A glass-ceramic may be defined as a ceramic which is processed into its final shape as a glass, and is then induced to crystallize by a controlled heat- treatment. Accordingly, glass-ceramics are polycrystalline materials formed by the controlled devitrification of a parent glass. Glass-ceramics generally have improved mechanical properties over the parent glass and are commonly used in the manufacture of kitchenware.

Enstatite is a naturally-occurring magnesium- silicate ceramic whose chemical formula is MgSiO..

The main commercial application of synthetic enstatite to date has been in the electrical insulator field.

Enstatites exhibit relatively high fracture toughness for ceramic materials, thought to be due to the high aspect ratio of the crystallites effectively raising the energy required per unit length to propagate a crack.

US-4,687,749 relates to the production of glass- ceramic articles in which enstatite constitutes the predominant crystal phase. A problem exists, however, in that the crystallization is not controlled and the precursor glasses therefore exhibit marginal glass

stability and frequently crack during the crystallization heat-treatment.

The present invention aims to provide a glass- ceramic material having improved mechanical properties and which is suitable for use in biomedical applications.

Accordingly, in a first aspect the present invention provides a glass-ceramic material having a fracture toughness greater than or equal to 3.6 MNm~3/2 and comprising: (a) a major crystalline phase comprising enstatite (MgSiO3) or one or more polymorphs thereof; (b) one or more minor crystalline phases comprising at least one of Mg2SiO4, SiO2, Na4Mg2Si3O10and/orNa2Mg6F2(Si4O11)2;TiO2,MgO, and (c) a residual glassy phase; which glass-ceramic is obtainable by heating a parent glass composition comprising in the range of from 20 to 60 wt. % MgO, from 35 to 65 wt. % SiO2, from 1 to 20 wt. % TiO2 and from 0 to 15 wt. % Na2O, preferably 1 to 15 wt. % Na2O.

The chemical composition of the residual glassy phase is difficult to characterise, but it is possible that it comprises one or more of Na2O, SiO2, Na2O-SiO2

and Na2O-Si02-Ti02.

The glass-ceramic is preferably obtainable by heating a parent glass composition comprising in the range of from 20 to 35 wt. % MgO, from 50 to 65 wt. % SiO2, from 4 to 15 wt. % Ti02 (preferably from 5 to 15 wt. % TiO2) and from 1 to 12 wt. % Na2O. More preferably, the glass-ceramic is obtainable by heating a parent glass composition comprising in the range of from 24 to 30 wt. % MgO, from 54 to 62 wt. % SiO2 (preferably from 54 to 61 wt. % SiO2), from 4 to 15 wt. % TiO2 (preferably from 5 to 15 wt. % Tir2) and from 1 to 10 wt. % Na2O.

The weight ratio of MgO to SiO2 is preferably in the range of from 25: 75 to 40: 60, more preferably from 32: 68 to 38: 62.

Preferred TiO2 and Na2O levels range from 5 to 10 wt. % and 1 to 6 wt. % Na20 respectively (preferably from 6 to 8 wt. % TiO2 and 1 to 5 wt. % Na2O) based on the total weight of the parent glass composition.

The parent glass composition may also comprise a small amount of MnO, for example from 1 to 2 wt. % MnO, for the purpose of stabilising one or more of the polymorphs of enstatite (protoenstatite) in some systems. Whilst the parent glass composition may include other constituents, the presence of Al2O3 and/or at least one of Li2O, CaO, SrO, La20 ,, Y203, K20 and BaO are not essential to the performance of the final material, in contrast to compositions disclosed in US-4,687,749. Accordingly, in a prefer-ed aspect

of the present invention the glass-ceramic material consists essentially of the recited phases (a), (b) and (c), together with unavoidable impurities.

The glass-ceramic according to the present invention has a fracture toughness greater than or equal to 3.6 MNm~3/2, although a fracture toughness greater than or equal to 3.8 MNm~3/2, preferably 4 MNm~3/2, more preferably 4.5 MNm~3/2, still more preferably 5 MNm~3/2, can be achieved.

The glass-ceramic according to the present invention typically has a flexural strength greater than or equal to 300 MPa, more typically greater than or equal to 325 MPa, still more typically greater than or equal to 350 MPa.

The glass-ceramic according to the present invention typically has a Vickers hardness of 600 or more for a 20 kg load.

The glass-ceramic according to the present invention typically has an average grain size in the range of from 5 to 15 um, more typically from 8 to 12 urn, still more typically approximately 10 um. The microstructure is characterised by the high aspect ratio of the enstatite crystals.

The degree of crystallinity in the glass-ceramic according to the present invention is typically up to 50% by volume, more preferably from 50 to 70% by volume.

The present invention also provides a bone replacement material which comprises a glass-ceramic as herein described.

The present invention also provides a composition which comprises a glass-ceramic or a synthetic bone material as herein described, together with a pharmaceutically acceptable diluent or carrier.

The glass-ceramic, synthetic bone material or composition as herein described may be used in a bone implant, joint implant, prosthesis, such as a finger joint prosthesis, or a filler.

In a second aspect, the present invention provides a process for the production of a glass- ceramic material, which process comprises: (i) providing a parent glass composition comprising in the range of from 20 to 60 wt. % MgO, from 35 to 65 wt. % Six2, from 1 to 20 wt. % TiO2 and from 0 to 15 wt. % Na2O, preferably 1 to 15 wt. % Na2O; (ii) heating the parent glass composition at a temperature and for a time sufficient to precipitate (a) a major crystalline phase comprising MgSi03 or one or more polymorphs thereof, (b) one or more minor crystalline phases comprising at least one of MgSiO4, Six2, MgO, TiO2, Na4Mg2Si301o and/or Na2Mg6F2 (Si4Oll) 2, and (c) a residual glassy phase.

In this process, a glass-ceramic component may be

formed by first shaping the parent glass, followed by heating to induce crystallization. The parent glass may be formed into the desired shape by any of the glass forming techniques conventional in the art. For example, casting by pouring the molten material into a suitable mould, blow-moulding, a float process, sintering finely divided parent glass particles, centrifugal casting and injection moulding. A particular feature of the process according to the present invention is that cracking is less frequent during casting compared with the prior art parent glass materials.

The parent glass composition preferably comprises in the range of from 20 to 35 wt. % MgO, from 50 to 65 wt. % Si02, from 4 to 15 wt. % TiO2 (preferably from 5 to 15 wt. % TiO2) and from 1 to 12 wt. % Na2O. More preferably, the parent glass composition comprises in the range of from 24 to 30 wt. % MgO, from 54 to 62 wt. % SiO2 (preferably from 54 to 61 wt. % SiO2), from 4 to 15 wt. % TiO2 (preferably from 5 to 15 wt. % TiO,) and from 1 to 10 wt. % Na2O.

The weight ratio of MgO to Si02 is preferably in the range of from 25: 75 to 40: 60, more preferably from 32: 68 to 38: 62.

Preferred TiO2 and Na20 levels range from 5 to 10 wt. % and 1 to 6 wt. % Na20 respectively (preferably from 6 to 8 wt. % TiO2 and preferably from 1 to 5 wt. % Na2O) based on the total weight of the parent glass composition.

In order to precipitate the various phases, the parent glass composition is typically heated at a temperature in the range of from 600 to 1300°C, preferably from 600 to 1200°C, more preferably from 1000 to 1200°C. Heating is typically carried out at a rate of up to 15°C/minute, preferably up to 10°C/minute, more preferably up to 7.5°C/minute, still more preferably up to 5°C/minute, still more preferably up to 2°C/minute, still more preferably up to 1°C/minute.

In general, a two-stage heat-treatment will be utilised in which the glass is first annealed, followed by controlled heating to produce a large number of nuclei for crystallization and subsequent crystal growth. The annealing step is also preferably carried out at a heating rate of up to 5°C/minute, more preferably up to 2°C/minute, still more preferably up to 1°C/minute. If desired the material may be cooled to room temperature after the annealing step.

A preferred heat-treatment comprises heating the annealed parent composition from room temperature to the peak crystallization temperature (Tc), which typically lies in the range of from 750 to 1200°C.

Heating is preferably performed at a controlled heating rate of up to 15°C/minute, more preferably up to 10°C/minute, still more preferably up to 5°C/minute, still more preferably up to 2°C/minute, still more preferably up to 1°C/minute. As the glass is heated to the final temperature a large number of dispersed nuclei are produced. Once the final

temperature has been reached, the glass is held at that temperature for a time sufficient to produce the desired size of crystallites, typically for 30 minutes or more, more typically for 2 hours or more, still more typically for 10 hours or more. This is then followed by gentle cooling to room temperature, preferably at a rate of up to 10°C/minute, more preferably up to 5°C/minute, still more preferably up to 2°C/minute, still more preferably up to 1°C/minute.

Cooling may be carried out in air.

An alternative heat-treatment involves determining the optimum nucleation temperature (Tn) of the given system. Tn is the temperature at which the maximum number of nuclei are produced in the shortest time within the glass. Tntypically lies in the range of from 650 to 900°C, more typically from 700 to 840°C, still more typically from 700 to 750°C. Once Tn has been determined, the annealed sample can be raised to Tn at a relatively high heating rate, for example up to 20°C/minute, more preferably up to 15°C/minute, still more preferably up to 10°C/minute and held at the temperature for a time sufficient to achieve the desired number of nuclei. The time will generally be from 1 to 5 hours. The material is then heated to Tc, again at a relatively high heating rate, for example up to 15°C/minute, more preferably up to 10°C/minute, still more preferably up to 7.5°C/minute.

Ttypically lies in the range of from 750 to 1200°C.

Once the final temperature has been reached, the glass is held at that temperature for a time sufficient to produce the desired size of crystallites. This will typically be for 30 minutes or more, more typically

for 2 hours or more, still more typically for 10 hours or more. This is then followed by gentle cooling to room temperature, preferably at a rate of up to 20°C/minute, more preferably up to 10°C/minute, still more preferably up to 5°C/minute, still more preferably up to 2°C/minute. Cooling may be carried out in air. In this manner the rate at which the sample can be heated to or cooled from the two critical temperatures Tn and Tc depends only on the thermal shock resistance of the sample. Tn and Tc may be determined in a conventional manner by, for example, differential thermal analysis (DTA).

The parent glass composition may be formed by heating mixed precursor powders comprising oxides and/or carbonates of sodium, silicon, titanium and magnesium, for example Na2CO3, SiO2, TiO2 and MgC03, at a temperature and for a time sufficient to form the parent glass. Heating of the precursor powders will generally involve the conventional steps of melting and homogenisation and optionally refining (or firing). Advantageously, the mixed precursor powders undergo a two-stage heat-treatment comprising: a first step of heating at a temperature in the range of from 800 to 1200°C, preferably 900 to 1100°C, for a time sufficient to reduce the volume of the precursor powders and to initiate the reaction; followed by a second step of heating at a temperature in the range of from 1450 to 1650°C, for a time sufficient to form the parent glass.

Accordingly, the present invention provides a <BR> <BR> <BR> high fracture toughness ( 3.6 MNm~3/2) glass-ceramic,

castable to near-net shape, intended for use as a joint replacement material in small, non-major load bearing joints, such as finger joints.

The composition and heat-treatment allow controlled crystallization of the desired phases.

The present invention will now be described further with reference to the following examples and drawings, in which: Figure 1 shows the distribution of X-ray intensity for the glass-ceramic material produced from the composition according to Example 1; Figure 2 is a scanning electron micrograph of an etched, polished surface of the glass-ceramic material produced from the composition according to Example 1; Figure 3 shows the heat treatment schedule for determining the optimum nucleation temperature of the composition according to Example 3; Figure 4 is a scanning electron micrograph of an etched, polished surface of the glass-ceramic material produced from the composition according to Example 4; Figure 5 is a scanning electron micrograph of an etched, polished surface of the glass-ceramic material produced from the composition according to Example 5;

Figure 6 is an Energy-Dispersive Spectroscopy (EDS) plot the glass-ceramic material produced from the composition according to Example 5; Figure 7 is a scanning electron micrograph of an etched, polished surface of the glass-ceramic material produced from the composition according to Example 6; Figure 8 is a scanning electron micrograph of an etched, polished surface of the glass-ceramic material produced from the composition according to Example 7; Figure 9 shows the distribution of X-ray intensity for the glass-ceramic material produced from the composition according to Example 7; Figure 10 is a scanning electron micrograph of an etched, polished surface of the glass-ceramic material produced from the composition according to Example 8; Figure 11 shows the distribution of X-ray intensity for the glass-ceramic material produced from the composition according to Example 8; Figure 12 is a scanning electron micrograph of an etched, polished surface of the glass-ceramic material produced from the composition according to Example 9; and Figure 13 shows the distribution of X-ray

intensity for the glass-ceramic material produced from the composition according to Example 9.

Examples 1 and 2 The initial production step is to mix the precursor powders consisting of Na2CO3, SiO2, TiO2, and MgC03 in the appropriate ratios in a pestle and mortar. The Na2CO3 is included to reduce the melting temperature and glass viscosity and the TiO2 is used as a nucleation catalyst. The design composition in weight percents for Examples 1 and 2 are given in Table 1 below. The mixed batch is then transferred to alumina crucibles where the precursor powder is fired at approximately 1000°C for about 3 hours to reduce the volume and initiate the reaction. The presintered'precursor is then transferred to a Platinum-Rhodium crucible in an electric furnace at 1550°C in order to form the parent glass. This is fused for a total of 4 hours, being splat-cooled, pulverised and re-melted once after two hours in order to ensure good mixing.

Table 1 Constituent MgO SiO2 TiO2 Na2O (wt.%) Example 1 25.5 54.5 10 10 Example 2 27 58 10 5 A hot mould is prepared, comprising a two-way split cylinder with a retaining ring, coated with a release agent (Colloidal) graphite suspension,

Ascheson Colloids Ltd) and is heated to 600°C. The hot mould is withdrawn from a second electric furnace prior to being filled with the molten glass. The filled mould is then reintroduced into the second furnace and maintained at approximately 600°C for about 1 hour before being cooled at a rate of approximately 1°C/min or less to room temperature.

The resulting cylinder of glass is sliced into disks approximately 3mm thick and crystallized by being heated in a third furnace at approximately 1°C/min to 1000°C, where they are held for 3 hours (Example 1) and 10 hours (Example 2) before being cooled, again at approximately 1°C/min, to room temperature.

Differential thermal analysis (DTA) has been performed in order to determine the crystallization behaviour, and shows that there are two crystallization events, whose exotherm maximas occur at approximately 840 and 880°C. With reference to Figure 1, X-ray diffraction (XRD) for the glass- ceramic produced from the composition according to Example 1 shows that there are two main phases precipitated, clinoenstatite (MgSiO3) and crystobalite (Si02). This implies that there is a residual glassy phase consisting of Na2O-rich silica glass between the crystallites.

Scanning electron microscopy on etched, polished surfaces shows that the microstructure consists of many spherulitic-type grains of enstatite. The fracture surfaces seem to suggest that the fracture path passes around, rather than through, the grains.

Figure 2 is a SEM micrograph of the final microstructure for the glass-ceramic material produced from the composition according to Example 1. The material was quenched after approximately 90 minutes and etched in 48% HF and the micrograph shows acicular surfaces. The crystallite size is approximately 10 um.

Flexural testing has been performed on polished samples using the ring-on-ring biaxial flexure test, and shows that the material has a mean flexural strength of 352 MPa with a Weibull modulus of 5.7.

Indentation fracture toughness tests were performed, and showed that the material had a mean fracture toughness of 4.56 MNm~3/2 with a standard deviation of 0.79 MNm~3/2, assuming a Young's modulus value of 140 GPa.

MTT assays have shown that the material is non- cytotoxic and behaves similarly to hydroxyapatite.

Testing using simulated body fluid (SBF) shows the precipitation of an apatite layer when held at 37°C for 1 week.

Examples 3 to 9 For Examples 3 to 9, parent glasses were prepared in the same way as in Example 1 above. Weight % and Mole % compositions are shown in Table 2 below. All compositions showed X-ray diffraction patterns consistent wi_h materials containing either proto-or clinoenstatite (MgSiO) as major phases, followed by

rutile (TiO2) as a secondary phase and quartz (SiO2) as a ternary phase when crystallised. There appeared to be a small degree of amorphous scattering indicative of a residual glassy phase in all of the crystallised compositions.

Table 2 Example Composition/wt% | Composition/mol% MgO SiO2 TiO2 Na2O MgO SiO2 TiO2 Na2O 3 28.5 61.2 5. 00 5. 28 37. 7 54. 4 3. 34 4.55 4 28.8 61.9 4. 00 5. 33 38. 0 54. 8 2. 66 4.57 5 27.9 59.9 7. 00 5. 17 37. 2 53. 6 4. 71 4.48 6 27.0 58.0 10. 0 5. 00 36. 4 52. 4 6. 80 4.38 7 27.9 59.9 7. 00 5. 17 37. 2 53. 6 4. 71 4.48 8 27.9 59.9 7. 00 5. 17 37. 2 53. 6 4. 71 4.48 9 27.9 59.9 7. 00 5. 17 37. 2 53. 6 4. 71 4.48 Example 3 After the parent glass had been produced as described above, small cubes measuring 5 mm to a side were cut using a diamond saw. Six of these cubes were analysed using a differential thermal analyser (Setaram LabSys DTA/DSC 1600) according to the heat treatment shown in Figure 3. The temperature represented by Tn in the figure was varied for each sample, being 700,710,720,730,740 and 750°C. The temperature at which the crystallisation exotherm was maximum was recorded for each sample is given in Table 3 below. A polynomial curve was fitted to a plot of these temperatures on the y-axis against T on the x- axis. The maximum of this curve, indicative of the optimum nucleation temperature of the composition, was 711°C.

Table 3 Nucleation hold Peak crystallisation temperature (Tn) °C temperature (Tc) °C 700 837 710 844 720 842 730 831 740 824 750 811 Example 4 The parent glass was prepared according to the method described previously and the composition described in Table 2. The glass casting was cut into slices approximately 3 mm thick and then crystallised at a heating rate of 10°C/min to 1200°C. The resulting glass-ceramic was then cooled at 10°C/min to room temperature. Specimens were embedded in epoxy resin, and were polished to < 1 mm diamond finish and then examined using scanning electron microscopy (SEM). The structure of the glass ceramic was composed of large, > lmm in diameter spherulitic crystals with interstitial voids. A SEM micrograph of part of the spherulites and a void is shown in Figure 4.

Example 5 All preparation conditions were the same as for Example 4 apart from the design composition shown in Table 2. SEM showed that the structure now consisted of a uniform dispersion of fine, high aspect ratio

crystals varying in their minor dimension from < 0.5 mm to = 1 mm and in major dimension from = 1 to 5 mm (Figure 5). Dispersed throughout the structure were larger, more equally-proportioned grains up to 2 mm in diameter. Energy-dispersive spectroscopy (Figure 6) showed that the white grains also seen in Figure 5 were titanium-rich in contrast to the other grains which were composed of magnesium and silicon, suggesting that the former were the rutile observed in XRD and the latter the enstatite.

Example 6 All preparation conditions the same as for Example 5 apart from the design composition shown in Table 2. SEM showed that the structure consisted of the same uniform dispersion of fine, high aspect ratio crystals, but in this case they were generally smaller than those observed in Example 5, and additionally appeared to have lower aspect ratios. There were none of the larger crystallites present, but there appeared to be an increase in the number of rutile crystals (Figure 7).

Example 7 The parent glass was prepared in the same fashion as previously described, but was heated at a rate of 2.5°C/min to a level of 1200°C before being cooled to room temperature at 10°C/min in order to crystallise it. Subseauently, samples were embedded in epoxy resin, sectioned and polished to < 1 mm prior to etching for 15 seconds in a mixture of 1% Hydrofluoric

/5% Hydrochloric acid. The specimens were then gold- coated and examined using SEM. The Example showed that the microstructure consisted of large crystals of enstatite (shown via XRD, Figure 8), frequently > 10 mm in diameter, and that the remaining glassy matrix surrounding them was severely cracked (Figure 9).

Example 8 The preparation conditions were the same as before except that the heating rate for crystallisation was 7.5°C/min to 1200°C before cooling. Examination of the crystalline microstructure showed that the enstatite crystals (Figure 10) were much smaller than those in Example 7, and that there was no cracking in the surrounding residual glass matrix. The final degree of crystallinity appeared to be in the order of 50% by volume, and the ratio of proto: clino-enstatite measured via XRD (Figure 11) had decreased in comparison to Example 7.

Example 9 The preparation conditions were the same as before except that the heating rae for crystallisation was 10°C/min to 1200°C before cooling.

Again, there was no cracking in the residual glass surrounding the crystalline enstatite phase (Figure 12), but the degree of crystallinity appeared to be lower than that in Example 8. XRD (Figure 13) again showed that the level of protoens atite had decreased with respect to the level of clincenstatite.

Indentation fracture toughness tests performed on Examples 3 to 9 showed that the material had a fracture toughness in excess of 3.6 MNm-3/2.