Hardenable two part acrylic composition

Abstract

A hardenable two part acrylic composition is described for the treatment of human or animal bone is described. The composition comprises a storage stable liquid first part and a storage stable liquid second part which react with each other upon mixing to form a cement which hardens. The composition further comprises an acrylic monomer component and an initiator component in an amount effective to polymerize the monomer component. The monomer component and the initiator component are generally located in separate parts of the two part composition so that the monomer component is storage stable. The liquid first part comprises emulsion polymerized acrylic polymer particles in a liquid carrier. A method of producing a hardenable two part acrylic composition is also described. The composition is particularly useful in a syringe or caulking gun having at least two barrels.

Claims

1. A hardenable two part acrylic composition comprising a storage stable liquid first part and a storage stable liquid second part which react with each other upon mixing to form a cement which hardens, the composition further comprising an acrylic monomer component and an initiator component in an amount effective to polymerize the monomer component, wherein the said monomer component and the said initiator component are located in separate parts of the said two part composition so that the monomer component is storage stable wherein the liquid first part comprises emulsion polymerized acrylic polymer particles in a liquid carrier and initiator and the second part comprises acrylic monomer and accelerator.

2. A hardenable two part acrylic composition comprising a storage stable liquid first part and a storage stable liquid second part which react with each other upon mixing to form a cement which hardens, the composition further comprising an acrylic monomer component and an initiator component in an amount effective to polymerize the monomer component, wherein the liquid first part comprises emulsion polymerized acrylic polymer particles in a liquid carrier and initiator and the second part comprises acrylic monomer and accelerator.

3. A hardenable two part acrylic composition according to claim 1, wherein the emulsion polymerized particles in a liquid carrier are in the form of an acrylic polymer emulsion.

4. A hardenable two part acrylic composition according to claim 1, wherein the liquid carrier is water.

5. A hardenable two part acrylic composition according to claim 2 or 3, wherein the acrylic polymer emulsion provides a continuous phase for the liquid first part.

6. A hardenable two part acrylic composition according to claim 2, 3 or 4, wherein the acrylic polymer emulsion consists of emulsion polymerized acrylic polymer particles, at least one emulsifier and water.

7. A hardenable two part acrylic composition according to claim 1, wherein the two part acrylic composition also comprises at least one further type of acrylic polymer particles.

8. A hardenable two part acrylic composition according to claim 1, wherein at least one further type(s) of acrylic polymer particles are polymer beads.

9. A hardenable two part acrylic composition according to claim 1, wherein the polymerized emulsion particles and, if present, further types of polymer particles form at least 98% of the polymer present in the two part acrylic composition prior to mixing.

10. A hardenable two part acrylic composition according to claim 1, wherein the first part further comprises a second or further population of emulsion polymerized acrylic polymer particles and wherein the z-average particle size of the second or further populations of emulsion polymerized acrylic polymer particles is in the range 10-2,000 nm.

11. A method of reducing dough time for a hardenable two part acrylic composition comprising the steps of combining a liquid first part as defined in claim 1 with a liquid second part as defined in claim 1.

12. A solid cement composition produced from mixing a two part acrylic composition according to claim 1.

13. A process of producing an acrylic cement from a two part acrylic composition according to claim 1 by mixing the said first and second parts.

14. A syringe or caulking gun having at least two barrels comprising the liquid first part according to claim 1 in a first barrel thereof and a liquid second part according to claim 1 in the second barrel thereof.

15. A hardenable two part acrylic composition according to claim 1 adapted for use in the treatment of human or animal bone.

16. A hardenable two part acrylic composition according to claim 1, wherein the Brookfield viscosity range at 25? C. for the liquid first part and liquid second part are between 10 and 10,000 centipoise.

17. A hardenable two part acrylic composition according to claim 1, wherein the first part further comprises a second or further population of emulsion polymerised acrylic polymer particles having a different respective z-average particle size(s) from the emulsion polymerised acrylic polymer particles of claim 1.

18. A hardenable two part acrylic composition according to claim 1, wherein the z-average particle size of the emulsion polymerized acrylic polymer particles and/or the second or further populations of emulsion polymerised acrylic polymer particles are independently in the range 10-2,000 nm.

19. A hardenable two part acrylic composition according to claim 1, wherein the first part further comprises two or more further types of acrylic polymer particle populations said further types having different respective mean diameter particle sizes from each other.

20. A hardenable two part acrylic composition according to claim 7, wherein the mean diameter particle size of the further acrylic polymer particles is 10-1,000 microns.

21. A hardenable two part acrylic composition comprising a storage stable liquid first part and a storage stable liquid second part which react with each other upon mixing to form a cement which hardens, the composition further comprising an acrylic monomer component and an initiator component in an amount effective to polymerize the monomer component, wherein the liquid first part comprises in a liquid carrier a first population of emulsion polymerized acrylic polymer particles and a second population of emulsion polymerised acrylic polymer particles having different z-average particle size's from the first emulsion polymerised acrylic polymer particles.

22. A hardenable two part acrylic composition according to claim 2, wherein there are two or more further types of acrylic polymer particle populations, said further types having different respective mean diameter particle sizes from each other and wherein the liquid first part comprises in a liquid carrier a first population of emulsion polymerized acrylic polymer particles and the said two or more further types of acrylic polymer particle populations said further types having different respective mean diameter particle sizes from each other.

23. A method of producing a hardenable two part acrylic composition comprising a storage stable liquid first part and a storage stable liquid second part which react with each other upon mixing to form a cement which hardens to a solid, comprising the steps of: (a) emulsion polymerizing an acrylic monomer composition in the presence of excess initiator to produce an acrylic polymer emulsion with residual initiator; or (b) emulsion polymerizing an acrylic monomer composition to produce an acrylic polymer emulsion and adding initiator to the emulsion; or (c) emulsion polymerizing an acrylic monomer composition to produce an acrylic polymer emulsion without excess initiator; (d) optionally, mixing the emulsion from (a) or (b) with at least one further type of acrylic polymer particles or mixing the emulsion from (c) with a solution of the said further type of acrylic polymer in acrylic monomer, to thereby produce a liquid acrylic polymer first part suitable for hardening at a predetermined rate in the joint presence of an acrylic monomer and initiator.

24. A liquid composition comprising emulsion polymerized acrylic polymer particles, optionally, mixed with at least one further type of non-emulsion polymerized acrylic particles, and wherein there is a polymerization initiator in the liquid composition at a level sufficient to cause the liquid composition to harden upon contact with a reactive monomer liquid.

25. A solid cement composition produced from mixing a two part acrylic composition according to any of claim 4, 7-10 or 15-20, wherein the cement is porous.

26. A solid cement composition according to claim 25, which is a bone cement and wherein the porosity including size and topography provides controlled release of antibiotics and other medicines into the surrounding bone and tissue.

27. A solid cement composition produced from mixing a two part acrylic composition according to claim 5, wherein the cement is porous.

28. A solid cement composition according to claim 27, which is a bone cement and wherein the porosity including size and topography provides controlled release of antibiotics and other medicines into the surrounding bone and tissue.

29. A solid cement composition produced from mixing a two part acrylic composition according to claim 6, wherein the cement is porous.

30. A solid cement composition according to claim 29, which is a bone cement and wherein the porosity including size and topography provides controlled release of antibiotics and other medicines into the surrounding bone and tissue.

Description

EXAMPLES

Characterisation Techniques

(1) The Z average emulsion particle size was determined using a Malvern Zetasizer nano series S particle size analyzer.

(2) Reduced viscosity (RV, dl/g) was measured in chloroform (1 wt % solution) using an Ubbelohde viscometer type OB at 25? C.

(3) Wt % residual dibenzoyl peroxide content was determined by a titration method.

(4) Brookfield viscometry (BV, centipoise (cPs)) was carried out using a Brookfield Viscometer model RVDV-E at 25? C. operating with spindle number 5 and speed 20 rpm, except for examples 47 onwards for which the spindle and speed were adjusted depending on the viscosity range being measured

(5) Weight average molecular weight, Mw, was determined by gel permeation chromatography using polymethyl methacrylate standards for calibration. Tetrahydrofuran was used as the mobile phase.

(6) Acrylic bead polymer mean diameter particle size was measured by a Coulter LS230 laser diffraction particle sizer.

(7) Dough and set times and maximum exotherm temperature were measured according to BS ISO 5833:2002

(8) The dough time is considered to be the length of time following the start of mixing for the mixture to achieve a dough-like mass that does not adhere to a gloved finger when gently touched.

(9) The set time is considered to be the time taken to reach a temperature midway between ambient and maximum.

(10) Flexural strength and flexural modulus were determined by a three-point bend test according to ISO 1567:1997. Compressive strength was determined according to ISO 5833:2002.

(11) Examples 1 to 4 describe the preparation of acrylic emulsions of solids contents varying from 32% wt to 54% wt.

Example 1

(12) Preparation of 32% wt Solids Acrylic Polymer Emulsion

(13) 2000 grams of deionised water is added to a five-liter round bottomed glass flask fitted with a nitrogen inlet, condenser and electrically operated stainless steel paddle stirrer. The water is heated to 80? C. by means of a water bath whilst stirring at 200 revolutions per minute (rpm). A flow of nitrogen is passed through the vapour space of the flask above the surface of the liquid.

(14) An emulsified monomer mixture is prepared consisting of 1000 grams methyl methacrylate, 1.8 grams of 1-dodecanethiol, 5.0 grams of sodium lauryl sulphate and 100 grams of deionised water. This mixture is stirred for 60 minutes prior to and throughout addition to keep it emulsified.

(15) With the temperature of the water at 80? C., a polymer seed (Stage 1) is prepared by adding 100 grams of the emulsified monomer mixture to the flask followed by 10 milliliters of a 2 wt % solution of potassium persulphate in deionised water. Following a slight exotherm, the reaction proceeds for thirty minutes until the temperature returns to 80? C.

(16) The core is then grown over the polymer seed particles (Stage 2) by firstly adding 10 milliliters of a 2 wt % solution of potassium persulphate in deionised water to the flask followed by continuous addition of 250 grams of the emulsified monomer mixture over approximately 45 minutes using a peristaltic pump. The reaction proceeds for a further 30 minutes after the completion of addition of the monomer mixture until the temperature returns to 80? C. This step is then repeated twice.

(17) 37.0 grams of 75% active dibenzoyl peroxide (BPO) are dissolved in the remaining emulsified monomer mixture with stirring for 45 minutes.

(18) The BPO-containing shell is then grown over the core (Stage 3) by firstly adding 10 milliliters of a 2 wt % solution of potassium persulphate in deionised water to the flask followed by continuous addition of the emulsified monomer mixture containing added BPO over approximately 30 minutes using a peristaltic pump. The reaction proceeds for a further fifteen minutes after all the monomer mixture has been added until the temperature has returned to 80? C.

(19) The resultant acrylic polymer emulsion is then cooled to below 40? C. and filtered through a 150 micron screen.

(20) The acrylic polymer emulsion has a solids content of 32% wt, reduced viscosity of 1.8 dl/g, residual dibenzoyl peroxide of 1.66% wt and a z-average emulsion particle size of 177 nm.

Example 2

(21) Preparation of 38% wt Solids Acrylic Polymer Emulsion

(22) 1200 grams of deionised water is added to a five-liter round bottomed glass flask fitted with a nitrogen inlet, condenser and electrically operated stainless steel paddle stirrer. The water is heated to 80? C. by means of a water bath whilst stirring at 200 revolutions per minute (rpm). A flow of nitrogen is passed through the vapour space of the flask above the surface of the liquid.

(23) An emulsified monomer mixture is prepared consisting of 1000 grams methyl methacrylate (MMA), 1.0 grams of 1-dodecanethiol, 5.0 grams of sodium lauryl sulphate and 200 grams of deionised water. This mixture is stirred for 60 minutes prior to and throughout addition to keep it emulsified.

(24) With the temperature of the water at 80? C., a polymer seed (Stage 1) is prepared by adding 100 grams of the emulsified monomer mixture to the flask followed by 10 milliliters of a 2 wt % solution of potassium persulphate in deionised water. Following a slight exotherm, the reaction proceeds for thirty minutes until the temperature returns to 80? C. To the remaining emulsified monomer mixture is added 1 g of sodium lauryl sulphate with stirring.

(25) The core is then grown over the polymer seed particles (Stage 2) by firstly adding 10 milliliters of a 2 wt % solution of potassium persulphate in deionised water to the flask followed by continuous addition of 250 grams of the emulsified monomer mixture over approximately 45 minutes using a peristaltic pump. The reaction proceeds for a further 30 minutes after the completion of addition of the monomer mixture until the temperature returns to 80? C. This step is then repeated twice.

(26) 35.0 grams of 75% active dibenzoyl peroxide are dissolved in the remaining emulsified monomer mixture with stirring for 45 minutes.

(27) The BPO-containing shell is then grown over the core (Stage 3) by firstly adding 10 milliliters of a 2 wt % solution of potassium persulphate in deionised water to the flask followed by continuous addition of the emulsified monomer mixture containing added BPO over approximately 30 minutes using a peristaltic pump. The reaction proceeds for a further fifteen minutes after all the monomer mixture has been added until the temperature has returned to 80? C.

(28) The resultant acrylic polymer emulsion is then cooled to below 40? C. and filtered through a 150 micron screen.

(29) The acrylic polymer emulsion has a solids content of 38% wt, reduced viscosity of 2.1 dl/g, Brookfield Viscosity of 50 cPs, residual dibenzoyl peroxide of 1.98% wt and a z-average emulsion particle size of 186 nm.

Example 3

(30) Preparation of 50% wt Solids Acrylic Polymer Emulsion

(31) The procedure of example 2 was repeated except 600 grams of deionised water are added to a five-liter round bottomed flask instead of 1200 grams.

(32) The resultant acrylic polymer emulsion has a solids content of 50% wt, reduced viscosity of 1.6 dl/g, Brookfield Viscosity of 540 cPs, residual dibenzoyl peroxide of 2.10% wt and a z-average emulsion particle size of 205 nm.

Example 4

(33) Preparation of 54% wt Solids Acrylic Polymer Emulsion

(34) The procedure of example 2 was repeated except 400 grams of deionised water are added to a five-liter round bottomed flask instead of 1200 grams.

(35) The resultant acrylic polymer emulsion has a solids content of 55% wt, reduced viscosity of 1.49 dl/g, Brookfield Viscosity of 7920 cPs, residual dibenzoyl peroxide of 2.20% wt and a z-average emulsion particle size of 191 nm.

(36) Examples 5, 7 to 12 and 19 describe the preparation of the liquid first part by mixing the acrylic polymer emulsions prepared in examples 2 to 4 with acrylic bead polymers. Hardenable compositions are subsequently prepared by mixing the liquid first part with the liquid second part.

Example 5

(37) Preparation of Liquid First Part Using 38% wt Solids Acrylic Polymer Emulsion

(38) To a 250 ml polypropylene beaker equipped with electric stirrer motor and stainless steel paddle stirrer is added 70 g of poly(methyl methacrylate) (PMMA) bead polymer (Colacryl? B866, obtained from Lucite International Speciality Polymers & Resins Limited with RV of 2.4 dl/g, Mw 421,200, residual dibenzoyl peroxide 2.94% wt, mean particle size 39 microns). Stirring is commenced at 100 rpm and 30 g of the 38% wt solids acrylic polymer emulsion from example 2 is added over 60 to 90 seconds. The stirrer speed is then increased to 800-1000 rpm and mixing is continued for a further 3 to 5 minutes until a uniform liquid mixture is obtained. The Brookfield viscosity of the liquid mixture is 7,000 cPs. The liquid mixture is stable with no separation after storage at 23? C. for several days.

Example 6

(39) Preparation of a Hardenable Composition

(40) A hardenable composition is prepared by mixing 17.2 g of the liquid first part of example 5 with 7 ml of MMA monomer containing 60 ppm hydroquinone (HQ) inhibitor and 1% N,N-dimethyl-para-toluidine (DMPT) accelerator (liquid second part). The mix ratio used is 14 g polymer (equivalent dry weight) to 7 ml monomer liquid. Before mixing, the two components are equilibrated for at least 10 hours in an incubator at 23? C. The required amount of liquid first part is placed into a polypropylene beaker, followed by the liquid second part. Timing is started from the point of adding the liquid second part to the liquid first part. Hand mixing is then carried out for 30 seconds using a metal spatula, whereupon the material is covered and left to stand. Periodically, the material is assessed for initial mix consistency and the dough and set times determined. The exotherm temperature is also measured by use of a thermocouple embedded in the middle of the curing mass.

(41) The following comparative examples were prepared to show the benefits of the invention over the prior art.

Comparative Example 1

(42) The PMMA bead polymer stated in example 5 (Colacryl? 8866) is employed on its own with no acrylic polymer emulsion added. 14 g of this PMMA bead polymer is mixed with 7 ml of MMA monomer containing 60 ppm hydroquinone (HQ) inhibitor and 1% N,N-dimethyl-para-toluidine (DMPT) accelerator and tested as described above.

Comparative Example 2

(43) This example is equivalent to example 6, except the acrylic polymer emulsion of example 2 is spray dried to form a powder before use. The blend ratio of PMMA bead polymer (Colacryl? B866) to the spray dried 38% wt solids emulsion of example 2 is 86/14% wt. 14 g of this blend of bead polymer and microporous acrylic polymer powder is then mixed with 7 ml of MMA monomer containing 60 ppm hydroquinone (HQ) inhibitor and 1% N,N-dimethyl-para-toluidine (DMPT) accelerator and tested as described above.

(44) Table 1 records the results. It can be seen that example 6 displays a lower exotherm temperature and shorter dough and set times compared to comparative example 1. Further, example 6 displays similar dough times to comparative example 2, but has a longer set time, thereby giving a longer working time to administer the hardenable composition before it sets solid. Example 6 also has a lower exotherm temperature than comparative example 2.

(45) TABLE-US-00001 TABLE 1 Identity and Dry Exotherm weight of weight of Dough Set temper- Example polymer polymer time time ature number component (g) mins:secs mins:secs (? C.) 6 Example 5, 14.0 3:10 11:50 83.0 17.2 g Comp. Colacryl? 14.0 10:30 18:40 92.2 Ex. 1 B866, 14.0 g Comp. Blend of 14.0 2:50 10:00 96.0 Ex. 2 Colacryl? B866 and spray dried emulsion of example 2, 86/14% wt, 14.0 g

Examples 7 to 12

(46) Preparation of Liquid First Part Using 50% wt Solids Acrylic Polymer Emulsion

(47) To a 250 ml polypropylene beaker equipped with electric stirrer motor and stainless steel paddle stirrer is added poly(methyl methacrylate) (PMMA) bead polymer (Colacryl? B866, obtained from Lucite International Speciality Polymers & Resins Limited with R V of 2.4 dl/g, Mw 421,200, residual dibenzoyl peroxide 2.94% wt, mean particle size 39 microns). Stirring is commenced at 100 rpm and 50% wt solids acrylic polymer emulsion from example 3 is added over 60 to 90 seconds. The stirrer speed is then increased to 800-1000 rpm and mixing is continued for a further 3 to 5 minutes until a uniform liquid mixture is obtained. The amounts of PMMA bead polymer and acrylic polymer emulsion used in each example are shown in table 3, along with the Brookfield viscosity of each liquid mixture. All the liquid mixtures are stable with no separation after storage at 23? C. for several days.

(48) TABLE-US-00002 TABLE 2 50% wt solids PMMA bead acrylic polymer polymer emulsion from Brookfield (Colacryl? B866) example 3 Viscosity Ex. (g) (g) (cPs) 7 55 45 4,200 8 65 35 5,720 9 70 30 >90,000 10 75 25 >90,000 11 80 20 >90,000 12 82.5 17.5 >90,000

Examples 13 to 18

(49) Preparation of Hardenable Compositions

(50) Hardenable compositions are prepared by mixing the liquids first part of examples 7 to 12 with MMA monomer containing 60 ppm hydroquinone (HQ) inhibitor and 1% N,N-dimethyl-para-toluidine (DMPT) accelerator (liquid second part). The mix ratio used is 14.0 g polymer (equivalent dry weight) to 7.0 ml monomer liquid. Before mixing, the two components are equilibrated for at least 10 hours in an incubator at 23? C. The required amount of liquid first part is placed into a polypropylene beaker, followed by the liquid second part. Timing is started from the point of adding the liquid second part to the liquid first part. Hand mixing is then carried out for 30 seconds using a metal spatula, whereupon the material is covered and left to stand. Periodically, the material is assessed for initial mix consistency and the dough and set times determined. The exotherm temperature is also measured by use of a thermocouple embedded in the middle of the curing mass. Table 3 records the results.

(51) It can be seen that the exotherm temperature, dough time and set time all decrease as the amount of acrylic polymer emulsion increases in the order of example 18 to 13. Further, examples 13 to 18 display lower exotherm temperatures and shorter dough and set times compared to comparative example 1, demonstrating the benefits of the invention over the prior art.

(52) TABLE-US-00003 TABLE 3 Identity and Dry weight of weight of Exotherm polymer polymer Dough time Set time temperature Ex. component (g) mins:secs mins:secs (? C.) 13 Example 7, 14.0 1:15 9:00 75.4 17.9 g 14 Example 8, 14.0 1:25 9:30 76.0 16.9 g 15 Example 9, 14.0 1:35 10:50 79.5 16.5 g 16 Example 10, 14.0 3:00 11:00 82.8 16.0 g 17 Example 11, 14.0 3:20 11:00 89.7 15.6 g 18 Example 12, 14.0 3:30 11:30 91.2 15.1 g

Example 19

(53) Preparation of Liquid First Part Using 54% wt Solids Acrylic Polymer Emulsion

(54) To a 250 ml polypropylene beaker equipped with electric stirrer motor and stainless steel paddle stirrer is added 65 g of poly(methyl methacrylate) (PMMA) bead polymer (Colacryl? B866, obtained from Lucite International Speciality Polymers & Resins Limited with RV of 2.4 dl/g, Mw 421,200, residual dibenzoyl peroxide 2.94% wt, mean particle size 39 microns). Stirring is commenced at 100 rpm and 35 g of 54% wt solids acrylic polymer emulsion from example 4 is added over 60 to 90 seconds. The stirrer speed is then increased to 800-1000 rpm and mixing is continued for a further 3 to 5 minutes until a uniform liquid mixture is obtained. The liquid mixture is stable with no separation after storage at 23? C. for several days.

Example 20

(55) Preparation of Hardenable Composition

(56) A hardenable composition is prepared by mixing 16.7 g of the liquid first part of example 19 with 7 ml of MMA monomer containing 60 ppm hydroquinone (HQ) inhibitor and 1% N,N-dimethyl-para-toluidine (DMPT) accelerator (liquid second part). The mix ratio used is 14 g polymer (equivalent dry weight) to 7 ml monomer liquid. Before mixing, the two components are equilibrated for at least 10 hours in an incubator at 23? C. The required amount of liquid first part is placed into a polypropylene beaker, followed by the liquid second part. Timing is started from the point of adding the liquid second part to the liquid first part. Hand mixing is then carried out for 30 seconds using a metal spatula, whereupon the material is covered and left to stand. Periodically, the material is assessed for initial mix consistency and the dough and set times determined. The exotherm temperature is also measured by use of a thermocouple embedded in the middle of the curing mass. Table 4 records the results.

(57) TABLE-US-00004 TABLE 4 Identity and Dry weight of weight of Exotherm polymer polymer Dough time Set time temperature Ex. component (g) mins:secs mins:secs (? C.) 20 Example 19, 14 1:00 10:00 80.8 16.7 g

(58) It can be seen that example 20 displays a lower exotherm temperature and shorter dough and set times compared to comparative example 1.

Examples 21 and 22

(59) Preparation of Hardenable Compositions Using a Liquid Second Part Containing Dissolved Polymer

(60) A 10% wt syrup of PMMA homopolymer in MMA monomer is prepared by dissolving 10 g of a PMMA bead polymer (free of residual initiator and with molecular weight Mw 426,700 daltons and reduced viscosity of 2.8 dl/g) in a mixture of 89 g of MMA monomer (stabilised with 60 ppm hydroquinone (HQ) inhibitor) and 1.0 g of N,N-dimethyl-para-toluidine (DMPT) accelerator. The Brookfield viscosity of the syrup is 220 cP.

(61) Hardenable compositions are prepared by mixing the liquids first part of examples 7 and 8 with this liquid second part. The mix ratio used is 14.0 g polymer (equivalent dry weight) in the liquid first part to 7.0 g liquid second part. Before mixing, the components are equilibrated for at least 10 hours in an incubator at 23? C. The required amount of liquid first part is placed into a polypropylene beaker, followed by the liquid second part. Timing is started from the point of adding the liquid second part to the liquid first part. Hand mixing is then carried out for 30 seconds using a metal spatula, whereupon the material is covered and left to stand. Periodically, the material is assessed for initial mix consistency and the dough and set times determined. The exotherm temperature is also measured by use of a thermocouple embedded in the middle of the curing mass. Table 5 records the results.

(62) TABLE-US-00005 TABLE 5 Identity and Dry weight of weight of Exotherm polymer polymer Dough time Set time temperature Ex. component (g) mins:secs mins:secs (? C.) 21 Example 7, 14.0 0:20 8:30 67.4 17.9 g 22 Example 8, 14.0 0:25 10:15 74.4 16.9 g

(63) It can be seen that examples 21 and 22 display much lower exotherm temperature and shorter dough and set times compared to comparative example 1. The effect of pre-dissolving some PMMA into the MMA monomer liquid to form a syrup as liquid second part is to produce a further lowering of the exotherm temperature and shortening of the dough and set times compared to the equivalent example without any PMMA pre-dissolved in the MMA monomer liquid, examples 13 and 14.

Examples 23 to 41

(64) Preparation of Hardenable Compositions with Varying Mechanical Properties

(65) The following examples show the effect of varying the composition of the liquid first part and the ratio of liquid first part to liquid second part on the mechanical properties of the resultant hardenable compositions. Flexural strength and flexural modulus were determined by a three-point bend test according to ISO 1567:1997. Compressive strength was determined according to ISO 5833:2002.

(66) The liquids first part of examples 23 to 41 were prepared in a similar manner to examples 10 to 12, except for the examples involving addition of barium sulphate. For these particular examples (examples 30, 38 and 39), the required amount of barium sulphate is added to the mixture containing PMMA bead polymer and acrylic polymer emulsion over 60-90 seconds with stirring at 100 rpm, prior to increasing the stirrer speed to 800-1000 rom and mixing for a further 3 to 5 minutes before a uniform liquid mixture is obtained. The 16% wt syrup of PMMA homopolymer in MMA monomer used as the liquid second part of examples 23 to 41, except for examples 31, 32, 39 and 40, is prepared by dissolving 16 g of a PMMA bead polymer (free of residual initiator and with molecular weight Mw 426,700 daltons and reduced viscosity of 2.8 dl/g) in a mixture of 82.4 g of MMA monomer (stabilised with 60 ppm hydroquinone (HQ) inhibitor) and 1.6 g of N,N-dimethyl-para-toluidine (DMPT) accelerator. The Brookfield viscosity of the syrup is 4,250 cP.

(67) The 20% wt syrups of poly(MMA-co-DMAEMA) copolymers in MMA monomer used as the liquid second part of examples 31, 32, 39 and 40 are prepared by dissolving 20 g of a poly(MMA-co-DMAEMA) copolymer (free of residual initiator) in a mixture of 78.4 g of MMA monomer (stabilised with 60 ppm hydroquinone (HQ) inhibitor) and 1.6 g of N,N-dimethyl-para-toluidine (DMPT) accelerator. For examples 31 and 39, the copolymer has a reduced viscosity of 0.50 dl/g and molecular weight Mw 69,900 daltons. The Brookfield viscosity of the syrup is 175 cP. For examples 32 and 40, the copolymer has a reduced viscosity of 1.52 dl/g and molecular weight Mw 260,000 daltons. The Brookfield viscosity of the syrup is 4,420 cP.

(68) The liquid second parts of examples 40 and 41 include the addition of barium sulphate. These are prepared by firstly dissolving the relevant PMMA homopolymer or poly(MMA-co-DMAEMA) copolymer in MMA monomer (stabilised with 60 ppm hydroquinone (HQ) inhibitor) and N,N-dimethyl-para-toluidine (DMPT) accelerator in a glass flask equipped with stirrer. The required amount of barium sulphate is then added with stirring at 500-600 rpm and left for 1 hour to disperse the barium sulphate in the monomer/polymer syrup.

(69) The hardenable compositions of examples 23 to 41 are prepared by mixing the two components by hand, as described for examples 21 and 22. The mix ratios used are either 14.0 g polymer (equivalent dry weight) in liquid first part to 7.0 g liquid second part or 14.0 g polymer (equivalent dry weight) in liquid first part to 14.0 g liquid second part.

(70) Table 6 provides details on the composition of each component, the mix ratios used and the mechanical properties obtained from each hardenable composition. It can be seen that the magnitude of mechanical properties for examples 23 to 28 varies with the relative amount of acrylic polymer emulsion used. This stems from the presence of the water in the acrylic polymer emulsion which leads to the creation of porosity in the final cured hardenable composition. Increased porosity through increasing the proportion of acrylic polymer emulsion leads to reduction in mechanical properties in comparison to comparative example 3 which contains no added water. This porosity allows the mechanical properties of the hardenable composition to be matched to those of e.g. vertebral bone, thereby avoiding well known problems associated through implantation of artificial materials that are higher in modulus than the surrounding natural bone. However, the formulation can be also altered to adjust the level of porosity and vary the mechanical properties, e.g. to achieve mechanical properties that satisfy the requirements of ISO 5833:2002.

(71) TABLE-US-00006 TABLE 6 Composition Composition Ratio of liquid Flexural Flexural Compressive of liquid of liquid first part:liquid strength Modulus Strength first part second part second part (MPa) (GPa) (MPa) Example 23 Mixture of PMMA 16% syrup of 14.0 g:14.0 g 84.1 2.54 99.9 bead polymer PMMA in MMA (Colacryl? B866), monomer containing 82.5 g and 50% 60 ppm HQ and solids PMMA 1.6% N,N- emulsion of dimethyl-para- example 3, 17.5 g. toluidine (DMPT) Example 24 Mixture of PMMA 16% syrup of 14.0 g:7.0 g 73.4 2.56 104 bead polymer PMMA in MMA (Colacryl? B866), monomer containing 82.5 g and 50% 60 ppm HQ and solids PMMA 1.6% N,N- emulsion of dimethyl-para- example 3, 17.5 g. toluidine (DMPT) Example 25 Mixture of PMMA 16% syrup of 14.0 g:14.0 g 70.8 2.42 95.4 bead polymer PMMA in MMA (Colacryl? B866), monomer containing 80.0 g and 50% 60 ppm HQ and solids PMMA 1.6% N,N- emulsion of dimethyl-para- example 3, 20.0 g. toluidine (DMPT) Example 26 Mixture of PMMA 16% syrup of 14.0 g:7.0 g 66.7 2.20 89.0 bead polymer PMMA in MMA (Colacryl? B866), monomer containing 80.0 g and 50% 60 ppm HQ and solids PMMA 1.6% N,N- emulsion of dimethyl-para- example 3, 20.0 g. toluidine (DMPT) Example 27 Mixture of PMMA 16% syrup of 14.0 g:14.0 g 71.4 2.45 91.0 bead polymer PMMA in MMA (Colacryl? B866), monomer containing 75.0 g and 50% 60 ppm HQ and solids PMMA 1.6% N,N- emulsion of dimethyl-para- example 3, 25.0 g. toluidine (DMPT) Example 28 Mixture of PMMA 16% syrup of 14.0 g:7.0 g 70.7 2.35 86.6 bead polymer PMMA in MMA (Colacryl? B866), monomer containing 75.0 g and 50% 60 ppm HQ and solids PMMA 1.6% N,N- emulsion of dimethyl-para- example 3, 25.0 g. toluidine (DMPT) Example 29 50% solids PMMA 16% syrup of 14.0 g:14.0 g 24.3 1.33 50.4 emulsion of PMMA in MMA example 3 (no monomer containing PMMA bead 60 ppm HQ and polymer). 1.6% N,N- dimethyl-para- toluidine (DMPT) Example 30 Mixture of 50% 16% syrup of 14.0 g:14.0 g 39.6 2.10 51.5 solids PMMA PMMA in MMA The amount of emulsion of monomer containing barium sulphate example 3, 60.0 g 60 ppm HQ and in the cured and barium 1.6% N,N- composition is sulphate, 40.0 g. dimethyl-para- 20 w/w % toluidine (DMPT) Example 31 Mixture of PMMA 20% syrup of 14.0 g:14.0 g 71.4 2.45 92.5 bead polymer poly(MMA-co- (Colacryl? B866), DMAEMA) 75.0 g and 50% (RV = 0.5) in MMA solids PMMA monomer containing emulsion of 60 ppm HQ and example 3, 25.0 g. 1.0% N,N- dimethyl-para- toluidine (DMPT) Example 32 Mixture of PMMA 20% syrup of 14.0 g:14.0 g 69.3 2.30 99.6 bead polymer poly(MMA-co- (Colacryl? B866), DMAEMA) 75.0 g and 50% (RV = 1.52) in MMA solids PMMA monomer containing emulsion of 60 ppm HQ and example 3, 25.0 g. 1.0% N,N- dimethyl-para- toluidine (DMPT) Example 33 Mixture of PMMA 16% syrup of 14.0 g:14.0 g 84.1 2.54 109 bead polymer PMMA in MMA (Colacryl? B866), monomer containing 82.5 g and 50% 60 ppm HQ and solids PMMA 1.6% N,N- emulsion of dimethyl-para- example 3, 17.5 g. toluidine (DMPT) Example 34 Mixture of PMMA 16% syrup of 14.0 g:14.0 g 68.7 2.79 83.4 bead polymer PMMA in MMA (Colacryl? B866), monomer containing 70.0 g and 50% 60 ppm HQ and solids PMMA 1.6% N,N- emulsion of dimethyl-para- example 3, 30.0 g. toluidine (DMPT) Example 35 Mixture of PMMA 16% syrup of 14.0 g:14.0 g 62.67 2.23 76.0 bead polymer PMMA in MMA (Colacryl? B866), monomer containing 65.0 g and 50% 60 ppm HQ and solids PMMA 1.6% N,N- emulsion of dimethyl-para- example 3, 35.0 g. toluidine (DMPT) Example 36 Mixture of PMMA 16% syrup of 14.0 g:14.0 g 54.9 2.07 72.7 bead polymer PMMA in MMA (Colacryl? B866), monomer containing 60.0 g and 50% 60 ppm HQ and solids PMMA 1.6% N,N- emulsion of dimethyl-para- example 3, 40.0 g. toluidine (DMPT) Example 37 Mixture of 16% syrup of 14.0 g:14.0 g 61.2 2.14 80.1 poly(MMA-co- PMMA in MMA styrene) bead monomer containing copolymer 60 ppm HQ and (Colacryl? 1.6% N,N- TS1260), 70.0 g dimethyl-para- and 50% solids toluidine (DMPT) PMMA emulsion of example 3, 30.0 g. Example 38 Mixture of PMMA 16% syrup of 14.0 g: 14.0 g 46.5 2.16 74.1 bead polymer PMMA in MMA The amount of (Colacryl? B866), monomer containing barium sulphate 35.0 g, 50% solids 60 ppm HQ and in the cured PMMA emulsion 1.6% N,N- composition is of example 3, dimethyl-para- 20 w/w % 25.0 g and barium toluidine (DMPT) sulphate, 40.0 g. Example 39 Mixture of PMMA 20% syrup of 14.0 g:14.0 g 45.1 2.50 74.7 bead polymer poly(MMA-co- The amount of (Colacryl? B866), DMAEMA) barium sulphate 35.0 g, 50% solids (RV = 0.5) in MMA in the cured PMMA emulsion monomer containing composition is of example 3, 60 ppm HQ and 20 w/w % 25.0 g and Barium 1.0% N,N- sulfate 40.0 g. dimethyl-para- toluidine (DMPT) Example 40 Mixture of PMMA Mixture 14.0 g:14.0 g 47.4 2.45 77.0 bead polymer consisting of The amount of (Colacryl? B866), 12.0 g of 20% barium sulphate 75.0 g and 50% syrup of in the cured solids PMMA poly(MMA-co- composition is emulsion of DMAEMA) 20 w/w % example 3, 25.0 g. (RV = 1.52) in MMA monomer containing 60 ppm HQ and 1.0% N,N- dimethyl-para- toluidine (DMPT) with 8.0 g of barium sulphate Example 41 Mixture of PMMA Mixture 14.0 g: 14.0 g 45.1 2.50 78.7 bead polymer consisting The amount of (Colacryl? B866), of 12.0 g of barium sulphate 75.0 g and 50% 16% syrup of in the cured solids PMMA PMMA in MMA composition is emulsion of monomer containing 20 w/w % example 3, 25.0 g. 60 ppm HQ and 1.6% N,N- dimethyl-para- toluidine (DMPT) with 8.0 g barium sulfate

(72) Examples 42 to 45 describe the preparation of acrylic emulsions of 50% wt solids and varying z-average particle size.

Example 42

(73) Preparation of ca. 50% wt Solids Acrylic Polymer Emulsion of 195 nm z-Average Particle Size

(74) 600 grams of deionised water is added to a five-liter round bottomed glass flask fitted with a nitrogen inlet, condenser and electrically operated stainless steel paddle stirrer. The water is heated to 80? C. by means of a water bath whilst stirring at 200 revolutions per minute (rpm). A flow of nitrogen is passed through the vapour space of the flask above the surface of the liquid.

(75) An emulsified monomer mixture is prepared consisting of 1000 grams methyl methacrylate, 0.5 grams of 1-dodecanethiol, 5.0 grams of sodium lauryl sulphate and 300 grams of deionised water. This mixture is stirred for 60 minutes prior to and throughout addition to keep it emulsified.

(76) With the temperature of the water at 80? C., a polymer seed (Stage 1) is prepared by adding 100 grams of the emulsified monomer mixture to the flask followed by 10 milliliters of a 2 wt % solution of potassium persulphate in deionised water. Following a slight exotherm the reaction proceeds for thirty minutes until the temperature returns to 80? C. To the remaining emulsified monomer mixture is added 1 g of sodium lauryl sulphate with stirring.

(77) The core is then grown over the polymer seed particles (Stage 2) by firstly adding 10 milliliters of a 2 wt % solution of potassium persulphate in deionised water to the flask followed by continuous addition of 300 grams of the emulsified monomer mixture over approximately 30 minutes using a peristaltic pump. The reaction proceeds for a further 15 minutes after the completion of addition of the monomer mixture until the temperature returns to 80? C. This step is then repeated twice.

(78) 35.0 grams of 75% active dibenzoyl peroxide (BPO) are dissolved in the remaining emulsified monomer mixture with stirring for 45 minutes.

(79) The BPO-containing shell is then grown over the core (Stage 3) by firstly adding 10 milliliters of a 2 wt % solution of potassium persulphate in deionised water to the flask followed by continuous addition of the emulsified monomer mixture containing added BPO over approximately 20 minutes using a peristaltic pump. The reaction proceeds for a further fifteen minutes after all the monomer mixture has been added until the temperature has returned to 80? C.

(80) The resultant acrylic polymer emulsion is then cooled to below 40? C. and filtered through a 150 micron screen.

(81) The resultant acrylic polymer emulsion has a solids content of 50% wt, reduced viscosity of 2.3 dl/g, Brookfield Viscosity of 287 cPs, residual dibenzoyl peroxide of 2.50% wt and a z-average emulsion particle size of 195 nm.

Example 43

(82) Preparation of ca. 50% wt Solids Acrylic Polymer Emulsion of 306 nm z-Average Particle Size

(83) 600 grams of deionised water is added to a five-liter round bottomed glass flask fitted with a nitrogen inlet, condenser and electrically operated stainless steel paddle stirrer. The water is heated to 80? C. by means of a water bath whilst stirring at 200 revolutions per minute (rpm). A flow of nitrogen is passed through the vapour space of the flask above the surface of the liquid.

(84) An emulsified monomer mixture is prepared consisting of 1000 grams methyl methacrylate, 0.5 grams of 1-dodecanethiol, 5.0 grams of sodium lauryl sulphate and 300 grams of deionised water. This mixture is stirred for 60 minutes prior to and throughout addition to keep it emulsified.

(85) With the temperature of the water at 80? C., a polymer seed (Stage 1) is prepared by adding 40 grams of the emulsified monomer mixture to the flask followed by 20 milliliters of a 2 wt % solution of potassium persulphate in deionised water. Following a slight exotherm the reaction proceeds for thirty minutes until the temperature returns to 80? C.

(86) The core is then grown over the polymer seed particles (Stage 2) by firstly adding 10 milliliters of a 2 wt % solution of potassium persulphate in deionised water to the flask followed by continuous addition of 300 grams of the emulsified monomer mixture over approximately 30 minutes using a peristaltic pump. The reaction proceeds for a further 15 minutes after the completion of addition of the monomer mixture until the temperature returns to 80? C. This step is then repeated twice.

(87) 35.0 grams of 75% active dibenzoyl peroxide (BPO) are dissolved in the remaining emulsified monomer mixture with stirring for 45 minutes.

(88) The BPO-containing shell is then grown over the core (Stage 3) by firstly adding 10 milliliters of a 2 wt % solution of potassium persulphate in deionised water to the flask followed by continuous addition of the emulsified monomer mixture containing added BPO over approximately 20 minutes using a peristaltic pump. The reaction proceeds for a further fifteen minutes after all the monomer mixture has been added until the temperature has returned to 80? C.

(89) The resultant acrylic polymer emulsion is then cooled to below 40? C. and filtered through a 150 micron screen.

(90) The resultant acrylic polymer emulsion has a solids content of 49.4% wt, reduced viscosity of 2.0 dl/g, Brookfield Viscosity of 62 cPs, residual dibenzoyl peroxide of 2.30% wt and a z-average emulsion particle size of 306 nm.

Example 44

(91) Preparation of ca. 50% wt Solids Acrylic Polymer Emulsion of 582 nm z-Average Particle Size

(92) 600 grams of deionised water is added to a five-liter round bottomed glass flask fitted with a nitrogen inlet, condenser and electrically operated stainless steel paddle stirrer. The water is heated to 80? C. by means of a water bath whilst stirring at 200 revolutions per minute (rpm). A flow of nitrogen is passed through the vapour space of the flask above the surface of the liquid.

(93) An emulsified monomer mixture is prepared consisting of 980 grams methyl methacrylate, 0.5 grams of 1-dodecanethiol, 5.0 grams of sodium lauryl sulphate and 300 grams of deionised water. This mixture is stirred for 60 minutes prior to and throughout addition to keep it emulsified.

(94) With the temperature of the water at 80? C., a polymer seed (Stage 1) is prepared by adding 20 grams of methyl methacrylate to the flask followed by a solution of 0.3 grams potassium persulphate in 10 milliliters of deionised water and react at 80? C. for 1 hour.

(95) The core is then grown over the polymer seed particles (Stage 2) by firstly adding 10 milliliters of a 2 wt % solution of potassium persulphate in deionised water to the flask followed by continuous addition of 300 grams of the emulsified monomer mixture over approximately 30 minutes using a peristaltic pump. The reaction proceeds for a further 15 minutes after the completion of addition of the monomer mixture until the temperature returns to 80? C. This step is then repeated twice.

(96) 35.0 grams of 75% active dibenzoyl peroxide (BPO) are dissolved in the remaining emulsified monomer mixture with stirring for 45 minutes.

(97) The BPO-containing shell is then grown over the core (Stage 3) by firstly adding 10 milliliters of a 2 wt % solution of potassium persulphate in deionised water to the flask followed by continuous addition of the emulsified monomer mixture containing added BPO over approximately 20 minutes using a peristaltic pump. The reaction proceeds for a further fifteen minutes after all the monomer mixture has been added until the temperature has returned to 80? C.

(98) The resultant acrylic polymer emulsion is then cooled to below 40? C. and filtered through a 150 micron screen.

(99) The resultant acrylic polymer emulsion has a solids content of 48.0% wt, reduced viscosity of 1.94 dl/g, Brookfield Viscosity of 21 cPs, residual dibenzoyl peroxide of 2.28% wt and a z-average emulsion particle size of 582 nm.

Example 45

(100) Preparation of ca. 50% wt Solids Acrylic Polymer Emulsion of 694 nm z-average Particle Size

(101) 600 grams of deionised water is added to a five-liter round bottomed glass flask fitted with a nitrogen inlet, condenser and electrically operated stainless steel paddle stirrer. The water is heated to 80? C. by means of a water bath whilst stirring at 200 revolutions per minute (rpm). A flow of nitrogen is passed through the vapour space of the flask above the surface of the liquid.

(102) An emulsified monomer mixture is prepared consisting of 985 grams methyl methacrylate, 0.5 grams of 1-dodecanethiol, 3.0 grams of sodium lauryl sulphate and 300 grams of deionised water. This mixture is stirred for 60 minutes prior to and throughout addition to keep it emulsified.

(103) With the temperature of the water at 80? C., a polymer seed (Stage 1) is prepared by adding 15 grams of methyl methacrylate to the flask followed by a solution of 0.3 grams potassium persulphate in 10 milliliters of deionised water and react at 80? C. for 1 hour.

(104) The core is then grown over the polymer seed particles (Stage 2) by firstly adding 10 milliliters of a 2 wt % solution of potassium persulphate in deionised water to the flask followed by continuous addition of 300 grams of the emulsified monomer mixture over approximately 30 minutes using a peristaltic pump. The reaction proceeds for a further 15 minutes after the completion of addition of the monomer mixture until the temperature returns to 80? C. This step is then repeated twice.

(105) 35.0 grams of 75% active dibenzoyl peroxide (BPO) are dissolved in the remaining emulsified monomer mixture with stirring for 45 minutes.

(106) The BPO-containing shell is then grown over the core (Stage 3) by firstly adding 10 milliliters of a 2 wt % solution of potassium persulphate in deionised water to the flask followed by continuous addition of the emulsified monomer mixture containing added BPO over approximately 20 minutes using a peristaltic pump. The reaction proceeds for a further fifteen minutes after all the monomer mixture has been added until the temperature has returned to 80? C.

(107) The resultant acrylic polymer emulsion is then cooled to below 40? C. and filtered through a 150 micron screen.

(108) The resultant acrylic polymer emulsion has a solids content of 48.0% wt, reduced viscosity of 1.90 dl/g, Brookfield Viscosity of 19 cPs, residual dibenzoyl peroxide of 2.60% wt and a z-average emulsion particle size of 694 nm.

Example 46

(109) The results of examples 42 to 45 show that the Brookfield viscosity of the acrylic polymer emulsions reduces as the particle size increases. An acrylic polymer emulsion mixture was prepared by taking equal amounts (100 g each) of the emulsions of examples 42 to 44. The Brookfield viscosity was 40 cPs. Table 7 shows the viscosity comparison between the single emulsions of examples 42, 43 and 44 with the mixture of emulsions, example 46.

(110) TABLE-US-00007 TABLE 7 Solids Z-average Brookfield content particle size viscosity Example (% wt) (nm) (cPs) 42 50.0 195 287 43 49.4 306 62 44 48.0 582 21 46 49.1 Mixture of 40 examples 42, 43 and 44 (equal amounts)

Examples 47 to 65

(111) Examples 47 to 65 involve the preparation of the liquid first part by mixing the acrylic polymer emulsions of examples 42, 43, 44 or 46 with either single acrylic bead polymers (examples 48 to 50, 52 to 54 and 56 to 58) or mixtures of acrylic bead polymers (examples 47, 51, 55 and 59 to 65). The acrylic bead polymers (described in detail in table 8) are selected from either PMMA homopolymers of different mean diameter particle size (designated (i), (ii) and (iii)) or copolymers, i.e. poly(methyl methacrylate-co-2-ethylhexyl acrylate) (poly(MMA-co-2EHA)) (designated (iv), (v), and (vi)) and poly(methyl methacrylate-co-styrene) (poly(MMA-co-sty) (designated (vii), (viii) and (ix)). The preparation method for the liquid first part of examples 47 to 61 is as follows:

(112) To a 250 ml polypropylene beaker equipped with electric stirrer motor and stainless steel paddle stirrer is added 70 g of acrylic bead polymer. Stirring is commenced at 100 rpm and 30 g of acrylic polymer emulsion is added over 60 to 90 seconds. The stirrer speed is then increased to 600-1000 rpm and mixing is continued for a further 3 to 5 minutes until a uniform liquid mixture is obtained. If a mixture of acrylic bead polymers is used, the mixture is firstly prepared by dry blending equal weights of each bead polymer in a suitable container.

(113) The same preparation method is used for examples 62 to 65 except that the ratio of acrylic bead polymer to acrylic polymer emulsion is varied from 70 g:30 g to 76 g:24 g.

(114) After preparation, the Brookfield viscosity of each liquid first part was measured and recorded in tables 9 to 14.

(115) An assessment of mixing and dispensing behaviour through a static mixer connected to compartments of a syringe or caulking gun was carried out as follows. The liquid first parts of examples 47 to 65 and the liquid second part of example 78 were filled into separate compartments of a 50 ml 1:1 vol:vol polypropylene cartridge available from Nordson EFD. A Nordson EFD Series 190 spiral mixer (11 mixing elements, 6.35 mm diameter, 8.6 cm length) was fitted to the twin compartments of the cartridge and the contents were dispensed as a homogeneous stream through the spiral mixer onto a flat surface for examination. The extent of flow of each mixture through the static mixer from entrance to exit was recorded. The characteristics of the resulting extrudate were also assessed and it was found that in all examples of continuous flow the extrudate retained its original shape. The results are reported in tables 9 to 14.

(116) The results of tables 9 to 14 show how the Brookfield viscosities of the liquid first part can be reduced. The following observations can be made: 1. Comparison of example 47 with examples 48 to 50, or example 51 with examples 52 to 54 or example 55 with examples 56 to 58 show that a liquid first part prepared by mixing an acrylic polymer emulsion with a mixture of acrylic bead polymers displays a lower Brookfield viscosity than a liquid first part containing a single type of acrylic bead polymer. 2. Comparison of examples 47, 51 and 55 shows that the Brookfield viscosity of the liquid first part reduces as the particle size of the acrylic polymer emulsion increases. 3. Example 61 shows that the liquid first part prepared by combining a mixture of acrylic polymer emulsions with a mixture of acrylic bead polymers displays a lower Brookfield viscosity than the liquid first part of examples 47 and 51.

(117) Examples 62 to 65 (table 14) show how the Brookfield viscosity of a liquid first part increases as the ratio of acrylic bead to acrylic polymer emulsion increases.

(118) TABLE-US-00008 TABLE 8 Acrylic bead polymers used in examples 47 to 65 Re- Mean duced Molec- Residual diameter Monomer identity Refer- Vis- ular dibenzoyl particle and copolymer ence cosity weight peroxide size composition number (dl/g) (Mw) (% wt) (microns) PMMA homopolymer (i) 2.29 414,150 2.83 42 PMMA homopolymer (ii) 6.62 686,390 0.23 89 PMMA homopolymer (iii) 7.05 724,680 0.24 156 Poly(MMA-co-2EHA) (iv) 2.00 442,140 1.16 28 92:8% wt Poly(MMA-co-2EHA) (v) 2.14 409,420 1.19 78 92:8% wt Poly(MMA-co-2EHA) (vi) 1.81 327,960 1.42 147 92:8% wt Poly(MMA-co-sty) (vii) 1.37 257,800 2.52 35 96:4% wt Poly(MMA-co-sty) (viii) 1.08 180,110 2.48 112 92.5/7.5% wt Poly(MMA-co-sty) (ix) 1.10 160,320 2.60 138 92.5/7.5% wt

(119) TABLE-US-00009 TABLE 9 Liquid first part prepared from PMMA beads and acrylic polymer emulsion of example 42 Acrylic Acrylic bead Acrylic polymer polymer Extent of polymer emulsion identity emulsion Brookfield flow through Example Acrylic bead polymer weight and Z-average weight viscosity static mixer Number identity (grams) particle size (grams) (cPs) (cm) 47 PMMA bead mixture - 70 Example 42: 30 20,250 3 equal parts of (i), (ii) and 195 nm (iii) 42, 89, 156 microns 48 PMMA (i), 42 microns 70 Example 42: 30 >90,000 1 195 nm 49 PMMA (ii), 89 microns 70 Example 42: 30 >90,000 1 195 nm 50 PMMA (iii), 156 microns 70 Example 42: 30 >90,000 1 195 nm

(120) TABLE-US-00010 TABLE 10 Liquid first part prepared from PMMA beads and acrylic polymer emulsion of example 43 Acrylic Acrylic bead Acrylic polymer polymer Extent of polymer emulsion identity emulsion Brookfield flow through Example Acrylic bead polymer weight and Z-average weight viscosity static mixer Number identity (grams) particle size (grams) (cPs) (cm) 51 PMMA bead mixture - 70 Example 43: 30 3,600 Continuous equal parts of (i), (ii) and 306 nm flow: - 8.6+ (iii) 42, 89, 156 microns 52 PMMA (i), 42 microns 70 Example 43: 30 >90,000 1 306 nm 53 PMMA (ii), 89 microns 70 Example 43: 30 >90,000 1 306 nm 54 PMMA (iii), 156 microns 70 Example 43: 30 >90,000 1 306 nm

(121) TABLE-US-00011 TABLE 11 Liquid first part prepared from PMMA beads and acrylic polymer emulsion of example 44 Acrylic Acrylic bead Acrylic polymer polymer Extent of polymer emulsion identity emulsion Brookfield flow through Example Acrylic bead polymer weight and Z-average weight viscosity static mixer Number identity (grams) particle size (grams) (cPs) (cm) 55 PMMA bead mixture - 70 Example 44: 30 1,950 Continuous equal parts of (i), (ii) and 582 nm flow: 8.6+ (iii) 42, 89, 156 microns 56 PMMA (i), 42 microns 70 Example 44: 30 33,400 6 582 nm 57 PMMA (ii), 89 microns 70 Example 44: 30 22,700 3 582 nm 58 PMMA (iii), 156 microns 70 Example 44: 30 9,500 4 582 nm

(122) TABLE-US-00012 TABLE 12 Liquid first part prepared from either poly(MMA-co-2EHA) bead mixture or poly(MMA- co-styrene) bead mixture and acrylic polymer emulsion of example 44 Acrylic Acrylic bead Acrylic polymer polymer Extent of polymer emulsion identity emulsion Brookfield flow through Example Acrylic bead polymer weight and Z-average weight viscosity static mixer Number identity (grams) particle size (grams) (cPs) (cm) 59 Poly(MMA-co-2EHA) 70 Example 44: 30 3,700 Continuous bead mixture - equal 582 nm flow: 8.6+ parts of (iv), (v) and (vi) 28, 78, 147 microns 60 Poly(MMA-co-sty) 70 Example 44: 30 2,250 Continuous bead mixture - equal 582 nm flow: 8.6+ parts of (vii), (viii) and (ix) 35, 112, 138 microns

(123) TABLE-US-00013 TABLE 13 Liquid first part prepared from PMMA bead mixture and acrylic polymer emulsion mixture of example 46 Acrylic Acrylic bead Acrylic polymer polymer Extent of polymer emulsion identity emulsion Brookfield flow through Example Acrylic bead polymer weight and Z-average weight viscosity static mixer Number identity (grams) particle size (grams) (cPs) (cm) 61 PMMA bead mixture - 70 Emulsion mixture 30 3,350 Continuous equal parts of (i), (ii) and from example 46 flow: 8.6+ (iii) 42, 89, 156 microns

(124) TABLE-US-00014 TABLE 14 Liquid first part prepared with varying ratio of PMMA bead mixture to acrylic polymer emulsion Acrylic Acrylic bead Acrylic polymer polymer Extent of polymer emulsion identity emulsion Brookfield flow through Example Acrylic bead weight and Z-average weight viscosity static mixer Number polymer identity (grams) particle size (grams) (cPs) (cm) 62 PMMA bead mixture - 70 Example 44: 30 1,950 Continuous equal parts of (i), (ii) and 582 nm flow: 8.6+ (iii) 42, 89, 156 microns 63 PMMA bead mixture - 72 Example 44: 28 4,020 Continuous equal parts of (i), (ii) and 582 nm flow: 8.6+ (iii) 42, 89, 156 microns 64 PMMA bead mixture - 74 Example 44: 26 28,020 4 equal parts of (i), (ii) and 582 nm (iii) 42, 89, 156 microns 65 PMMA bead mixture - 76 Example 44: 24 54,000 2 equal parts of (i), (ii) and 582 nm (iii) 42, 89, 156 microns

(125) TABLE-US-00015 TABLE 15 Brookfield viscosity of liquid first part prepared from acrylic polymer emulsion of example 44 and different mixtures of acrylic bead polymers Acrylic bead polymer identity and ratio (% wt) PMMA PMMA PMMA Brookfield Example homopolymer (i) homopolymer (ii) homopolymer (iii) viscosity Number 42 microns 89 microns 156 microns (cPs) 66 50 50 0 2,200 67 50 0 50 550 68 40 25 25 1,120 69 35 35 35 1,950 70 25 35 40 1,930 71 25 40 35 1,850 72 0 50 50 8,700 Poly(MMA-co-2EHA) Poly(MMA-co-2EHA) Poly(MMA-co-2EHA) 92:8% wt (iv) 92:8% wt (v) 92:8% wt (vi) 28 microns 78 microns 147 microns 73 50 0 50 1,800 74 40 25 35 2,400 75 35 35 35 3,700 76 25 35 40 6,600 77 25 40 35 7,300

Examples 66 to 77

(126) These examples show the viscosity-reducing effect on a liquid first part obtained from mixing a given acrylic polymer emulsion with mixtures of different ratios of acrylic bead polymers of different particle sizes. The results are presented in table 15. Two series of experiments were carried out. One series was based on PMMA homopolymers of different mean diameter particle size (designated (i), (ii) and (iii)). A second series was based on poly(MMA-co-2EHA) copolymers of different mean diameter particle size (designated (iv), (v), and (vi)). The details on polymers (i) to (vi) are provided in table 8. The general preparation method for the each liquid first part is as follows:

(127) To a 250 ml polypropylene beaker equipped with electric stirrer motor and stainless steel paddle stirrer is added 70 g of acrylic bead polymer mixture. The composition of the acrylic bead polymer mixture used for each example is detailed in table 15. Stirring is commenced at 100 rpm and 30 g of acrylic polymer emulsion of example 44 is added over 60 to 90 seconds. The stirrer speed is then increased to 600-1000 rpm and mixing is continued for a further 3 to 5 minutes until a uniform liquid mixture is obtained.

(128) Comparison of examples 66 to 72 with examples 56 to 58 shows that the use of a mixture of two or more PMMA bead polymers of different mean diameter particle size produces a liquid first part that demonstrates a lower Brookfield viscosity than when only a single PMMA bead polymer is used. Examples 73 to 77 show that a similar viscosity-reducing effect is produced when using mixtures of two or more poly(MMA-co-2EHA) bead copolymers of different mean diameter particle size.

Example 78

(129) Preparation of a Liquid Second Part Containing Dissolved Polymer and X-Ray Opacifier for Use in Making Hardenable Compositions

(130) The liquid second part is prepared as follows. Firstly, 10 g of a poly(MMA-co-DMAEMA) copolymer (free of residual initiator, RV=0.50 dl/g) and 10 g of a higher molecular weight poly(MMA-co-DMAEMA) copolymer (free of residual initiator, RV=1.52 dl/g) is dissolved in a mixture of 79.2 g of MMA monomer (stabilised with 60 ppm hydroquinone (HQ) inhibitor) and 0.8 g of N,N-dimethyl-para-toluidine (DMPT) accelerator. 60 g of this monomer/polymer syrup is then transferred to a glass flask equipped with stirrer and 40 g of barium sulphate is added slowly over two minutes with stirring at 500-600 rpm. Stirring is continued for 5 hours to disperse the barium sulphate in the monomer/polymer syrup. The Brookfield viscosity of the resultant liquid second part is 2,734 cPs.

Example 79

(131) Preparation of a Hardenable Composition Using the Liquid First Part of Example 60 and the Liquid Second Part of Example 78

(132) The preparation of a hardenable composition from combining the liquid first part of example 60 with the liquid second part of example 78 is described as follows. Before mixing, the two components are equilibrated for at least 10 hours in an incubator at 23? C. 14.0 g of the liquid first part of 60 is placed into a polypropylene beaker followed by 14.0 g of the liquid second part of example 78. Hand mixing is then carried out at 23? C. for 30 seconds using a metal spatula, whereupon the material is covered and left to stand. Periodically, the material is assessed for initial mix consistency. When the dough time is achieved, the doughed mixture is removed from the beaker and further mixed by hand manipulation for 30 seconds. For preparing specimens for mechanical testing, the dough is packed into metal moulds preconditioned at 23? C. and allowed to harden under pressure (2 bar). The specimens are demoulded 30 minutes after the set time. Table 16 records the results.

(133) TABLE-US-00016 TABLE 16 Mechanical properties of hardenable composition prepared from mixing the liquid first part of example 60 with the liquid second part of example 78 Compres- Flexural Flexural sive Example Composition of liquid strength Modulus Strength number first part (MPa) (GPa) (MPa) 79 Ex. 60: Poly(MMA-co-sty) 50.5 2.16 73.1 bead mixture - equal parts of (vii), (viii) and (ix) 35, 112, 138 microns: PMMA emulsion of exam- ple 44 (blend ratio bead polymer:emulsion = 70:30% wt)

(134) It can be seen that the hardenable composition of example 79 displays mechanical properties that exceed the minimum requirements of ISO 5833:2002Implants for surgeryAcrylic resin cements, i.e. compressive strength ?70 MPa, flexural modulus ?1.8 GPa and flexural strength ?50 MPa.

(135) Attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference.

(136) All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive.

(137) Each feature disclosed in this specification (including any accompanying claims, abstract and drawings) may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.

(138) The invention is not restricted to the details of the foregoing embodiment(s). The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.