymerized, in the range of 23 °C to 70 °C. The acrylate bone cement composition of claim 1 or 2, wherein the C₁-C₂ alkyl methacrylate is methylmethacrylate. The acrylate bone cement composition of any of claims 1 to 3, wherein the straight or branched long chain substituent of the long chain monofunctional (meth)acrylate of component A is an alkyl radical or a polyalkylene glycol radical which contains 6 to 18 carbon atoms. The acrylate bone cement composition of claim 4, wherein the long chain (meth)acrylate of component A is selected from the group consisting of ethylhexyl methacrylate, isodecylmethacrylate, n-decylmethacrylate, and laurylmethacrylate. The acrylate bone cement composition of any of claims 1 to 5, wherein the cyclic substituent of the cyclic methacrylate of component A is cycloalkyl, arylalkyl, cycloalkenyl, cycloalkenyloxyalkyl, or cycloalkyloxyalkyl, which groups may optionally be substituted, where appropriate, with from one to four lower alkyl groups. The acrylate bone cement composition of claim 6, wherein the cyclic methacrylate of component A is selected from the group consisting of iso-bornylmethacrylate, dicyclopentenyloxyethylmethacrylate, 4-tert. butylcyclohexylmethacrylate, and 3,3,5- trimethylcyclohexylmethacrylate. The acrylate bone cement composition of any of claims 1-7, wherein the liquid component A contains a crosslinking agent in an amount of at the most 10% by weight, preferably at the most 4% by weight, and more preferably at the most 1% by weight, calculated on Component A. The acrylate bone cement composition of any of claims 1-8, wherein the liquid component A contains an activator. The acrylate bone cement composition of claim 2, wherein the activator is a combination of N,N-dimethyl-para-toluidine and N,N-hydroxypropyl-para-toluidine. The acrylate bone cement composition of claim 9, wherein the activator is N,N-dimethylaminophen ethanol or N,N-diethylaminophenyl acetic acid. The acrylate bone cement composition of any of claims 1 to 11, wherein the polymer of component B is poly(butylmethacrylate-co-methylmethacrylate). The acrylate bone cement composition of claim 12, wherein the content of butylmethacrylate in the poly(butylmethacrylate-co-methylmethacrylate) copolymer is in the range of 30-60% by weight, preferably in the range of 35-50% by weight, in particular about 40% by weight. The acrylate bone cement composition of any of claims 1 to 11, wherein the polymer of component B is polyethylmethacrylate. The acrylate bone cement composition of any of claims 1-14, wherein the polymer component B contains an initiator, preferably benzoyl peroxide. An acrylate bone cement composition according to claim 1 prepared from a liquid monomeric (meth)acrylate component A and a polymer powder component B having a particle size within the range of 20 to 400 microns wherein component B comprises a (meth)acrylate polymer or copolymer or a mixture thereof having a glass transition temperature in the range of 37 °C to 90 °C; and wherein Component A comprises a mixture of 20-75% by weight of methylmethacrylate, 5-40% by weight of straight or branched chain methacrylate having a molecular weight of at least 168 and 6-18 carbon atoms in the straight or branched chain substituents, and 5-60% by weight of a cyclic methacrylate having a molecular weight of at least 168 and 6-18 carbon atoms in the cyclic substituents, said mixture having a glass transition temperature, when polymerized, in the range of 37 °C to 70 °C; whereby, when the liquid monomer component A is admixed with the polymer component B in a weight ratio of 1:2, a bone cement composition having a glass transition temperature in the range of 37 °C to 70 °C is obtained. An acrylate bone cement surgery kit comprising a package A containing a measured amount of a mixture of 20-75% by weight of C₁-C₂ alkyl methacrylate, 5-40% by weight of a straight or branched monofunctional long chain (meth)acrylate having a molecular weight of at least 168 and 6-18 carbon atoms in the straight or branched chain substituents, and 5-60% by weight of a cyclic (meth)acrylate having a molecular weight of at least 168 and 6-18 carbon atoms in the cyclic substituents, said mixture having a glass transition temperature, when polymerized, in the range of 23 °C to 70 °C; and a package B containing a measured amount of a polymer powder component comprising (meth)acrylate polymers or copolymers or a mixture thereof having a glass transition temperature in the range of 37 °C to 90 °C, whereby, when the liquid monomeric component of package A is admixed with the polymer component of package B in a weight ratio from 1:1.5 to 1:2.5, the resulting bone cement composition has a glass transition temperature in the range of 37 °C to 70 °C.

Inventors: DAHL THOMSEN LYDIA, KINDT-LARSEN TURE, DAHL THOMSEN, LYDIA, KINDT-LARSEN, TURE
Applicants: JENSEN JORGEN STEEN, WOLLF & KAABER AS, JENSEN, JORGEN STEEN, WOLLF & KAABER A/S
Application year: 1989
Main classification: A61L25
IPC codes: A61L26, A61L24