Technical Field The present invention relates to polymer bone cements formed by mixing a liquid monomer and a particulate polymer.

Background Art Polymer bone cement ^' s are used, for example, for fixing and mending prostheses and are generally formed by mixing liquid monomer with particulate polymer. Such cements are known to those skilled in the art. See for example U.S. Patent No. 4,268,639 to Seidel et al . where various formulations are described. In fact, extensive work has been done in this field as can be seen from the patents discussed briefly below. U.S. Patent No. 4,490,497 to Eyrard et al. discloses a component system for surgical cement including a liquid acrylic monomer/polymer mixture and a polymer powder. The polymer powder has a particle size of between 20 and 150 microns in diameter. An inhibitor is used to prevent curing temperatures from exceeding about 55°C. See Col. 3, lines 33-40. The Eyrard et al. patent notes that the 20-150 micron size powder is particularly advantageous for achieving a homogeneous adhesive structure (Col. 2, lines 25-40) and that inert fillers with a particle diameter from about 10 to 500 microns may be incorporated into the cement.

U.S. Patent No. 4,396,476 to Roemer et al. discloses a hardenable, oldable mixture for use in medical applications comprising a crosslinked polymer admixed with polymer particles having a size range from about 0.001 to 500 microns in diameter. This patent states in column 5, lines 9-11 that preferably 50% of the particles are less than 150 microns in diameter. In column 16, lines 38-41 it is disclosed that 46% by weight of the particles are below 74 microns in size and that the balance are below 500 microns in size.

U.S. Patent No. 4,383,826 to Butler et al. describes a bone cement composition including fillers. In

column 3, lines. 16-18 it is noted in passing that it is "possible" and useful to use combinations of fillers of low and high particle sizes.

U.S. Patent No. 4,373,217 to Draenert discloses implantation materials comprising a polymeric base of an acrylate having 5-35% by weight of resorbable phosphate particles (50-300 microns in diameter) disposed therein. Draenert notes at the bottom of column 2 that the phosphate particles improve heat removal. U.S. Patent No. 4,341,691 to Anuta describes a low-viscosity bone cement consisting of a liquid monomer (methyl methacrylate) and polymer beads (polymethyl methacrylate) ranging in size from about 10 to 425 microns. A portion of the polymer beads are milled to increase the surface area thereof. It should be noted that there are various mixture additives disclosed by Anuta including- barium sulphate, hydroquinone, N,N-dimethyl-p- toluidine, and benzoyl peroxide.

The specific heat production (Kcal/gram of composition) in polymer bone cements is directly proportional to the amount of monomer in the liquid/particulate dough, roughly 130 Kcal/gram of monomer in the case of monomethyl methacrylate, a known monomeric component. The relatively high heat of formation for polymer bone cement structures is due to the relatively high liquid content of the cement-forming mixtures. High curing temperatures due to the amount of heat released contributes to bone necrosis, and ultimately, to failure of the surgery performed. In this connection, it is noted that commercial bone cements require 1 part liquid monomer for each 2 parts of powdered polymer.

In order to reduce curing temperature of bone cement various methods have been attempted. U.S. Patent No. 4,093,576 to de ijn describes, for example, a bone cement mixed with a high viscosity aqueous gel. The purpose of the gel is to maintain the curing temperature at relatively low levels. See column 1, lines 38-50. It should be noted that the gel admittedly reduces the

strength of the cement. As will be appreciated by those skilled in the art, suitable mechanical properties such as strength of the formed product, acceptable setting times and dough viscosities are absolutely required in commercially useful bone cements.

Additional attempts' to reduce the problems caused by excessive heat release and attendant high temperatures accompanying the use of bone cements include: 1. Diminishing the amount of cement;

2. Using heat abductors, i.e. metal implants;

3. Precooling the implant, the cement or the bone;

4. Increasing the heat capacity of the cement by addition of heavy metals, or melting crystalline monomers;

5. Retarding the polymerization rate; and

6. Diminishing the amount of monomer by increasing the powder-to-liquid ratio, or by addition of granulate polymer.

All of the foregoing methods have met with only limited success because of the demanding performance criteria involved. The search has continued for new and improved bone cements and methods for producing such cements. This invention was made as a result of that search.

OBJECTS AND SUMMARY OF THE INVENTION Accordingly, it is a general object of the present invention to avoid or substantially alleviate the above-noted problems of the prior art. Another object of the present invention is to provide a bone cement with low heats of formation and low curing temperatures.

A further object of the invention to provide a polymer bone cement with low curing temperatures while maintaining high mechanical strength of the formed bone cement structure.

Yet another object of the invention to provide a bone cement wherein the dough formed by the particulate

polymer and the liquid monomer has suitable viscosity for a substantial length of time.

Still another object of the present invention is to provide a method for producing this improved bone cement.

Other objects and advantages of the present invention will become readily apparent upon consideration of the following summary of the invention and description of its preferred embodiments. The present invention provides, in one aspect, a polymer bone cement which has a relatively low heat of formation, yet maintains the required properties in terms of strength, curing times and dough viscosities. The bone cement forms a polymer structure which inςludes at least about 70 per cent by weight of a particulate polymer mixed with up to about 30 per cent or less by weight liquid monomer based upon the weight of the total bone cement composition. The particulate polymer portion of the mixture has a powder component wherein substantially all of the particles have a grain size of up to about 130 micron and a granulate component with a grain size of at least about 350 microns. The components of the particulate portion of the mixture are proportioned so that there is at least one part granulate for each part of powder.

In another aspect, the present invention provides a method for preparing this improved bone cement. This method comprises producing a bone cement structure from a self curing composition by the steps of mixing 1 part of liquid monomer with 1 to 1.5 parts of polymer powder of a particle size less than about 130 microns and upon thickening thereof, admixing at least about 1 part of polymer granulate of a particle size of more than 350 microns therewith to form a homogeneous mixture.

Brief Description of the Drawings The invention is described in detail below with reference to the drawings. In the drawings:

Figure 1 is an enlarged schematic illustration of the bone cement of this invention; and

Figure 2 is a diagram illustrating two possible size distributions of the powder component of the bone cement mixtures wherein the cumulative weight percent of powder particles which are smaller than a given particle size is plotted against each size.

Detailed Description As indicated hereinabove, the bone cement of the present invention comprises as solid particulate component and a liquid component which will be described in connection with Figure 1.

The particulate component includes a powder 2 and a granulate 3. ^■ Powder 2 is preferably a conventional powder which is typically used in bone cements. Such a powder has particles substantially all of which have grain sizes up to about 130 microns, preferably from about 5 to about 120 microns. Two such powders are illustrated in Figure 2. Granulate 3 in which substantially all of the particles have a grain size of generally at least ^" about 350, typically from about 350 to about 1000, and preferably from about 350 to about 500 microns. The use of this mixture of powder and granulate reduces the mean porosity in the mixture of the bone cement 1 without causing any mechanical problems during and subsequent to polyme ization.

The bone cement of the present thus reduces the amount of liquid required for adequately moistening the mixture without adversely affecting the mechanical properties of the dough or fully formed product. Inasmuch as the amount of liquid is reduced, the temperature during polyerization is correspondingly reduced to such values that no layers of necrotic bone tissue appear around the bone cement 1.

Granulate 3 _s preferably made by using the same or chemically related substances as powder 2, both of which are mixed with a liquid monomer for the subsequent

polymerization process. In the present case the liquid monomer is monomethyl methacrylate and the granulate is preferably formed from liquid substantially consisting of monomethyl methacrylate. The mixing operation for producing the bone cement according to the invention is preferably carried out by first adding powder 2 to the liquid monomer and thereafter introducing granulate 3 into that mixture. Then, the liquid monomer/powder/granulate mixture is further mixed as required and applied to the bone surface. As may be seen, by adding granulate 3 to the liquid monomer/powder mixture, the specific generation of heat is substantially reduced when the bone cement cures during use. Accordingly, heat necrosis in the surrounding bone and thus, mechanical loosening of the prostheses is obviated.

When the grain size of the granulate is much larger than the mean grain size of the powder, the porosity of the mixture is substantially reduced. The reduction of porosity is advantageous if, when using a powder having a grain size not exceeding 130 microns, a granulate with a grain size of 350-1000 microns is used. A substantial grain size in the granulate of up to just below 1000 microns may be advantageous when the bone cement is used where the size of the cavity between the bone surface and the prothesis is relatively large. A particularly advantageous bifurcated particle size distribution of the powder component is achieved by using a powder with a size range of about 5-120 microns and a granulate having a size range of about 350-500 microns.

In terms of weight per cent particulate polymer of the total mixture, the invention includes mixtures generally with at least about 70 percent by weight polymer powder and granulate and 30 percent or less liquid monomer; typically about 70-90 percent powder and granulate; and preferably about 75-85 percent by weight polymer. With respect to the ratio of granulate to powdered polymer, there is included generally at least one

part granulate per part powder; typically from about 1 to 4 parts granulate per part powder and preferably from about 1.2 to 3 parts granulate per part powder.

The invention is further illustrated below in the following examples:

Example I This example illustrates the preparation of a prior art bone cement which lacks the granulate component of the invention. A commercial bone cement composed of one part liquid monomer and two parts polymer powder (sold by Merck of West Germany under the mark Palacos) is chilled to 4 degrees and mixed with a spatula for 45 seconds. The particles have a size distribution roughly as illustrated in Fig. 2, i.e. virtually all particles have a grain size between 0 and 150 microns, the mean size being between 40 and 80 microns. In this and the examples below, parts of solid components are expressed in grams, while parts of liquid components are expressed in milliliters. Example II

In accordance with the invention, the new cement comprises 1 part liquid monomer (methylmetharcylate essentially), 1.5 parts polymer powder consisting essentially of polymethyl methacrylate, and 2 parts polymer granulate with a particle size of 350 to 500 microns. The granulate is made by grinding and sifting polymerized methyl methacrylate.

The ingredients are chilled to 4° C. The liquid and the powder are mixed by hand for 15 seconds, and then the granulate is added and mixed for 30 seconds. The powder may be of a size indicated in Fig. 2 discussed above.

Comparative Mechanical Tests For purposes of testing, a cement syringe ,is filled with the cement dough of Examples I and II respectively and a cement gun, commercially available from Howmedica of Rutherford, New Jersey, was used to pressurize the cement into a hollow metal mold

(12x12x120mm). The cement bars were allowed to harden at room temperature (20-25°C) for 40 hours before being tested. Bending Test Six bars (12x12x120mm) of each material are examined by a three-point bending test with an Instron instrument. The force is applied at a velocity of 2 microns per minute centrally between two supports which are 100 microns apart. The applied load and the bar deflection were measured simultaneously until rupture.

The maximum flexural strength, the maximum strain and the tangent modulus of elasticity are calulated according to ASTM D790 (Annual Book of ASTM Standards 1980). Compression Test Six bars (12x12x20 mm) of each material are examined with the Instron testing instrument for compression properties. The force is applied at a velocity of 1 microns per minute on the 12x12 mm area. The applied load and the deformation are measured simultaneously and the test is terminated after reaching the compressive yield point. The yield strength, yield strain, 0.1% proof stress and modulus of elasticity are calculated according to ASTM D695. Impact Test and Hardness Test Six bars (12x12x50 mm) of each material are tested with an Alpha-testing device, having a pendulum of 1 kpm capacity, for impact properties according to the Charpy-method (ASTM D256). The bars are broken by a single swing of the pendulum centrally between two supports which are 40 microns apart. The energy absorbed per cross-section area (fracture area) is determined.

The hardness according to the Rockwell L scale of all these bars is measured on their free surfaces. Five readings for each specimen were performed. Results of Mechanical Tests

During the bending test all bars are fractured in the middle, i.e. in the area of maximum deformation, and no defects were seen in the fracture surfaces of any

of the materials. During the compression test no specimen fails in a shattering fracture. During the impact test all bars are completely broken into two pieces.

The results of these tests are shown in Table 1. The new cement composition has 8-20 per cent lower flexural and compressive properties compared to the standard cement. The yield strain, however, is increased by 8 percent. There are no significant differences in impact strength and hardness, thus there are no serious difficulties with the mechanical properties of the new

Done cement. Perhaps more importantly, it should be noted that the inventive bone cement of Example II had only 1 part of monomer per 4 1/2 parts of mixture, while the mixture of Example I had 1 part of monomer per 3 parts of mixture. Accordingly, the inventive bone cement in accordance with Example II produces 33% less heat than the conventional bone cement of Example I; inasmuch as the heat released is directly proportional to the amount of liquid in the composition.

Table 1

Results of Investigated Mechanical Properties

Mean (SD)

Bone Cement Bone Cement Composition of of

Example II Example I Flexural properties

Max. flexural strength MPa 50.7 (1.6 ) 63.4 (5.0 ) Maximum strain % 2.85 (0.18) 3.33 (0.23)

Modulus of elasticity GPa 1.97 (0.08) 2.15 (0.12)

Max. deflection at mm 3.82 (0.24) 4.46 (0.36) rupture

Co oressive properties

Yield of strength MPa 58.9 (3.1 ) 69.2 (2.8 )

Yield strain % 7.94 (1.89) 7.34 (0.34)

0.1% Proof stress MPa 44.8 (2.4 ) 52.1 (2.8 )

Modulus of elasticity GPa 1.29 (0.21) 1.48 (0.08)

Impact properties

Impact strength kJm ^"2 7.33 (1.09) 7.14 (1.90)

Hardness Rockwell L 72 (4) 71 (7)

Example III This eample illustrates a preferred embodiment of the bone cement of the present invention prepared according to the method of Example II. 1. Liquid monomer 20 milliliters of monomethyl methacrylate or a homolog a stabilizer (e.g. a hydroquinone or an amine ( other known additives may be used)

Powder polymer 20 grams of polymethyl methacrylate or polymethyl methacrylate-copolymer (bead size 5-120 micron) an initiator (e.g. a peroxide) contrast medium (other known additives may be used)

Granulate polymer 60 grams of polymethyl methacrylate or polymethyl methacrylate-copolymer (bead size (+350, - 500 microns prepared by sieving ground polymer) (other known additives may be used)

The relative amount of monomer in the cement dough, and thus the specific heat production, is reduced by 40 percent in this composition over currently available mixtures.

Examples IV and V

Example

IV V

Powder (grain. size smaller than 135 microns) Polymethyl methacrylate 87.5% by weight Benzyl peroxide 2.5% by weight 30g 20g

Bariumsulphate 10.0% by weight

Liquid

Monoethylmethacrylate 97.5% by volume

N-N-Dimethyl-p-toluidine 2.5% by volume , 20ml 20ml Hydroquinone 75 ppm

Density of Liquid approx. 0.944 g/ml

Granulate (grain size 350-1000 microns) Polymethyl methacrylate or a 40g 60g granulate substance produced by the powder and liquid defined above

Total parts in composition described 90 100

Although the invention has been described in detail hereinabove, various modifications will be apparent to those of ordinary skill in the art. Such modifications, are within the spirit and scope of the present invention which is limited and defined only by the appended claims.